Evaluation of a Plant-Based Infant Formula Containing Almonds and Buckwheat on Gut Microbiota Composition, Intestine Morphology, Metabolic and Immune Markers in a Neonatal Piglet Model.

A controlled-neonatal piglet trial was conducted to evaluate the impact of a plant-based infant formula containing buckwheat and almonds as the main source of protein compared to a commercially available dairy-based formula on the gut health parameters. Two day old piglets were fed either a plant-based or a dairy-based formula until day 21. Gut microbiome, cytokines, growth and metabolism related outcomes, and intestinal morphology were evaluated to determine the safety of the plant-based infant formula. This study reported that the plant-based formula-fed piglets had a similar intestinal microbiota composition relative to the dairy-based formula-fed group. However, differential abundance of specific microbiota species was detected within each diet group in the small and large intestinal regions and fecal samples. Lactobacillus delbrueckii, Lactobacillus crispatus, and Fusobacterium sp. had higher abundance in the small intestine of plant-based formula-fed piglets compared to the dairy-based group. Bacteroides nordii, Enterococcus sp., Lactobacillus crispatus, Prevotella sp., Ruminococcus lactaris, Bacteroides nordii, Eisenbergiella sp., Lactobacillus crispatus, Prevotella sp., and Akkermansia muciniphila had greater abundance in the large intestine of the plant based diet fed piglets relative to the dairy-based diet group. In the feces, Clostridiales, Bacteroides uniformis, Butyricimonasvirosa, Cloacibacillus porcorum, Clostridium clostridioforme, and Fusobacterium sp. were abundant in dairy-based group relative to the plant-based group. Lachnospiraceae, Clostridium scindens, Lactobacillus coleohominis, and Prevetolla sp. had greater abundance in the feces of the plant-based group in comparison to the dairy-based group. Gut morphology was similar between the plant and the dairy-based formula-fed piglets. Circulatory cytokines, magnesium, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), vitamin D, vitamin K, and IgE levels were similar among all piglets independent of dietary group. Overall, the present study demonstrated that a plant-based formula with buckwheat and almonds as the primary source of protein can support similar gut microbiota growth and health outcomes compared to a dairy-based infant formula.

Evaluation of the Safety of a Plant-Based Infant Formula Containing Almonds and Buckwheat in a Neonatal Piglet Model.

A randomized neonatal piglet trial was conducted to evaluate the safety and the effects of a plant-based formula containing almonds and buckwheat as the main ingredients on growth and plasma parameters. From postnatal day (PND) 2 to 21, the piglets were fed a dairy-based milk formula (Similac Advance) or a plant-based formula (Else Nutrition) and all piglets were euthanized at day 21. No diarrhea was observed after PND 8 and all the piglets completed the trial. Body growth, kcal intake, the complete plasma count parameters and hematological parameters were within the reference range in both groups. Organ growth and development was similar between the two groups. Plasma glucose was higher in the dairy-based-fed piglets relative to the plant-based at 2 weeks of age. Liver function biomarkers levels were greater in the plasma of the plant-based compared to the dairy-based fed group. In addition, calcium levels were higher in the plant-based fed piglets at 1 week of age. Thus, the plant-based formula tested in this study was well tolerated by the piglets and supported similar growth compared to dairy-based milk formula. Therefore, the results support the safety of the tested plant-based infant formula during the neonatal period in comparison to the dairy-based formula fed group.

Potential shifts in dominant forest cover in interior Alaska driven by variations in fire severity.

