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Ectopic expression of anticancer genes (ACGs) imposes antineoplastic effects on transformed cells. Clinically, reduced expression of these genes has been linked with poor prognosis, metastasis and chemo/radiotherapy resistance in cancers. Identifying expression pattern of ACGs is crucial to establish their prognostic and therapeutic relevance in colorectal cancer (CRC). In addition to the clinical perspective, naturally occurring compounds can be explored in parallel for inducing ACGs to achieve cancer cell-specific death.Expression profiles of three ACGs (NOXA, PAR-4, TRAIL) were identified via real-time PCR in CRC clinical isolates. Time lapse-based expression modifications in ACGs were studied in a CRC liver metastasis animal model using microarray methodology. Effects of a purified plant protein (riproximin) on selected ACGs were identified in three primary and metastatic CRC cell lines by real-time PCR. Lastly, importance of the ACGs in a cellular environment was highlighted via bioinformatic analysis.ACGs (except NOXA) were persistently downregulated in clinical isolates when comparing the overall mean expression values with normal mucosa levels. In vivo studies showed a prominent inhibition of NOXA and PAR-4 genes in implanted CRC cells during rat liver colonization. TRAIL showed deviation from this theme while showing marked induction during the early period of liver colonization (days 3 and 6 after CRC cell implantation). Riproximin exhibited substantial potential of inducing ACGs at transcriptome levels in selected CRC cell lines. Bioinformatic analysis showed that vital molecular/functional aspects of a cell are associated with the presence of ACGs.ACGs are downregulated in primary and metastatic phase of CRC. Riproximin effectively induces ACGs in CRC cells and can be exploited for clinical investigations over time.

Post-mitotic central nervous system (CNS) neurons have limited capacity for regeneration, creating a challenge in the development of effective therapeutics for spinal cord injury or neurodegenerative diseases. Furthermore, therapeutic use of human neurotrophic agents such as nerve growth factor (NGF) are limited due to hampered transport across the blood brain barrier (BBB) and a large number of peripheral side effects (e.g. neuro-inflammatory pain/tissue degeneration etc.). Therefore, there is a continued need for discovery of small molecule NGF mimetics that can penetrate the BBB and initiate CNS neuronal outgrowth/regeneration. In the current study, we conduct an exploratory high-through-put (HTP) screening of 1144 predominantly natural/herb products (947 natural herbs/plants/spices, 29 polyphenolics and 168 synthetic drugs) for ability to induce neurite outgrowth in PC12 dopaminergic cells grown on rat tail collagen, over 7 days. The data indicate a remarkably rare event-low hit ratio with only 1/1144 tested substances (

Le présent article analyse l’écologie alimentaire du poisson (Labeobarbus altianalis) Cyprinidae de manière à ressortir la qualitative et quantitative du régime alimentaire de ce poisson en fonction de la taille ; la détermination de son rythme d’activités trophique et locomotrice et enfin établir la relation existant entre l’activité trophique et locomotrice de Labeobarbus altianalis dans les différent sites de capture. L’échantillonnage dans les affluents de la rivière Luhoho a été effectué au mois de mars et de juin 2014. Pour chaque sortie, des échantillons de poissons étaient récolté dans chaque affluent de la rivière Luhoho. Chaque fois l’échantillonnage se faisait le matin, midi et soir respectivement entre 6h-9h, 10h-12h et 14h-18h. Lespoissons étaient capturés par 2 pêcheurs utilisant chacun un filet épervier de 10mm de maille d’entre-noeuds et de 2 m² de surface attachés à une longue corde au milieu et entouré dans sa périphérie par des plombs. Le temps du prélèvement du filet variait entre 2 et 3 minutes. L’analyse de résultats permet de conclure quel’espèce Labeobarbus altianalis des affluents de la rivière Luhoho est un poisson phytoplanctonophage se nourrissant essentiellement des diatomées (Bacillariophycées), des Cyanophytes, des Chlorophytes et d’Euglenophytes dans tous les sites considérés et à tous les âges. Son activité locomotrice serait plus intense entre 6 heures et 18heures à Tchinganda et Eke. Par contre, à Tchoko et Nyamunene, c’est entre 14 heures et 18 heures qu’il se déplace intensément. L’activité locomotrice de ce poisson serait liée à la recherche de la nourriture. Il existe un lien étroit entre l’activité locomotrice de ce poisson et son alimentation dans tous les quatre sites d’échantillonnage choisis.Mots clés : Biologie, régime alimentaire, cycle nycthermal, Labeobarbus altianalis, Luhoho, République Démocratique du Congo

The purpose of this study was to determine the best estimate of glomerular filtration rate (GFR) to adjust vancomycin (VAN) dosage in critically ill patients. Seventy-eight adult intensive care unit patients received a 15 mg/kg loading dose of VAN plus a 30 mg/kg/day continuous infusion. Steady-state concentration was measured 48 hours later and the dose was adjusted to obtain a target concentration ranging from 20 to 25 mg/1. GFR was estimated by measured creatinine clearance (CLCR), Cockcroft, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. The required dose providing the target concentration was 36±17 mg/kg/day. The first dosage had to be increased in 51% of all patients and in 84% of trauma patients (highest GFR), but had to be decreased in 17% of patients. The closest relationship between clearances of vancomycin was observed with CKD-EPI to GFR. The correlation between clearances of vancomycin and measured CLCR was significant but was rather poor with Cockcroft and Modification of Diet in Renal Disease equation. On the Bland and Altman plots, measured CLCR provided a lower bias but a larger confidence interval and a weaker precision than CKD-EPI. For VAN dose adjustments in intensive care unit patients, Cockcroft formula and Modification of Diet in Renal Disease should be used with caution. In clinical practice, the physician does not have at their disposal the patient's measured CLCR when prescribing. The CKD-EPI appears to be the best predictor of clearances of vancomycin for calculation of a therapeutic VAN regimen.

