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Inheritable traits of cattle were modified in various ways at different times by diverse cultures. A large collection of seventeenth century cattle remains excavated from 71 silos in the Largo do Coreto in Carnide, Lisbon, included 47 com- plete and 44 distal ends of metacarpals. These provide an opportunity to make a detailed osteometric and archaeogenetics study. While morphological changes such as size increase, as detected in bone measurements, indicate improvement for larger animals, ancient DNA is useful for studying evolutionary trajectories and modes of improvement of domestic animals. High-throughput sequencing can show evolutionary processes at unprecedented resolution. We generated whole-genome shotgun resequencing data for 6 Carnide specimens on the Illumina HiSeq X Ten platform. Mean en- dogenous DNA content for these samples varied between 1% (CAR008) and 4% (CAR014), and their mitogenomes were sequenced to between 3.56x and 33.44x mean depth of coverage, respectively. The Carnide cattle belong to the Europe- an-T3 (CAR002 and CAR021) and African-T1 haplogroups (CAR008, CAR009, CAR014, and CAR016). These haplogroups are also present in extant native breeds from the Iberian Peninsula, corroborating the hypothesis of a genetic continuity of maternal lineages over time. The admixture of African taurine cattle observed in these specimens from the Modern period supports the idea that current genetic diversity of Iberian cattle derives from the dispersal of a heterogeneous population since early times along the Mediterranean basin. In addition, the biological sex of the Carnide specimens was consistently determined by our genomic analysis and osteometric measurements. Further analyses of whole-genome nuclear data are needed to infer specific biological properties, for example, the coat color of these animals, as well as the variability of genes linked to body size, meat, and milk production traits.

BackgroundMethotrexate (MTX) is the preferred initial disease-modifying drug (DMARD) for rheumatoid arthritis (RA). However, up to 50% of patients respond inadequately to MTX (1). Clinically useful predictors that effectively identify patients with RA who are likely to respond to MTX are lacking. Whether machine learning (ML) can provide robust and clinically useful prediction of response to MTX monotherapy in the first months of treatment in patients with early RA using uniformly collected baseline demographics and clinical data has not been investigated in large patient populations.ObjectivesWe aimed to identify clinical predictors of response to MTX as the first DMARD among patients with RA using ML methods.MethodsRandomized clinical trials (RCT) of patients with RA who were DMARD-naïve and randomized to placebo plus MTX were identified and accessed through the Clinical Study Data Request Consortium and Vivli Center for Global Clinical Research Data. Studies with available Disease Activity Score with 28-joint count and erythrocyte sedimentation rate (DAS28-ESR) at baseline, 12 and 24 weeks were included. Latent class modeling of MTX response was performed. Least absolute shrinkage and selection operator (LASSO) and random forest were used to identify predictors of response.ResultsA total of 775 patients from 4 RCTs were included (mean age 50 years, 80% female). Two distinct classes of patients were identified based on DAS28-ESR change over 24 weeks: “good responders” and “poor responders” to MTX treatment (Figure 1). Baseline DAS28-ESR, anti-citrullinated protein antibody (ACPA) and health assessment questionnaire (HAQ) score were the top predictors of good response to MTX using LASSO (Area Under the Curve [AUC] 0.79) and Random Forest models (AUC 0.68) in the external validation set. DAS28-ESR≤7.4, ACPA positive and HAQ≤2 provided the highest likelihood of response (Table 1). Among patients with 12-week DAS28-ESR>3.2, at least 1 point improvement in DAS28-ESR baseline-to-12-week was predictive of achieving DAS28-ESR≤3.2 at 24 weeks.Table 1.Matrix prediction model: Probability of achieving a good response to methotrexate at 24 weeksDAS28ESR≤7.480.1 (76.4, 83.8)77.3 (70.6, 84)PositiveACPA Status77.1 (68.6, 85.6)74.1 (63.3, 84.9)Negative>7.440.3 (32.1, 48.5)36.5 (29.3, 43.6)Positive36.2 (23.3, 49.1)32.5 (20.9, 44.1)Negative≤2>2HAQFootnote: The number in each cell represents the percentage and 95% CI of achieving the outcome, based on the combination of predictors at baseline. DAS28-ESR: Disease Activity Score with 28-joint count with erythrocyte sedimentation rate; HAQ: Health assessment questionnaire score; ACPA: Anti-citrullinated protein antibody.Figure 1.Two patient class trajectories identified with latent class modeling of DAS28-ESR (N=775)ConclusionWe have developed and externally validated a prediction model for response to MTX within 24 weeks in DMARD-naïve patients with RA, providing variably weighted clinical features and defined cut-offs for clinical decision-making. Trajectory of DAS28-ESR change over 24 weeks in patients with moderate-to-high RA disease activity at baseline who are starting MTX can be predicted by baseline DAS28-ESR, ACPA status and HAQ-score. Patients with at least 1 unit decline in DAS28-ESR within the first 12 weeks of treatment who have not achieved low disease activity by week 12, may be more likely to achieve low disease activity at 24 weeks. These parameters should be considered as part of the clinical decision-making process when initiating MTX in DMARD-naïve patients with RA.References[1]Aletaha D, Smolen JS. Effectiveness profiles and dose dependent retention of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. An observational study. J Rheumatol. 2002;29(8):1631-8.AcknowledgementsThis abstract is based on research using data from data contributors UCB and Roche that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.Disclosure of InterestsStephanie Duong: None declared, Cynthia S. Crowson: None declared, Arjun Athreya: None declared, Elizabeth Atkinson: None declared, John M Davis III Grant/research support from: Pfizer, Kenneth J Warrington Speakers bureau: Chemocentryx, Consultant of: Roche/Genentech, Eric Matteson: None declared, Richard Weinshilboum Shareholder of: OneOme, Liewei Wang Shareholder of: OneOme, Elena Myasoedova: None declared.

Osteometric data from > 450 modern wild rabbits, mostly from Portugal, Spain and France, show an inverse correlation between their size and the temperature of the environment, in accordance with Bergmann’s rule. Similar measurements made on some 1660 rabbit bones from 14 Portuguese late Pleistocene and Holocene archaeological sites indicate that rabbits became considerably smaller at the Pleistocene–Holocene boundary. Thus, rabbit size varies or varied with temperature both today and in the past. A direct temperature–size relationship was assumed, and the regression of modern rabbit bone size on temperature was then used to calibrate the temperature equivalent for the change of size of rabbit bones in the past. The result indicates a Last Glacial Maximum to present-day difference, Δt°, of 7 or 8 °C. An alternative interpretation that does not assume a direct temperature–size relationship would indicate that the environment in Portugal 15 000–30 000 years ago was similar to that in northern France today.

