Optimized meropenem dosage regimens using a pharmacokinetic/pharmacodynamic population approach in patients undergoing continuous venovenous haemodiafiltration with high-adsorbent membrane.

BACKGROUND: The pharmacokinetics (PK) of antibiotics change during sepsis and continuous renal replacement therapies in critically ill patients. Limited evidence exists on the use of the oXiris® high-adsorbent membrane. OBJECTIVES: To develop a PK/pharmacodynamic (PD) model for meropenem in critically ill sepsis patients undergoing continuous venovenous haemodiafiltration (CVVHDF) with the oXiris® membrane, and to design an optimal dosing regimen assessed according to the PTA. METHODS: A prospective, open-label, observational PK trial was performed (EUDRACT 2011-005902-30). We conducted PK studies (plasma and ultrafiltrate) for at least 24 h after concomitant administration of CVVHDF and meropenem 1 g q8h. We constructed a PK model using the non-linear mixed-effects approach (NONMEM 7.3). We evaluated the suitability of different dosage regimens using Monte Carlo simulations and calculated the PTA as the percentage of subjects achieving a given percentage of time above the MIC (fT>MIC). RESULTS: The PK of meropenem was best captured by a two-open-compartment model with zero-order input kinetics and first-order elimination. Extracorporeal CL was 7.78 L/h [relative standard error (RSE) 16.45 L/h] and central compartment V (Vc) was 24.9 L (RSE 13.73 L). Simulations showed that, for susceptible Pseudomonas aeruginosa isolates (EUCAST MIC ≤2 mg/L) and attainment of 100%fT>MIC, 500 mg q8h given as extended (EI) or continuous infusion (CI) would be sufficient. For a target of 100%fT>4×MIC, CI of 3000 mg q24h or 2000 mg q8h administered as EI or CI would be required. CONCLUSIONS: We have constructed a PK model of meropenem in sepsis patients undergoing CVVHDF using the oXiris® membrane. This tool will support physicians when calculating the optimal initial dose.

Optimization of cosmetic preservation: water activity reduction.

OBJECTIVE: Preservation of cosmetics is a prerequisite for industrialization, and among the proposed solutions, self-preserved cosmetics are of great interest. One key influencing parameter in self-preservation is water activity; its reduction can help to fight against microbial growth in cosmetic products. This work presents a study on the influence of humectants on water activity and its consequence on the preservation of cosmetic formulations. METHODS: First, water-humectants mixtures were considered. The influence of glycol and glycerin content, glycol chemical structure, glycerin purity and formulation process on the water activity of the binary mixture was studied. Molecular modelling was performed for a better understanding of the impact of glycol chemistry. Then, the results were applied to five different cosmetic formulations to get optimized products. Challenge test on five strains was carried out in that sense. RESULTS: We showed that the higher the humectants concentration, the lower the water activity. Glycol chemical structure also influenced water activity: propan-1,2-diol was more efficient than propan-1,3-diol, certainly because of a better stabilization in water of propan-1,2-diol as shown by DFT calculation. A drop by drop introduction of glycol in water favoured aw reduction. The best water activity loss was 6.6% and was reached on the cream formulation whose preservation was improved as evidenced by challenge test. CONCLUSION: Fabrication process as well as humectants concentration were shown to influence water activity. The hydroxyl group positions as well as the presence of an alkyl group on the glycol carbon chain impacted water binding as suggested by DFT calculation. Reducing aw improved the preservation of a cosmetic cream, inhibiting or slowing down the growth of bacteria and fungi.

Animal board invited review: Improving animal health and welfare in the transition of livestock farming systems: Towards social acceptability and sustainability.

