Gériatrie [Geriatry]

This review discuss several studies published in 2007 that will modify current therapeutic attitudes. New evidence confirm that antipsychotics increase mortality in demented elderly persons with behavioral symptoms. Unfortunately, donepezil was no more effective than placebo to treat agitation in these patients. Aspirine, nonsteroidal anti-inflammatories, as well as supplementation with folate, vitamines B6 and B12 did not prove beneficial to prevent cognitive decline. Hormonal substitution with DHEA, testosterone, and growth hormone is ineffective as anti-aging medicine, while calcium and vitamin d'effectiveness was confirmed in fracture prevention. Finally, several studies report prognostic information that will prove important to improve preparation plan for future heat wave.

Cultivation of Flammulina velutipesmushroom using various agro-residues as a fruiting substrate

The objective of this work was to evaluate the feasibility of different agro-residues as a carbon source in the fruiting substrates of Flammulina velutipesmushroom and the effect of supplementation with the nitrogen sources spent brewer's yeast and rice bran. The following fruiting substrates were evaluated: rubber wood sawdust (SD), paddy straw (PS), palm empty fruit bunches (EFB), and palm-pressed fiber (PPF). Cultivation was done on each agro-residue, based on formulations consisting of two substrates at the ratios of 3:1, 1:1, and 1:3. Mycelial growth rate and basidiocarp yield were evaluated. The best fruiting substrates were PS+EFB (25:75), PS+PPF (50:50), and PPF (100), with biological efficiency of 185.09±36.98, 150.89±50.35, and 129.06±14.51%, respectively. No significant effects of supplementation with rice bran and spent yeast were observed on mycelial growth rate and biological efficiency. The cultivation of F. velutipes on oil palm wastes does not require additional nitrogen sources.

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

Milk yield and reproductive performance of dairy heifers and cows supplemented with polyunsaturated fatty acids

The objective of this work was to determine productive and fertility responses of Holstein-Friesian heifers and cows to supplementation with extruded linseed and soybean as sources of polyunsaturated fatty acids (PUFAs). Supplementation had a positive effect on profitability, with significant increases in milk yield in supplemented cows, but not in heifers. Treatments had no effect on milk fat content, but higher milk protein contents were observed with supplementation. A higher conception rate was found for supplemented heifers, but not for cows. Fat sources containing PUFAs are recommended for dairy cattle supplementation, since they improve fertility in heifers and milk yield in cows.

Medication exposure during pregnancy: a pilot pharmacovigilance system using health and demographic surveillance platform.

BACKGROUND: There is limited safety information on most drugs used during pregnancy. This is especially true for medication against tropical diseases because pharmacovigilance systems are not much developed in these settings. The aim of the present study was to demonstrate feasibility of using Health and Demographic Surveillance System (HDSS) as a platform to monitor drug safety in pregnancy. METHODS: Pregnant women with gestational age below 20 weeks were recruited from Reproductive and Child Health (RCH) clinics or from monthly house visits carried out for the HDSS. A structured questionnaire was used to interview pregnant women. Participants were followed on monthly basis to record any new drug used as well as pregnancy outcome. RESULTS: 1089 pregnant women were recruited; 994 (91.3%) completed the follow-up until delivery. 98% women reported to have taken at least one medication during pregnancy, mainly those used in antenatal programmes. Other most reported drugs were analgesics (24%), antibiotics (17%), and antimalarial (15%), excluding IPTp. Artemether-lumefantrine (AL) was the most used antimalarial for treating illness by nearly 3/4 compared to other groups of malaria drugs. Overall, antimalarial and antibiotic exposures in pregnancy were not significantly associated with adverse pregnancy outcome. Iron and folic acid supplementation were associated with decreased risk of miscarriage/stillbirth (OR 0.1; 0.08 - 0.3). CONCLUSION: Almost all women were exposed to medication during pregnancy. Exposure to iron and folic acid had a beneficial effect on pregnancy outcome. HDSS proved to be a useful platform to establish a reliable pharmacovigilance system in resource-limited countries. Widening drug safety information is essential to facilitate evidence based risk-benefit decision for treatment during pregnancy, a major challenge with newly marketed medicines.

Intragastric and Intranasal Administration of Lactobacillus paracasei NCC2461 Modulates Allergic Airway Inflammation in Mice.

