The Knife's Edge of Tolerance: Inducing Stable Multilineage Mixed Chimerism but With a Significant Risk of CMV Reactivation and Disease in Rhesus Macaques.

Although stable mixed-hematopoietic chimerism induces robust immune tolerance to solid organ allografts in mice, the translation of this strategy to large animal models and to patients has been challenging. We have previously shown that in MHC-matched nonhuman primates (NHPs), a busulfan plus combined belatacept and anti-CD154-based regimen could induce long-lived myeloid chimerism, but without T cell chimerism. In that setting, donor chimerism was eventually rejected, and tolerance to skin allografts was not achieved. Here, we describe an adaptation of this strategy, with the addition of low-dose total body irradiation to our conditioning regimen. This strategy has successfully induced multilineage hematopoietic chimerism in MHC-matched transplants that was stable for as long as 24 months posttransplant, the entire length of analysis. High-level T cell chimerism was achieved and associated with significant donor-specific prolongation of skin graft acceptance. However, we also observed significant infectious toxicities, prominently including cytomegalovirus (CMV) reactivation and end-organ disease in the setting of functional defects in anti-CMV T cell immunity. These results underscore the significant benefits that multilineage chimerism-induction approaches may represent to transplant patients as well as the inherent risks, and they emphasize the precision with which a clinically successful regimen will need to be formulated and then validated in NHP models.

Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice.

OBJECTIVES: Endocannabinoid system (ECS) overactivation is associated with increased adiposity and likely contributes to type 2 diabetes risk. Elevated tissue cannabinoid receptor 1 (CB1) and circulating endocannabinoids (ECs) derived from the n-6 polyunsaturated acid (PUFA) arachidonic acid (AA) occur in obese and diabetic patients. Here we investigate whether the n-3 PUFA docosahexaenoic acid (DHA) in the diet can reduce ECS overactivation (that is, action of ligands, receptors and enzymes of EC synthesis and degradation) to influence glycemic control. This study targets the ECS tonal regulation of circulating glucose uptake by skeletal muscle as its primary end point. DESIGN: Male C57BL/6J mice were fed a semipurified diet containing DHA or the control lipid. Serum, skeletal muscle, epididymal fat pads and liver were collected after 62 and 118 days of feeding. Metabolites, genes and gene products associated with the ECS, glucose uptake and metabolism and inflammatory status were measured. RESULTS: Dietary DHA enrichment reduced epididymal fat pad mass and increased ECS-related genes, whereas it reduced downstream ECS activation markers, indicating that ECS activation was diminished. The mRNA of glucose-related genes and proteins elevated in mice fed the DHA diet with increases in DHA-derived and reductions in AA-derived EC and EC-like compounds. In addition, DHA feeding reduced plasma levels of various inflammatory cytokines, 5-lipoxygenase-dependent inflammatory mediators and the vasoconstrictive 20-HETE. CONCLUSIONS: This study provides evidence that DHA feeding altered ECS gene expression to reduce CB1 activation and reduce fat accretion. Furthermore, the DHA diet led to higher expression of genes associated with glucose use by muscle in mice, and reduced those associated with systemic inflammatory status.

Low to moderate alcohol consumption on serum vitamin D and other indicators of bone health in postmenopausal women in a controlled feeding study.

The objective of this study was to evaluate the effect of 8 weeks of no alcohol, low (1 drink or 15 g/day) and moderate (2 drinks or 30 g/day) alcohol consumption on markers of bone health: fasting serum 25-hydroxy vitamin D (25(OH)D), osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), urine deoxypyridinoline (DPD) and helical peptide (HP) in postmenopausal women (n=51). Compared with no alcohol, 1 or 2 drinks/day for 8 weeks had no significant impact on any of the bone markers. Within each alcohol group, obese women had significantly lower serum 25(OH)D and higher DPD concentrations than normal weight women. Season significantly affected the concentrations of serum 25(OH)D, but there was no significant interaction between alcohol and season on serum 25(OH)D concentrations. Low or moderate alcohol consumption for 8 weeks had no significant impact on markers of bone health in postmenopausal women.