The need to integrate more clearly societal expectations on livestock farming has led the authors of this article to consider that livestock farming systems must be redesigned to position health and welfare at the heart of their objectives. This article proposes a vision of the advances in knowledge required at different scales to contribute to this transformation. After defining health and welfare of animals, the article emphasises the need to consider health in a broader perspective, to deepen the question of positive emotional experiences regarding welfare, and raises the question of how to assess these two elements on farms. The positive interactions between health and welfare are presented. Some possible tensions between them are also discussed, in particular when improving welfare by providing a more stimulating and richer environment such as access to outdoor increases the risk of infectious diseases. Jointly improving health and welfare of animals poses a number of questions at various scales, from the animal level to the production chain. At the animal level, the authors highlight the need to explore: the long-term links between better welfare and physiological balance, the role of microbiota, the psycho-neuro-endocrine mechanisms linking positive mental state and health, and the trade-off between the physiological functions of production, reproduction and immunity. At the farm level, in addition to studying the relationships at the group level between welfare, health and production, the paper supports the idea of co-constructing innovative systems with livestock farmers, as well as analysing the cost, acceptability and impact of improved systems on their working conditions and well-being. At the production chain or territory levels, various questions are raised. These include studying the best strategies to improve animal health and welfare while preserving economic viability, the labelling of products and the consumers' willingness to pay, the consequences of heterogeneity in animal traits on the processing of animal products, and the spatial distribution of livestock farming and the organisation of the production and value chain. At the level of the citizen and consumer, one of the challenges is to better inter-relate sanitary and health perspectives on the one hand, and welfare concerns on the other hand. There is also a need to improve citizens' knowledge on livestock farming, and to develop more intense and constructive exchanges between livestock farmers, the livestock industry and citizens. These difficult issues plead for interdisciplinary and transdisciplinary research involving various scientific disciplines and the different stakeholders, including public policy makers through participatory research.

Characterisation and quantification of flavonoids in Iris germanica L. and Iris pallida Lam. resinoids from Morocco.

INTRODUCTION: Iris resinoid obtained from Iris germanica or Iris pallida rhizomes is widely used in the perfume industry but its chemical composition has not yet been reported. Nevertheless, very active compounds have been identified in iris rhizomes including iridals and isoflavones. OBJECTIVE: In this first study concerning iris resinoid composition, flavonoids were qualitatively and quantitatively investigated in I. germanica and I. pallida resinoids. METHODOLOGY: Resinoids were first fractionated by reverse-phase flash chromatography in order to obtain fractions containing all isoflavones. These fractions were analysed by HPLC-DAD (diode array detector) and the fractions containing isoflavones were analysed by HPLC-QTOF (quadrupole time of flight)-MS. Then, the main isoflavones were isolated and identified by NMR and high-resolution mass spectroscopy (HRMS). Finally, total and individual isoflavones were quantified by HPLC-DAD at 265 nm using an external calibration method with irigenin as the external standard. RESULTS: Eight isoflavones were identified in both resinoids (irigenin, iristectorigenin A, nigricin, nigricanin, irisflorentin, iriskumaonin methyl ether, irilone, iriflogenin), one isoflavone only was identified in I. germanica resinoid (irisolidone), whereas one isoflavone (8-hydroxyirigenin), one isoflavanone (2,3-dihydroirigenin) and one benzophenone (2,6,4'-trihydroxy-4-methoxybenzophenone) only were identified in I. pallida resinoid. Isoflavones were quantified in I. germanica and I. pallida resinoids at 180 ± 1.6 mg/g and 120 ± 3.3 mg/g respectively. CONCLUSION: The study shows that I. germanica and I. pallida resinoids are rich in flavonoids and that these two Iris species can be distinguished by simply analysing the polyphenol fraction.

Proteomic profile evolution during steatosis development in ducks.

We investigated a protein profile evolution during steatosis in ducks using 2-dimensional electrophoresis gels to better understand the mechanisms underlying liver steatosis at the level of hepatic proteins in waterfowl. Two-dimensional electrophoresis gels were performed in the liver at different stages of steatosis in the duck. Mule ducks were slaughtered after 0, 14, or 23 meals of overfeeding, according to commercial conditions. Thirty-one proteic spots were differentially expressed between 3 or 2 durations of overfeeding: 3 spots were differentially expressed between the 3 times and 28 spots were differentially expressed between 2 times. The identified proteins (14) could be regrouped into 5 categories: enzymes, translation factors, proteins involved in cell structure, proteins with antioxidant properties, and proteins that can link calcium. This study opens new research areas in the understanding of steatosis in waterfowl, such as cell structure and oxidative stress.