Annales Francaises d'Oto-Rhino-Laryngologie et de pathologie cervico-faciale - Vol. 130 - N° 4 - p. 236-240

European Annals of Otorhinolaryngology, Head and Neck Diseases - Vol. 130 - N° 4 - p. 233-236

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of lecithins (Lipidol) for all animal species. The additive consists predominantly of lecithins and other extracted substances. Lecithins are usually phospholipids, composed of phosphoric acid with choline (or ethanolamine, inositol, serine or hydrogen in phosphatidic acid), glycerol and one or two fatty acids. Lecithins are safe for all target species. Setting a maximum content for lecithins is not considered necessary. The use of lecithins in animal nutrition does not pose any risk to the consumer. Lecithins are not irritant to the skin and eyes, not skin sensitisers and not harmful by inhalation. No risk for the environment is expected from the use of lecithins in animal nutrition. Lecithins are considered efficacious as emulsifiers at the recommended use levels.

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of lecithins for all animal species. The additive consists predominantly of lecithins derived from rapeseed, sunflower and soybean, with other plant extracts. Three different forms of the additive are produced: regular liquid lecithins, hydrolysed liquid lecithins and de‐oiled lecithin powder. Lecithins are usually phospholipids, composed of phosphoric acid with choline (or ethanolamine, inositol, serine or hydrogen, in phosphatidic acid), glycerol and one or two fatty acids. Lecithins are safe for all target species. Setting a maximum content for lecithins is not considered necessary. The use of lecithins in animal nutrition does not pose any risk to the consumer. Lecithins are not irritant to the skin and eyes, not skin sensitisers and not harmful by inhalation. No risk for the environment is expected from the use of lecithins in animal nutrition. Lecithins are considered efficacious as emulsifiers at the recommended use levels.

Kidneys are involved in essential complex procedures that maintain the body in equilibrium and preservetheinterior environment necessary for life Nephritis and nephrosis were ranked among the leading causes of death in all ages in the last global burden of disease assessment of the World Health Organization WHO Regarding kidney disease therapeutics the unfavourable extra target effects the narrow therapeutic index the inactivation of the drug before reaching its target or the affected normal distribution due to the pathophysiology of diseases all of these conducted to the requirement of new therapeutic aspects An efficient kidney specific drug delivery system will serve as fascinating approach and attractive option conquering such problems improving the therapeutic index and direct to a favourable pharmacokinetic profile of drugs Such breakthrough in renal targeting will provide an efficacious major key for controlling the incidence of those problems affording a logical treatment methodology managing all at risk patients representing a major intention for therapy and impart an attractive pharmacological implement to elucidate the mechanisms of drug action in the kidney Several attempts to achieve the optimal renal delivery systems had been investigated low molecular weight proteins LMWPs low molecular weight chitosan LMWC Poly vinylpyrrolidone co dimethyl maleic acid PVD anionized polyvinylpyrrolidone PVP galectin carbohydrate recognition domain G C and most recently epsilon poly l lysine derivatives epsilon PLL and the carrier peptide KKEEE K The majority of kidney specific delivery systems target the proximal tubular cells The specific uptake of the carriers by renal proximal tubular cells is attributed in many cases to megalin mediated endocytosis Moreover the overall charge of the carrier seems to play a key role in kidney specific drug delivery On the other hand mesangial cells represent a particularly suitable target for drug delivery by particulate drug delivery systems such as nanoparticles or liposomes taking into account the particle diameter In this review we summarize briefly the aforementioned issues

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of the product BIOSTRONG® 510 (essential oil from thyme and star anise, crushed dried spices and crushed dried herbs), when used as a feed additive for chickens for fattening and rearing to point of lay and minor avian species for fattening and rearing to point of lay. BIOSTRONG® 510 is a preparation of partially microencapsulated essential oils from thyme and star anise, dried herbs and dried spices. The FEEDAP Panel concludes that BIOSTRONG® 510 is safe for chickens for fattening at the proposed conditions of use and that this conclusion can be extended to chickens reared for laying and extrapolated to all minor poultry species for fattening and reared to point of lay. The FEEDAP Panel concludes that the use of BIOSTRONG® 510 as an additive in the feed for chickens for fattening does not present risk for the consumer of meat and meat products. Irritancy studies have not been provided, however, because of the content of saponins, the FEEDAP Panel assumes that the additive is highly irritant to mucous membranes, and considers that measures to minimise exposure by all routes are necessary for the handling of this product. The use of BIOSTRONG® 510 at the recommended levels is not considered to be a risk for the environment. The FEEDAP Panel considers that BIOSTRONG® 510 has the potential to be efficacious in improving performance of chickens for fattening. This conclusion can be extended to chickens reared for laying and extrapolated to all minor poultry species for fattening and reared to point of lay at the same dose.

Iron oxides black, red and yellow are intended to be used as colourings to add and restore colour to feedingstuffs at a recommended concentration between 500 and 1,200 mg/kg. No data on the tolerance of target animals were provided. The iron oxides black, red and yellow are excreted essentially unchanged in the faeces of the target animals. Iron absorption from these water insoluble iron oxides is low. However, no conclusion on the safety of the iron oxides under assessment for the target animals could be made as a sufficient biological and toxicological database, particularly genotoxicity data, was not available. The use of the iron oxides in animal nutrition is unlikely to result in a direct exposure of the consumer and would not influence the iron content of edible tissues and products from animals treated with iron oxides. Consequently, the supplementation of feed for food‐producing animals with the iron oxides under assessment would not provide a risk to consumers. Iron oxide black, red and yellow should be considered as irritant to skin and eyes. In the absence of any information, the Panel on Additives and Products or Substances used in Animal Feed FEEDAP cannot conclude on the potential of the additives to be a skin sensitiser. As the inhalation of iron oxides could cause unspecific lung inflammation, inhalation exposure of users should be considered to be a hazard. As there is concern about the possible genotoxicity of iron oxides, any route of exposure should be considered as hazardous. The use of iron oxide black, red and yellow in animal nutrition does not pose a risk to the environment. The iron oxides are effective in colouring feedingstuffs.