Artificial ionospheric layers during pump frequency stepping near the 4th gyroharmonic at HAARP.

We report on artificial descending plasma layers created in the ionosphere F region by high-power high-frequency (HF) radio waves from High-frequency Active Auroral Research Program at frequencies f(0) near the fourth electron gyroharmonic 4f(ce). The data come from concurrent measurements of the secondary escaping radiation from the HF-pumped ionosphere, also known as stimulated electromagnetic emission, reflected probing signals at f(0), and plasma line radar echoes. The artificial layers appeared only for injections along the magnetic field and f(0)>4f(ce) at the nominal HF interaction altitude in the background ionosphere. Their average downward speed ~0.5 km/s holds until the terminal altitude where the local fourth gyroharmonic matches f(0). The total descent increases with the nominal offset f(0)-4f(ce).

2011 and 2012 Early Careers Achievement Awards: improving the production, environmental, and economic efficiency of the stocker cattle industry in the southeastern United States.

Grazing forages on small-grain fields can be a profitable "second crop" for grain producers and an opportunity for cow-calf producers to retain ownership of weaned calves. The increasing costs of conventional tillage and movement of soil nutrients into surface water creates a need for more sustainable production practices to be incorporated by producers into wheat pasture production systems. Research at the Livestock and Forestry Research Station near Batesville, AR, and the Southwest Research and Extension Center near Hope, AR, has been conducted over a 9-yr span to characterize the impacts of pasture systems on forage production, animal performance, soil quality, water runoff, and the economics associated with the stocker cattle enterprises. Gains of growing cattle grazing nontoxic endophyte-infected tall fescue and small-grain forages can be increased by 80 and 150%, respectively, compared with grazing Bermuda grass or toxic endophyte-infected tall fescue. Producers grazing spring-calving cowherds can use these improved forages to accelerate stocker performance when retaining calves in the fall and improve net returns by 99% with winter annual or nontoxic tall fescue production systems compared with Bermuda grass or toxic tall fescue. Rainfall simulation of small grain pastures indicates that runoff volume and nutrient load does not differ between conventionally tilled fields and no-till fields in the spring before tillage when soil surface cover is similar. In the fall after tillage, however, conventionally tilled fields had 4 times greater runoff; hence, there was 1.9 times greater N runoff and 3.2 times greater P runoff in conventionally tilled fields compared with no-till. Total natural rainfall runoff from conventionally tilled wheat fields were 2 times greater than from no-till fields with 25 mm rainfall events yet were 4 times greater with 62-mm rainfall events. Soil analysis shows that soil aggregate content was greater in no-till compared with conventional till, indicating greater soil porosity, improved water infiltration rate, and reduced erositivity of soil. Carbon concentration in no-till soils was 50% greater than conventional tillage after 9 yr. These experiments show that production systems can be designed that maintain livestock production, increase soil quality, reduce nutrient discharge, and promote improved economic returns.

The hereditary predisposition to hip osteoarthritis and its association with abnormal joint morphology.