Duration of transport and holding in lairage at constant postprandial delay to slaughter--effects on fatty liver and breast muscle quality in mule ducks.

The present study was designed to evaluate the effect of preslaughter transport (30 vs. 150 min) and holding of mule ducks in lairage in their transport crates (15 vs. 120 min) on the quality of the meat and fatty liver. A total of 120 birds were allocated in a 2 × 2 factorial design with a constant postprandial delay to slaughter (8 h), to avoid the confounding between the effects of the experimental treatments and those of fasting duration. Under such conditions, extending the transport or holding duration did not induce a loss in preslaughter live weight or liver weight. Similarly, breast muscle glycogen stores were not affected by the treatments, nor was the kinetics of postmortem pH decline affected. The mechanical resistance of raw meat obtained by the compression test significantly increased with holding duration. The gross chemical composition of the livers did not differ significantly among the preslaughter treatments. Residual blood in the liver, as indicated by heme pigment concentration, was enhanced with a longer transport, but this effect was more pronounced after the longest holding duration, as shown by a significant interaction. This, however, did not significantly affect the incidence of appearance defects or the commercial grading of the livers. The percentage of fat loss during the cooking of canned livers was significantly reduced when the transport duration was increased. This effect could not be explained on the basis of the current knowledge for determining the technological quality of fatty liver. The identification of biological markers of liver quality is currently underway in our laboratory. Further investigations studying the differential expression of these biological markers according to preslaughter conditions would provide a better understanding of the effect of transport duration on liver processing yield.

Are one early muscle pH and one early temperature measurement sufficient to detect PSE breast meat in turkeys?

1. Within a large flock of turkey toms (2000 BUT9 conventionally reared and slaughtered), early muscle pH measurements were randomly done to distinguish two groups of birds presenting low (fast glycolysing, GR) or normal (normal glycolysing, GN) values. 2. Subsequently, ultimate pH values and meat quality parameters were also recorded. Meat quality parameters from GR or GN samples differ more or less indicating more or less severe PSE conditions. Proteins extracted from the samples at 20 min post mortem were similar while they differed greatly at 24 h post mortem. Moreover, among the GR birds, a subgroup of animals (called AB) presented SDS-PAGE profiles largely different from other GR or GN birds. 3. All the subsequent analysis developed on meat quality parameters as well as for protein extractabilities also differed between AB and other animals indicating that they must be considered differently in term of PSE syndrome development. 4. Western blots against Myosin Heavy Chain and actin at 24 h post mortem indicate that myofibrillar protein alterations are different in AB and GR or GN samples. 5. At 20 min post mortem, glycogen content was lowest in AB samples while the glycolytic potential was similar in all samples at the time of death. Measurements of PFK enzyme specific activity did not indicate a different regulation of post mortem glycolysis in AB samples. 6. Our results suggest that a unique pH measurement at 20 min post is insufficient to detect animals more prone to developing a severe PSE syndrome in turkeys. In consequence, it is suggested that a more precise evaluation of the kinetics of pH and temperature decrease has to be conducted to understand the aetiology of meat quality parameter alterations in poultry.

Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.

An alternative method for irones quantification in iris rhizomes using headspace solid-phase microextraction.

INTRODUCTION: The essential oil obtained from iris rhizomes is one of the most precious raw materials for the perfume industry. Its fragrance is due to irones that are gradually formed by oxidative degradation of iridals during rhizome ageing. OBJECTIVE: The development of an alternative method allowing irone quantification in iris rhizomes using HS-SPME-GC. METHODOLOGY: The development of the method using HS-SPME-GC was achieved using the results obtained from a conventional method, i.e. a solid-liquid extraction (SLE) followed by irone quantification by CG. RESULTS: Among several calibration methods tested, internal calibration gave the best results and was the least sensitive to the matrix effect. The proposed method using HS-SPME-GC is as accurate and reproducible as the conventional one using SLE. These two methods were used to monitor and compare irone concentrations in iris rhizomes that had been stored for 6 months to 9 years. CONCLUSION: Irone quantification in iris rhizome can be achieved using HS-SPME-GC. This method can thus be used for the quality control of the iris rhizomes. It offers the advantage of combining extraction and analysis with an automated device and thus allows a large number of rhizome batches to be analysed and compared in a limited amount of time.

