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Background: Reflective portfolios were introduced to dietetic practice placements in 2005, providing evidence for learning outcomes achieved and acting as a summative assessment tool. Portfolios may measure clinical competence more effectively than conventional examinations, but can be time consuming and subjective. The present study investigated current dietetic students' experiences and perceptions of the use and effectiveness of portfolio based learning and assessment during practice placements. Methods: Current UK dietetic students, who had completed a B or B and C placement, were invited to participate, via University course leaders, in an online questionnaire exploring opinions and experiences of portfolio preparation, generation, assessment, and personal and professional development and reflection. Results: One hundred and fourteen students from 11 Universities participated. Seventy-seven percent would have liked more information about portfolio construction prior to placement. Eighty percent of students believed that reflection helped monitor their strengths and weaknesses. Perceived reflective skills were significantly positively correlated with students' perceived writing skills ( P < 0.0005) and academic ability ( P = 0.002). Of the respondents, 92% agreed the portfolio was a valuable learning experience; however, 76% agreed that the amount of paperwork involved was excessive and 67% felt there were inconsistencies in portfolio assessment by different supervisors. Conclusions: Portfolio weaknesses identified are not specific to dietetics but are inherent to portfolio assessment across many professions. The introduction of national standardised assessment processes, practices, tools and training for assessors may help improve inter-departmental and inter-rater reliability, respectively. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients with intestinal failure require long-term parenteral nutrition owing to impaired enteral nutrition absorption. A potential complication is essential fatty acid deficiency (EFAD), resulting from decreased linoleic and α-linolenic acid concentrations and defined by an increased triene:tetraene ratio (TTR; Mead acid:arachidonic acid). Historically, soybean oil lipid emulsion (SOLE) was the only commercially available parenteral lipid in the United States. Recently, a composite lipid emulsion (CLE) and fish oil lipid emulsion (FOLE) received US Food and Drug Administration approval. This study investigated whether lipid emulsion regimen impacts EFAD incidence in pediatric patients with intestinal failure., Methods: This study was a 10-year retrospective cohort study of pediatric patients with intestinal failure who received parenteral SOLE, CLE, or FOLE. The primary outcome was EFAD incidence, defined as a TTR ≥ 0.2. Secondary outcomes included TTR ≥ 0.05, cholestasis incidence, lipid dose effect on EFAD incidence, and fatty acid parameter differences., Results: A total of 144 fatty acid profiles from 47 patients were reviewed. EFAD did not occur in any lipid emulsion group. There were no differences in the incidence of TTR ≥ 0.05 or cholestasis. The effect of dose could not be evaluated because of no EFAD incidence. Lastly, although each group had varied fatty acid parameters, none saw decreased essential fatty acid levels., Conclusion: This study found that, with close monitoring, the lipid emulsion regimen did not impact EFAD incidence. This suggests that FOLE and CLE do not increase EFAD risk compared with SOLE in pediatric patients with intestinal failure., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Maintenance of mitochondrial health, which is supported in part by dietary antioxidants such as selenium (Se) and vitamin E (vitE), is pertinent to optimizing athletic performance. Deficiencies in Se and vitE negatively impact muscle health but mitochondrial adaptations to various levels of dietary Se and vitE are poorly understood. Young Quarter Horses (mean ± SD: 17.6 ± 0.9 mo) undergoing submaximal exercise training were used to test the hypothesis that a proprietary antioxidant blend containing elevated Se yeast (EconomasE, Alltech, Inc., Nicholasville, KY) would improve mitochondrial characteristics compared to Se at current requirements, even with reduced vitE intake. Horses were balanced by age, sex, body weight (BW), and farm of origin and randomly assigned to one of three custom-formulated concentrates fed at 1% BW (dry matter, DM basis) for 12 wk: 1) 100 IU vitE/kg DM and 0.1 mg Se/kg DM (CON, n = 6); 2) no added vitE plus EconomasE to provide 0.1 mg Se/kg DM (ESe1, n = 6); or 3) no added vitE plus EconomasE to provide 0.3 mg Se/kg DM (ESe3, n = 6). Samples collected at week 0 and 12 were analyzed for serum Se and middle gluteal glutathione peroxidase (GPx) and