OBJECTIVE: Genetic factors and abnormalities of joint morphology are important in the aetiology of hip osteoarthritis (OA). The extent to which genetic influences are manifest through joint morphology has undergone limited investigation. Using a cohort with an hereditary predisposition to end-stage hip OA and a control group with no inherited risk, we aimed to identify associations with abnormal joint morphology and clinical features. DESIGN: One hundred and twenty-three individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) (termed 'sibkids') were compared with 80 spouse controls. Morphology was assessed using standardised radiographs and cam, dysplasia, and pincer deformities defined. Regression modelling described the association of cohort with abnormal joint morphology, adjusting for confounders [age, gender, body mass index (BMI), OA, and osteophyte]. RESULTS: Sibkids had an odds ratio of 2.1 [95%confidence interval (CI) 1.3-3.5] for cam deformity. There were no differences in the prevalence of dysplasia or pincer deformities. In both groups, hips with cam deformities or dysplasia were more likely to have clinical features than normal hips [odds ratio (OR) 4.46 (1.8-11.3), and 4.40 (1.4-14.3) respectively]. Pincer deformity was associated with positive signs in the sibkids but not in the controls (OR 3.0; 1.1-8.2). DISCUSSION: After adjustment for confounders that cause secondary morphological change, individuals with an hereditary predisposition to end-stage hip OA had a higher prevalence of morphological abnormalities associated with hip OA. Sibkids were more likely to demonstrate clinical features in the presence of pincer deformity, suggesting that the genes are acting not only through abnormal morphology but also through other factors that influence the prevalence of pain.

Genetic predisposition to the presence and 5-year clinical progression of hip osteoarthritis.

OBJECTIVE: Genetic factors are important in the aetiology of hip osteoarthritis (OA), but studies are limited by cross-sectional design and poor association with clinically important disease. Identifying cohorts with progressive OA will facilitate development of OA biomarkers. Using a middle-aged cohort with genetic predisposition to hip OA and a control group, we compared the prevalence of clinical and radiographic hip OA and incidence of progression over 5 years. DESIGN: 123 individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) ('sibkids') were compared with 80 (mean age 54 years) controls. The prevalence of radiographic OA [scored according to Kellgren & Lawrence (K&L)], clinical features, and incidence of clinical progression over a 5-year period were compared. A multivariate logistic regression model was used to adjust for confounders. RESULTS: Sibkids had odds ratios (ORs) of 2.7 [95% confidence interval (CI) 1.1-6.3, P = 0.02] for hip OA (K&L grade ≥2), 3.4 (1.4-8.4, P = 0.008) for clinical signs, and 2.1 (0.8-5.8, P = 0.14) for signs and symptoms. Over 5 years, sibkids had ORs of 4.7 (1.7-13.2, P = 0.003) for the development of signs, and 3.2 (1.0-10.3, P = 0.047) for the development of signs and symptoms. DISCUSSION: Compared to a control group and after adjustment for confounders, individuals with genetic predisposition to end-stage hip OA have higher prevalence of OA, clinical features, and progression. In addition to structural degeneration, the inherited risk may include predisposition to pain. Genetically-loaded cohorts are useful to develop hip OA biomarkers, as they develop progressive disease at a young age.

Do abnormalities in regional cerebral blood flow in anorexia nervosa resolve after weight restoration?

OBJECTIVE: Previous studies have demonstrated localised abnormalities of cerebral blood flow in anorexia nervosa, suggesting reduction of cerebral activity and function in specific regions. There is debate as to whether such findings are secondary to starvation or indicative of a primary abnormality predating the illness, representing an underlying biological substrate. This small study, the first in early onset anorexia nervosa, reports findings of regional cerebral blood flow (rCBF) at both baseline and follow up. METHOD: Nine participants who had previously undergone rCBF studies at the start of treatment, had a repeat scan at an average of 4.2 years later. RESULTS: Seven out of the nine had persisting reduced cerebral blood flow in one area of the brain, predominantly the medial temporal region. DISCUSSION: These data suggest that in the majority of cases rCBF does not return to normal following weight restoration. The implications for future research are explored.

Attenuation of radiation- and chemoradiation-induced mucositis using gamma-D-glutamyl-L-tryptophan (SCV-07).