Comparison of nonlinear and spline regression models for describing mule duck growth curves.

This study compared models for growth (BW) before overfeeding period for male mule duck data from 7 families of a QTL experimental design. Four nonlinear models (Gompertz, logistic, Richards, and Weibull) and a spline linear regression model were used. This study compared fixed and mixed effects models to analyze growth. The Akaike information criterion was used to evaluate these alternative models. Among the nonlinear models, the mixed effects Weibull model had the best overall fit. Two parameters, the asymptotic weight and the inflexion point age, were considered random variables associated with individuals in the mixed models. In our study, asymptotic weight had a greater effect in Akaike's information criterion reduction than inflexion point age. In this data set, the between-ducks variability was mostly explained by asymptotic BW. Comparing fixed with mixed effects models, the residual SD was reduced in about 55% in the latter, pointing out the improvement in the accuracy of estimated parameters. The mixed effects spline regression model was the second best model. Given the piecewise nature of growth, this model is able to capture different growth patterns, even with data collected beyond the asymptotic BW.

Review. Sulfur-containing volatile compounds in seafood: occurrence, odorant properties and mechanisms of formation.

An inventory of the most part of sulfur-containing volatile compounds (SCVCs) present in seafood was carried out. These molecules constitute key compounds to understand and improve seafood quality. According to their nature, concentration and environmental parameters (temperature), they can move the overall seafood odor from desirable to rotten. Sulfury odors can also indicate problems in sanitary quality. Thus, it is essential to monitor the generation of these compounds to better control the organoleptic and sanitary quality of seafood. SCVC were divided in two categories: aliphatic compounds and cyclic compounds. Among cyclic SCVC, several families of compounds can be distinguished as thiophenes, thiazoles and their respective derivatives. The main pathways of formation of SCVC in seafood are investigated in order to better understand their presence in seafood aroma. Microbial mediated enzymatic reactions are mainly implied in the generation of aliphatic SCVC whereas Maillard reactions are involved in the generation of cyclic SCVC. A small part of SCVC could also derive from the environment by direct bioaccumulation of S-containing molecules or precursors. Then, the occurrence of SCVC in seafood is discussed according to the extraction methods, analysis methods - sometimes olfactometric methods and the species - the state and the average biochemical composition of the seafood matrix in which they were recovered. Finally, among the identified SCVC, the odorant properties of odor-active volatile compounds were investigated. Aromatic notes and odorant thresholds for odorant SCVC of seafood aroma are listed. Both pathways of formation and lists of SCVC linked to their odorant properties constitute important indicators to optimise seafood quality from an organoleptic and sanitary point of view.

Comparison of the composition and sensory characteristics of goose fatty liver obtained by overfeeding and spontaneous fattening1.

