10

Studies aiming at explaining specialization along latitudinal gradients of plant-herbivore interactions have, to date, yielded inconclusive results. Here we propose the use of steep altitudinal gradients for dissecting factors driving evolution of polyphagy in insect herbivores. First, we test whether colonization of high elevation environment favours increased niche-breadth in two disparate insect groups - the wood-boring beetles and the pollinator group of bees - and show increased polyphagy at higher altitudes in both groups. We then assess classic assumptions transferred from the 'latitude-niche-breadth hypothesis', particularly the increase in environmental variability at high, compared to low, altitude. Finally, we discuss alternative mechanisms shaping the observed pattern of increased polyphagy in altitude, including variation in plant quality and predator pressure at different altitudes. We thus suggest evidence for the 'altitude niche-breadth hypothesis', in which both abiotic and biotic conditions, including increased variability and an increase of the potential feeding niche-breadth, promote evolution for increased insect polyphagy in altitude.

Variability of resting energy expenditure in healthy volunteers during fasting and continuous enteral feeding.

The magnitude of variability in resting energy expenditure (REE) during the day was assessed in nine healthy young subjects under two nutritional conditions: 1) mixed nutrient (53% carbohydrate, 30% fat, 17% protein) enteral feeding at an energy level corresponding to 1.44 REE; and 2) enteral fasting, with only water allowed. In each subject, six 30-min measurements of REE were performed using indirect calorimetry (hood system) at 90-min intervals from 9 AM to 5 PM. The mean REE and respiratory quotient were significantly (p less than .01) greater during feeding than during fasting (1.08 +/- 0.07 [SEM] vs. 1.00 +/- 0.06 kcal/min and 0.874 +/- 0.007 vs. 0.829 +/- 0.008 kcal/min, respectively). Mean postprandial thermogenesis was 4.9 +/- 0.4% of metabolizable energy administered. The intraindividual variability of REE throughout the day, expressed as the coefficient of variation, ranged from 0.7% to 2.0% in the fasting condition and from 1.2% to 4.1% in the feeding condition. There was no significant difference between the REE measured in the morning and that determined in the afternoon.

Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial.

BACKGROUND: Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. METHODS: In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386. FINDINGS: Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9-6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84-1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69-1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67-0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1-43·4) after conventional chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045). INTERPRETATION: Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules. FUNDING: French Ministry of Health.

Transcript profiling suggests that differential metabolic adaptation of mice to a high fat diet is associated with changes in liver to muscle lipid fluxes.

Genetically homogenous C57Bl/6 mice display differential metabolic adaptation when fed a high fat diet for 9 months. Most become obese and diabetic, but a significant fraction remains lean and diabetic or lean and non-diabetic. Here, we performed microarray analysis of "metabolic" transcripts expressed in liver and hindlimb muscles to evaluate: (i) whether expressed transcript patterns could indicate changes in metabolic pathways associated with the different phenotypes, (ii) how these changes differed from the early metabolic adaptation to short term high fat feeding, and (iii) whether gene classifiers could be established that were characteristic of each metabolic phenotype. Our data indicate that obesity/diabetes was associated with preserved hepatic lipogenic gene expression and increased plasma levels of very low density lipoprotein and, in muscle, with an increase in lipoprotein lipase gene expression. This suggests increased muscle fatty acid uptake, which may favor insulin resistance. In contrast, the lean mice showed a strong reduction in the expression of hepatic lipogenic genes, in particular of Scd-1, a gene linked to sensitivity to diet-induced obesity; the lean and non-diabetic mice presented an additional increased expression of eNos in liver. After 1 week of high fat feeding the liver gene expression pattern was distinct from that seen at 9 months in any of the three mouse groups, thus indicating progressive establishment of the different phenotypes. Strikingly, development of the obese phenotype involved re-expression of Scd-1 and other lipogenic genes. Finally, gene classifiers could be established that were characteristic of each metabolic phenotype. Together, these data suggest that epigenetic mechanisms influence gene expression patterns and metabolic fates.

Influence of nutrition on urinary oxalate and calcium in preterm and term infants.