Levucell® SB is the trade name for a feed additive based on viable cells of a strain Saccharomyces cerevisiae. Saccharomyces cerevisiae is considered by EFSA to be suitable for the Qualified Presumption of Safety (QPS) approach to establishing safety for the target species, consumers and the environment. The identity of the strain present in the additive was established. Accordingly, this strain is presumed safe for the target species, consumers of products from animals fed the additive and the environment. Based on the data provided, the formulation Levucell® SB20, the uncoated form, is not a skin or eye irritant or a skin sensitiser. Inhalation exposure is unlikely. Encapsulation used in two other forms (Levucell® ME10 and Levucell® ME Titan) is not expected to introduce hazards for users. Based on the results of the studies provided, the FEEDAP Panel concludes that the additive has the potential to be efficacious in sows at the recommended dose of 1 × 109 CFU/kg feed and in weaned piglets at the recommended dose 2 × 109 CFU/kg feed. The different forms of the additive are considered to be equivalent when used to deliver the same dose.

The compound under assessment, dicopper oxide, contains ≥ 86% copper (Cu). Dicopper oxide is a safe source of copper for chickens for fattening. This conclusion is extended to all animal species/categories provided the maximum authorised copper content in feed is respected. There is no indication that the toxicity of dicopper oxide is essentially different from that described for divalent copper. As dicopper oxide is used as a substitute for other copper‐containing additives and its bioavailability is in the range of copper sulphate, the standard copper‐containing additive, no influence of the use of dicopper oxide in animal nutrition on the copper content of food of animal origin is expected. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) concludes that the use of dicopper oxide in animal nutrition is of no concern for consumer safety. Dicopper oxide is not an irritant to skin but a moderate irritant to the eye. Owing to the nickel content in the additive, it should be considered as a dermal and respiratory sensitiser. Dicopper oxide poses a risk to users upon inhalation exposure. There was no available evidence suggesting that dicopper oxide would pose additional risks to the environment than the other sources of copper already authorised. The substitutive use of dicopper oxide for other copper compounds would therefore not change the previous conclusion of the Panel concerning safety from the environment. Based on the results of a tolerance study in chickens for fattening and a short‐term bioavailability study, the FEEDAP Panel concluded that dicopper oxide is an effective source of copper for all animal species.

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of dry grape extract when used as feed flavouring for all animal species and categories. The additive under assessment (dry grape extract) is a mixture of two extracts from seeds and skin of Vitis vinifera subsp. vinifera. Flavouring preparations produced from food, such as extracts of grapes, can be used in and on food without specific authorisation. The FEEDAP Panel concludes that the additive dry grape extract is safe at the maximum proposed use level (100 mg/kg complete feed) for all animal species except dogs, for which no safe dietary concentration could be established. No safety concern would arise for the consumer from the use of the dry grape extract up to the highest safe level in feeds. The grape seed extract tested are irritating to skin and eyes. However, the extent to which these observations would also apply to the behaviour of the complete additive containing grape skin extracts in addition is unknown. In the absence of data, it is not possible to conclude on the potential of the additive to be skin or respiratory sensitiser. The use of dry grape extract at the maximum proposed dose is not considered to be a risk for the environment. Since the major component of the additive, the proanthocyanidin‐rich seed extract, is recognised to provide flavour in food and its function in feed would be essentially the same, no demonstration of efficacy is considered necessary.

The additive is a mixture of the partial esters of sorbitol and its mono‐ and dianhydrides with edible commercial oleic acid and condensed with approximately 20 moles of ethylene oxide per mole of sorbitol and its anhydrides. It contains a minimum of 65% of oxyethylene groups, equivalent to not less than 96.5% of polyoxyethylene (20) sorbitan monooleate on the anhydrous basis and less than 3% water. The following concentrations of polyoxyethylene (20) sorbitan monooleate per kg complete feedingstuffs are considered safe: 1,260 mg for salmonids, 1,100 mg for cattle for fattening, 830 mg for pigs for fattening and sows, 750 mg for turkeys for fattening, 720 mg for dairy cows, 500 mg for piglets, 420 mg for chickens for fattening and laying hens, 1,320 mg for dogs and 1,100 mg for cats; and 5,000 mg/kg milk replacer are considered safe for calves. The use of polyoxyethylene (20) sorbitan monooleate as feed additive for all animal species at the maximum concentration proposed of 5,000 mg/kg complete feedingstuffs would not raise concerns for the consumer. Polyoxyethylene (20) sorbitan monooleate is non‐irritant to skin and eyes, and is not a skin sensitiser. There is evidence that dermal or oral exposure to the additive can exacerbate the symptoms in individuals who are already sensitised. Users are unlikely to be exposed to the additive by inhalation. The lack of data and the inherent uncertainties do not allow concluding on the safety for the environment. Polyoxyethylene (20) sorbitan monooleate is a recognised emulsifier used in food and it is expected to have the same effect when applied to feed. From the practical examples provided, polyoxyethylene (20) sorbitan monooleate appears to be effective in aiding and maintaining the homogeneous distribution of feed materials and/or additives in feedingstuffs.