mitochondrial enzyme activities by kinetic colorimetry and mitochondrial capacities by high-resolution respirometry. Data were analyzed using mixed linear models in SAS v9.4 with repeated measures (time) and fixed effects of time, diet, and time × diet; horse(diet) served as a random effect. Serum Se tended to increase in all horses by week 12 (P = 0.08) but was unaffected by diet. Muscle GPx activity remained similar among all horses throughout the duration of the study. Mitochondrial volume density (citrate synthase [CS] activity), integrative function (cytochrome c oxidase [CCO] activity per mg protein), and integrative (per mg tissue) oxidative (P) and electron transfer (E) capacities increased from week 0 to 12 in all horses (P ≤ 0.01). Intrinsic (relative to CS) CCO activity decreased in all horses (P = 0.001), while intrinsic P and E capacities decreased only in ESe1 horses from week 0 to 12 (P ≤ 0.002). These results suggest that feeding EconomasE to provide 0.3 mg Se/kg DM may prevent adverse effects of removing 100 IU dietary vitE/kg DM on mitochondria in young horses. More research is needed to determine optimal dietary Se and vitE levels in performance horses to maximize mitochondrial energy production., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This retrospective study evaluated the phenotypic and genotypic features of 14 patients with McArdle disease attending the West of Scotland adult muscle clinic. Although all patients experienced exercise-induced cramps, exercise intolerance and hyperCKaemia, only 71% (n = 10) experienced the second wind phenomenon, rhabdomyolysis and/or myoglobinuria. We observed a high rate of fixed muscle weakness (50%; n = 7), coronary artery disease (36%; n = 5), and psychological comorbidity (50%; n = 7). Although 79% had symptom onset in the first decade of life, the mean age at presentation and at genetic diagnosis was 43.8 years and 47.7 years, respectively. 93% had at least one copy of the common PYGM pathogenic variant, c.148C > T, p.(Arg50*), with 50% (n = 7) of the cohort being homozygous. Our cohort highlights the phenotypic variability seen in McArdle disease and underscores the potential for late-onset presentations. It emphasises the need for improved awareness and recognition of this condition amongst neurologists, rheumatologists and general physicians. A history of exercise intolerance and second wind phenomenon may not always be volunteered by the patient, underscoring the need to ask specific questions in clinic to extrapolate the relevant symptoms in this patient cohort., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65-1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016-19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: -0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses., (© Crown copyright 2020.)

Stress negatively affects the gastrointestinal tract (GIT) barrier function, resulting in compromised animal health. A deeper understanding of how diet and stress impacts the GIT barrier function in feedlot cattle is needed. Aspirin decreases mucus production and mucosal repair in the GIT and could be used as a model for GIT barrier dysfunction research. The objective of this study was to evaluate the effectiveness of aspirin to induce GIT barrier dysfunction in beef cattle. In experiment 1, sixteen crossbred heifers (425.0 ± 8.6 kg) were allotted to 0, 50, 100, or 200 mg/kg body weight (BW) aspirin doses based on BW. Experiment 1 consisted of two periods separated by 4 wk where four heifers per treatment received the same aspirin dose during each period. Heifers were fed a 49.4% corn silage and 50.6% concentrate diet. The 200 mg/kg BW aspirin treatment was dosed as a 100 mg/kg BW aspirin oral bolus 36 and 24 h prior to Cr-ethylenediaminetetraacetic acid (EDTA) dosing (1 liter; 180 mM). The 50 and 100 mg/kg BW aspirin treatments were dosed as an oral bolus 24 h prior to Cr-EDTA dosing. Urine was collected every 3 h for 48 h and analyzed for Cr. Serum was collected at 0 and 48 h and analyzed for lipopolysaccharide-binding protein (LBP), interleukin-6, serum amyloid A (SAA), haptoglobin, and aspartate aminotransferase. In experiment 2, sixteen crossbred steers (576.0 ± 14.2 kg) fed a similar diet were allotted by BW to the 0 and 200 mg/kg BW aspirin treatments (eight steers/treatment) and were slaughtered 24 h after the last dose. Jejunal tissues were collected, and claudin (CLDN) 1, 2, and 3, occludin, and zonula occludens tight junction messenger ribonucleic acid (mRNA) expression was determined. Data were analyzed using the MIXED procedure of SAS. Urinary Cr excretion increased linearly at hours 3, 6, 9, and 12 (P ≤ 0.04) as aspirin dose increased from 0 to 200 mg/kg. Aspirin linearly increased Cr absorption (P = 0.02) and elimination (P = 0.04) rates and linearly decreased mean retention time