Large fire years in which >1% of the landscape burns are becoming more frequent in the Alaskan (USA) interior, with four large fire years in the past 10 years, and 79 000 km2 (17% of the region) burned since 2000. We modeled fire severity conditions for the entire area burned in large fires during a large fire year (2004) to determine the factors that are most important in estimating severity and to identify areas affected by deep-burning fires. In addition to standard methods of assessing severity using spectral information, we incorporated information regarding topography, spatial pattern of burning, and instantaneous characteristics such as fire weather and fire radiative power. Ensemble techniques using regression trees as a base learner were able to determine fire severity successfully using spectral data in concert with other relevant geospatial data. This method was successful in estimating average conditions, but it underestimated the range of severity. This new approach was used to identify black spruce stands that experienced intermediate- to high-severity fires in 2004 and are therefore susceptible to a shift in regrowth toward deciduous dominance or mixed dominance. Based on the output of the severity model, we estimate that 39% (approximately 4000 km2) of all burned black spruce stands in 2004 had <10 cm of residual organic layer and may be susceptible a postfire shift in plant functional type dominance, as well as permafrost loss. If the fraction of area susceptible to deciduous regeneration is constant for large fire years, the effect of such years in the most recent decade has been to reduce black spruce stands by 4.2% and to increase areas dominated or co-dominated by deciduous forest stands by 20%. Such disturbance-driven modifications have the potential to affect the carbon cycle and climate system at regional to global scales.

Phenolic acids in black raspberry and in the gastrointestinal tract of pigs following ingestion of black raspberry.

Black raspberries (BRB) contain high levels of polyphenols and have been demonstrated to be chemopreventive. In order to investigate the underlying mechanism and study the metabolism of anthocyanins, pigs were fed freeze-dried BRB powder or purified diet (control) and three segments of the gastrointestinal (GI) tract (small intestine, cecum, and colon; 4 h after feeding) were collected for analysis of phenolic acids. Protocatechuic acid was the major phenolic acid (8.35 mg/100 g, dry weight (DW)) in BRB, followed by p-coumaric acid (1.63 mg/100 g, DW), caffeic acid (1.34 mg/100 g, DW), ferulic acid (0.24 mg/100 g, DW), and 3-hydroxybenzoic acid (0.20 mg/100 g, DW). Recoveries of these five phenolic acids in the whole GI tract were 199.9 +/- 54.0%, 7.0 +/- 3.0%, 37.0 +/- 9.7%, 56.6 +/- 31.3%, and 916.8 +/- 642.3% (mean +/- SEM, n = 5), respectively, and quantities in contents of the GI tract ranged from 0.13 +/- 0.05 micromol (p-coumaric acid) to 23.47 +/- 6.09 micromol (protocatechuic acid) (mean +/- SEM, n = 5). Six other phenolic acids were detected primarily in the cecum and/or colon which were not in BRB, with total contents in the GI tract ranging from 0.18 +/- 0.18 micromol (homovanillic acid) to 8.49 +/- 4.31 micromol (homoprotocatechuic acid). Total phenolic acids in the GI tract were 49.32 +/- 16.37 micromol (mean +/- SEM, n = 5). Phenolic acids measured in the GI tract accounted for only 6.31% of the degraded anthocyanins.

Expression of a functional single-chain antibody via Corynebacterium pseudodiphtheriticum.

Antibody-based therapeutics are effective against conditions ranging from acute infections to malignancy. They may prove crucial in combating bioterrorism and responding to drug-resistant and emerging pathogens. At present the cost of producing therapeutic monoclonal antibodies is between $1,000 to $6,000 per gram. The need to administer antibodies parenterally at frequent intervals further drives the cost of this treatment. Here we present an antibody delivery system, termed paratransgenesis, with the potential to overcome these limitations. The paratransgenic approach involves genetically transforming a commensal or symbiont bacterium to express foreign molecules that target pathogens. We describe transformation of Corynebacterium pseudodiptheriticum, a commensal bacterium found in the human respiratory tract, to express a murine single-chain antibody binding progesterone. The antibody was functional and bound specifically to progesterone in a concentration-dependent manner. This marker antibody system is the precursor to development of expression systems producing recombinant humanized single-chain antibodies. Studies are in progress evaluating fitness, transgene stablility, and pathogenecity of the genetically engineered C. pseudodiptheriticum. We anticipate developing a repertoire of expressed molecules targeting infectious agents and surface epitopes of pulmonary mass lesions. If expression systems for anti-pathogen molecules in C. pseudodiptheriticum and other respiratory commensal bacteria can be optimized, these bacteria have the potential for a range of therapeutic and prophylactic applications.

Fate of anthocyanins and antioxidant capacity in contents of the gastrointestinal tract of weanling pigs following black raspberry consumption.