OBJECTIVE: To evaluate the efficacy of a novel immunomodulating peptide (SCV-07) in attenuating the course of radiation-induced mucositis in an established animal model of oral mucositis (OM). MATERIAL AND METHODS: In three separate experiments, golden Syrian hamsters received either an acute radiation challenge to the buccal mucosa of eight fractionated doses of 7.5 Gy of radiation over a 2-week-period, or a combination of acute radiation and cisplatin. In each experiment, animals were treated with varying doses or schedules of SCV-07 or placebo. OM was scored in a blinded fashion using digital images obtained during the experimental period. RESULTS: We found that SCV-07 reduced the severity and duration of both acute and fractionated radiation-induced OM. Similarly, when radiation and chemotherapy were used to induce OM, treatment with SCV-07 significantly reduced the duration of ulcerative OM. The therapeutic benefit was dependent on both dose and schedule of administration. CONCLUSION: Taken together, we found SCV-07 was able to modify the duration and severity of oral mucositis and was dependent on schedule and dose.

Genetic influences in the progression of tears of the rotator cuff.

The aim of this study was to investigate genetic influences on the development and progression of tears of the rotator cuff. From a group of siblings of patients with a tear of the rotator cuff and of controls studied five years earlier, we determined the prevalence of tears of the rotator cuff with and without associated symptoms using ultrasound and the Oxford Shoulder Score. In the five years since the previous assessment, three of 62 (4.8%) of the sibling group and one of the 68 (1.5%) controls had undergone shoulder surgery. These subjects were excluded from the follow-up. Full-thickness tears were found in 39 of 62 (62.9%) siblings and in 15 of 68 (22.1%) controls (p = 0.0001). The relative risk of full-thickness tears in siblings as opposed to controls was 2.85 (95% confidence interval (CI) 1.75 to 4.64), compared to 2.42 (95% CI 1.77 to 3.31) five years earlier. Full-thickness tears associated with pain were found in 30 of 39 (76.9%) tears in the siblings and in eight of 15 (53.3%) tears in the controls (p = 0.045). The relative risk of pain associated with a full-thickness tear in the siblings as opposed to the controls was 1.44 (95% CI 2.04 to 8.28) (p = 0.045). In the siblings group ten of 62 (16.1%) had progressed in terms of tear size or development compared to one of 68 (1.5%) in the control group which had increased in size. Full-thickness rotator cuff tears in siblings are significantly more likely to progress over a period of five years than in a control population. This implies that genetic factors have a role, not only in the development but also in the progression of full-thickness tears of the rotator cuff.

Evaluation of simple and looped suture and new material for flexor tendon repair.

Flexor tendon repair strength is proportional to the number of suture strands crossing the repair site but it is not clear if each strand needs to result from a separate pass through the tendon. We examined whether one throw of looped suture across a repair site equals two separate throws of suture and whether fewer passes with stronger material such as Fiberwire is equivalent to more passes with a comparatively weaker material such as Supramid. When evaluating the repairs for force required to generate a 2 mm gap and for gap formed at the instant prior to failure, looped suture cannot substitute for two separate passes of suture (Supramid Kessler looped vs. separate passes, 14 N vs. 35 N and 8.8 mm vs. 4.1 mm, respectively; Fiberwire Kessler looped vs. separate passes, 25 N vs. 43 N and 7.6 mm vs. 4.6 mm, respectively; all p<0.05). Two-stranded Fiberwire Kessler repair equalled four-stranded cruciate repair with Supramid for all tested parameters (force at 2 mm gap: 17 N vs. 22 N, respectively; force at failure: 42 N vs. 46 N; and gap formed prior to instant of failure: 6.9 mm vs. 5.6 mm; all p>0.05).

Improvement of bone quality in gonad-intact middle-aged male rats by long-chain n-3 polyunsaturated fatty acid.