Introduction/aim Nosocomial infections (NIs) occurrence during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support and their complications appear to contribute to the high mortality rates (40–60%) of these patients. The most common ones are ventilator-associated pneumonia and bloodstream infections (BSI). In clinical practice, detection of NIs is difficult due to confounding factors caused by the device. The objectives of our study were to analyze BSI and positive tracheal aspirate (TA) culture incidences, distribution of microorganisms and risk factors in adult undergoing veinoarterial ECMO (VA-ECMO). Methods We prospectively and consecutively included all adult patients who underwent VA-ECMO between May 2014 and March 2016 in our intensive care unit. Anamnestic data, blood culture and TA culture were analyzed. Primary endpoint was the occurrence of a BSI or a positive TA culture more than 24 hours after ECMO initiation and within 48 hours after ECMO discontinuation. Results Among the 56 patients who underwent ECMO support for more than 48 hours, the BSI prevalence was 27.4 cases per 1000 ECMO days and microorganisms associated were most frequently gram-negative bacilli. As for positive TA cultures, microorganisms associated were oropharyngeal germs and gram-negative bacilli. Two risk factors were associated with nosocomial bacteria occurrence in TA cultures: prior antibiotics and duration of mechanical ventilation more than 5 days. We demonstrated a link between “positive TA culture” and “positive blood culture” and we showed a protective effect of using an antibioprophylaxis on “positive TA culture” and “global positive cultures” development ( Table 1 ). Conclusion Use of an antibioprophylaxis at ECMO implantation is associated with a decrease of global positive cultures development.

Extracorporeal membrane oxygenation (ECMO) has become standard supportive therapy during critical cardiorespiratory situations. Anticoagulation is mandatory to prevent obstruction of the circuit. The optimal heparin infusion rate is estimated for each patient according to a dose–response relationship that is usually measured with the activated clotting time (ACT). Preliminary data suggests that ACT gives a wrong estimate of this relationship so we compared it to anti-Xa activity during heparin infusion. We performed an observational prospective cohort study on 65 consecutive patients treated with ECMO and unfractionated heparin between January 2014 and April 2015 in the intensive care unit of the Rangueil University Hospital in Toulouse, France. ACT was measured with Hemocron®Low Range for a target 180–220 s. Anti-Xa activity was measured for a target 0.2–0.4 UI/mL with STA-Liquid anti-Xa on the STAR® coagulometer. The dose–response relationship and risk of over and under dosage were analyzed on the first 5 days of treatment divided each in 2 periods of 12 h. This dose–response relationship over time was studied with a generalized mixed effects model. The study protocol was approved by our institutional ethics and research committee (no. 11-0214). ACT results are independent (P = 0.55) of the daily amount of heparin administered (IU/kg/day) while anti-Xa activity results show a clear quadratic dose–response relationship (P Fig. 1 ).

Introduction/Aim Detection of nosocomial infections (NIs) occurring during extracorporeal membrane oxygenation (ECMO) is difficult and their related side effects appear to contribute to the high mortality rates (40–50%) of these patients. The most common ones are ventilator-associated pneumonia and bloodstream infections (BSI). Thus we empirically developed a standardized protocol with systematic blood cultures on days 2, 6, 10 and 15. The objectives of this study were to analyze BSI incidence, distribution of microorganisms, risk factors in adult undergoing ECMO support and to evaluate the efficiency of our protocol. Methods We prospectively included all adult patients who underwent veinoarterial (VA-ECMO) or veinovenous extracorporeal membrane oxygenation (VV-ECMO) between May 2014 and March 2016. Anamnestic data and blood culture results using the protocol and additional blood samples were analyzed. Results Among the 81 patients who underwent ECMO support for more than 48 hours, 10 patients in the VA-ECMO group (n = 10/56; 17.9%) and 3 patients in the VV-ECMO group (n = 3/25; 12%) developed 18 BSI, corresponding to a global rate of 22.4 BSI per 1000 ECMO days. Microorganisms associated with these infections were most frequently gram-negative bacilli. Only the duration of ECMO was significantly correlated with BSI occurrence, with a median duration of 6.5 days for “patients without BSI” and of 14 days for “patients with BSI” (P = 0.0170). The efficiency of the protocol in diagnosing BSI was roughly 5% (5/96) for the VA-ECMO group and around 6% (3/49) for the VV-ECMO group. Conclusion Probability of developing BSI in adults undergoing ECMO increases with ECMO duration. Systematic blood cultures do not appear to be an effective way of improving BSI detection.

Annales Francaises d'Oto-Rhino-Laryngologie et de pathologie cervico-faciale - Vol. 129 - N° 5 - p. 319-323

Resume La chirurgie de la base du crâne a beaucoup evolue avec le developpement des techniques endoscopiques. Les premieres interventions concernaient des lesions sellaires, puis d’autres regions ont progressivement ete abordees. De nombreuses pathologies sont aujourd’hui accessibles a cette chirurgie. L’attrait principal de la voie endoscopique reside dans l’acces direct qu’elle offre a nombre de lesions sinusiennes ou intracrâniennes, evitant le prejudice d’une incision cutanee, d’un volet osseux facial ou crânien, et de la retraction cerebrale, inevitable dans les abords neurochirurgicaux classiques. La morbi-mortalite est diminuee, et indirectement la duree d’hospitalisation, le cout de la prise en charge. Le nombre croissant de publications sur ces techniques montre d’ailleurs l’interet qu’elles suscitent. Nous proposons une mise au point sur les voies d’abord endoscopiques de la base du crâne. Les indications sont discutees, et les grands principes de la chirurgie endonasale endoscopique sont rappeles. Les progres effectues dans le domaine de l’exposition et surtout de la reconstruction sont detailles, en montrant qu’ils ont permis d’effectuer des resections plus larges en gardant une morbidite raisonnable. Nous evoquons enfin les limites de cette chirurgie, et rappelons que, bien que souvent qualifiee de « mini-invasive », elle n’en est pas pour autant denuee de toute morbidite.

L’indication de nutrition enterale chez un patient hyperglycemique s’inscrit, soit dans le cadre d’un diabete, soit lors d’une situation pathologique aigue compliquee d’une hyperglycemie de stress. Dans ces situations d’hyperglycemie, quel produit et quelle strategie adopter pour mener au mieux une nutrition enterale adaptee ? Quel traitement de l’hyperglycemie proposer ? La prise en charge repose sur ces deux axes interdependants. Elle ne sera efficace que si l’apport nutritionnel couvre les besoins energetiques du patient et que le traitement de l’hyperglycemie est ajuste en regard, pour limiter hyper- et hypoglycemies, et donc les complications qui y sont rattachees.