Spontaneous liver steatosis can be experimentally induced in domestic Greylag geese by combining a short photoperiod with a sequence of feed restriction followed by ad libitum corn feeding. This could offer an alternative to the conventional "foie gras" production system based on overfeeding. The present work aimed at comparing the compositional characteristics, sensory profile, and acceptability by a consumer panel of fatty livers obtained by overfeeding and spontaneous fattening. In all, 210 male geese were used: 125 geese were raised over a 31-wk period to produce fatty liver without overfeeding ("alternative livers") and 85 were raised using conventional methods with overfeeding ("conventional livers"). Mean liver weight was over 1 kg (1,102 g) in the conventional group and 445 g in the alternative group. The characteristics of the livers were studied in 2 subpopulations: 44 conventional livers representative of the experimental population (mean liver weight 1,064 g) and 42 alternative livers weighing more than 400 g (mean 702 g). Compared with the alternative livers, livers from the conventional group showed significantly (P < 0.05) higher dry matter and lipid contents, lighter color (L*), and lower yellowness (b*). The neutral lipids of alternative livers contained significantly less triglycerides and free fatty acids and significantly more cholesterol and cholesterol esters than those from conventional livers. Detailed analysis of the fatty acid composition of triglycerides showed that the proportion of mono- and polyunsaturated fatty acids was significantly higher in the alternative livers. However, covariance analysis suggested that these differences in lipid composition were mainly due to differences in lipid content between both types of livers. The evaluation of cooked livers by a trained expert panel revealed significant differences in the sensory profile between the conventional and alternative livers. The acceptability by a consumer panel was significantly lower in alternative compared to conventional livers. This difference was not related to weight and/or lipid content since livers of similar weight range (800 to 1,000 g) were compared and showed clear-cut differences for hedonic scores.

Natural and anthropogenic oil impacts on benthic foraminifera in the southern Gulf of Mexico.

The Campeche Sound is the major offshore oil producing area in the Southern Gulf of Mexico (SGoM). To evaluate the impact of oil related activities in the ocean floor sediments, we analyzed the geochemical (major and trace element, organic carbon and hydrocarbon concentrations) and biological (benthic foraminifera) composition of 62 superficial sediment samples, from 13 to 1336 m water depth. Cluster and Factor analysis of all the variables indicate that their distribution patterns are mainly controlled by differences between the terrigenous and carbonate platforms in the SGoM. Benthic foraminiferal assemblages were abundant and diverse, and their distribution patterns are mainly determined by water depth and sedimentary environment. However, most of the abundant species are opportunistic and/or low-oxygen tolerant, and many of their tests show oil stains and infillings, characteristic of oil polluted locations, suggesting the environment has been modified by natural seepage or oil-related activities. To determine if these conditions are natural or anthropogenic in origin, pre - industrial settings should be studied. Organic carbon (Corg) content (0.6-2.9%) and total hydrocarbon concentrations (PAHs 1.0-29.5 µg kg-1) were usually higher around the oil platforms area, the natural hydrocarbon seeps ("chapopoteras") area and offshore rivers, but there is no accumulation of oil related trace elements in these areas. However, the comparison with international sediment quality benchmarks indicates that Cd, Cr and Ni concentrations are above the threshold effect level, and also As, Ba and Cu are above the probable effect level benchmarks, which indicate that these element concentrations might be of potential ecological concern. Comprehensive studies involving different proxies, and assessing pre-industrial conditions, must be undertaken before assessing environmental health of marine benthic ecosystems.

Convolutional Neural Network-Based Automated Segmentation of the Spinal Cord and Contusion Injury: Deep Learning Biomarker Correlates of Motor Impairment in Acute Spinal Cord Injury.

BACKGROUND AND PURPOSE: Our aim was to use 2D convolutional neural networks for automatic segmentation of the spinal cord and traumatic contusion injury from axial T2-weighted MR imaging in a cohort of patients with acute spinal cord injury. MATERIALS AND METHODS: Forty-seven patients who underwent 3T MR imaging within 24 hours of spinal cord injury were included. We developed an image-analysis pipeline integrating 2D convolutional neural networks for whole spinal cord and intramedullary spinal cord lesion segmentation. Linear mixed modeling was used to compare test segmentation results between our spinal cord injury convolutional neural network (Brain and Spinal Cord Injury Center segmentation) and current state-of-the-art methods. Volumes of segmented lesions were then used in a linear regression analysis to determine associations with motor scores. RESULTS: Compared with manual labeling, the average test set Dice coefficient for the Brain and Spinal Cord Injury Center segmentation model was 0.93 for spinal cord segmentation versus 0.80 for PropSeg and 0.90 for DeepSeg (both components of the Spinal Cord Toolbox). Linear mixed modeling showed a significant difference between Brain and Spinal Cord Injury Center segmentation compared with PropSeg (P < .001) and DeepSeg (P < .05). Brain and Spinal Cord Injury Center segmentation showed significantly better adaptability to damaged areas compared with PropSeg (P < .001) and DeepSeg (P < .02). The contusion injury volumes based on automated segmentation were significantly associated with motor scores at admission (P = .002) and discharge (P = .009). CONCLUSIONS: Brain and Spinal Cord Injury Center segmentation of the spinal cord compares favorably with available segmentation tools in a population with acute spinal cord injury. Volumes of injury derived from automated lesion segmentation with Brain and Spinal Cord Injury Center segmentation correlate with measures of motor impairment in the acute phase. Targeted convolutional neural network training in acute spinal cord injury enhances algorithm performance for this patient population and provides clinically relevant metrics of cord injury.