The effect of long-chain n-3 polyunsaturated fatty acid (PUFA) on bone measurements was evaluated in gonad-intact middle-aged male rats. Seven rats were killed on day 0 of dietary intervention to determine bone parameters at baseline. Experimental rats (7/group) were fed one of the following lipid treatments (g/kg diet): 167 g safflower oil + 33 g menhaden oil (N6+N3 diet, control), 200 g safflower oil (N6 diet), or 190 menhaden oil + 10 g corn oil (N3 diet). After 20 weeks of dietary treatment, all groups had lower values for peak load and ultimate stiffness in femurs compared to baseline values. Rats fed the N3 diet had the highest values for peak load, ultimate stiffness, and Young's modulus compared with those fed the N6 and control diets. Compared to baseline, all dietary treatment groups had significantly lower values for trabecular thickness and number in proximal tibia but higher values for trabecular separation and formation rate in proximal tibia and endocortical bone formation rate in tibial shaft. Compared with the control group, rats fed the N3 diet had lower values for formation rate, osteoclast number, and eroded surface in proximal tibia but higher values for periosteal mineral apposition and formation rates in tibia shaft. These findings indicate that a diet rich in long-chain n-3 PUFA mitigate aging-induced loss of bone integrity in intact middle-aged male rats through reducing bone turnover rate by suppressing both bone formation and resorption as a result of a larger net bone volume and modulating endocortical and cancellous bone compartments.

Gene expression changes in peripheral blood cells provide insight into the biological mechanisms associated with regimen-related toxicities in patients being treated for head and neck cancers.

UNLABELLED: Patients treated with radiotherapy are prone to a constellation of local and systemic toxicities including mucositis, xerostomia, fatigue and anorexia. The biological complexities and similarities underlying the development of toxicities have recently been realized. Mucosal barrier injury is one of the best studied, and gene expression patterns, based on animal tissue samples, have added to its understanding. While investigations gene expression based on tissue samples was valuable, its use precludes more generalizable conclusions relative to common pathogenic mechanisms. Additionally, attempting to define the kinetics of changes in gene expression by sequential sampling is pragmatically unrealistic. Our objectives were: 1. to determine if changes in gene expression could be detected during toxicity development using PBM from patients receiving chemoradiation; 2. to characterize the relationship of expressed genes using graph theory and pathway analysis; and 3. to evaluate potential relationships between the expression of particular genes, canonical pathways, and functional networks in explaining the pathogenesis of regimen-related toxicities. DESIGN: Microarray analysis was performed using PBM-derived cRNA obtained before and 2 weeks after the initiation of chemoradiation in five patients with head and neck cancer who developed documented regimen-related toxicities. We created a database of those genes newly expressed at 2 weeks and evaluated their potential significance relative to toxicity, by canonical pathway analysis, compilation of regional networks around focus genes, and development of a model globalizing the individual functional networks. There was strong concordance between known pathogenic mechanisms of toxicity and the genes, pathways, and networks developed by our data. A role was elicited for unsuspected genes in toxicity development. Our results support the concept that radiation induced toxicities have common underlying mechanisms and demonstrate the utility of PBM as an RNA source for genetic studies. This methodology could be broadly applicable to the study of regimen-related toxicities.

Human fibroblast growth factor 20 (FGF-20; CG53135-05): a novel cytoprotectant with radioprotective potential.

The aim was to evaluate the radioprotective properties of recombinant human fibroblast growth factor 20 (FGF-20; CG53135-05) in vitro and in vivo and to examine its effects on known cellular pathways of radioprotection. Relative transcript levels of the cyclooxygenase 2 (COX2), Mn-super oxide dismutase (SOD), CuZn-SOD, extracellular (EC)-SOD, nuclear respiratory factor 2 (Nrf2), glutathione peroxidase 1 (GPX1) and intestinal trefoil factor 3 (ITF3) genes, which are involved in radiation response pathways, were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in NIH/3T3, IEC18, CCD-18Co, CCD-1070sk and human umbilical vein endothelial cells (HUVEC) cells exposed to FGF-20. Activation of the radioprotective signal transduction pathways initiating with the serine/threonine Akt kinase and the extracellular regulated kinase (ERK) were analysed. Levels of intracellular hydrogen peroxide and cytosolic redox potential were also measured in irradiated and unirradiated cells in the presence or absence of FGF-20. The effects of FGF-20 on cell survival in vitro following ionizing radiation were evaluated using clonogenic assays. To test the potential activity of FGF-20 as a radioprotectant in vivo, mice were administered a single dose of FGF-20 (4 mg kg(-1), intraperitoneally (i.p.) 1 day before lethal total-body irradiation and evaluated for survival. In vitro exposure to FGF-20 increased expression of the Nrf2 transcription factor and oxygen radical scavenging enzymes such as MnSOD, activated signal transduction pathways (ERK and Akt) and resulted in increased survival of irradiated cells in vitro. FGF-20 treatment also resulted in a concomitant reduction in intracellular levels of injurious reactive oxygen species (ROS) following acute ionizing irradiation. Finally, prophylactic administration of FGF-20 to mice before potentially lethal, whole-body X-irradiation led to significant increases in overall survival. FGF-20 reduced the lethal effects of acute ionizing radiation exposure in cells by up-regulating important signalling and free radical scavenging pathways. Survival-sparing effects of FGF-20 prophylaxis in acutely irradiated mice presumably are elicited by comparable mechanisms. These results indicate that FGF-20, has significant radioprotective attributes with potential applications in clinical and non-clinical exposure settings.