Introduction En dehors des formes secondaires a des traumatismes de guerre ou des effondrements de bâtiments, le pronostic des rhabdomyolyses severes reste mal connu. En particulier, les facteurs predictifs d’insuffisance renale aigue severe et du recours a une epuration extra-renale (EER) ne sont pas clairement etablis, empechant de definir de nouveaux axes d’amelioration therapeutique. Patients/Materiels et methodes Etude retrospective multicentrique colligeant les donnees cliniques et biologiques des patients adultes admis entre 2008 et 2017 en soins intensifs de nephrologie ou en reanimation pour une rhabdomyolyse severe (CPK maximales > 5000 UI/L). Identification des facteurs predictifs a l’admission du developpement d’une IRA severe necessitant une EER et de la mortalite a j28. Les donnees sont representees sous forme de mediane et interquartiles. Observation/Resultats Parmi les 387 patients inclus (homme, 70 % ; âge median 49 ans [34–62]), la principale cause de rhabdomyolyse etait une immobilisation prolongee (n = 131, 34 %), suivie par un crush syndrome (n = 108, 28 %), une ischemie aigue de membre (n = 60, 15 %), un etat de mal (n = 15, 4 %), une hyperthermie maligne (n = 7, 2 %) ou une autre cause (n = 66, 17 %). A l’admission, les CPK medians etaient a 8167 UI/L [3173–19 604], la myoglobine a 8433 mg/L [3272–21 715], le phosphore a 1,27 mmol/L [0,89–1,69 mmol/L], la calcemie a 2,07 mmol/L [1,83–2,22], la creatininemie a 128 μmol/L [90–198] et le score SOFA a 8 [4–11]. Au cours de l’hospitalisation, 315 patients (81 %) ont presente une IRA dont 171 (44 %) une IRA stade 3. Cent-trois patients (26 %) ont necessite une EER, 229 (59 %) une ventilation mecanique et 185 (48 %) un support par amines vasopressives. Les facteurs independamment associes a la mortalite a j28 (n = 42, 11 %) etaient la cause de la rhabdomyolyse (hyperthermie maligne), l’âge, le taux de lactates a l’entree, un TP 8000/mm3) a l’admission etaient des facteurs predictifs independants d’EER, tandis qu’un crush syndrome etait protecteur. Discussion/Conclusion Dans cette large cohorte de 389 patients, le recours a une EER est independamment associe a la mortalite a j28. La phosphoremie et la myoglobinemie sont deux facteurs modifiables associes au risque d’EER.

Aim The purpose of our study was to define and validate a population-pharmacokinetic model including the influence of patients' characteristics on the pharmacokinetics of cefepime. Patients and methods A total of 55 patients were randomized in Group 1 (34 patients, 320 cefepime concentrations) for the model building and Group 2 (21 patients, 196 cefepime concentrations) for the validation group. They received cefepime as 2 g A 2 or as 4 g continuously. The population pharmacokinetic analysis was carried out using NONMEM and a baseline model was constructed for studying the influence of demographic and biological variables. The model was then validated by a comparison of the predicted and observed concentrations in Group 2. A final model was elaborated from the whole population. Results Total clearance (CL) was significantly correlated with the serum creatinine (CREA) and the central volume of distribution (V1) was correlated with the body weight (WT). The final model was: CL = 7.14 + (-0.0133 A CREA). V1 = (-16.8) + (0.475 A WT). Q (intercompartmental clearance) = 10.5. V2 = 18.1. The mean pharmacokinetic parameters and their individual variability were: CL (8.24 l/h, 45%), V1 (20.89 l, 60%), V2 (17.95 l, 49%), total volume (38.85 l, 42%) and Q (10.56 l/h, 9%). The bias (1.07 mg/l, IC 95% = -40.46 -+42.60), precision (21.19%) and AFE (1.15) demonstrated the performance of the model. Conclusion We have developed and validated a pharmacokinetic model to estimate cefepime concentrations. We showed that serum creatinine and body weight are factors that may influence the standard dose of cefepime. Our model enabled us to predict cefepime concentrations in other patients.

The additive RONOZYME® NP is a preparation of 6‐phytase produced by a genetically modified strain of Aspergillus oryzae. This product is authorised in the European Union as a feed additive for poultry, weaned piglets, pigs for fattening and sows. The authorisation of RONOZYME® NP for use in pigs for fattening is at a minimum dose of 1,500 FYT/kg feed (recommended range 1,500–3,000 FYT/kg feed). The applicant requested to modify the terms of the authorisation for this species/category of animals, by lowering the minimum recommended dose from 1,500 to 1,000 FYT/kg feed. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded in previous assessments that the additive is safe for the target species, the consumers and the environment, and that the solid forms of the additive are regarded as dermal and eye irritants and all forms are assumed to be respiratory sensitisers. The reduction in the dose proposed would not change the previous conclusions regarding the safety for the target animals, consumer, user and environment. Three trials carried out with growing pigs were submitted in order to support the efficacy at the new recommended dose. In all the trials faecal apparent digestibility of phosphorus was measured, retention was measured only in one trial. The demonstration of efficacy for a phytase requires three studies showing positive and significant effects on the retention of phosphorus. In the trials submitted, the phosphorus retention was studied only in one trial; consequently the efficacy at the newly recommended dose was not demonstrated.