The role of ghrelin in the energy homeostasis of elderly people: a population-based study.

OBJECTIVE: Ghrelin is a hormone secreted mainly in the stomach which stimulates appetite and food intake. Endocrine factors are among the causes of anorexia in elderly people. The main objective of the present study was to examine the effect of age on ghrelin levels in non-institutionalized elderly people. DESIGN AND SETTING: Observational, cross-sectional, population-based study. PARTICIPANTS: A random sample of men aged 70 yr or older was taken from the municipal census. MEASUREMENTS: All participants underwent a physical examination which measured weight and height, grip strength, functional capacity (according to the Barthel Index) and nutritional status (according to the short form of the Mini Nutritional Assessment). Blood was taken for basic biochemical analysis, determination of somatotropic, corticotropic, and gonadotropic hormones, and for measurement of ghrelin and cholecystokinin. RESULTS: 152 men with a mean (SD) age of 76.7 (5.4) yr were recruited. Mean ghrelin levels were 1143 (401) pg/ml. A weak negative correlation was found between ghrelin levels and age (r=-0.16, p=0.057). Multiple linear regression analysis showed a significant and independent effect of age (beta=-12.1, p=0.049), body mass index (BMI) (beta=-22.0, p=0.021), and creatinine levels (beta=407.7, p=0.002) on ghrelin. No correlations with age and BMI were found for cholecystokinin. CONCLUSIONS: There is a slight decrease in ghrelin levels with age in older men aged 70 yr or more, although the clinical relevance of this finding remains unclear.

[Trans obturator tape (TOT) for female stress incontinence. Experience with three years follow-up in 200 patients]. / Cinta trans-obturadora (TOT) en la corrección de la incontinencia de orina de esfuerzo. Experiencia de tres años con 200 pacientes.

OBJECTIVE: To evaluate the security and effectiveness of the TOT in the female incontinence surgical treatment according to our experience. PATIENT AND METHOD: Prospective study of 200 patients underwent TOT at Gynecology Unit of the Obstetrics and Gynecology Department in Barros Luco-Trudeau Hospital between January 2003 and October 2006. Polypropilene, macropore, mofilament mesh (Prolene) was used. The mean age was 52 years old, parity 3. RESULTS: The mean surgical time of TOT was 15 minutes. In 184 (92%) patients obtained cure, 6 (3%) improvement and 10 (5%) fails. Three cases of bladder injury occurred (one perforation with the scissor and two with TOT needle during the learning phase). During the immediately postoperative time: one case of partial urethral obstruction, two cases of urinary infection and three with pain of the legs. During the delayed postoperative time a case of fail was observed after trauma. CONCLUSION: According to our experience with 200 cases, the TOT appears as a safe and effective technique in the surgical treatment of the stress urinary incontinence.

High postmortem temperature in muscle has very similar consequences in two turkey genetic lines.