Upward movement of tritium from contaminated groundwaters: a numerical analysis.

This paper describes a research-oriented modelling exercise that addresses the problem of assessing the movement of tritium from a contaminated perched aquifer to the land surface. Participants were provided with information on water table depth, soil characteristics, hourly meteorological and evapotranspiration data. They were asked to predict the upward migration of tritium through the unsaturated soil into the atmosphere. Eight different numerical models were used to calculate the movement of tritium. The modelling results agree within a factor of two, if very small time and space increments are used. The agreement is not so good when the near-surface soil becomes dry. The modelling of the alternate upward and downward transport of tritium close to the ground surface generally requires rather complex models and detailed input because tritium concentration varies sharply over short distances and is very sensitive to many interactive factors including rainfall amount, evapotranspiration rate, rooting depth and water table position.

Anthocyanin quantification and radical scavenging capacity of Concord, Norton, and Marechal Foch grapes and wines.

The anthocyanin content and the radical scavenging capacity of three non-Vitis vinifera grapes (Marechal Foch, Norton, and Concord varieties) were determined. Analyses of anthocyanins in the skin (S) and wine (W) of these grape varieties were performed by spectrophotometry, HPLC with electrochemical detection, and matrix-assisted laser desorption ionization (MALDI). The total anthocyanin contents of S samples were 258 +/- 37 mg/100 g of wet weight for Foch, 888 +/- 78 mg/100 g for Norton, and 326 +/- 5.9 mg/100 g for Concord grapes. The malvidin 3,5-diglucoside content quantified by HPLC indicated that Norton S had the highest amount of the compound (327 +/- 110 mg/100 g). The MALDI mass spectrometric analysis indicated an abundance of malvidin glucosides in W of Foch grapes and in S and W of Norton grapes and of cyanidin aglycon in S and W of Concord grapes. S samples were subjected to a radical scavenging capacity test using the 2,2-diphenyl-1-picrylhydrazyl radical and compared to Trolox. The radical scavenging capacity for Foch S was 0.78 mM Trolox equiv, that of Concord S, 0.80 Trolox equiv, and that of Norton S was highest at 0.95 Trolox equiv. The higher concentrations of malvidin 3,5-diglucoside in S of grape varieties were associated with greater radical scavenging capacity.

Hepatozoon griseisciuri in grey squirrels (Sciurus carolinensis): changes of blood leucocyte numbers resulting from infection.

