Intestinal microbiota lipid metabolism varies across rainbow trout (Oncorhynchus mykiss) phylogeographic divide.

AIMS: This study focused on intestinal microbiome variation across the phylogeogrpahic divide of rainbow trout and its potential functional effects on ocean migration. METHODS AND RESULTS: Hindgut intestinal contents were analysed using the 16S V4 hypervariable ribosomal gene region. Core microbiome taxonomies and overall microbial diversity were identified across the species phylogeographic divide with increased diversity found in Eastern Cascade fish. To determine potential functional differences between groups PICRUSt metagenomics analysis was utilized, revealing significant enrichment of lipid and fatty acid metabolism genes in Western Cascade fish microbiomes. CONCLUSIONS: Decreased levels of intestinal microbial lipid metabolism in Eastern Cascade rainbow trout suggests increased lipid absorption in these fish given the consistent diets. Such absorption, and potential storage, would be an evolutionary benefit for increased migration distances experienced by Eastern Cascade fish. Core microbiome differences, and their functional associations, suggest evolutionary differences at the genetic level noticeably contribute to intestinal microbial community diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: The possibility of genetic variation controlling intestinal microbiome diversity could have significant impacts on strain selection for rainbow trout aquaculture, especially given the consistent rearing conditions experienced in our sample populations likely result in differences in intramyocellular lipid storage.

Radiomics for Predicting Lung Cancer Outcomes Following Radiotherapy: A Systematic Review.

Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the individualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms 'radiomics' and 'lung cancer' according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance. Radiomics studies were defined as those manuscripts describing the extraction and analysis of at least 10 quantifiable imaging features. Only those studies assessing disease control, survival or toxicity outcomes for patients with lung cancer following radical radiotherapy ± chemotherapy were included. Study titles and abstracts were reviewed by two independent reviewers. The Radiomics Quality Score was applied to the full text of included papers. Of 244 returned results, 44 studies met the eligibility criteria for inclusion. End points frequently reported were local (17%), regional (17%) and distant control (31%), overall survival (79%) and pulmonary toxicity (4%). Imaging features strongly associated with clinical outcomes include texture features belonging to the subclasses Gray level run length matrix, Gray level co-occurrence matrix and kurtosis. The median cohort size for model development was 100 (15-645); in the 11 studies with external validation in a separate independent population, the median cohort size was 84 (21-295). The median number of imaging features extracted was 184 (10-6538). The median Radiomics Quality Score was 11% (0-47). Patient-reported outcomes were not incorporated within any studies identified. No studies externally validated a radiomics signature in a registered prospective study. Imaging-derived indices attained through radiomic analyses could equip thoracic oncologists with biomarkers for treatment response, patterns of failure, normal tissue toxicity and survival in lung cancer. Based on routine scans, their non-invasive nature and cost-effectiveness are major advantages over conventional pathological assessment. Improved tools are required for the appraisal of radiomics studies, as significant barriers to clinical implementation remain, such as standardisation of input scan data, quality of reporting and external validation of signatures in randomised, interventional clinical trials.

Indoor carbon monoxide and PM2.5 concentrations by cooking fuels in Pakistan.

UNLABELLED: In developing countries biomass combustion is a frequently used source of domestic energy and may cause indoor air pollution. Carbon monoxide (CO)and particulate matter with an aerodynamic diameter of 2.5 lm or less (PM2.5)were measured in kitchens using wood or natural gas (NG) in a semi-rural community in Pakistan. Daytime CO and PM2.5 levels were measured for eight continuous hours in 51 wood and 44 NG users from December 2005 to April 2006. The laser photometer PM2.5 (Dustrak, TSI) was calibrated for field conditions and PM2.5 measurements were reduced by a factor of 2.77. CO was measured by an electrochemical monitor (Model T15v, Langan). The arithmetic mean for daytime CO concentration was 29.4 ppm in wood users; significantly higher than 7.5 ppm in NG users (P < 0.001). The arithmetic mean for daytime PM2.5 concentrations was 2.74 mg/m3 in wood users; significantly higher than 0.38 mg/m3 in NG users (P < 0.001). Higher peak levels of CO and PM2.5 were also observed in wood users. Time spent in the kitchen during fuel burning was significantly related to increasing CO and PM2.5 concentrations in wood users.These findings suggest that cooking with wood fuel may lead to hazardous concentrations of CO and PM2.5. PRACTICAL IMPLICATIONS: Biomass combustion is frequently used in developing countries for cooking. This study showed very high level of air pollution in kitchens using wood as the cooking fuel. Many people, especially women and children, are vulnerable to exposure to very high levels of air pollutants as they spend time in the kitchen during cooking hours.