In the present study, we artificially generated pale, soft, exudative turkey meat by holding muscles immediately after death at 40 degrees C for 6 h. Two genetic types (BUT9 and Label) were compared. When muscles were kept at 40 degrees C, BUT9 muscles exhibited higher lightness values than Label muscles. Drip, thawing, and cook losses were higher for muscles held at 40 degrees C, compared with those held at 4 degrees C, regardless of genetic type. A significant decrease in meat tenderness was found for muscles kept at 40 degrees C. For both genetic types, protein extractabilities either with low ionic strength or high ionic strength buffer decreased for muscles held at 40 degrees C. These fractions were analyzed by using SDS-PAGE, and proteins that differed from the 4 degrees C and 40 degrees C treatments were identified using a matrix-assisted laser desorption ionization time-of-flight mass spectrometer. We reported the alteration of various proteins, such as alpha-actinin, myosin heavy chain, myokinase, phosphorylase, and ATP synthase.

AML multi-gene panel testing: A review and comparison of two gene panels.

BACKGROUND/OBJECTIVE: Risk adapted therapy is standard practice in Acute Myeloid Leukemia (AML). A common diagnostic approach involves focusing on a three gene panel (CEPBA, FLT3, and NPM1). However, a complete representation of prognostic and predictive factors in AML necessitates an expanded series of genes, due to the dynamic interactions present between concurrent mutations. Hence, the current study aims to describe the benefits of an expanded risk profile in an unselected cohort of AML cases. METHODS: The genomes of 11 randomly selected patients with AML were sequenced using next generation sequencing. A narrow three gene panel and broader 50 gene panel were contrasted. RESULTS: The expanded gene panel detected one additional pathogenic mutation in five patients and two pathogenic mutations in two patients, resulting in a change in their risk profile. Only 5/11 (45%) of AML patients demonstrated a pathogenic mutation on the 3 gene profile, however all patients had at least one detectable pathogenic mutation on the broader gene panel. The detection of a concurrent mutation by the expanded gene panel reversed the favorable risk profile for three patients. CONCLUSIONS: Detection of concurrent mutations enables rejection or validation of prognoses associated with NPM1 or CEBPA mutations. DNMT3a and TP53 mutations in AML have a pertinent prognostic and therapeutic value for patients and their addition enhances the current three gene panel. In our small study, the three gene panel changed the prognosis for three patients (3/11, 27%) with the detection of commonly occurring AML mutations.

A kinetic study of the natural induction of liver steatosis in Greylag Landaise geese: the role of hyperphagia.

We have previously demonstrated that a sharp rise in feed intake (hyperphagia) and spontaneous liver steatosis could be experimentally induced in domestic Greylag geese by combining a short photoperiod and a sequence of feed restriction followed by ad libitum corn feeding during the fall and the winter. In this previous work, however, individual feed intake could not be recorded. The present study aimed at evaluating the relationship between level and pattern of hyperphagia and liver weight with an individual control of feed intake in individually housed (IH) geese, while comparing the performances with group housed (GH) geese. A total of 300 male geese of 19 weeks of age, were provided with corn ad libitum after an initial feed restriction period. From 21 to 23 weeks of age, the daylight duration was progressively reduced from 10 to 7 h and kept as such until the end of the experiment (week 36). In all, 30 GH and 30 IH geese were slaughtered at 19, 27, 30, 32 and 36 weeks of age. Feed intake was measured per group in GH geese and individually in IH geese. During the 1st week of corn feeding, the average feed intake rose up to 600 g/goose per day in GH geese but not in IH geese where the feed intake rose gradually from 300 to 400 g/day. The liver weight increased from 93 g (week 19) to 497 g (week 32; P<0.05) in GH birds. In IH birds, liver weights were, on average, much lower (ranging from 220 to 268 g) than in GH birds (P<0.05). In GH and IH bird, the variability in the individual response to corn feeding was very high (liver weight cv ranging from 63% to 83% depending on slaughter age). A close correlation between corn consumption and liver weight was evidenced in IH birds at each slaughter age (R 2 ranging from 0.62 to 0.79), except at 36 weeks of age where this correlation was weak (R 2=0.14). The variability in the extent of liver steatosis is very high and our results in IH birds clearly point out the major role of hyperphagia, mainly at the beginning of the ad libitum corn feeding period, on the development of spontaneous liver steatosis.