The additive, a natural mixture of dolomite plus magnesite and magnesium‐phyllosilicates, is intended to be used as a technological additive (functional groups: anticaking agents) in feedingstuffs for all animal species. The additive is safe in complete feed for dairy cows, piglets and pigs for fattening at a maximum concentration of 20,000 mg/kg. No conclusions can be drawn for all the other animal species/categories. The additive is not genotoxic. As the additive is essentially not absorbed from the gut lumen, the Panel on Additives and Products or Substances used in Animal Feed considers that use of the additive in animal nutrition is safe for consumers of food products from animals fed diets containing the additive. The additive is not an irritant to the eyes and the skin, it is not a skin sensitiser and it is of low toxicity by the inhalation route. The components of the additive (dolomite, magnesite, talc and chlorite) are natural constituents of soil. Consequently, the use of the additive in animal nutrition will not pose a risk to the environment. The additive is effective as an anticaking agent at a minimum inclusion level of 5,000 mg/kg feed.

Humans have had cancer throughout documented history; hence it is no surprise that people have written about this deadly disease through ancient history. The Edwin Smith Papyrus, the oldest description of cancer, was discovered around 3000-2500 BC in Egypt describing 8 breast tumors that were eradicated by cauterization with a fire drill. As expected back then, the statement of the Egyptian writers about the disease was, “There is no treatment” [1].

The vertical cylinder electrode configuration, rotating or not, is one of the most used electrochemical configurations for electrochemical processes study. Homogeneous accelerations, like gravity or inertial one, leads to a buoyant force and then to natural free flow, induced by density gradient which occurs, for example, during electrodeposition process. There is good accord between experimental and numerical results when the configuration is horizontal or when there is an intense forced convective flow. But there is rather interesting modifications when the homogeneous acceleration value is modified or when the studied electrochemical process is under natural diffusion condition. Very strong forced flows, with rotating disk or cylinder, are usually used to avoid the impact of this phenomenon. But, the convective transport is not so easy to impose: for example, during scale up of the laboratory scale process; or because of the non continuous growth of electrodeposits which leads to dendrite or columnar materials at micrometer or nanometer scales, which increase the importance in the void space of the natural diffusion transport. There is few knowledge of the impact of the acceleration forces upon the deposit properties at continuous and mesoscopic scales. In the present work, predictive calculation results of the deposition rate and the deposit structure with uniform buoyant force are presented. Numerical simulations for 0, 1 and 10 times the normal earth acceleration have been performed and are explored in details. Continuous scale calculations have been done using the finite volume method. The mesoscopic properties in term of structure are obtained using random walker calculations. The link between the inputs of this algorithm with the outputs of the continuous scale calculations is discussed. Finally, qualitative and quantitative evolution of the structure with acceleration is proposed.

Background Administration of two doses of hepatitis A (HA) vaccine to children ≥2 years of age has been shown to be protective. The present study assessed whether HA vaccine can be administered as early as 6 months of age and whether it can be administered concomitantly with a hexavalent (HV) vaccine at this age. Methods In an open label, randomized, parallel group study, the liquid HV vaccine (HEXAVAC ® ) (diphtheria, tetanus, 2-component acellular pertussis, inactivated poliomyelitis vaccine, Haemophilus influenzae type b conjugated to tetanus protein and hepatitis B) was administered at 2, 4, 6, and 12 months of age to all children. HA vaccine (VAQTA ® ) was given at 7 and 13 months in the separate administration group (Group 1) and at 6 and 12 months in the concomitant administration group (Group 2). Serum samples were obtained at 2, 7, 12, and 14 months in Group 1 and at 2, 7, 12, and 13 months in Group 2. The primary immunogenicity outcomes were the seroconversion rates for HA 1 month after the second dose of HA vaccine in initially seronegative subjects, and the seroconversion rates for each HV antigen 1 month after the third dose of the HV vaccine (both at 7 months of age). Results HA seropositivity rates 1 month after the second dose were 100% in both groups, regardless of initial serostatus. The responses to each HV antigen 1 month after the third dose were similar in both groups. The vaccines were generally well tolerated in both groups regardless of vaccine(s) administered. Conclusions A schedule of two doses of HA vaccine, 6 months apart beginning at 6 months of age is highly immunogenic and well tolerated when administered alone or concomitantly with HV vaccine at 6 and 12 months of age.

Aim The standard dosage recommendations for beta-lactam antibiotics can result in very low drug levels in intensive care (IC) patients and burn patients in the absence of renal dysfunction. We studied the pharmacokinetic parameters and serum concentrations of ceftazidime (CF) and cefepime (CE) in burn patients and analyzed the modifications according to clinical and biological parameters and in particular age and creatinine clearance. Material and methods Two pharmacokinetic studies were carried out with daily doses of 1 g x 6 for CF (n = 17) and 2 g x 3 for CE (n = 13). Creatinine clearance (CL(CR)) was both estimated and measured. Blood was sampled at steady state after an initial and a subsequent antibiotic dose. C(max) (maximal) and C(min) (minimal) concentrations were measured by HPLC. The influence of clinical and biological data was analyzed using ANOVA, ANCOVA and stepwise multiple linear regression. Results The ratio of C(min) to the low MIC break point (4 mg/l) was lower than 4 in 52% of subjects receiving CF and in 80% of subjects receiving CE. The C(min) of CF was correlated with measured CL(CR) and was higher in mechanically ventilated patients than in non-ventilated patients. The clearance of CF was correlated with age. The C(min) of CE was correlated with age and drug clearance with measured CL(CR). Therefore dosage adjustment of these drugs in burn patients needs to take into account age, measured creatinine clearance and the danger of low concentrations occurring when the creatinine clearance is greater than 120 ml x min(-1). Conclusion In burn patients, the pharmacokinetic disposition of CF and CE was much more variable than in healthy subjects. Age and CL(CR) were predictors of the disposition of these antibiotics. Shortening the dosage interval or using continuous infusions will prevent low serum levels and keep trough levels above the MIC for longer periods of time. In view of the lack of a bedside measurement technique for ceftazidime and cefepime levels, we suggest a more frequent use of measured CL(CR) in order to attain efficacious clinical concentrations.