Pharmacodynamics and pharmacokinetics of the novel thrombopoietin mimetic peptide RWJ-800088 in humans.

RWJ-800088 is a novel thrombopoietin mimetic peptide for the treatment of thrombocytopenia. The objectives of this study were to evaluate the pharmacokinetics, pharmacodynamics, and safety of ascending doses of RWJ-800088 administered as a single intravenous delivery in a double-blind, placebo-controlled study with five parallel groups of eight healthy human subjects each. Platelet counts and functionality, peripheral stem cells, drug concentrations, and routine laboratory parameters were measured frequently up to day 29, and antibody formation was measured up to days 56-72. At doses > or = 0.75 microg/kg of RWJ-800088, platelet levels showed dose-related elevation as compared to results with placebo. The pharmacokinetic profile was characterized for doses of 2.5 and 3.0 microg/kg, although the dose relationship could not be fully defined. The two highest doses of RWJ-800088 appeared to increase burst-forming units-erythroid and colony-forming unit counts, suggesting some effects on progenitor lineages. RWJ-800088 was well tolerated, with no evidence of antibody formation in this single-dose study. Additional patient studies are warranted to investigate the therapeutic use of this novel peptide.

Effects of bovine serum concentrate, with or without supplemental micronutrients, on the growth, morbidity, and micronutrient status of young children in a low-income, peri-urban Guatemalan community.

OBJECTIVE: To determine the effects of dietary supplements containing bovine serum concentrate (BSC, a source of immunoglobulins) and/or multiple micronutrients (MMN) on children's growth velocity, rates of common infections, and MN status. DESIGN: Randomized, controlled, community-based intervention trial. SETTING: Low-income, peri-urban Guatemalan community. SUBJECTS: Children aged 6-7 months initially. INTERVENTIONS: Children received one of four maize-based dietary supplements daily for 8 months, containing: (1) BSC, (2) whey protein concentrate (WPC, control group), (3) WPC+MMN, or (4) BSC+MMN. RESULTS: There were no significant differences in growth or rates of morbidity by treatment group. Children who received MMN had lower rates of anemia and (in the group that received WPC+MMN) less of a decline in serum ferritin than those who did not, but there were no differences in other biochemical indicators of MN status by treatment group. CONCLUSIONS: MMN supplementation reduced anemia and iron deficiency in this population, but the MMN content and source of protein in the supplements did not affect other indicators of MN status, growth or morbidity.

Use of androgenesis for estimating maternal and mitochondrial genome effects on development and oxygen consumption in rainbow trout, Oncorhynchus mykiss.

Chromosome set manipulation was used to produce rainbow trout, Oncorhynchus mykiss, with identical nuclear backgrounds, but different maternal backgrounds to determine mitochondrial effects on development rate and oxygen consumption. Significant differences in development rate and oxygen consumption were observed between groups from different females. Development rates ranged from a mean of 317.97 degree days ( degrees d) to 335.25 degrees d in progeny from different females. Mean oxygen consumption rates ranged from 3.31 micromol O2 g(-1) wet mass h(-1) to 9.66 micromol O2 g(-1) wet mass h(-1). Oxygen consumption and development rate analysis revealed the two slowest developing groups had the highest oxygen consumption rates. Development rate differences between second generation clonal females indicate that mitochondrial genomes play a significant role on early development and are comparable to development rate differences between clonal lines of rainbow trout. These results indicate that selection for mitochondrial genomes could increase growth rates and possibly food conversion ratios in aquaculture species.

The Food Marketing Institute and the National Council of Chain Restaurants: animal welfare and the retail food industry in the United States of America.

In order to achieve real change, there must be a motivating force and all the stakeholders need to be involved. This is the premise of the animal welfare programme developed for the food retail, wholesale and chain restaurant industries in the United States of America (USA) by the Food Marketing Institute (FMI) and the National Council of Chain Restaurants (NCCR). This paper outlines a collaborative process that retailers and producers in the USA are using to enhance the care and welfare of animals in commercial food production. Although the efforts of the FMI and the NCCR are still underway, the process provides one example of how different parts of the food production system can work together to achieve positive change.

Effect of infections on plasma zinc concentration and implications for zinc status assessment in low-income countries.