Many fruits are rich in anthocyanins (ACNs). ACNs have high antioxidant capacity, but because of their apparent low bioavailability, their possible roles in health promotion in vivo are still in question. The objectives of these studies were to determine the fate of ACNs within the gastrointestinal (GI) tract and the effect on the bioavailability and subsequent metabolism of ACNs. Five weanling pigs were fed freeze-dried black raspberry (Rubus occidentalis L.) powder by oral administration, which provided 1146.1 +/- 44.6 micromol TE of oxygen radical absorbance capacity with fluorescein as a fluorescent probe (ORAC(FL)) per kg and 50.5 +/- 3.7 mg per kg total ACNs. After 4 h, the pigs were sacrificed and the contents of five GI segments (duodenum, jejunum, ileum, cecum, and colon) were collected and analyzed for their total antioxidant capacity (TAC, measured as ORAC(FL)) and ACNs. The recoveries of TAC and total ACNs were 46.5 +/- 3.5 and 41.7 +/- 4.9%, respectively. Both total ACNs and TAC were recovered primarily in the ileum, cecum, and colon at 4 h after a meal. Cyanidin aglycone with different sugar moieties showed significant differences in their recovery within the GI tract with sambubiose > sambubiose-rhamnose = rutinose >> glucose. Recovery of ACNs within the GI tract was positively and linearly associated with urinary ACN recovery, which suggests that stability within the GI tract and not decreased absorption accounts for the increased recovery. The environment of different segments of the GI tract may determine the stability of individual ACNs. Complex ACNs containing di- or triglycosides disappeared more slowly in the GI tract than simple ACNs such as a monoglycoside. TAC and total ACNs remained high 4 h after feeding, which indicates that ACNs provide significant antioxidant protection in the environment of the gut epithelium.

Aglycones and sugar moieties alter anthocyanin absorption and metabolism after berry consumption in weanling pigs.

To investigate the absorption and metabolism of anthocyanins (ACNs) with different aglycones and sugar moieties, weanling pigs (11.4 +/- 3.8 kg) were fed, in a single meal, a freeze-dried powder of chokeberry, black currant, or elderberry at a single dose of 229, 140, or 228 mumol total ACN/kg body weight (BW), respectively. These berries provided ACNs with differences in aglycone as well as some unique differences in the sugar moieties. The relative proportions of the different metabolites depended upon concentrations, quantities consumed, and types of glycoside of ACNs in the berry. Delphinidin ACNs were not metabolized to any measurable extent. Cyanidin ACNs were metabolized via methylation and glucuronidation as well as by formation of both derivatives on the same ACN molecule. ACNs with either a di- or trisaccharide attached to them were excreted in the urine primarily as the intact form. Over 80% of the ACN compounds containing rutinose or sambubiose, which were excreted in the urine from black currant, elderberry, or Marion blackberry, were excreted as the intact molecule. The limited metabolism of these ACNs that did occur was via methylation. ACN monoglycosides other than the glucoside were metabolized via methylation and/or glucuronide formation. The monoglucuronide that formed represented a small proportion of the metabolites relative to the methylated or the mixed methylated and glucuronide forms of ACNs. The data clearly demonstrate that the aglycone and the sugar moieties can alter the apparent absorption and metabolism of ACNs.

Pelargonidin is absorbed and metabolized differently than cyanidin after marionberry consumption in pigs.