BackgroundGrowing evidence from observational studies indicates that patients with rheumatoid arthritis (RA) have a higher risk of developing dementia. However, the incidence of dementia among RA patients has declined in recent years 1. It is unknown if this reflects broader trends of dementia incidence over time, changes in the prevalence or treatment of associated comorbidities, advances yielding better control of inflammation in RA, or other factors (e.g., environmental risk factors). Longitudinal population-based studies assessing risk factors for dementia among RA patients are scarce 2.ObjectivesWe aimed to identify risk factors for incident dementia in a large inception cohort of patients with RA.MethodsThis retrospective population-based cohort study included residents of Olmsted County, MN, who were ≥50 years when they met 1987 ACR criteria for incident RA in 1980-2014. All individuals were followed until death/migration or 12/31/2019. Patients with dementia before RA incidence were excluded (n=12). Incident dementia was defined as two relevant ICD-9/10 codes at least 30 days apart. Risk factors including socio-demographics, RA disease characteristics and medications, cardiovascular/cerebrovascular disease (CVD) risk factors and other comorbidities were abstracted from medical records. Any CVD was defined as coronary heart disease (i.e., angina pectoris, coronary artery disease, myocardial infarction, coronary revascularization procedures, cerebral stroke or heart failure (HF). Association of individual risk factors with incident dementia was examined using Cox proportional hazard models. Three models were utilized: Model 1, adjusting for age, sex, and calendar year of RA incidence; Model 2, adding smoking, obesity, hypertension, diabetes mellitus, and hyperlipidemia to the first; and Model 3, adding ‘any CVD’ to the second. Time-dependent covariates were used to represent factors that developed during follow-up.ResultsThe study included 886 patients with RA (mean age 65 years, 65% females). During the follow-up period (median=8.5 years), 103 patients developed dementia. Mean age at the diagnosis of dementia was 82.3 (7.2) years. The cumulative incidence of dementia increased by 2-3% every 5 years after the diagnosis of RA. Older age at RA incidence (Hazard Ratio (HR) 1.14 per 1 year increase, confidence interval (CI): 1.12-1.17) was consistently associated with risk of dementia. Presence of rheumatoid nodules (HR 1.76, CI: 1.05-2.95), large joint swelling (HR 2.11, CI: 1.33-3.34), hypertension (HR 1.84, CI: 1.19-2.85), HF (HR 2.72, CI: 1.29-5.74), and depression (HR 2.23, CI: 1.36-3.67) at baseline or during the first year after RA incidence were significantly associated with risk of dementia. Large joint swelling (HR 2.03, CI: 1.14-3.60), any CVD (HR 2.25, CI: 1.38-3.66), anxiety (HR 1.86, CI: 1.16-2.97), and depression (HR 2.63, CI: 1.76-3.93) at any time during the disease increased the risk of dementia. Among CVD conditions, stroke (HR 3.16, CI: 1.84-5.43) and HF (HR 1.82, CI: 1.10-3.00) significantly increased risk of dementia. After adjusting for CVD risk factors (Model 2), or CVD risk factors plus any CVD (Model 3), all the covariates listed above were still significantly associated with the risk of dementia.ConclusionApart from age, CVD (particularly hypertension), depression and anxiety, which are universally recognized risk factors for dementia, we observed that clinically active RA was associated with an elevated risk of dementia incidence among RA patients. Studies are ongoing to further evaluate the role of systemic inflammation and its interactions with other risk factors in dementia overall and by dementia subtype in patients with RA.References[1]Kronzer V L et al. Trends in incidence of dementia among patients with rheumatoid arthritis: A population based cohort study. Semin. Arthritis Rheum.51, 853–857 (2021)[2]Wallin K et al. Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later: A population based study J. Alzheimer’s Dis.31, 669–676 (2012)AcknowledgementsThis work was supported by grants from the National Institutes of Health, NIAMS (R01 AR46849) and NIA (R01 AG068192, R01 AG034676).Disclosure of InterestsChanakya Kodishala: None declared, Cassondra A Hulshizer: None declared, Vanessa Kronzer: None declared, John M Davis III Grant/research support from: Pfizer, Vijay K Ramanan: None declared, Maria Vassilaki Shareholder of: Abbott Laboratories, Johnson and Johnson, Medtronic, and Amgen, Consultant of: F. Hoffmann-La Roche Ltd, Grant/research support from: F. Hoffmann-La Roche Ltd and Biogen, Michelle Mielke Consultant of: Biogen, Brain Protection Company, and LabCorp, Cynthia S. Crowson: None declared, Elena Myasoedova: None declared

BackgroundFlare of rheumatoid arthritis (RA) disease activity is an important aspect of RA disease experience for patients with RA, associated joint damage and comorbidity. Major advancements in treatment of RA in recent decades resulted in improving trends in RA disease activity and increasing rates of remission. However, flares in RA remain common and some patients are still unable to achieve remission. Disease-modifying antirheumatic drugs have a major impact on controlling RA disease activity, minimizing the likelihood of flares. The effect of environmental factors on the pattern of flares and remissions in RA is less studied. Previous studies showed conflicting results regarding the likelihood of flare and remission occurrence across the seasons of the year.ObjectivesTo assess the seasonal pattern in the occurrence of flares and remissions in a population-based cohort of patients with RA.MethodsThis retrospective population-based cohort study included patients with RA (age ≥30 years) who met 1987 ACR criteria in 1988-2007. A retrospective review of each clinical visit in the medical records was performed to ascertain flare or remission status. A flare was defined as an episodic worsening of RA disease activity that leads to initiation, change or increase of treatment. Remission was defined as the absence of disease activity based on a tender joint count of 0, a swollen joint count of 0 and an ESR less than 10 mm/h. Seasons were defined as: winter (Dec, Jan, Feb), spring (Mar, Apr, May), summer (June, July, Aug) and autumn (Sep, Oct, Nov). All subjects were followed until death, migration or July 1, 2012. Generalized linear models with random effects to account for multiple visits per patient were used for data analyses.ResultsThe study included 650 RA patients (mean age 55.8 years; 69% female) with a mean follow up of 10.3 years. In a total of 17,323 clinical visits, patients were flaring in 2887 (17%) visits. The incidence of RA flares was 15% higher in the spring than in the winter (OR 1.15: CI: 1.02-1.29, p=0.045) after adjusting for age, sex and RA duration. There was no change in flare pattern between winter and summer or autumn. Remission rate did not differ between the seasons. (3df test p=0.65).ConclusionPatients with RA were more likely to experience flares in spring as compared to winter, and there were no differences in flare rates for the rest of the seasons. Remission rates were similar between the seasons of the year. The reasons for this seasonal effect on flare pattern is unknown, and the role of patient-related and environmental risk factors remains to be investigated. Our findings on the seasonality in flare occurrence can be used to inform patients about the risk of RA disease flares throughout the year.Disclosure of InterestsRabia Javed: None declared, Cynthia S. Crowson: None declared, John M Davis III Grant/research support from: Received research grant from Pfizer for rheumatoid arthritis., Elena Myasoedova: None declared.