Introduction. Preclinical and clinical evidences for a role of oral probiotics in the management of allergic diseases are emerging. Aim. We aimed at testing the immunomodulatory effects of intranasal versus intragastric administration of Lactobacillus paracasei NCC2461 in a mouse model of allergic airway inflammation and the specificity of different probiotics by comparing L. paracasei NCC2461 to Lactobacillus plantarum NCC1107. Methods. L. paracasei NCC2461 or L. plantarum NCC1107 strains were administered either intragastrically (NCC2461) or intranasally (NCC2461 or NCC1107) to OVA-sensitized mice challenged with OVA aerosols. Inflammatory cell recruitment into BALF, eotaxin and IL-5 production in the lungs were measured. Results. Intranasal L. paracasei NCC2461 efficiently protected sensitized mice upon exposure to OVA aerosols in a dose-dependent manner as compared to control mice. Inflammatory cell number, eotaxin and IL-5 were significantly reduced in BALF. Intranasal supplementation of L. paracasei NCC2461 was more potent than intragastric application in limiting the allergic response and possibly linked to an increase in T regulatory cells in the lungs. Finally, intranasal L. plantarum NCC1107 reduced total and eosinophilic lung inflammation, but increased neutrophilia and macrophages infiltration. Conclusion. A concerted selection of intervention schedule, doses, and administration routes (intranasal versus intragastric) may markedly contribute to modulate airway inflammation in a probiotic strain-specific manner.

Sputum containing zinc enhances carbapenem resistance, biofilm formation and virulence of Pseudomonas aeruginosa.

Pseudomonas aeruginosa chronic lung infections are the leading cause of mortality in cystic fibrosis patients, a serious problem which is notably due to the numerous P. aeruginosa virulence factors, to its ability to form biofilms and to resist the effects of most antibiotics. Production of virulence factors and biofilm formation by P. aeruginosa is highly coordinated through complex regulatory systems. We recently found that CzcRS, the zinc and cadmium-specific two-component system is not only involved in metal resistance, but also in virulence and carbapenem antibiotic resistance in P. aeruginosa. Interestingly, zinc has been shown to be enriched in the lung secretions of cystic fibrosis patients. In this study, we investigated whether zinc might favor P. aeruginosa pathogenicity using an artificial sputum medium to mimic the cystic fibrosis lung environment. Our results show that zinc supplementation triggers a dual P. aeruginosa response: (i) it exacerbates pathogenicity by a CzcRS two-component system-dependent mechanism and (ii) it stimulates biofilm formation by a CzcRS-independent mechanism. Furthermore, P. aeruginosa cells embedded in these biofilms exhibited increased resistance to carbapenems. We identified a novel Zn-sensitive regulatory circuit controlling the expression of the OprD porin and modifying the carbapenem resistance profile. Altogether our data demonstrated that zinc levels in the sputum of cystic fibrosis patients might aggravate P. aeruginosa infection. Targeting zinc levels in sputum would be a valuable strategy to curb the increasing burden of P. aeruginosa infections in cystic fibrosis patients.

Contributions of the peroxisome and β-oxidation cycle to biotin synthesis in fungi.

The first step in the synthesis of the bicyclic rings of D-biotin is mediated by 8-amino-7-oxononanoate (AON) synthase, which catalyzes the decarboxylative condensation of l-alanine and pimelate thioester. We found that the Aspergillus nidulans AON synthase, encoded by the bioF gene, is a peroxisomal enzyme with a type 1 peroxisomal targeting sequence (PTS1). Localization of AON to the peroxisome was essential for biotin synthesis because expression of a cytosolic AON variant or deletion of pexE, encoding the PTS1 receptor, rendered A. nidulans a biotin auxotroph. AON synthases with PTS1 are found throughout the fungal kingdom, in ascomycetes, basidiomycetes, and members of basal fungal lineages but not in representatives of the Saccharomyces species complex, including Saccharomyces cerevisiae. A. nidulans mutants defective in the peroxisomal acyl-CoA oxidase AoxA or the multifunctional protein FoxA showed a strong decrease in colonial growth rate in biotin-deficient medium, whereas partial growth recovery occurred with pimelic acid supplementation. These results indicate that pimeloyl-CoA is the in vivo substrate of AON synthase and that it is generated in the peroxisome via the β-oxidation cycle in A. nidulans and probably in a broad range of fungi. However, the β-oxidation cycle is not essential for biotin synthesis in S. cerevisiae or Escherichia coli. These results suggest that alternative pathways for synthesis of the pimelate intermediate exist in bacteria and eukaryotes and that Saccharomyces species use a pathway different from that used by the majority of fungi.

Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial.

BACKGROUND: Enteral nutrition (EN) is recommended for patients in the intensive-care unit (ICU), but it does not consistently achieve nutritional goals. We assessed whether delivery of 100% of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition (SPN) could optimise clinical outcome. METHODS: This randomised controlled trial was undertaken in two centres in Switzerland. We enrolled patients on day 3 of admission to the ICU who had received less than 60% of their energy target from EN, were expected to stay for longer than 5 days, and to survive for longer than 7 days. We calculated energy targets with indirect calorimetry on day 3, or if not possible, set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men, respectively. Patients were randomly assigned (1:1) by a computer-generated randomisation sequence to receive EN or SPN. The primary outcome was occurrence of nosocomial infection after cessation of intervention (day 8), measured until end of follow-up (day 28), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00802503. FINDINGS: We randomly assigned 153 patients to SPN and 152 to EN. 30 patients discontinued before the study end. Mean energy delivery between day 4 and 8 was 28 kcal/kg per day (SD 5) for the SPN group (103% [SD 18%] of energy target), compared with 20 kcal/kg per day (7) for the EN group (77% [27%]). Between days 9 and 28, 41 (27%) of 153 patients in the SPN group had a nosocomial infection compared with 58 (38%) of 152 patients in the EN group (hazard ratio 0·65, 95% CI 0·43-0·97; p=0·0338), and the SPN group had a lower mean number of nosocomial infections per patient (-0·42 [-0·79 to -0·05]; p=0·0248). INTERPRETATION: Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient. FUNDING: Foundation Nutrition 2000Plus, ICU Quality Funds, Baxter, and Fresenius Kabi.

Genetic association analyses reveal a role for vitamin D insufficiency in hepatitis C virus-associated hepatocellular carcinoma development

Background: V itamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. Methods: Associations between t he r isk o f HCV-related HCC development and CYP2R1 , GC, and DHCR7 genotypes, which are genetic determinants of reduced 25-OH-vitamin D3 (25[OH]D3) serum levels, were determined. Results: A t otal of 5604 HCV-infected patients, 1279 with a nd 4325 without progression to HCC, w ere identified. The well-known association between 25(OH)D3 s erum levels and variations in CYP2R1 ( rs1993116, rs10741657), GC ( rs2282679), a nd DHCR7 ( rs7944926, rs12785878) g enotypes was also apparent in patients w ith chronic hepatitis C. The same genotypes of t hese single nucleotide polymorphisms (SNPs), w hich are associated with reduced 25(OH)D3 s erum levels, were significantly associated with HCV-associated HCC (P=0.07 [OR=1.13] for CYP2R1 , P=0.007 [OR=1.56] for GC, P=0.003 [OR=1.42] for DHCR7; ORs for risk genotypes). In contrast, no association between t hese genetic variations and the o utcome of antiviral therapy with pegylated interferon-α and ribavirin ( P>0.2 for e ach SNP) or liver fibrosis progression rate (P>0.2 for each SNP) was observed, s uggesting a specific influence o f the genetic d eterminants of 25(OH)D3 s erum levels o n hepatocarcinogenesis. Conclusions: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related HCC development. Controlled clinical trials to assess the benefit of vitamin D supplementation in HCVinfected patients with advanced liver fibrosis or cirrhosis are warranted.

Independent sources of condition dependency and multiple pathways determine a composite trait: lessons from carotenoid-based plumage colouration.