of Cr (P = 0.02). Aspirin increased SAA (P = 0.04) and tended to increase LBP (P = 0.09) in serum but did not affect any other serum inflammatory marker (P ≥ 0.19). Aspirin tended to increase jejunal CLDN-1 mRNA expression (P = 0.10) but did not affect the mRNA expression of other genes regulating tight junction function (P ≥ 0.20). Results from this study indicate that aspirin disrupts the GIT barrier function in beef cattle and has a potential as a model in GIT permeability research., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The standard low-phosphorus diet restricts pulses, nuts, and whole grains and other high phosphorus foods to control hyperphosphatemia. We conducted a randomized controlled trial to evaluate the effectiveness, safety, and tolerability of the modified diet, which introduced some pulses and nuts, increased the use of whole grains, increased focus on the avoidance of phosphate additives, and introduced the prescription of low-biological-value protein such as bread., Methods: We conducted a multicenter, pragmatic, parallel-arm, open-label, randomized controlled trial of modified versus standard diet in 74 adults on hemodialysis with hyperphosphatemia over 1 month. Biochemistry was assessed using monthly laboratory tests. Dietary intake was assessed using a 2-day record of weighed intake of food, and tolerability was assessed using a patient questionnaire., Results: There was no significant difference in the change in serum phosphate between the standard and modified diets. Although total dietary phosphorus intake was similar, phytate-bound phosphorus, found in pulses, nuts, and whole grains, was significantly higher in the modified diet ( P  < 0.001). Dietary fiber intake was also significantly higher ( P  < 0.003), as was the percentage of patients reporting an increase in bowel movements while following the modified diet ( P  = 0.008). There was no significant difference in the change in serum potassium or in reported protein intake between the 2 diets. Both diets were similarly well tolerated., Conclusion: The modified low phosphorus diet was well tolerated and was associated with similar phosphate and potassium control but with a wider food choice and greater fiber intake than the standard diet., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Offspring adrenal function may be negatively affected in utero by maternal stressors such as microbial infection. Maternal supplementation with immunomodulatory compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) may help minimize the adverse effects of maternal stress on fetal hypothalamic-pituitary-adrenal development and improve offspring health. Presently, n-3 PUFA sources are primarily fish-based, but n-3 PUFA microalgae (AL) may be an alternative. Previously, it was determined that maternal AL or fish oil (FO) supplementation to sows, in addition to maternal stress induced by Escherichia coli lipopolysaccharide (LPS) challenge appeared to have a greater influence on the stress response of male offspring compared to females. To further elaborate on these findings, this study assessed the effects of maternal AL or FO supplementation combined with a maternal LPS challenge on adrenal gene expression in male offspring fed a nursery diet containing low-quality protein sources. Forty-eight sows were fed gestation diets starting on gestation day (gd) 75 containing either 3.12% AL, 3.1% FO, or a control diet containing 1.89% corn oil. On gd 112, half the sows in each treatment were administered 10 ​μg/kg LPS i.m . Piglets were weaned at 21 days of age onto a common low-quality plant-based protein diet, and one week after weaning, four piglets per sow were administered 40 ​μg/kg LPS i.m . Two hours later, the piglets were euthanized to obtain adrenal tissue, and total RNA was extracted to carry out transcriptome analysis using the Affymetrix GeneChip WT Plus assay and subsequent validation by real-time PCR. Analysis revealed that adrenal steroidogenesis, fatty acid metabolism and immune function were significantly influenced by maternal diet and stress. Increased expression of immune-related genes including lymphocyte antigen 96, TLR-2 and NF-κB suggests that maternal AL supplementation may increase offspring sensitivity to inflammation after weaning. Decreased expression of lymphocyte antigen 96 in male offspring from sows receiving maternal LPS challenge also suggests a possible role of maternal stress in diminishing the offspring immune response to immune stress challenge. Increased expression of the genes encoding the 11BHSD2 enzyme in offspring from sows fed FO may also reduce the magnitude of the stress response. These data provide insight to the immune and metabolic mechanisms that may be influenced by maternal diet and stress., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Author(s).)