BackgroundComorbidities in ankylosing spondylitis (AS) occur more frequently than in the general population and are associated with higher morbidity and mortality. Some comorbidities may occur together, making one more likely in the presence of another, and different combinations of comorbidities may have differential considerations for AS management and outcomes.ObjectivesTo examine the association of baseline comorbidities with disease activity and functional status in AS.MethodsWe used baseline data from the Prospective Study Of Ankylosing Spondylitis (PSOAS) cohort, a multicenter, prospective cohort from five centers (4 in the US, 1 in Australia). AS patients ≥ 18 years fulfilling mNY criteria for AS (2002-20) were included. Patient-reported AS comorbidities (N=28) and extra-musculoskeletal manifestations (EMMs, N=2) within 3 years of enrollment (prespecified on the baseline case-report form) and only those occurring in ≥1% were included. Undocumented comorbidities were assumed to be absent if missing in 50% of patients were excluded. Comorbidity clusters were identified using K-median clustering. The optimal number of clusters was determined using scree plot of the sum of squared errors and “elbow” on the graph line. Baseline characteristics of the clusters were compared, and associations of with disease activity and functional status measures (primary outcomes: ASDAS-CRP and BASFI) were examined using linear regression adjusted for age and sex.ResultsThere were 1,270 AS patients included with a mean age of 44.6 ±14.3 years, 74.4% males, and 81.2% whites. Mean AS symptom duration was 20.6±5.6 years, 81.6% HLA-B27 positive, and CRP elevated in 27.5% of patients at baseline. Depression was the most prevalent comorbidity (31.4%) followed by hypertension (26.1%); uveitis was the most common EMM (30.4%). The five clusters identified included depression (27%), no comorbidities (22%), hypertension (21%), uveitis (20%), and asthma/low bone mass (10%) (Figure 1). The cluster with no comorbidities was significantly younger, with lower symptom duration (pTable 1.Age and sex adjusted associations between comorbidity clusters, compared to cluster 3, and baseline disease activity/ functional status measures in ankylosing spondylitis based on Linear regression models.Cluster 1 (depression)Cluster 3 (hypertension)Cluster 4 (uveitis)Cluster 5 (asthma, low bone mass)OutcomesCoef (95% CI)Coef (95% CI)Coef (95% CI)Coef (95% CI)ASDAS-CRP0.98 (0.78-1.18)0.43 (0.18-0.68)0.04 (-0.19-0.27)0.16 (-0.12-0.44)BASFI (0-10)1.92 (1.51-2.34)1.00 (0.53-1.48)-0.03 (-0.49-0.42)0.64 (0.076-1.20)Enthesitis count1.17 (0.73-1.61)0.73 (0.19-1.26)0.18 (-0.32-0.68)0.48 (-0.13-1.08)Swollen joint count (0-44)0.27 (-0.08-0.62)0.43 (-0.01-0.86)0.31 (-0.09-0.71)-0.95 (-0.58-0.39)Tender joint count (0-46)1.24 (0.59-1.88)0.44 (-0.34-1.23)0.56 (-0.18-1.29)0.34 (-0.55-1.23)BASDAI (0-10)2.30 (1.88-2.71)0.88 (0.36-1.40)0.30 (-0.17-0.78)0.61 (0.03-1.19)Patient Global (0-10)2.25 (1.82-2.68)0.76 (0.21-1.30)-0.22 (-0.71-0.27)0.29 (-0.31-0.89)Patient Pain (0-10)2.45 (1.95-2.94)1.00 (0.37-1.62)0.19 (-0.38-0.75)0.16 (-0.54-0.85)Spinal pain (0-10)2.40 (1.89-2.91)1.05 (0.41-1.70)0.43 (-0.16-1.01)0.76 (0.04-1.47)Figure 1.Comorbidity clusters in PSOAS cohort at baselineConclusionDistinct comorbidity clusters were identified in AS patients in the PSOAS cohort. In addition to the number of comorbidities, the type of comorbidity seems to be important. Depression and hypertension clusters seem to be associated with worse disease activity and function.Disclosure of InterestsParas Karmacharya: None declared, Cynthia S. Crowson: None declared, Dilli Poudel: None declared, John M Davis III Consultant of: Dr. Davis has received consulting fees and/or honoraria from AbbVie and Sanofi-Genzyme (less than $10,000 each), Grant/research support from: Dr. Davis has received research support from Pfizer., Alexis Ogdie Consultant of: Dr. Ogdie has served as a consultant for AbbVie, Amgen, BMS, Celgene, Corrona, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB (less than 10,000 each), Grant/research support from: Dr. Ogdie has received grants from Novartis and Pfizer to Penn and from Amgen to Forward (grants more than 10,000)., Jean Liew Grant/research support from: Dr. Liew received grant/research support from Pfizer (> $10,000), Michael Ward: None declared, Mariko Ishimori: None declared, Michael Weisman Consultant of: Dr. Weisman received consulting fees for Novartis, UCB, Gilead, and GSK (< $10,000)., Matthew Brown: None declared, Mohammad Rahbar: None declared, Mark Hwang: None declared, John D Reveille Consultant of: JDR received consulting fees for UCB (< $10,000), Grant/research support from: Dr. Reveille received research support from Lilly and Janssen unrelated to this work., Lianne S. Gensler Consultant of: Dr. Gensler has received consulting fees for AbbVie, Eli Lilly, GSK, Gilead, Pfizer (< $10,000)., Grant/research support from: Dr. Gensler received grant/research support from UCB and Novartis (> $10,000).