Few data for normal urinary oxalate (Ox) and calcium (Ca) excretion related both to gestational age and nutritional factors have been reported in preterm or term infants. We therefore determined the molar Ox and Ca to creatinine (Cr) ratios in spot urines from 64 preterm and 37 term infants aged 1-60 days, either fed formula or human milk (HM). Only vitamin D was supplemented; renal or metabolic diseases were excluded. Urinary Ox/Cr ratio was higher in preterm than in term infants, both when formula fed (1st month 253 vs. 180 mmol/mol and 2nd month 306 vs. 212 mmol/mol; P<0.05) or HM fed (206 vs. 169 mmol/ mol and 283* vs. 232 mmol/mol; *P<0.05). Ox/Cr was also higher in formula- than HM-fed preterm infants. The ratio increased during the first 2 months of life irrespective of nutrition. Urinary Ca/Cr ratio was comparable in all groups during the 1st month of life, except for a lower (P < 0.05) value in term infants fed HM (0.10 mol/mol). It increased in all groups during the 2nd month of life, being highest in HM-fed preterm infants (1.86 mol/mol). In conclusion, urinary Ox and Ca excretion is influenced by both gestational age and nutrient intake in preterm and term infants.

Implications of diagnosis related groups (DRGs) for the management of hospitals.

Although tremendous advances have been made in the diagnosis and treatment of patients, hospital administrative systems have progressed relatively slowly. The types of information available to managers in industrial sectors are not available in the health sector. For this reason, many phenomena, such as the variations of average costs and lengths of stay between different hospitals, have remained poorly explained.The DRG system defines groups of patients that consume relatively homogeneous quantities of hospital resources. On the basis, it is possible to standardize average lengths of stay and average hospital costs in terms of the differences in case mix treated. Thus DRGs can serve as an explanation of variations in these factors between different hospitals, and also (but not only) for prospective reimbursement schems. As in a number of other European countries, a project has been set up in Switzerland to examine the possibilities of using DRGs in hospital management, planning and financing.

Pratiques comptables des hôpitaux et faisabilité d'un calcul de coûts basés sur les Diagnosis Related Groups

Travaux effectués dans le cadre de l'étude "Case Mix" menée par l'Institut universitaire de médecine sociale et préventive de Lausanne et le Service de la santé publique et de la planification sanitaire du canton de Vaud, en collaboration avec les cantons de Berne, Fribourg, Genève, Jura, Neuchâtel, Soleure, Tessin et Valais

Ispol'zovanie metodov teorii vosstanovleniia v modeliakh optimal'nogo dobyvaniia pishchi [Restoration theory in models of optimal feeding behavior]

The method of stochastic dynamic programming is widely used in ecology of behavior, but has some imperfections because of use of temporal limits. The authors presented an alternative approach based on the methods of the theory of restoration. Suggested method uses cumulative energy reserves per time unit as a criterium, that leads to stationary cycles in the area of states. This approach allows to study the optimal feeding by analytic methods.

Faktorenanalytische Untersuchung und Rehabilitätsbestimmung der statischen und dynamischen Pupillometrie bei Normalpersonen und psychopathologischen Gruppen [Factor analytic study and determination of rehabilitation of static and dynamic pupillometry in normal persons and psychopathologic groups]

Variables measured during static and dynamic pupillometry were factor-analyzed. Following factors were obtained regardless whether investigations were carried out in normals or in psychiatric patients: A static factor, a dynamic factor, a stimulus-specific factor and a restitution-dependent factor. Evaluation of reliability in normals demonstrated a high reliability for the static variables of pupillometry.

ANIBAL, stable isotope-based quantitative proteomics by aniline and benzoic acid labeling of amino and carboxylic groups

Identification and relative quantification of hundreds to thousands of proteins within complex biological samples have become realistic with the emergence of stable isotope labeling in combination with high throughput mass spectrometry. However, all current chemical approaches target a single amino acid functionality (most often lysine or cysteine) despite the fact that addressing two or more amino acid side chains would drastically increase quantifiable information as shown by in silico analysis in this study. Although the combination of existing approaches, e.g. ICAT with isotope-coded protein labeling, is analytically feasible, it implies high costs, and the combined application of two different chemistries (kits) may not be straightforward. Therefore, we describe here the development and validation of a new stable isotope-based quantitative proteomics approach, termed aniline benzoic acid labeling (ANIBAL), using a twin chemistry approach targeting two frequent amino acid functionalities, the carboxylic and amino groups. Two simple and inexpensive reagents, aniline and benzoic acid, in their (12)C and (13)C form with convenient mass peak spacing (6 Da) and without chromatographic discrimination or modification in fragmentation behavior, are used to modify carboxylic and amino groups at the protein level, resulting in an identical peptide bond-linked benzoyl modification for both reactions. The ANIBAL chemistry is simple and straightforward and is the first method that uses a (13)C-reagent for a general stable isotope labeling approach of carboxylic groups. In silico as well as in vitro analyses clearly revealed the increase in available quantifiable information using such a twin approach. ANIBAL was validated by means of model peptides and proteins with regard to the quality of the chemistry as well as the ionization behavior of the derivatized peptides. A milk fraction was used for dynamic range assessment of protein quantification, and a bacterial lysate was used for the evaluation of relative protein quantification in a complex sample in two different biological states

Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients

Résumé Introduction : Les patients nécessitant une prise en charge prolongée en milieu de soins intensifs et présentant une évolution compliquée, développent une réponse métabolique intense caractérisée généralement par un hypermétabolisme et un catabolisme protéique. La sévérité de leur atteinte pathologique expose ces patients à la malnutrition, due principalement à un apport nutritionnel insuffisant, et entraînant une balance énergétique déficitaire. Dans un nombre important d'unités de soins intensifs la nutrition des patients n'apparaît pas comme un objectif prioritaire de la prise en charge. En menant une étude prospective d'observation afin d'analyser la relation entre la balance énergétique et le pronostic clinique des patients avec séjours prolongés en soins intensifs, nous souhaitions changer cette attitude et démonter l'effet délétère de la malnutrition chez ce type de patient. Méthodes : Sur une période de 2 ans, tous les patients, dont le séjour en soins intensifs fut de 5 jours ou plus, ont été enrôlés. Les besoins en énergie pour chaque patient ont été déterminés soit par calorimétrie indirecte, soit au moyen d'une formule prenant en compte le poids du patient (30 kcal/kg/jour). Les patients ayant bénéficié d'une calorimétrie indirecte ont par ailleurs vérifié la justesse de la formule appliquée. L'âge, le sexe le poids préopératoire, la taille, et le « Body mass index » index de masse corporelle reconnu en milieu clinique ont été relevés. L'énergie délivrée l'était soit sous forme nutritionnelle (administration de nutrition entérale, parentérale ou mixte) soit sous forme non-nutritionnelle (perfusions : soluté glucosé, apport lipidique non nutritionnel). Les données de nutrition (cible théorique, cible prescrite, énergie nutritionnelle, énergie non-nutritionnelle, énergie totale, balance énergétique nutritionnelle, balance énergétique totale), et d'évolution clinique (nombre des jours de ventilation mécanique, nombre d'infections, utilisation des antibiotiques, durée du séjour, complications neurologiques, respiratoires gastro-intestinales, cardiovasculaires, rénales et hépatiques, scores de gravité pour patients en soins intensifs, valeurs hématologiques, sériques, microbiologiques) ont été analysées pour chacun des 669 jours de soins intensifs vécus par un total de 48 patients. Résultats : 48 patients de 57±16 ans dont le séjour a varié entre 5 et 49 jours (motif d'admission : polytraumatisés 10; chirurgie cardiaque 13; insuffisance respiratoire 7; pathologie gastro-intestinale 3; sepsis 3; transplantation 4; autre 8) ont été retenus. Si nous n'avons pu démontrer une relation entre la balance énergétique et plus particulièrement, le déficit énergétique, et la mortalité, il existe une relation hautement significative entre le déficit énergétique et la morbidité, à savoir les complications et les infections, qui prolongent naturellement la durée du séjour. De plus, bien que l'étude ne comporte aucune intervention et que nous ne puissions avancer qu'il existe une relation de cause à effet, l'analyse par régression multiple montre que le facteur pronostic le plus fiable est justement la balance énergétique, au détriment des scores habituellement utilisés en soins intensifs. L'évolution est indépendante tant de l'âge et du sexe, que du status nutritionnel préopératoire. L'étude ne prévoyait pas de récolter des données économiques : nous ne pouvons pas, dès lors, affirmer que l'augmentation des coûts engendrée par un séjour prolongé en unité de soins intensifs est induite par un déficit énergétique, même si le bon sens nous laisse penser qu'un séjour plus court engendre un coût moindre. Cette étude attire aussi l'attention sur l'origine du déficit énergétique : il se creuse au cours de la première semaine en soins intensifs, et pourrait donc être prévenu par une intervention nutritionnelle précoce, alors que les recommandations actuelles préconisent un apport énergétique, sous forme de nutrition artificielle, qu'à partir de 48 heures de séjour aux soins intensifs. Conclusions : L'étude montre que pour les patients de soins intensifs les plus graves, la balance énergétique devrait être considérée comme un objectif important de la prise en charge, nécessitant l'application d'un protocole de nutrition précoce. Enfin comme l'évolution à l'admission des patients est souvent imprévisible, et que le déficit s'installe dès la première semaine, il est légitime de s'interroger sur la nécessité d'appliquer ce protocole à tous les patients de soins intensifs et ceci dès leur admission. Summary Background and aims: Critically ill patients with complicated evolution are frequently hypermetabolic, catabolic, and at risk of underfeeding. The study aimed at assessing the relationship between energy balance and outcome in critically ill patients. Methods: Prospective observational study conducted in consecutive patients staying 5 days in the surgical ICU of a University hospital. Demographic data, time to feeding, route, energy delivery, and outcome were recorded. Energy balance was calculated as energy delivery minus target. Data in means+ SD, linear regressions between energy balance and outcome variables. Results: Forty eight patients aged 57±16 years were investigated; complete data are available in 669 days. Mechanical ventilation lasted 11±8 days, ICU stay 15+9 was days, and 30-days mortality was 38%. Time to feeding was 3.1 ±2.2 days. Enteral nutrition was the most frequent route with 433 days. Mean daily energy delivery was 1090±930 kcal. Combining enteral and parenteral nutrition achieved highest energy delivery. Cumulated energy balance was between -12,600+ 10,520 kcal, and correlated with complications (P<0.001), already after 1 week. Conclusion: Negative energy balances were correlated with increasing number of complications, particularly infections. Energy debt appears as a promising tool for nutritional follow-up, which should be further tested. Delaying initiation of nutritional support exposes the patients to energy deficits that cannot be compensated later on.