Many colour ornaments are composite traits consisting of at least four components, which themselves may be more complex, determined by independent evolutionary pathways, and potentially being under different environmental control. To date, little evidence exists that several different components of colour elaboration are condition dependent and no direct evidence exists that different ornamental components are affected by different sources of variation. For example, in carotenoid-based plumage colouration, one of the best-known condition-dependent ornaments, colour elaboration stems from both condition-dependent pigment concentration and structural components. Some environmental flexibility of these components has been suggested, but specifically which and how they are affected remains unknown. Here, we tested whether multiple colour components may be condition dependent, by using a comprehensive 3 × 2 experimental design, in which we carotenoid supplemented and immune challenged great tit nestlings (Parus major) and quantified effects on different components of colouration. Plumage colouration was affected by an interaction between carotenoid availability and immune challenge. Path analyses showed that carotenoid supplementation increased plumage saturation via feather carotenoid concentration and via mechanisms unrelated to carotenoid deposition, while immune challenge affected feather length, but not carotenoid concentration. Thus, independent condition-dependent pathways, affected by different sources of variation, determine colour elaboration. This provides opportunities for the evolution of multiple signals within components of ornamental traits. This finding indicates that the selective forces shaping the evolution of different components of a composite trait and the trait's signal content may be more complex than believed so far, and that holistic approaches are required for drawing comprehensive evolutionary conclusions.

Compliance with preoperative oral nutritional supplements in patients at nutritional risk─only a question of will?

BACKGROUND/OBJECTIVES: Preoperative nutrition has been shown to reduce morbidity after major gastrointestinal (GI) surgery in selected patients at risk. In a randomized trial performed recently (NCT00512213), almost half of the patients, however, did not consume the recommended dose of nutritional intervention. The present study aimed to identify the risk factors for noncompliance. SUBJECTS/METHODS: Demographic (n=5) and nutritional (n=21) parameters for this retrospective analysis were obtained from a prospectively maintained database. The outcome of interest was compliance with the allocated intervention (ingestion of ⩾11/15 preoperative oral nutritional supplement units). Uni- and multivariate analyses of potential risk factors for noncompliance were performed. RESULTS: The final analysis included 141 patients with complete data sets for the purpose of the study. Fifty-nine patients (42%) were considered noncompliant. Univariate analysis identified low C-reactive protein levels (P=0.015), decreased recent food intake (P=0.032) and, as a trend, low hemoglobin (P=0.065) and low pre-albumin (P=0.056) levels as risk factors for decreased compliance. However, none of them was retained as an independent risk factor after multivariate analysis. Interestingly, 17 potential explanatory parameters, such as upper GI cancer, weight loss, reduced appetite or co-morbidities, did not show any significant correlation with reduced intake of nutritional supplements. CONCLUSIONS: Reduced compliance with preoperative nutritional interventions remains a major issue because the expected benefit depends on the actual intake. Seemingly, obvious reasons could not be retained as valid explanations. Compliance seems thus to be primarily a question of will and information; the importance of nutritional supplementation needs to be emphasized by specific patients' education.

Preoperative nutritional screening by the specialist instead of the nutritional risk score might prevent excess nutrition: a multivariate analysis of nutritional risk factors.

BACKGROUND: The aim of the current study was to assess whether widely used nutritional parameters are correlated with the nutritional risk score (NRS-2002) to identify postoperative morbidity and to evaluate the role of nutritionists in nutritional assessment. METHODS: A randomized trial on preoperative nutritional interventions (NCT00512213) provided the study cohort of 152 patients at nutritional risk (NRS-2002 ≥3) with a comprehensive phenotyping including diverse nutritional parameters (n=17), elaborated by nutritional specialists, and potential demographic and surgical (n=5) confounders. Risk factors for overall, severe (Dindo-Clavien 3-5) and infectious complications were identified by univariate analysis; parameters with P<0.20 were then entered in a multiple logistic regression model. RESULTS: Final analysis included 140 patients with complete datasets. Of these, 61 patients (43.6%) were overweight, and 72 patients (51.4%) experienced at least one complication of any degree of severity. Univariate analysis identified a correlation between few (≤3) active co-morbidities (OR=4.94; 95% CI: 1.47-16.56, p=0.01) and overall complications. Patients screened as being malnourished by nutritional specialists presented less overall complications compared to the not malnourished (OR=0.47; 95% CI: 0.22-0.97, p=0.043). Severe postoperative complications occurred more often in patients with low lean body mass (OR=1.06; 95% CI: 1-1.12, p=0.028). Few (≤3) active co-morbidities (OR=8.8; 95% CI: 1.12-68.99, p=0.008) were related with postoperative infections. Patients screened as being malnourished by nutritional specialists presented less infectious complications (OR=0.28; 95% CI: 0.1-0.78), p=0.014) as compared to the not malnourished. Multivariate analysis identified few co-morbidities (OR=6.33; 95% CI: 1.75-22.84, p=0.005), low weight loss (OR=1.08; 95% CI: 1.02-1.14, p=0.006) and low hemoglobin concentration (OR=2.84; 95% CI: 1.22-6.59, p=0.021) as independent risk factors for overall postoperative complications. Compliance with nutritional supplements (OR=0.37; 95% CI: 0.14-0.97, p=0.041) and supplementation of malnourished patients as assessed by nutritional specialists (OR=0.24; 95% CI: 0.08-0.69, p=0.009) were independently associated with decreased infectious complications. CONCLUSIONS: Nutritional support based upon NRS-2002 screening might result in overnutrition, with potentially deleterious clinical consequences. We emphasize the importance of detailed assessment of the nutritional status by a dedicated specialist before deciding on early nutritional intervention for patients with an initial NRS-2002 score of ≥3.