The fauna of Neolithic Lameiras includes abundant sheep. Many could be securely identified by applying criteria described by the late Joachim Boessneck as well as metrical methods. Sheep bones from Early Neolithic contexts, several dated directly via 14C, pinpoint the arrival here, 5450 cal BC, of this exotic animal three thousand years after its domestication 5000 km to the east. Thus sheep were transported at a rate of 1,6 km per year – considerably faster than suggested by the ‘wave of advance’ theory. It therefore seems probable that part of the journey was undertaken by ship. Most of the mammal remains identified at Lameiras belonged to domesticated forms and besides sheep and some goat, they include cattle and pig. Zooarchaeologically there is little difference between Early and Late Neolithic. However the Neolithic spectrum of species contrasts with that from a small assemblage in the underlying Mousterian level as well as other pre-Neolithic assemblages in Portugal. It is possible that in southern Portugal the adoption of animal husbandry was sudden. Measurements of the remains of Canis, Bos, Ovis, Capra and Sus compared with an increasingly large corpus of data from the South-Western part of the Iberian Peninsula indicate several occasions when these animals underwent size changes. Bos, Capra and Canis were considerably larger in the Pleistocene – a size difference now documented in other regions. Besides a Pleistocene-Holocene reduction in size, they underwent a further diminution associated with their domestication. It is possible that aurochs and wild boar recovered some of their former size after the Neolithic, perhaps due to a relaxation of hunting pressure after the Mesolithic. Domestic sheep, goats and cattle increased in size in more recent times perhaps reflecting Moslem and Christian improvements., La fauna neolítica de Lameiras incluye numerosas ovejas. Muchas pudieron ser identificadas al aplicar los criterios descritos por el fallecido J. Boessneck y por métodos métricos. Los huesos de oveja de los contextos del Neolítico temprano, algunos datados a través del C14, apuntan a la llegada de esta especie hacia el 5.450 cal. D.C. 3.000 años después de su domesticación a 5.000 km de distancia hacia el Oriente. De este modo, las ovejas fueron transportadas a un ritmo de 1,6 km al año lo cual es considerablemente más rápido que lo sugerido por la llamada teoría de la “ola de avance”. Por ello, parece probable que parte de este viaje se haya llevado a cabo en barco. La mayoría de los restos de mamíferos identificados en Lameiras representan formas domésticas que además de la oveja y alguna cabra incorporan vacuno y porcino. Desde un punto de vista zooarqueológico existe poca diferencia entre el Neolítico temprano y tardío. Sin embargo, el espectro de especies neolíticas contrasta con el de una pequeña muestra en el nivel musteriense que subyace a estos depósitos así como a otras muestras preneoliticas en Portugal. Es posible que en el sur de Portugal la adopción de la práctica ganadera haya sido rápida. Los valores de los restos de Canis, Bos, Ovis, Capra y Sus apuntan a varios momentos en los cuales los animales sufrieron cambios de tamaño, datos que encajan con el corpus osteométrico que se viene recopilando para el sector sudoccidental de la Península Ibérica. Bos, Capra y Canis eran considerablemente más grandes en el Pleistoceno, una diferencia de talla ahora documentada en otras regiones. Además de la reducción de tamaño durante la transición Pleistoceno-Holoceno estas especies sufrieron otra adicional asociada con su proceso de domesticación. Es posible que tanto uros como jabalíes recuperasen parte de sus antiguas tallas al concluir el Neolítico. Quizás ello se deba a una relajación en la presión de caza operada tras el Mesolítico. Las ovejas, cabras y vacas domésticas aumentaron de tamaño en épocas más recientes reflejando posiblemente mejoras en las prácticas pecuarias de musulmanes y cristianos.

We investigated the genetic, composition of six Canis remains from western Iberia, directly radiocarbon dated to 7,903-7,570 years (cal BP). They were identified as dogs via their qrchaeological and depositional context, osteometry, and a high percentage of aquatic diet shared with humans. For comparison, genetic data were obtained from an additional 37 Iberian dog remains from the Neolithic to Late Antiquity, as well as two Palaeolithic anda a Chalcolithic Canis identified as wolves. Previous data indicated that dog mtDNA haplogroup A (HgA) is prevalent in extant European dogs (>50%), in the Near East and Asia, but rare or absent (

Monocyte chemoattractant protein 1 (MCP-1) is known to be an important chemokine for macrophage recruitment. Thus, targeting MCP-1 may prevent the perturbations associated with macrophage-induced inflammation in adipose tissue. However, inconsistencies in the available animal literature have questioned the role of this chemokine in this process. The purpose of this study was to examine the role of MCP-1 on obesity-related pathologies. Wild-type and MCP-1-deficient mice on an friend virus B NIH (FVB/N) background were assigned to either low-fat diet or high-fat diet (HFD) treatment for a period of 16 weeks. Body weight and body composition were measured weekly and monthly, respectively. Fasting blood glucose and insulin, and glucose tolerance were measured at 16 weeks. Macrophages, T-cell markers, inflammatory mediators and markers of fibrosis were examined in the adipose tissue at the time of killing the mice. As expected, HFD increased adiposity (body weight, fat mass, fat percent and adipocyte size), metabolic dysfunction (impaired glucose metabolism and insulin resistance) macrophage number (CD11b+F480+ cells, and gene expression of EMR1 and CD11c), T-cell markers (gene expression of CD4 and CD8), inflammatory mediators (pNFκB and pJNK, and mRNA expression of MCP-1, CCL5, C-X-C motif chemokine-14, tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) and fibrosis (expression of IL-10, IL-13, TGF-β and matrix metalloproteinase-2 (MMP2); P

This commentary discusses nephron protection in diabetic kidney disease and describes the way in which renin–angiotensin system inhibitors and the sodium–glucose cotransporter 2 inhibitor empagliflozin have renoprotective effects.

An experiment was conducted to measure the apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of fatty acids in diets containing 0 or 30% corn distillers dried grains with solubles (DDGS) and 0, 5, or 10% tallow. Barrows (n = 24; initial BW = 25 kg) were surgically fitted with a T-cannula at the distal ileum. Pigs (n = 4/diet) were randomly assigned to diets: corn-soybean meal control (CON), CON plus 5% tallow (5T0D), CON plus 10% tallow (10T0D), CON plus 30% DDGS (0T30D), CON plus 5% tallow and 30% DDGS (5T30D), and CON plus 10% tallow and 30% DDGS (10T30D). Eight replicates per treatment were achieved by randomizing diets among pigs for a second collection period. Each pig was fed their respective diet for a 5-d adaptation period followed by 3-d fecal collection and 2-d ileal digesta collection periods. The AID and ATTD of fatty acids was calculated using the index method and acid-insoluble ash as an indigestible marker. When tallow was added to diets with 0% DDGS, there was no effect on AID of palmitic acid (C16:0) or SFA, while AID of stearic acid (C18:0) was increased (66.87% for CON, 72.06% for 5T0D, and 76.81% for 10T0D; P < 0.01). However, when diets contained 30% DDGS, the AID of all SFA was reduced as levels of tallow increased C16:0 (77.62% for 0T30D, 69.66% for 5T30D, and 68.43% for 10T30D), C18:0 (85.87% for 0T30D, 64.08% for 5T30D, and 61.25% for 10T30D), and SFA (79.88% for 0T30D, 68.23% for 5T30D, and 66.29% for 10T30D). The AID of MUFA was not affected when tallow was added to diets with 30% DDGS but actually increased in 5T0D and 10T0D. The amount of apparent ileal digested fatty acids increased with the addition of DDGS and tallow regardless of their digestibility. Amounts of ileal digested MUFA and PUFA increased when both DDGS (P < 0.01) and tallow (P < 0.01) were included in the diet compared to when either ingredient was excluded. For ileal digestible SFA, an interaction (P < 0.01) between DDGS and tallow was observed. Interactions between DDGS and tallow were observed for ATTD of all fatty acids (P < 0.01), except for linoleic acid and PUFA, which were not affected by dietary treatment. The amount of ileal digestible PUFA increased with tallow addition independent from the inclusion level of DDGS and it was a function the dietary concentration of the fatty acid. Adding tallow to corn-soybean based diets increased the amount of digested SFA, but in diets with DDGS, the increment in amount of ileal digestible SFA was less prominent due to lesser digestibility of SFA.