The development of intervention programs to control zinc deficiency is hampered by the lack of sensitive, specific, low-cost indicators of zinc status. The mean plasma zinc concentration of groups of individuals has been suggested as a possible indicator of a population's zinc status because the plasma zinc concentration seems to predict whether growth will increase in response to zinc supplementation. However, experimental studies in both animal models and adult human volunteers as well as clinical studies of infected and noninfected adults indicate that systemic infections that produce an acute phase response also cause the plasma zinc concentration to fall. Therefore, concerns have been raised about the usefulness of plasma zinc concentration as an indicator of zinc status in populations with high prevalences of infections. By contrast with the aforementioned studies in adults, cross-sectional, community-based surveys of children with and without common infections have not found any association between the presence of infection and plasma zinc concentration, possibly because the severity of those infections observed in children in field settings was less than that of the infections studied in adults. Thus, it appears that the mean plasma zinc concentration may be a useful indicator of population zinc status for children in low-income countries despite the high prevalence of common childhood infections encountered in these settings.

Nonabsorbable marker and single, random stool samples used for measuring intestinal absorption of macronutrients in infants and children.

To measure intestinal absorption by using a single, random stool sample, polyethylene glycol (PEG), 1 g/d, and a constant diet were given to healthy infants, with a constant PEG-to-macronutrient ratio. After 10 d equilibration, apparent intestinal absorption of macronutrients was estimated from a standard 3-d metabolic balance and compared with that estimated by using the ratio of PEG to macronutrients in a single random sample of feces. Correlation coefficients for this comparison were 0.649, 0.715, and 0.924 for nitrogen, carbohydrate, and fat, respectively. Additionally, apparent intestinal absorptions estimated from two separate consecutive 3-d metabolic-balance studies were compared, showing correlation coefficients of 0.106, 0.653, and 0.463 for nitrogen, carbohydrate, and fat, respectively. The random sample-marker technique appears to be acceptable for measuring apparent absorption of macronutrients and is at least as accurate as a standard 3-d metabolic-balance study.

Relative effects of diarrhea, fever, and dietary energy intake on weight gain in rural Bangladeshi children.

Quantitative studies of morbidity, food intake, and somatic growth were done prospectively during 14 mo for 70 children aged 5-18 mo in two Bangladeshi villages. When random-effect regression models were used, monthly changes in weight were inversely related to proportions of days in the month with fever and diarrhea and positively related to energy intake per kilogram body weight. Interestingly, weight changes did not vary with age in this interval. Estimates indicate that increasing energy intakes to the recommended World Health Organization level would have a significantly greater effect on weight gain than would the elimination of diarrhea and fever. With energy at recommended intake and diarrhea and fever prevalence as found in US children, weight gain is predicted to be near that of the international reference population. Therefore, interventions aimed at improving dietary intake may be as important as infection-control programs for improving growth of children in poor developing nations.

A new approach to characterize whole-gut transit in infants with use of a nonabsorbable intestinal marker.

To characterize mouth to anus transit of intestinal contents, polyethylene glycol (PEG) was given as an intestinal marker to 11 healthy infants, and daily fecal collections were analyzed for PEG concentration per unit of dry stool weight for 9-15 d. Fecal PEG excretion followed first-order kinetics. Thus, half-life (t1/2) and volume of distribution (Vd) of PEG in the gut could be computed for each of seven infants who received continuous daily PEG doses and t1/2 only for four infants who received a single PEG dose. t1/2 of PEG in the gut was 0.99 +/- 0.48 d (means +/- SD). Vd for PEG in the gut was 18.74 +/- 15.38 g of fecal dry weight. We propose that whole-gut transit be expressed in terms of t1/2 and Vd of intestinal contents because these may better characterize the changes in intestinal transit that occur with disease or dietary modifications.

Malnutrition is a determining factor in diarrheal duration, but not incidence, among young children in a longitudinal study in rural Bangladesh.

Diarrhea and malnutrition are common in young children in developing countries and a reciprocal relationship has been postulated with diarrhea leading to malnutrition and malnutrition predisposing to diarrhea. To investigate the importance of malnutrition as a determining factor in diarrheal illnesses, data were analyzed from a longitudinal community-based study done in rural Bangladesh. Children classified by nutritional status according to a variety of anthropometric indicators were prospectively evaluated for incidence, duration, and etiology of diarrhea. Children with low weight for length had longer durations of diarrhea than better nourished children; however, children of differing nutritional status had similar diarrheal incidences. The duration of diarrhea, including that associated with enterotoxigenic Escherichia coli and Shigella, increased progressively as nutritional status indicators worsened. These results suggest that nutritional interventions alone are unlikely to reduce the high incidence of diarrhea, but that efforts to improve nutritional status may have a beneficial effect on the duration of diarrhea and its unfavorable nutritional consequences.