Much of the equine population is obese and therefore predisposed to the development of additional health concerns such as equine metabolic syndrome (EMS). However, pharmacologic treatments for EMS are limited. Omega-3 fatty acid supplementation is a therapeutic strategy in humans with metabolic dysfunction that improves insulin sensitivity and reduces inflammation, but the effects of omega-3 fatty acid supplementation in horses with EMS are unclear. Therefore, in this pilot study, 10 mixed-sex and mixed-breed horses with EMS were fed a docosahexaenoic acid (DHA)-rich microalgae containing 16 g DHA/horse/d or served as controls for 46 days. Inflammatory status was measured using serologic enzyme-linked immunosorbent assay and in peripheral blood mononuclear cells (PBMCs) using flow cytometry and reverse transcription polymerase chain reaction. Circulating fatty acids, triglyceride, leptin, and adiponectin concentrations were also determined. Insulin and glucose dynamics were assessed with oral sugar test (OST) and frequently sampled intravenous glucose tolerance testing. Postsupplementation, treated horses had an increase in many circulating fatty acids, including DHA (P < .001). Treated horses also had lower serum triglycerides postsupplementation (P = .02) and a trend (P = .07) for reduced PBMC tumor necrosis factor α. Interestingly, after 46 days, control horses had an increase in insulin responses to the OST (P = .01), whereas treated horses did not (P = .69). These pilot data indicate that DHA-rich microalgae supplementation alters circulating fatty acids, modulates metabolic parameters, and may reduce inflammation in horses with EMS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women. Women with PCOS are at increased risk of developing several metabolic and reproductive abnormalities, including metabolic syndrome. Underlying the combined metabolic and reproductive dysfunction is lipotoxicity, defined as the ectopic deposition of lipid in nonadipose tissue where it induces oxidative stress linked with insulin resistance and inflammation., Objective: To examine what metabolic components underlie insulin resistance in PCOS, how lipotoxicity through insulin resistance impairs metabolism and reproduction in these women, and why evidence-based, individualized management is essential for their care., Evidence Acquisition: PubMed search was performed using relevant terms to identify journal articles related to the subject. Relevant textbook chapters were also used., Results: Polycystic ovary syndrome by Rotterdam criteria represents a complex syndrome of heterogeneous expression with variable adverse metabolic and reproductive implications. Women with classic PCOS are often insulin resistant and at greatest risk of developing metabolic syndrome with preferential fat accumulation and weight gain. Moreover, PCOS women may also have an altered capacity to properly store fat, causing ectopic lipid accumulation in nonadipose tissue, including the ovaries, where it can perpetuate insulin resistance and inflammation and harm the oocyte., Conclusions and Relevance: A personalized approach to managing PCOS is essential to improve the health of all PCOS women through cost-effective prevention and/or treatment, to minimize the risk of pregnancy complications in those individuals wishing to conceive, and to optimize the long-term health of PCOS women and their offspring.

A 2-part experiment was conducted to determine the effects of a blend of specialized mannan- and glucan-rich fractions of yeast (Select-TC, Alltech Inc.) on the health status and performance of steers during the first 2 mo of the feedlot period. Eighty crossbred steers were acquired from commercial sale barns in Mississippi and Georgia and transported to Purdue University. All animals were fed a corn silage-based receiving diet and were checked and treated daily for respiratory disease as needed following established treatment protocols. In Exp. 1, 64 steers (246.5 ± 4.7 kg initial weight) were blocked by BW and randomly allocated to 2 treatments to determine the impact of supplementation of a hydrolyzed mannan- and glucan-rich yeast fraction for 56 d on BW, ADG, daily DMI, and G:F: hydrolyzed yeast fed at 13 g (as-fed)/steer daily (TC) or nonsupplemented control (CON). Steers in Exp. 1 were housed in bedded pens with 2 animals per pen [n = 16 pens (32 steers)/treatment]. In Exp. 2, 16 steers (247.1 ± 5.4 kg initial BW) were similarly allotted to 2 treatments (CON and TC), individually penned, and subjected to a lipopolysaccharide (LPS) endotoxin challenge on day 62 or 63 after the start of the study to determine the animal's response to an inflammatory agent. Serum samples