Crossbred pigs (n = 315) were blocked by initial BW (6.8 ± 1.1 kg) and randomly assigned to 1 of 4 dietary treatments to evaluate the effects of dietary inclusion of tallow and corn distillers dried grains with solubles (DDGS) on pig growth, carcass traits, and pork fat quality. Diets consisted of a corn-soybean meal control diet (CON) and another 3 corn-soybean meal diets containing 5% tallow (T), 30% DDGS (D), or 5% tallow plus 30% DDGS (TD) in a 2 × 2 factorial arrangement of treatments. Diets were formulated to contain similar levels of available P and standardized ileal digestible Lys:ME among treatments. Pigs were housed in 40 pens, with 7 to 8 pigs per pen, to provide 10 replicates per treatment. Overall ADG did not differ among treatments. Compared with CON (2.76 kg/d) and T (2.59 kg/d), feeding 30% DDGS reduced the ADFI (interaction, P > 0.05) of pigs when fed with 5% tallow (2.45 kg/d for TD) but not when fed alone (2.76 kg/d for D). There was no effect of DDGS on overall G:F, but pigs fed diets with tallow had greater (P < 0.01) G:F (0.4) than pigs fed no tallow (0.37). Feeding tallow increased (P < 0.01) HCW, carcass yield, and backfat depth of pigs independent of DDGS. Feeding DDGS reduced (P < 0.01) belly firmness, as measured by belly flop angle, independent of tallow (D = 71.8° and TD = 57.7° vs. CON = 134.0° and T = 113.4°) and tallow also tended to reduce belly firmness (P < 0.10). Feeding DDGS and tallow reduced the concentration of SFA in belly fat, while the concentration of MUFA were increased (P < 0.01) by feeding tallow but not DDGS. Conversely, feeding DDGS increased (P < 0.01) the concentration of PUFA in belly fat but there was no effect of tallow. An interaction (P = 0.03) between DDGS and tallow for iodine value (IV) of belly fat was observed, in which addition of tallow or DDGS increased the IV of belly fat (64.22 for T and 71.22 for D vs. 59.01 for CON) but addition of both reduced IV (67.88 for TD). The IV of belly fat and backfat were correlated (P < 0.01) with the IV product of the diet fed in phase 3 (r = 0.49 and r = 0.81, respectively). In conclusion, adding 5% tallow to 30% DDGS diets improved G:F and carcass yield while reducing the IV of belly fat. However, pork fat firmness as measured by belly flop angle was not improved.

6Li selective inversion NMR experiments are used to reveal Li ion exchange rates and energy barriers for Li ion hopping in monoclinic Li3Fe2(PO4)3. The three crystallographically unique Li sites in this material are well resolved by magic-angle spinning, thus allowing for the examination of all three exchange processes. We have revisited this material using selective inversion to probe dynamics, and energy barriers over the temperature range 268–397 K are found to be 0.37 ± 0.07, 0.53 ± 0.02, and 0.52 ± 0.03 eV for the three unique exchange pairs. The results presented here are consistent with the known Li3Fe2(PO4)3 crystal structure. The selective inversion experiment is more robust than 2D EXSY for the determination of energy barriers by NMR; this can be attributed to the efficiency of the one-dimensional technique, and an exchange model that accounts for multisite exchange and fast spin–lattice relaxation. Moreover, bond valence sum density maps provide a meaningful depiction of lithium ion diffusion p...

Climate change (CC) is projected to increase the frequency and severity of natural disturbances (wildfires, insect outbreaks, and debris flows) and shift distributions of terrestrial ecosystems on a global basis. Although such terrestrial changes may affect stream ecosystems, they have not been incorporated into predictions of stream responses to CC. Here, we introduce a conceptual framework to evaluate to what extent responses of streams to CC will be driven by not only changes in thermal and hydrologic regimes, but also alterations of terrestrial processes. We focused on forested watersheds of western North America because this region is projected to experience CC-induced alteration of terrestrial processes. This provided a backdrop for investigating interactive effects of climate and terrestrial responses on streams. Because stream responses to terrestrial processes have been well-studied in contexts largely independent of CC research, we synthesized this knowledge to demonstrate how CC-induced alterations of terrestrial ecosystems may affect streams. Our synthesis indicated that altered terrestrial processes will change terrestrial–aquatic linkages and autotrophic production, potentially yielding greater sensitivity of streams to CC than would be expected based on shifts in temperature and precipitation regime alone. Despite uncertainties that currently constrain predictions regarding stream responses to these additional pathways of change, this synthesis highlighted broader effects of CC that require additional research. Based on widespread evidence that CC is linked to changing terrestrial processes, we conclude that accurate predictions of CC effects on streams may be coupled to the accuracy of predictions for long-term changes in terrestrial ecosystems.

Animal remains from excavations of the Iron Age II (end IVth century - early IIIrd century BC) and Roman Republican (Ist century BC) part of a defensive ditch of Odemira hillfort in SW Portugal are described. Most derive from domesticated animals like cattle, goats and pigs, and a hunted animal, red deer. There are two substantial changes between Iron Age and Roman times. The first is a huge increase in the frequency of red deer. This may reflect a rise in the status of the inhabitants. The second is a change in the age-at-slaughter of the cattle: most Iron Age cattle were slaughtered quite young while those in Roman times were not slaughtered until old. This probably reflects a change in the management strategy of cattle. In the Iron Age the emphasis in cattle production was for meat while the Romans kept cattle more for their power and milk. Other animals present include birds, dog, fox, horse, rabbit, and in the Roman period, some marine shells.

Aims The aim of this study was to evaluate dental students’ self-perceived communication skills for patient motivation over the course of their training. Materials and methods Pre-clinical and clinical dental students at the University of Bern School of Dental Medicine were surveyed annually from 2008 to 2011 utilising a written questionnaire. Self-reported data were pooled from all classes per time-point in the curriculum. Results A total of 157 students were surveyed from five classes with an overall response rate of 94.8%. A total of 393 questionnaires were available for analysis. The self-perceived skill-sets for general patient care and patient communication were rated at the end of the first clinical year with mean Visual Analog Scale values of 75.0 ± 1.6 and 75.1 ± 1.5, respectively. During the second clinical year, the self-perceived skills increased in both patient care (82.5 ± 1.2, P = 0.0004) and patient communication (81.4 ± 1.4, P = 0.0034). The students rated their competence higher when providing oral hygiene instructions as opposed to motivating patients to quit tobacco use, modify their diet or employ stress-reduction strategies (P < 0.005). At the end of the pre-clinical year, 74.5% of the students expressed interest in receiving more extensive communication training (P < 0.004). Conclusions Though dental students in this study demonstrated a steady increase in their level of comfort motivating patients to utilise oral hygiene instructions, they also expressed the desire for more motivational training early in their curriculum. Therefore, these results may indicate the need to enhance communications training in patient motivation on all behavioural aspects early in the dental curriculum.