Numbers of leucocytes in squirrels with gametocytes of Hepatozoon in their blood (infected) were compared with animals without gametocytes (uninfected). Typical values for leucocytes/mm3 blood in uninfected squirrels were: leucocytes 5.7 x 10(3), granulocytes 3.4 x 10(3), lymphocytes 2.0 x 10(3) and monocytes 0.3 x 10(3) cells. Infection caused an increase in monocytes, lymphocytes and granulocytes, and there was a significant positive association between parasitaemia level and numbers of both total leucocytes and monocytes. Infected animals had more uninfected monocytes/mm3 blood than did uninfected animals. The proportions of monocytes were more variable over time in infected animals, but no shift between infected and uninfected status was detected. Transfer of serum from infected squirrels to mice resulted in elevated counts of total blood leucocytes, monocytes and granulocytes, but not of lymphocytes, as compared with controls. Serum from squirrels with high parasitaemias had a more marked effect than serum from squirrels with low parasitaemias. Results indicate an infection-related monocytosis, possibly controlled by cytokines, that increases the number of cells available for invasion by gametocytes, thus enhancing the chances of parasite transmission.

The nosological status of early onset anorexia nervosa.

BACKGROUND: Although cases of early onset anorexia nervosa have been described, there has been no systematic comparison of early onset cases with classic cases of later onset, or with other forms of early onset eating disturbance. METHOD: A consecutive series of patients referred to two specialist child and adolescent eating disorder services with a clinical diagnosis of eating disorder (N = 126) was systematically assessed using a child version of the Eating Disorder Examination (EDE) and the K-SADS interview. RESULTS: Of 86 patients with a diagnosis of eating disorder of early onset, 38 received a clinical diagnosis of anorexia nervosa (AN). The remainder were mainly diagnosed as having food avoidance emotional disorder (25 patients) and selective eating (17 patients). Six received other diagnoses (bulimia nervosa, or functional dysphasia). These 48 patients were combined to form a group of early onset non-AN eating disturbance. In terms of specific eating disorder psychopathology and general psychopathology, the early onset AN group was very similar to the late onset AN sample. When the two early onset groups were compared, there was a marked difference between them in terms of eating disorder psychopathology. A discriminant function analysis using the EDE information produced a clear discrimination, with the EDE restraint and shape concern subscales doing most of the discrimination work. CONCLUSIONS: The specific psychopathology of AN of early onset is very similar to that of classic adolescent onset AN. Other forms of early onset eating disorder do not evidence this specific psychopathology.

Fatty acid analysis of wild ruminant tissues: evolutionary implications for reducing diet-related chronic disease.

HYPOTHESES: Consumption of wild ruminant fat represented the primary lipid source for pre-agricultural humans. Hence, the lipid composition of these animals' tissues may provide insight into dietary requirements that offer protection from chronic disease in modern humans. METHOD: We examined the lipid composition of muscle, brain, marrow and subcutaneous adipose tissue (AT) from 17 elk (Cervus elaphus), 15 mule deer (Odocoileus hemionus), and 17 antelope (Antilicapra americana) and contrasted them to wild African ruminants and pasture and grain-fed cattle. RESULTS: Muscle fatty acid (FA) was similar among North American species with polyunsaturated fatty acids/saturated fatty acids (P/S) values from 0.80 to 1.09 and n-6/n-3 FA from 2.32 to 2.60. Marrow FA was similar among North American species with high levels (59.3-67.0%) of monounsaturated FA; a low P/S (0.24-0.33), and an n-6/n-3 of 2.24-2.88. Brain had the lowest n-6/n-3 (1.20-1.29), the highest concentration of 22:6 n-3 (elk, 8.90%; deer, 9.62%; antelope, 9.25%) and a P/S of 0.69. AT had the lowest P/S (0.05-0.09) and n-6/n-3 (2.25-2.96). Conjugated linoleic acid (CLA) isomers were found in marrow of antelope (1.5%), elk (1.0%) and deer (1.0%), in AT (deer, 0.3%; antelope, 0.3%) in muscle (antelope, 0.4%; elk, trace), but not in brain. CONCLUSIONS: Literature comparisons showed tissue lipids of North American and African ruminants were similar to pasture-fed cattle, but dissimilar to grain-fed cattle. The lipid composition of wild ruminant tissues may serve as a model for dietary lipid recommendations in treating and preventing chronic disease.