Can we translate vitamin D immunomodulating effect on innate and adaptive immunity to vaccine response?

Vitamin D (VitD), which is well known for its classic role in the maintenance of bone mineral density, has now become increasingly studied for its extra-skeletal roles. It has an important influence on the body's immune system and modulates both innate and adaptive immunity and regulates the inflammatory cascade. In this review our aim was to describe how VitD might influence immune responsiveness and its potential modulating role in vaccine immunogenicity. In the first instance, we consider the literature that may provide molecular and genetic support to the idea that VitD status may be related to innate and/or adaptive immune response with a particular focus on vaccine immunogenicity and then discuss observational studies and controlled trials of VitD supplementation conducted in humans. Finally, we conclude with some knowledge gaps surrounding VitD and vaccine response, and that it is still premature to recommend "booster" of VitD at vaccination time to enhance vaccine response.

Effects of Dietary Fat Oxidation Products and Flavonols on Lipoprotein Oxidation

Various studies suggest that oxidative modifications of low density lipoprotein (LDL), and also other lipoproteins, have an important role in the development of atherosclerosis. In addition to the oxidation products formed endogenously, oxidised triacylglycerols (TAG) and oxysterols in the diet contribute to the oxidised lipoproteins found in circulation. However, studies on both the effect of oxidised dietary lipids on lipoprotein lipid oxidation and the reactions that modify oxidised fat after ingestion have been scarce. Studies on the effects of dietary antioxidants on the lipid oxidation in vivo and the risk of atherosclerosis have been inconclusive. More clinical trials are needed to test the importance of lipoprotein oxidation as a cardiovascular risk factor in humans. In the recent years, various methods have been optimised and applied to the analysis of lipid oxidation products in vivo, and information on the molecular structures of oxidised lipids in plasma, lipoproteins and atherosclerotic plaques has started to accumulate. However, specific structures of oxidised TAG molecules present in these tissues and lipoprotein fractions have not been investigated earlier. In the orginal research in this thesis, an approach based on highperformance liquid chromatographyelectrospray ionisationmass spectrometry (HPLCESIMS) and baseline diene conjugation (BDC) methods was used in order to investigate lipid oxidation level and oxidised TAG molecular structures in pig and human lipoproteins after dietary interventions. The approach was optimised with human LDL samples, which contained various oxidation products of TAG. LDL particles of hyperlipidaemic subjects contained an elevated amount of conjugated dienes. In the pig studies, several oxidised TAG structures with hydroxy, keto, epoxy or aldehydic groups were found in chylomicrons and VLDL after diets rich in sunflower seed oil. Also, the results showed that oxidised sunflower seed oil increased the oxidation of lipoprotein lipids and their TAG molecules. TAG hydroperoxides could be detected neither in the small intestinal mucosa of the pigs fed on the oxidised oil nor in their chylomicrons or VLDL.6 In the clinical studies, dietary flavonol aglycones extracted from sea buckthorn berries did not have an effect on lipoprotein lipid oxidation and other potential risk factors of atherosclerosis, but their absorption was demonstrated. Oil supplementation seemed to increase the bioavailability of the flavonols. Oxidised TAG molecules were detected in LDL particles of the subjects after both flavonol and control diets.