Taxonomic over-splitting of extinct or endangered taxa, due to an incomplete knowledge of both skeletal morphological variability and the geographical ranges of past populations, continues to confuse the link between isolated extant populations and their ancestors. This is particularly problematic with the genusEquus.To more reliably determine the evolution and phylogeographic history of the endangered Asiatic wild ass, we studied the genetic diversity and inter-relationships of both extinct and extant populations over the last 100,000 years, including samples throughout its previous range from Western Europe to Southwest and East Asia. Using 229 bp of the mitochondrial hypervariable region, an approach which allowed the inclusion of information from extremely poorly preserved ancient samples, we classify all non-African wild asses into nine clades that show a clear phylogeographic structure revealing their phylogenetic history. This study places the extinct European wild ass,E. hydruntinus, the phylogeny of which has been debated since the end of the 19thcentury, into its phylogenetic context within the Asiatic wild asses and reveals recent gene flow events between populations currently regarded as separate species. The phylogeographic organization of clades resulting from these efforts can be used not only to improve future taxonomic determination of a poorly characterized group of equids, but also to identify historic ranges, interbreeding events between various populations, and the impact of ancient climatic changes. In addition, appropriately placing extant relict populations into a broader phylogeographic and genetic context can better inform ongoing conservation strategies for this highly endangered species.

Epidemiologic studies suggest an association between physical activity (PA) and breast cancer risk. We examined the relationship between voluntary wheel running and breast cancer in C3(1)/SV40Tag mice. Female FVB/N and C3(1)/SV40Tag mice were assigned to either PA [C3(1)-PA] (n=12) or sedentary (Sed) [C3(1)-Sed] (n=15) treatment and were placed in a cage with access to a running wheel (PA) or without (Sed) from 4 to 24 weeks of age (sacrifice). Physical activity data were analyzed for running distance, time and speed. Body composition was examined at 12 weeks of age. Tumors were counted twice weekly and at sacrifice to assess multiplicity. Tumor volume was calculated using external calipers [0.52 x (largest diameter) x (smallest diameter)2]. Heart and body weight were also recorded at sacrifice. Results showed that voluntary wheel running reduced tumor volume per tumor [C3(1)-Sed, 422.3±89.9 mm(3); C3(1)-PA, 260.2±61.7 mm(3)] (P

The Richard F. Caris Mirror Lab at the University of Arizona is responsible for production of the eight 8.4 m segments for the primary mirror of the Giant Magellan Telescope, including one spare off-axis segment. We report on the successful casting of Segment 4, the center segment. Prior to generating the optical surface of Segment 2, we carried out a major upgrade of our 8.4 m Large Optical Generator. The upgrade includes new hardware and software to improve accuracy, safety, reliability and ease of use. We are currently carrying out an upgrade of our 8.4 m polishing machine that includes improved orbital polishing capabilities. We added and modified several components of the optical tests during the manufacture of Segment 1, and we have continued to improve the systems in preparation for Segments 2-8. We completed two projects that were prior commitments before GMT Segment 2: casting and polishing the combined primary and tertiary mirrors for the LSST, and casting and generating a 6.5 m mirror for the Tokyo Atacama Observatory.

Noise can become uncomfortable for us in many situations both indoors and outdoors. External noise consists of activities (airplanes flying overhead, traffic on the road, etc.) that are either loud enough to be considered uncomfortable when outdoors, or are of an elevated volume to the extent that they infiltrate buildings at levels considered uncomfortable. In the case of internal uncomfortable noise, this can either stem from noisy activities that occur inside the building (people speaking loudly, printers, etc.), or when an unexpected sound suddenly permeates an area that has a very low level of background noise. The most common manner by which to mitigate excess noise is through the use of certain materials, which either insulate against noise passing through the material, or absorb the noise wavelengths. In the case of the latter, vertical gardens present themselves as not only an aesthetic element in architecture, but also as a potential acoustic control tool in building design. For this work 10 m2 of vertical garden substrate modules was tested in a full size reverberation chamber. The objective was to open the doors for vertical gardens to be used in architectural acoustic design.

To characterize the white matter structural changes at the tract level and tract group level, comprehensive analysis with 4 metrics derived from diffusion tensor imaging (DTI), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD), was conducted. Tract groups, namely limbic, commissural, association, and projection tracts, include white matter tracts of similar functions. Diffusion tensor imaging data were acquired from 61 subjects (26 Alzheimer's disease [AD], 11 subjects with amnestic mild cognitive impairment [aMCI], and 24 age-matched controls). An atlas-based approach was used to survey 30 major cerebral white matter tracts with the measurements of FA, MD, AxD, and RD. Regional cortical atrophy and cognitive functions of AD patients were also measured to correlate with the structural changes of white matter. Synchronized structural changes of cingulum bundle and fornix, both of which are part of limbic tract group, were revealed. Widespread yet distinctive structural changes were found in limbic, commissural, association, and projection tract groups between control and AD subjects. Specifically, FA, MD, and RD of limbic tracts, FA, MD, AxD, and RD of commissural tracts, MD, AxD, and RD of association tracts, and MD and AxD of projection tracts are significantly different between AD patients and control subjects. In contrast, the comparison between aMCI and control subjects shows disruption only in the limbic and commissural tract groups of aMCI subjects. MD values of all tract groups of AD patients are significantly correlated to cognitive functions. Difference between AD and control and that between aMCI and control indicates a progression pattern of white matter disruption from limbic and commissural tract group to other tract groups. High correlation between FA, MD, and RD measurements from limbic tracts and cortical atrophy suggests the disruption of the limbic tract group is caused by the neuronal damage.

The effectiveness of two different selective inversion methods is investigated to determine timescales of Li ion mobility in paramagnetic Li intercalation materials. The first method is 1D exchange spectroscopy, which employs a 90°-τ(1)-90° sequence for selective inversion of a Li resonance undergoing site exchange. The experiment is most easily applied when the first delay period, τ(1), is set to the frequency difference between two resonances undergoing ion exchange. This enables the determination of ion hopping timescales for single exchange pair systems only. To measure ion dynamics in systems having more than one exchange process, a second selective inversion method was tested on two paramagnetic Li intercalation materials. This second technique, replaces the 90°-τ(1)-90° portion of 1D EXSY with a long, selective shaped pulse (SP). Two paramagnetic solid-state materials, which are both cathode materials for lithion ion batteries, were chosen as model compounds to test the effectiveness of both the selective inversion methods. The first compound, Li(2)VPO(4)F, was chosen as it hosts two Li sites with 1-exchange process. The second model compound is a 3-site, 3-exchange process system, Li(2)VOPO(4). For the 2-site material, Li(2)VPO(4)F, the timescales of the single A-B exchange process were found to be within error of one another regardless of the inversion method. For the 3 Li-site material Li(2)VOPO(4), the three exchange processes, AB, BC, and AC, were found to be on the millisecond timescale as revealed using the SP method. These timescales were determined over a variable temperature range where activation energies extended from 0.6 ± 0.1 eV up to 0.9 ± 0.2 eV.

An electrochemical and structural study of the two-electron redox couple comprising the tavorite-type series of fluorophosphates Li1±xVPO4F (x = 0, 1)shows that both intercalation of LiVPO4F with L...