Seasonal changes in nutritional status and the prevalence of malnutrition in a longitudinal study of young children in rural Bangladesh.

During longitudinal field studies of the growth, dietary intake, and morbidity from infectious diseases of children between 6 and 60 months of age in two rural villages of Bangladesh, seasonal fluctuations in growth, nutritional status, and the prevalence of malnutrition were observed. The weight, length, arm circumference, and triceps skinfold thickness of 197 children were measured monthly for 15 months and compared with sex-specific local village norms and international reference populations. The percentages of expected weight for length, arm circumference for age, triceps skinfold thickness for age, and the percentages of expected monthly increments of weight and length for age were the indicators most sensitive to seasonal changes. The percentages of expected weight for age and length for age also changed significantly by month of year, but were less responsive to seasonal variation. The periods of greatest nutritional deficit depended on which anthrometric indicator was used to define nutritional status, but generally occurred during the monsoon and persisted until the subsequent harvest period. However, the fall in mean percentage of expected length for age and the increase in the prevalence of stunting occurred several months after the periods of greatest malnutrition identified by the other measurements. The importance of selecting the appropriate anthropometric techniques to detect seasonal changes and the implications of such changes are discussed.

PIP: During longitudinal field studies of the growth, dietary intake, and morbidity from infectious diseases of children between 6 and 60 months of age in 2 villages of rural Bangladesh, seasonal fluctuations in growth, nutritional status, and the prevalence of malnutrition were observed. The weight, length, arm circumference, and triceps skinfold thickness of 197 children were measured monthly for 15 months and compared with sex specific local village norms and international reference populations. The percentages of expected weight for length, arm circumference for age, triceps skinfold thickness for age, and the percentages of expected monthly increments of weight and length for age were the indicators most sensitive to seasonal changes. The percentages of expected weight for age and length for age also changed significantly by month of year, but were less responsive to seasonal variation. The periods of greatest nutritional deficit depended on which anthropometric indicator was used to define nutritional status, but generally occurred during the monsoon and persisted until the subsequent harvest period. However, the fall in mean percentage of expected length for age and the increase in prevalence of stunting occurred several months after the periods of greatest malnutrition identified by the other measurements. The importance of selecting the appropriate anthropometric techniques to detect seasonal changes and the implications of such changes are discussed.

Relationship of the xylose absorption status of children in Bangladesh to their absorption of macronutrients from local diets.

We compared the results of xylose absorption tests from 31 asymptomatic Bangladeshi children with their ability to absorb macronutrients from cereal-vegetable diets, as determined by metabolic balance studies. The xylose test results ranged from 9.8 to 37.0% excretion of the ingested dose, with more than half of the values less than 20% excretion. Nevertheless, the apparent absorption of macronutrients during 7-day balance studies ranged from 89.8 to 97.7% of intake for carbohydrate, 81.7 to 98.7% for fat, and 47.3 to 78.9% for nitrogen. There was a statistically significant correlation between the xylose test results and apparent carbohydrate absorption for one diet group only (r = 0.76, p less than 0.05), but not between the xylose results and other indicators of intestinal function of nutrition status. We conclude that diminished absorption of xylose, which is commonly recognized among asymptomatic residents of the tropics, does not necessarily indicate impaired absorption of macronutrients from the customary diet. Therefore, tropical enteropathy may not have major nutritional significance for those individuals with manifestations of the syndrome.

Validation of the deuterium oxide method for measuring average daily milk intake in infants.

The deuterium oxide elimination method for measuring average daily milk intake was validated against measured formula intake in 16 studies of 11 infants in a metabolic ward. Deuterium oxide (approximately 0.10 g/kg body wt) was given orally. Deuterium enrichment was measured in urine samples collected predose, as available for 6-h postdose for TBW determination, and at 24 h and 5-10 d postdose for HDO elimination calculated according to the two-point method. Urine samples were vacuum distilled, water was reduced to hydrogen gas, and deuterium enrichment was measured by isotope-ratio mass spectrometry. Milk intake was measured throughout the elimination period from prefeeding and postfeeding bottle weights (n = 12) or volumes (n = 4). Without corrections for atmospheric water influx, milk intake was overestimated by 76 g/d (6%). With corrections for estimated metabolic water production, isotopic fractionation, and atmospheric water influx, deuterium measured 98% +/- 3% or 1300 g milk intake/d compared with actual milk intake of 1329 +/- 206 g/d.