Objective: The pharmacokinetics of ceftazidime, the antibiotic of choice for treating acute P. aeruginosa infections, may be modified in bums patients. The aim of this study was to identify the factors causing variations in the serum antibiotic concentrations in bums patients. Methods: 30 patients with serious burns were randomly divided into two groups. Group 1 received a dose of ceftazidime of 2 × 3 g/24 hours. The second group received the same dose but divided into 6 administrations. Blood samples were taken at 24 (M1) and 48 hours (M2) after the start of treatment and the peak and trough serum concentrations of ceftazidime measured by HPLC. Depending on the results, frequency and/or dose was modified to obtain trough concentrations (C min ) equal to 16 mg/l, i.e. 4 times the MIC. Either the same dose was maintained, but mostly divided up, or it was increased to 1 g × 8 administrations or it was decreased to 1 g × 4 or 1 g × 3. The serum concentrations ofceftazidime obtained were analyzed taking into account the characteristics of the burns patients (multivariate correlation). Results: From the first sample (Ml) C min was lower than the target concentration in 50% of the patients in Group 1 and 20% in Group 2. The modification of the dosing regimen put into place after the first analysis, led to the patients being further divided into four groups before the second blood sampling. Finally, 5 patients ended up in Group 1. In all patients and for all administration times, a negative correlation was found between C min and the creatinine clearance, calculated by using Cockcroft's formula. Conclusion: This study highlights the peculiarities of ceftazidime pharmacokinetics seen in bums patients with high interindividual variability. Based on C min monitoring and a predefined therapeutic range, dose adjustment was often required. Ceftazidime clearance is correlated with creatinine clearance (Cockcroft's formula), suggesting that this parameter could be used for a priori or a posteriori dose individualization. To respect the summary of the product characteristics (SPC) and reduce the variability in trough concentrations, the dose should be fractionated (1 g × 6) over a 24-hour period or even given as a continuous infusion. Trough concentrations must be evaluated to adapt the dosage regimen to attain target concentrations of 4 × the MIC.

PepSoyGen‐C is described as pure cultures of Aspergillus oryzae and Bacillus subtilis added simultaneously to feed materials to reduce antinutritional factors. The applicant is seeking its authorisation as a technological additive, under a newly proposed, currently non‐existent functional group, “substances for the reduction of anti‐nutritional factors”. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) considers that the two microbial cultures should be regarded as two independent feed additives that are the subject of the evaluation. The additives are poorly characterised. The inclusion level is likely to be 2 % by weight of the total substrate. The ratio of the two cultures is described as 50/50 on a weight basis. A dose expressed in colony‐forming units per kilogram of feed is not proposed. No evidence of toxigenic potential or resistance to antibiotics of human and veterinary importance was found, according to the current guidance documents. Therefore, the B. subtilis additive is presumed safe for target animals, consumers of products fed the additive and the environment. The B. subtilis additive should be considered as having the potential to be a skin and eye irritant and a skin sensitiser and be treated accordingly. In the absence of data on production of toxic secondary metabolites in A. oryzae, the FEEDAP Panel cannot draw conclusions on its safety for the target species and consumers of products fed the additive. The A. oryzae additive should be considered as having the potential to be a skin and eye irritant and a skin and respiratory sensitiser and be treated accordingly. The use of the additive as a technological feed additive is not expected to pose a risk to the environment. The FEEDAP Panel cannot draw conclusions on the efficacy of the additives in reducing antinutritional factors in soybean and other feed materials.

Vor 2 Jahren wurde in Amerika die Women’s Health Initiative (WHI)-Studie abgebrochen. Vor einem Jahr erschien die britische One-Million-Women-Studie und trug zusammen mit der WHI-Studie dazu bei, dass die Diskussion um die Hormonersatztherapie neu entfacht wurde. Seitdem wird in den Medien, unter Wissenschaftlern und Ärzten diskutiert und abgewogen. Von Einigkeit kann noch nicht gesprochen werden, allerdings haben die Deutsche Gesellschaft für Senologie und die Deutsche Gesellschaft für Gynäkologie und Geburtshilfe dazu klare Stellungnahmen abgegeben. Ein zentrales Thema der Diskussionen sind Zusammenhänge von Hormonsubstitution und Mammakarzinom. Aus In-vitro-Untersuchungen ist bekannt, dass Östrogene das Brustepithel stimulieren und dass eine verlängerte Östrogenexposition, z.B. durch frühe Menarche und späte Menopause, das Mammakarzinomrisiko erhöhen kann. Indikationen der Hormontherapie (seither als Hormonersatztherapie bekannt) sind bisher klimakterische Beschwerden, Osteoporoseprophylaxe, Verbesserung kognitiver Leistungsfähigkeit sowie Demenzprophylaxe. Diese Indikationen werden vor dem Hintergrund aktueller Studiendaten diskutiert.

Resume Les glycopeptides representent le traitement de choix des infections severes a SAMR. La Vancomycine reste la reference. On peut cependant lui reprocher sa lenteur de bactericidie qui est de 24 a 48 heures. Objectif – Le but de cette etude prospective, randomisee ouverte, est de tenter de montrer chez des patients de reanimation, l'amelioration de la vitesse de bactericidie in vivo grâce a l'administration de Cefpirome a la dose de 4 g/24 heures pendant 48 heures, en association a la Vancomycine, traitement conventionnel des infections a SAMR. Methodes – Cette etude prospective a ete realisee chez 20 patients qui presentaient une pneumonie severe ( n =16) ou une bacteriemie ( n =4). Ils ont ete randomises pour recevoir soit Vancomycine 2 g/jour en perfusion continue (Groupe 1, n =10), soit Vancomycine 2 g/jour associe au Cefrom 2 g × 2/jour (Groupe 2, n =10). Le taux de guerison, les parametres bacteriologiques (cinetique de bactericidie et pouvoir bactericide du serum in vivo au pic et a la vallee), les durees de ventilation et de sejour, ont ete compares dans les deux groupes. Resultats – On ne notait pas de difference significative au niveau de l'evolution clinique entre les deux groupes. La cinetique de bactericidie etait meilleure dans le Groupe 2 (40 % vs 60 % apres six heures a la dilution de 1/8 e ) mais la difference n'etait pas significative. Cependant le pouvoir bactericide du serum etait plus important dans le Groupe 2 : pouvoir bactericide a la dilution de 1/16 e (68 % vs 88,8 % : NS) et surtout a la dilution de 1/32 e (10,5 % vs 50 % : p p