6Li selective inversion NMR studies are used to probe details of Li mobility in Li2VPO4F. Two crystallographically unique Li sites were resolved under magic-angle spinning (25–40 kHz) with paramagnetic shifts arising at 46 and −47 ppm (330 K). The rate of exchange between these sites was evaluated using selective inversion (or one-dimensional exchange (1D EXSY)) NMR. This methodology relies on relaxation-based experiments that provide a means for mobility time scales to be determined for materials in which Li+ ions exchange slowly relative to their T1 spin–lattice relaxation. This situation is particularly relevant to cathode materials for lithium ion batteries, where the unpaired electrons of the transition-metal centers provide a dominant mechanism for rapid relaxation. In Li2VPO4F, Li1–Li2 exchange pair jump rates extend from 24 (±1) to 55 (±4) Hz over a temperature range of 330–350 K. The activation energy for this ion exchange process was measured to be 0.44 (±0.06) eV.

Many observational epidemiologic studies suggest an association between exercise and breast cancer risk. However, the lack of controlled experimental studies that examine this relationship and the mechanisms involved weaken the basis for inferring a causal relationship. Inflammation plays a role in breast cancer progression and exercise has been reported to reduce inflammation; however, the anti-inflammatory effects of exercise in breast cancer have yet to be established. We examined the relationship between exercise training and systemic inflammation in relation to breast cancer progression in C3(1)SV40Tag mice. Female C3(1)SV40Tag mice were assigned to either exercise (Ex) or sedentary (Sed) treatment (n=12-14/group). Beginning at 4 wks of age mice (Ex) were run on a treadmill for 60 min/d (20 m/min and 5% grade), 6 d/wk for a period of 20 wks. Mice were examined weekly for palpable tumors, and tumor number and volume were recorded. At 24 wks of age mice were sacrificed and a more direct measure of tumor number and volume, and spleen weight was recorded. Plasma was analyzed for MCP-1 and IL-6 concentration using ELISA. Ex reduced palpable tumor number at sacrifice (24 wks) by approximately 70% (P0.05). Tumor volume was also reduced in Ex at 21-23 wks (P0.05). This reduction in tumor progression by Ex was associated with a reduction in plasma concentration of MCP-1 and IL-6, and spleen weight (P0.05). These data provide strong support for a beneficial effect of exercise training on tumor progression in the C3(1)SV40Tag mouse model of breast cancer that may be partly mediated by its anti-inflammatory potential.

Background: Individuals with nonalcoholic fatty liver disease (NAFLD) have excess intrahepatic triglycerides. This is due, in part, to increased hepatic synthesis of fat from carbohydrates via lipogenesis. Although weight loss is currently recommended to treat NAFLD, little attention has been given to dietary carbohydrate restriction. Objective: The aim of this study was to determine the effectiveness of 2 wk of dietary carbohydrate and calorie restriction at reducing hepatic triglycerides in subjects with NAFLD. Design: Eighteen NAFLD subjects (n = 5 men and 13 women) with a mean (6SD) age of 45 6 12 y and a body mass index (in kg/m 2 ) of 35 6 7 consumed a carbohydrate-restricted (,20 g/d) or calorierestricted (1200–1500 kcal/d) diet for 2 wk. Hepatic triglycerides were measured before and after intervention by magnetic resonance spectroscopy. Results: Mean (6SD) weight loss was similar between the groups (24.0 6 1.5 kg in the calorie-restricted group and 24.6 6 1.5 kg in the carbohydrate-restricted group; P = 0.363). Liver triglycerides decreased significantly with weight loss (P , 0.001) but decreased significantly more (P = 0.008) in carbohydrate-restricted subjects (255 6 14%) than in calorie-restricted subjects (228 6 23%). Dietary fat (r = 0.643, P = 0.004), carbohydrate (r = 20.606, P = 0.008), posttreatment plasma ketones (r = 0.755, P = 0.006), and respiratory quotient (r = 20.797, P , 0.001) were related to a reduction in liver triglycerides. Plasma aspartate, but not alanine, aminotransferase decreased significantly with weight loss (P , 0.001). Conclusions: Two weeks of dietary intervention (’4.3% weight loss) reduced hepatic triglycerides by ’42% in subjects with NAFLD; however, reductions were significantly greater with dietary carbohydrate restriction than with calorie restriction. This may have been due, in part, to enhanced hepatic and whole-body oxidation. This trial was registered at clinicaltrials.gov as NCT01262326. Am J Clin Nutr doi: 10.3945/ajcn.110.007674.

Aim Skeletal muscle interleukin-6 (IL-6) expression is induced by continuous contraction, overload-induced hypertrophy and during muscle regeneration. The loss of IL-6 can alter skeletal muscle’s growth and extracellular matrix remodeling response to overload-induced hypertrophy. IGF-1 gene expression and related signaling through Akt/mTOR is a critical regulator of muscle mass. The significance of IL-6 expression during the recovery from muscle atrophy is unclear. This study’s purpose was to determine the effect of IL-6 loss on mouse gastrocnemius (GAS) muscle mass during recovery from hindlimb suspension (HS)-induced atrophy.

Aim: Overloading healthy skeletal muscle produces myofibre hypertrophy and extracellular matrix remodelling, and these processes are thought to be interdependent for producing muscle growth. Inflammatory cytokine interleukin-6 (IL-6) gene expression is induced in overloaded skeletal muscle, and the loss of this IL-6 induction can attenuate the hypertrophic response to overload (OV). Although the OV induction of IL-6 in skeletal muscle may be an important regulator of inflammatory processes and satellite cell proliferation, less is known about its role in the regulation of extracellular matrix remodelling. The purpose of the current study was to examine if OV-induced extracellular matrix remodelling, muscle growth, and associated gene expression were altered in mice that lack IL-6, when compared with wild-type mice. Methods: Male C57/BL6 (WT) and C57/BL6 × IL-6−/− (IL-6−/−) mice (10 weeks of age) were assigned to either a sham control or synergist ablation OV treatments for 3, 21 or 56 days. Result: Plantaris muscle mass increased 59% in WT and 116% in IL-6−/− mice after 21 day OV. Myofibre CSA was also increased by 21 day OV in both WT and IL-6−/− mice. OV induced a twofold greater increase in the volume of non-contractile tissue in IL-6−/− muscle compared to WT. OV also induced a significantly greater accumulation of hydroxyproline and procollagen-1 mRNA in IL-6−/− muscle, when compared with WT muscle after 21 day OV. Transforming growth factor-β and insulin-like growth factor-1 mRNA expression were also induced to a greater extent in IL-6−/− muscle when compared with WT muscle after 21 day OV. There was no effect of IL-6 loss on the induction of myogenin, and cyclin D1 mRNA expression after 3 day OV. However, MyoD mRNA expression in 3 day OV IL-6−/− muscle was attenuated when compared with WT OV mice. Conclusion: IL-6 appears to be necessary for the normal regulation of extracellular matrix remodelling during OV-induced growth.

We describe six cervid bones — a distal humerus, three distal tibiae, and two astragali — from two Roman sites, Sao Pedro Fronteira and Torre de Palma, in the Alentejo of Portugal. They are identified on morphological and osteometric grounds as fallow deer, Dama dama. They represent the earliest Holocene evidence for this species in Portugal, and it is suggested that, like the camel, the Romans were responsible for its spread within their Empire. While remains of this animal have not so far been reported in any Moslem period assemblages, there is documentary evidence for the existence of fallow deer in Portugal in the 12th and 13th centuries AD, although the possibility that fallow deer disappeared with the end of Roman rule should be considered.