Body composition of children recovering from severe protein-energy malnutrition at two rates of catch-up growth.

Twenty-two children with severe protein-energy malnutrition were randomly assigned to dietary treatments that permitted either moderate (4-6 g.kg-1.d-1) rates of weight gain (MG, n = 11) or rapid (12-16 g.kg-1.d-1) rates of weight gain (RG, n = 11) to test the hypothesis that restoration of weight deficits by the RG group restores reference body composition. Final total body water was 60 +/- 4% of body weight in the MG group and 62 +/- 3% in the RG group (NS) indicating reference body composition was attained by both groups. Composition of weight gained was measured by energy and nitrogen balance from doubly labeled water and metabolic collection data. In early recovery, the percent (+/- SEM) protein, fat, and water in weight gain was 20 +/- 1%, 40 +/- 8%, and 40 +/- 10% in the MG group and 14 +/- 1%, 43 +/- 4%, and 43 +/- 12% in the RG group. In late recovery these were 13 +/- 1%, 42 +/- 7%, and 47 +/- 14% in the MG group and 12 +/- 1%, 46 +/- 4%, and 42 +/- 6% in the RG group. We conclude that the nutritional therapy used to promote rapid weight gain restores reference body composition and significantly reduces time required for catch-up growth.

Potential for misclassification of infants' growth increments by using existing reference data.

The observed variances in monthly weight and length gains of 96 Peruvian infants were compared with predicted variances obtained by applying the reference curve-fitting methods to the same Peruvian data. Predicted variance estimates were significantly less (P less than 0.0001) than the observed variances from 2 to 12 mo of age. The extent of underestimation in total variance that occurred when 1-mo growth-increment reference data were generated by curve-fitting and interpolation was approximated. This underestimation, caused by not taking into account infants' random deviations from their own growth trajectories, ranged from 59% to 94% and resulted in misclassification of approximately 24-67% of infants as abnormal gainers (below the 5th percentile or above the 95th percentile with respect to existing reference data) in the intervals evaluated.

Effect of dietary viscosity on energy intake by breast-fed and non-breast-fed children during and after acute diarrhea.

To determine the effect of dietary viscosity on energy consumption by young children, 56 Peruvian children 9-20 mo of age with acute diarrhea were randomly assigned to either a liquid or semisolid diet, with or without added amylase to reduce viscosity. Intakes of the study diet, breast milk, and other foods were measured for 2 consecutive d during and again after illness. Total 24-h energy intake (chi +/- SD) during diarrhea, 349.4 +/- 121.8 kJ/kg (83.6 +/- 29.1 kcal/kg) was 18% less than intake after recovery, 428.9 +/- 141.0 kJ/kg (102.6 +/- 33.7), P < 0.001. In the ANOVA breast-fed children consumed significantly less total energy (P = 0.008) and energy from the study diet (P = 0.02) than non-breast-fed children. Breast milk intake did not change with illness. There was no significant relationship between viscosity of the study diet and either total energy intake or intake of energy from the study diet. Energy intake by these children was primarily determined by health status and breast-feeding practice, not by dietary viscosity.

Nutritional consequences of low dose milk supplements consumed by lactose-malabsorbing children.

The nutritional consequences of supplementary milk consumption by lactose-malabsorbing children were determined by nutrient balance studies. Twelve subjects received a marginally adequate rice and vegetable base-line diet alone and with simulated milk supplements containing either glucose or lactose during three separate balance periods. The diets were equally well accepted and tolerated. The children gained significantly more weight and had improved apparent nitrogen absorption and retention on the milk supplemented diets (P less than 0.001), and there was no difference between the effects of glucose milk and lactose milk. Fecal wet weights and energy and carbohydrate excretions were modestly increased with the lactose-containing diet, but not significantly so. It is suggested that low dose milk supplements can be well utilized when consumed by lactose malabsorbers in conjunction with other foods. Milk consumption need not be discouraged for populations among whom lactose malabsorption is widely prevalent, but milk should be provided in relatively low doses and the clinical responses to its consumption should be monitored.

Failure of a large dose of vitamin A to enhance the antibody response to tetanus toxoid in children.

Field studies to determine the effects of a large dose of water miscible vitamin A on selected parameters of children's immunological function were completed in rural Bangladesh. There was no difference between vitamin A treated or control groups in tetanus antitoxin responses after tetanus toxoid immunization or in skin test reactivity to common antigens. Subsequent studies with mice demonstrated vitamin A dose-related antitoxin responses, but the animals required amounts of vitamin that would be likely cause undesirable side effects if administered in similar doses to children.