Protein turnover and thermogenesis in response to high-protein and high-carbohydrate feeding in men.

The rates of energy expenditure and wholebody protein turnover were determined during a 9-h period in a group of seven men while they received hourly isocaloric meals of high-protein (HP) or high-carbohydrate (HC) content. Their responses to feeding were compared with those to a short period of fasting (15-24 h). The 9-h thermic response to the repeated feeding of HP meals was found to be greater than that to the HC meals (9.6 +/- 0.6% vs 5.7 +/- 0.4% of the energy intake, respectively, means +/- SEM, p less than 0.01). The rate of whole-body nitrogen turnover over 9 h increased from 17.6 +/- 2.2 g on the fasting day to 27.4 +/- 1.4 g during HC feeding (NS) and there was a further increase to 58.2 +/- 5.3 g resulting from HP feeding (p less than 0.001). By using theoretical estimates (based upon ATP requirements) of the metabolic cost of protein synthesis, 36 +/- 9% of the thermic response to HC feeding and 68 +/- 3% of the response to HP feeding could be accounted for by the increases in protein synthesis compared with the fasting state.

Plants and tortoises: mutations in the Arabidopsis jasmonate pathway increase feeding in a vertebrate herbivore.

Photosynthetic tissues, the major food source of many invertebrates and vertebrates, are well defended. Many defence traits in leaves are controlled via the jasmonate signalling pathway in which jasmonate acts as a hormone by binding to a receptor to activate responses that lead to increased resistance to invertebrate folivores. We predicted that mutations in jasmonate synthesis might also increase the vulnerability of leaves to vertebrate folivores and tested this hypothesis using the Eastern Hermann's tortoise (Eurotestudo boettgeri) and an Arabidopsis thaliana (Brassicaceae) allene oxide synthase (aos) mutant unable to synthesize jasmonate. Tortoises preferred the aos mutant over the wild type (WT). Based on these results, we then investigated the effect of mutating jasmonate perception using a segregating population of the recessive A. thaliana jasmonate receptor mutant coronatine insensitive1-1 (coi1-1). Genotyping of these plants after tortoise feeding revealed that the homozygous coi1-1 receptor mutant was consumed more readily than the heterozygous mutant or the WT. Therefore, the plant's ability to synthesize or perceive jasmonate reduces feeding by a vertebrate herbivore. We also tested whether or not tortoise feeding behaviour was influenced by glucosinolates, the principal defence chemicals in Arabidopsis leaves with known roles in defence against many generalist insects. However, in contrast to what has been observed with such insects, leaves in which the levels of these compounds were reduced genetically were consumed at a similar rate to those of the WT.