SrBi2OB4O9is a novel centrosymmetric borate oxide forming in the SrO–Bi2O3–B2O3system. Its crystal structure has been determinedab initiofrom high-resolution X-ray and neutron powder diffraction data with the help of11B MAS-NMR data. SrBi2OB4O9crystallizes with a triclinic unit-cell witha=6.8657(1) Å,b=9.7976(1) Å,c=6.8148(1) Å,α=109.1270(8)°,β=101.8971(8)°,γ=96.1445(8)°,V=416.17(1) Å3,Z=2, space group P-1. Its structure consists of Bi2O4+layers alternating along thebaxis with SrB4O94−layers containing isolated B4O96−(〈2Δ〉Δ) tetraborate anions.

Carbohydrate restriction is a common weight-loss approach that modifies hepatic metabolism by increasing gluconeogenesis (GNG) and ketosis. Because little is known about the effect of carbohydrate restriction on the origin of gluconeogenic precursors (GNG from glycerol [GNGglycerol] and GNG from lactate/amino acids [GNGphosphoenolpyruvate {PEP}]) or its consequence to hepatic energy homeostasis, we studied these parameters in a group of overweight/obese subjects undergoing weight-loss via dietary restriction. We used 2H and 13C tracers and nuclear magnetic resonance spectroscopy to measure the sources of hepatic glucose and tricarboxylic acid (TCA) cycle flux in weight-stable subjects (n = 7) and subjects following carbohydrate restriction (n = 7) or calorie restriction (n = 7). The majority of hepatic glucose production in carbohydrate restricted subjects came from GNGPEP. The contribution of glycerol to GNG was similar in all groups despite evidence of increased fat oxidation in carbohydrate restricted subjects. A strong correlation between TCA cycle flux and GNGPEP was found, though the reliance on TCA cycle energy production for GNG was attenuated in subjects undergoing carbohydrate restriction. Together, these data imply that the TCA cycle is the energetic patron of GNG. However, the relationship between these two pathways is modified by carbohydrate restriction, suggesting an increased reliance of the hepatocyte on energy generated outside of the TCA cycle when GNGPEP is maximal. Conclusion: Carbohydrate restriction modifies hepatic GNG by increasing reliance on substrates like lactate or amino acids but not glycerol. This modification is associated with a reorganization of hepatic energy metabolism suggestive of enhanced hepatic β-oxidation. (HEPATOLOGY 2008;48:1487–1496.)

Exercise stress is associated with increased risk for upper respiratory tract infection. We have shown that exercise stress can increase susceptibility to infection. Quercetin, a flavonoid present in a wide variety of fruits and vegetables, has been reported to inhibit infectivity and replication of a broad spectrum of viruses and may offset the increase in susceptibility to infection associated with stressful exercise. This study examined the effects of quercetin feedings on susceptibility to the influenza virus A/Puerto Rico/8/34 (H1N1) following stressful exercise. Mice were randomly assigned to one of four treatment groups: exercise-placebo, exercise-quercetin, control-placebo, or control-quercetin. Exercise consisted of a run to fatigue (∼140 min) on a treadmill for 3 consecutive days. Quercetin (12.5 mg/kg) was administered via gavage for 7 days before viral challenge. At 30 min after the last bout of exercise or rest, mice ( n = 23–30) were intranasally inoculated with a standardized dose of influenza virus (0.04 hemagglutinating units). Mice were monitored daily for morbidity (time to sickness), symptom severity, and mortality (time to death) for 21 days. Exercise stress was associated with an increased susceptibility to infection [morbidity, mortality, and symptom severity on days 5–7 ( P < 0.05)]; quercetin offset the increase in susceptibility to infection [morbidity, mortality, and symptom severity on days 5–7 ( P < 0.05)] that was associated with stressful exercise. These data suggest that short-term quercetin feedings may prove to be an effective strategy to lessen the impact of stressful exercise on susceptibility to respiratory infection.

This study of osteometric variation of sheep and cattle remains from archaeological sites in southern Portugal—the part that was once ruled by the Moslems—reveals an increase in size of the sheep in Moslem times and a subsequent increase of the cattle following the Christian conquest. It is assumed that a size increase reflects improvement. Sheep size increase is easy to understand given the Moslem fondness for mutton. The later size increase of the cattle is less easy to understand but could reflect a dietary switch from mutton to beef as well as the need for bovine power.

Exhaustive exercise has been associated with an increased risk for upper respiratory tract infections in mice and humans. We have previously shown (Brown AS, Davis JM, Murphy AE, Carmichael MD, Ghaffer A, Mayer EP. Med Sci Sports Exerc 36: 1290–1295, 2004) that female mice are better protected from the lethal effects of herpes simplex virus type 1 (HSV-1) infection, both at rest and following exercise stress, but little is known about possible mechanisms. This study tested the effects of estrogen on HSV-1 infection and macrophage antiviral resistance following repeated exhaustive exercise. Female mice were assigned to either exercise (Ex) or control (C): intact female (I-C or I-Ex), ovariectomized female (O-C or O-Ex), or ovariectomized estrogen-supplemented female (E-C or E-Ex). Exercise consisted of treadmill running to volitional fatigue (∼125 min) for 3 consecutive days. Intact female mice had a later time to death than O and E ( P < 0.05) and fewer deaths than both O and E ( P < 0.05). Exercise stress was associated with increased time to sickness ( P < 0.05) and symptom severity at days 6 and 12–21 postinfection ( P < 0.05) and decreased macrophage antiviral resistance ( P < 0.001) in all groups. E had increased symptom severity at days 6 and 13–21 postinfection ( P < 0.05). Results indicate that intact female mice are better protected from the lethal effects of HSV-1 infection and that exercise stress had a similar negative impact in all groups. This protective effect was lost in ovariectomized mice, but it was not reinstated by 17β-estradiol replacement. This indicates that other ovarian factors, alone or in combination with estrogen, are responsible for the protective effects in females.

Immune changes following 2 h of intensive cycling with or without rest intervals were measured in trained cyclists (n = 12) who functioned as their own controls during two test sessions that were separated by two weeks. Subjects cycled for 2.0 h at approximately 64 % Watts(max) continuously (C) or with 3-min rest intervals (R) interspersed every 10 min (2.6 h total time), with the order of the sessions randomized. Blood samples were collected 30-min pre-exercise, and immediately and 1-h postexercise, and assayed for blood leukocyte subset counts, plasma IL-6, IL-10, IL-1ra, IL-8, PHA-induced lymphocyte proliferation, and natural killer cell activity (NKCA). Significant time effects were measured for all immune measures, but no significant differences in the pattern of change were found between C and R exercise trials. In conclusion, immune changes induced by 2 h of intense and prolonged exercise paralleled those measured when athletes rested 3 min every 10 min of exercise.