Le present article analyse l’ecologie alimentaire du poisson ( Labeobarbus altianalis ) Cyprinidae de maniere a ressortir la qualitative et quantitative du regime alimentaire de ce poisson en fonction de la taille ; la determination de son rythme d’activites trophique et locomotrice et enfin etablir la relation existant entre l’activite trophique et locomotrice de Labeobarbus altianalis dans les different sites de capture. L’echantillonnage dans les affluents de la riviere Luhoho a ete effectue au mois de mars et de juin 2014. Pour chaque sortie, des echantillons de poissons etaient recolte dans chaque affluent de la riviere Luhoho. Chaque fois l’echantillonnage se faisait le matin, midi et soir respectivement entre 6h-9h, 10h-12h et 14h-18h. Les poissons etaient captures par 2 pecheurs utilisant chacun un filet epervier de 10mm de maille d’entre-noeuds et de 2 m² de surface attaches a une longue corde au milieu et entoure dans sa peripherie par des plombs. Le temps du prelevement du filet variait entre 2 et 3 minutes. L’analyse de resultats permet de conclure que l’espece Labeobarbus altianalis des affluents de la riviere Luhoho est un poisson phytoplanctonophage se nourrissant essentiellement des diatomees (Bacillariophycees), des Cyanophytes, des Chlorophytes et d’Euglenophytes dans tous les sites consideres et a tous les âges. Son activite locomotrice serait plus intense entre 6 heures et 18heures a Tchinganda et Eke. Par contre, a Tchoko et Nyamunene, c’est entre 14 heures et 18 heures qu’il se deplace intensement. L’activite locomotrice de ce poisson serait liee a la recherche de la nourriture. Il existe un lien etroit entre l’activite locomotrice de ce poisson et son alimentation dans tous les quatre sites d’echantillonnage choisis. Mots cles : Biologie, regime alimentaire, cycle nycthermal, Labeobarbus altianalis, Luhoho, Republique Democratique du Congo

It is clear that to meet the new demands of wireless customers, conventional cellular service providers and upcoming Personal Communication Service (PCS) providers for conventional phone service and high bandwidth wireless LAN must upgrade their networks to provide complete radio coverage. This evolution has motivated the need for low-cost systems that transport radio signals to and from areas of poor signal coverage. The most important area where this problem must be solved is inside of buildings, since this is where people spend most of their time. Unfortunately, the in-building enviroment is also the ost challenging area to provide radio coverage due to severe attenuation and multi-path effects. The problem must be tackled from the viewpoint of optimization of performance/cost ratio of the network. In this paper, we describe a system-level approach to tackle this problem. We demonstrate how one can trade-off hardware performance, which represent cost, with proper choice of system architecture which includes, among other factors, in-buiding radio environment, to arrive at an optimum network solution technically and economically.

Dabigatran is a direct thrombin inhibitor indicated for stroke and systemic embolism prevention in patients with non-valvular atrial fibrillation. No reversal agent exists, but hemodialysis has been proposed as dabigatran removal method. We report a case of an 80-year-old man presenting hemorrhage with dabigatran overdose caused by obstructive acute renal failure. Before nephrostomy, several hemodialysis sessions were necessary to remove dabigatran probably because of its large volume of distribution.

We describe the case of a 19-year-old male diagnosed with Reye syndrome within the context of viral pericarditis and salicylate ingestion. He presented a fatal brain oedema without liver failure. Brain biopsies obtained during a decompressive craniectomy led to the diagnosis.

Traumatic brain injuries are fairly sensitive to hypoxia. For patient with associated lung and brain traumas, different means used to improve oxygen blood level are poorly described. We report the use of ECMO in a refractory hypoxemia occurred to a multitrauma young patient with neurological lesions.

We describe experimentally and theoretically three techniques used to transmit narrowband millimeter-wave (MM-wave) analog signals over optical fiber: 1) narrowband MM-wave optical transmitters based on resonant modulation of monolithic semiconductor lasers, 2) feedforward optical modulation, and 3) a passively mode-locked laser operating in an optoelectronic phase-locked loop. The resonant modulation response at the cavity round-trip frequency is fully characterized for multiple-contact lasers under various bias conditions. Issues such as modulation efficiency, passband bandwidth, noise, and intermodulation distortion are addressed. A system implementation of resonant modulation is presented in which two simultaneous 2.5-Mb/s BPSK channels centered at a subcarrier frequency of 41 GHz is transmitted over 400 m of single-mode fiber. Simple microstrip matching circuits are fabricated at 41 GHz to couple the MM-wave signals into the laser. Resonant modulation of single-contact lasers is also reported. Next, implementation of a tunable MM-wave (30-300 GHz) optical transmitter based on feedforward optical modulation is presented, and the fundamental performance of this technique investigated in terms of noise and dynamic range. Feedforward modulation is used to transmit 300-Mb/s data at 39 GHz over 2.2 km of single-mode fiber. Finally, a passively mode-locked monolithic semiconductor laser operating in an optoelectronic phase-locked loop is implemented as a narrowband MM-wave optical transmitter at 46 GHz. The phase-locked loop bandwidth, MM-wave tracking capability, and fundamental limit to the stability of the MM-wave subcarrier is established. The relative merits of the three techniques are discussed and compared. The MM-wave subcarrier transmission results presented here represent the highest reported to date. >