Weaning pigs (7.9 +/- 1.7 kg) were fed a freeze-dried powder of marionberry (MB) by stomach tube to study the absorption and metabolism of anthocyanins. Four major anthocyanins (ACNs) were found in MB: cyanidin-3-glucoside (Cy-3-glc, 78%), cyanidin-3-rutinoside (Cy-3-rutin, 20%), pelargonidin-3-glucoside (Pg-3-glc, 0.4%), and 1 unknown acylated cyanidin-based ACN (UACy, 1.5%). In the urine, the 4 original ACNs and 11 metabolites were identified and quantified. The main metabolites were glucuronidated and/or methylated forms of the original anthocyanins. Total recovery of the 4 original ACNs plus their related metabolites was 0.087 +/- 0.034% for Cy-3-glc, 0.084 +/- 0.026% for Cy-3-rutin, 0.583 +/- 0.229% for Pg-3-glc and 0.036 +/- 0.011% for UACy (mean +/- SD, n = 3), respectively. For the individual ACNs, the amount of metabolites recovered from Cy-3-rutin was lower than that of the original intact Cy-3-rutin, whereas the amounts of metabolites from Cy-3-glc and Pg-3-glc in the urine were much higher than their original forms. In pig plasma, the 2 original ACNs, Cy-3-glc and Cy-3-rutin, and a trace of 1 metabolite (cyanidin monoglucuronide) were detected. The plasma concentration:dose ratio of Cy-3-rutin was higher than that of Cy-3-glc. Different aglycones and/or sugar moieties may influence the absorption and metabolism of ACNs. Cy-3-glc and Cy-3-rutin had similar apparent excretion rates relative to dose, whereas Pg-3-glc had a much higher total urinary excretion than cyanidin-based anthocyanins. Most of Cy-3-glc and Pg-3-glc were excreted in the form of metabolites, whereas most of the Cy-3-rutin was excreted in its original unmetabolized form. Urinary recovery of the acylated anthocyanin was lower than that of nonacylated anthocyanins.

HER-2/neu overexpression as a poor prognostic factor for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous stem cell transplantation.

PURPOSE: High-dose chemotherapy with autologous stem cell transplantation (HDCT) produces a high tumor response rate for patients with metastatic breast cancer and have 20% long-term progression-free survival. Overexpression of HER-2/neu oncoprotein predicts outcome in patients with breast cancer given standard-dose chemotherapy. Therefore, we evaluated whether the HER-2/neu overexpression in the primary tumor predicts clinical outcome in patients with metastatic breast cancer given HDCT. EXPERIMENTAL DESIGN: A total of 236 patients were given standard-dose induction chemotherapy followed by stem cell collection; high-dose chemotherapy with cyclophosphamide, thiotepa, and carmustine; and stem cell infusion. HER-2/neu expression was assessed by immunostaining with anti-HER-2/neu e2-4001 monoclonal antibody in 63 patients. RESULTS: Clinical characteristics and survival were similar for patients with known and unknown HER-2/neu status. HER-2/neu was overexpressed in 22 of 63 tumors (35%). There was some tendency for HER-2/neu overexpression to be associated with the absence of estrogen or progesterone receptors. In considering the association of HER-2/neu expression with patient outcomes, HER-2/neu overexpression was associated with generally shorter overall survival (P = 0.02) and progression-free survival (P < 0.01), and this association persisted to a lesser extent after adjustment for differences in important prognostic factors between the two groups. CONCLUSION: We conclude that HER-2/neu overexpression may represent an additional prognostic factor for patients with metastatic breast cancer who undergo HDCT.

Who is enrolled in for-profit vs. nonprofit Medicare HMOs?

We compare the characteristics of enrollees in for-profit and nonprofit Medicare health plans using nationwide data from the 1996 Medicare Current Beneficiary Survey. We find few differences in overall health status, limitations in activities of daily living (ADLs), or history of chronic disease. However, older Americans enrolled in for-profit plans are substantially poorer and less educated than those enrolled in nonprofit plans, are more likely to have joined their plan recently, and are more likely to have joined a plan with the expectation of reducing their out-of-pocket health care costs.

Making survey results easy to report to consumers: how reporting needs guided survey design in CAHPS. Consumer Assessment of Health Plans Study.

OBJECTIVES: CAHPS is designed to report information about health care quality from the consumer perspective. Enrollees are surveyed about their experiences with their health plan and medical care, and results are reported to other consumers choosing among health plans. Based on survey instruments designed to elicit reliable and valid information about health plan experiences from plan enrollees, the aim of the CAHPS team was to design a series of reporting products that present survey results so that consumers find the information understandable, meaningful, and useful in choosing among health plans. METHODS: Design of the survey instruments and reporting products were closely linked. The approach to reporting was based on previous research on consumers' information interests and needs in evaluating and choosing among plans. Cognitive tests were conducted with consumers to get their reactions to mock-ups of various approaches to reporting CAHPS survey results. RESULTS: Findings from previous research and cognitive testing, together with feedback from various experts and the public, were used to modify the survey questions, response options, and reporting formats to make it easier for consumers to understand and use reports. Changes included dropping topics of less interest to consumers, changing question wordings that were hard to understand, minimizing the number of different response categories, and revising questions to make them easier to group together for purposes of reporting. CONCLUSIONS: The CAHPS focus on reporting results to consumers presented an unusual challenge for survey design, requiring close coordination between instrument design and report development to produce a survey and reporting kit that serves consumers' information needs.

Behavioural adjustment in school of very low birthweight children.

The school-based behavioural adjustment at 7-8 years of a cohort of 243 prematurely born, very low birthweight (< 1501 g) children and their normal birthweight controls is reported. The findings indicate that the children born preterm (both male and female) were rated by their teachers as expressing more behaviour problems than their controls, and were less well adjusted to the school environment. The deficits noted in the preterms applied across the social classes, with no amelioration noted in preterms of higher social class. It is speculated that the problem behaviours reflect a failure in self-regulatory functions.

A guide to facilitating consumer choice.

Some purchasers and policymakers are advocating models that offer consumers a choice of health plans as a way to help them choose a plan that best meets their needs and to create incentives for health plans to compete on the basis of efficiency, quality, and service. A review of six consumer-choice models indicates that these objectives can be met if purchasers (1) create a level field for comparison through standardized benefits and structured enrollment processes; (2) offer a limited number of plans that meet appropriate selection criteria; (3) provide comprehensive, objective, and reliable consumer information; (4) support the process with education; and (5) hold plans accountable through uniform reporting of performance data.

The social competence of very-low-birthweight children: teacher, peer, and self-perceptions.

Whether very-low birthweight (VLBW less than or equal to 1500 gm) children differ from normal birthweight (NBW greater than 2500 gm) children with respect to social (as opposed to intellectual) competence has been a relatively neglected issue. The social competence at school age of 183 VLBW children was therefore compared with that of 183 NBW children born at the same hospital matched for age, gender, social class, parity, and maternal age. A multi-informant, multidefinitional approach to social competence was adopted involving teacher, (same-gender) peer, and self-ratings of the 366 children's levels of social maladjustment, social skill, and peer acceptance. VLBW children from the upper, middle, and lower social classes received significantly higher mean sadness/unhappiness scores (even with IQ covaried) than their NBW counterparts. Mean scores for the VLBW group were also higher for social withdrawal, and lower for both social skill and peer acceptance. Possible antecedents and consequences of such group differences in affect and sociability are suggested.

The hyperactive child at adolescence: cognitive, emotional, and social functioning.

In view of the paucity of detailed follow-up studies on hyperactive children, the performance of 15 adolescents diagnosed hyperactive 5 years previously was compared to that of a control group of equivalent age, sex, intelligence, and social class. Eleven cognitive tests measuring sustained attention, visual-motor and motor skills, abstraction, and reading ability, as well as three self-assessment tests examining self-esteem, activity level, social functioning, academic status, and career aspirations were administered. The hyperactives performed significantly worse than the controls on the sustained attention, visual-motor, and motor tasks, and on two of the four reading tests. They also gave themselves significantly lower ratings on some of the self-esteem and sociability items. It would appear that the hyperactives at adolescence still have attentional and stimulus-processing difficulties, which affect not only their academic performance but also their social functioning.

Communication style and effectiveness in homogeneous and heterogeneous dyads of retarded children.

The channels, styles, and successfulness of communication used by retarded children when teaching a simple board game to a listener of similar or dissimilar age and ability to themselves were investigated. Forty children, half of high level and half of low level (means MAs=6.6 and 3.7 years, mean CAs-15.5 and 11.2 years, respectively) instructed a naive listener either at their own or at the other level, after they had been taught the game by the experimenter. Both high- and low-level speakers altered their channels and styles of communication to low-level listeners along the dimensions found by Shatz and Gelman (1973) with nonretarded children. However, the communication shifts, particularly those produced by high-level speakers, were ineffective in producing listener understanding. We concluded than communication-skills training for retarded children must be concentrated not only on the linguistic form, but also on the functional appropriateness of the children's utterances.