and rectal temperatures were taken every half an hour from -2 to 8 h relative to LPS injection from steers in Exp. 2. Data were analyzed as a complete randomized block design using the MIXED procedure of SAS. Morbidity for both experiments did not differ (P ≥ 0.16). Weight, ADG, DMI, and G:F did not differ among treatments (P ≥ 0.32) in Exp. 1. After the LPS infusion in Exp. 2, rectal temperatures (P = 0.03) and serum NEFA concentration (P = 0.04) were decreased in TC compared with CON steers. Concentrations of blood urea nitrogen (P = 0.31), glucose (P = 0.70), insulin (P = 0.57), and cortisol (P = 0.77) did not differ by treatment after LPS administration. Serum IL-6 concentrations were decreased (P < 0.0001), and interferon-γ concentrations tended to be greater (P = 0.07) in TC compared with CON steers after LPS infusion. Serum cytokine and metabolite results indicate that Select-TC improved health and metabolic status of LPS-challenged cattle, but this did not result in quantifiable improvements in performance in the conditions observed in this study., (© The Author(s) 2018. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Our main objective was to evaluate the effects of feeding α-amylase (Amaize, Alltech Inc., Nicholasville, KY, USA) for 140 days on skeletal muscle and liver gene transcription in beef steers. Steers fed Amaize had lower average daily gain (p = .03) and gain:feed ratio (p = .05). No differences (p > .10) in serum metabolites or carcass traits were detected between the two groups but Amaize steers tended (p < .15) to have increased 12th rib fat depth. Microarray analysis of skeletal muscle revealed 21 differentially expressed genes (DEG), where 14 were up-regulated and seven were down-regulated in Amaize-fed steers. The bioinformatics analysis indicated that metabolic pathways involved in fat formation and deposition, stress response, and muscle function were activated, while myogenesis was inhibited in Amaize-fed steers. The quantitative PCR results for liver revealed a decrease (p < .01) in expression of fatty acid binding protein 1 (FABP1) and 3-hydroxybutyrate dehydrogenase 1 (BDH1) with Amaize. Because these genes are key for intracellular fatty acid transport, oxidation and ketone body production, data suggest a reduction in hepatic lipid catabolism. Future work to investigate potential positive effects of Amaize on cellular stress response, muscle function, and liver function in beef cattle appears warranted., (© 2018 Japanese Society of Animal Science.)

Heterotrophic production of microalgae biomass provides a consistent, high-quality source of docosahexaenoic acid (DHA; C22:6 n-3) in triglyceride oils that could be used as a ration supplement for feedlot steers to improve nutritional qualities of beef. Sixty Angus × Simmental steers (438 ± 6.4 kg) were allotted to two treatments (30 steers each, six pens, five steers/pen) to determine the effects of ForPLUS (DHA-rich microalgae Aurantiochytrium limacinum; 63.6% fat; 17.9% DHA; 30 mg/kg Sel-Plex; Alltech Inc.) on performance, insulin sensitivity, LM fatty acid composition, and meat quality. Steers were fed basal diets containing 45% corn, 30% distillers dried grains with solubles, 20% corn silage, and 5% supplement. Basal diets were formulated to contain 16.1% CP and 1.32 Mcal/kg NEg. Treatments were delivered to steers in a ground corn-based top-dress (454 g total/steer) and contained no microalgae for control steers or 100 g/steer daily of ForPLUS for microalgae steers. A glucose tolerance test (GTT) was performed 10 d prior to slaughter. Steers were slaughtered when a target pen BW of 621 kg was achieved. Fatty acid oxidation potential was determined by measuring thiobarbituric acid reactive substances (TBARS) on LM samples collected 24 h after slaughter and aged for 48 h or 21 d. Weight and BW gain did not differ during the study (P ≥ 0.13); however, steers fed microalgae remained in the feedlot seven more days compared to steers fed the control diet (111 vs. 104 d; P = 0.04). Overall DMI decreased (P = 0.002) and G:F increased during the second half of the study (P = 0.04) in steers fed microalgae compared to steers fed the control diet. Steers fed microalgae secreted less insulin (P = 0.01) and took longer to clear glucose (P = 0.01) during a 2-h GTT. Carcass traits did not differ between treatments (P ≥ 0.23). Microalgae had no effect on n-6 content (P = 0.67), but more than doubled the n-3 fatty acid percentage and the n-3:n-6 ratio of the LM (P < 0.0001). The percentage of n-3 fatty acids C20:5 and C22:6 were increased (P < 0.0001) 4-fold and 6.25-fold, respectively, by microalgae supplementation. Concentration of TBARS did not differ in LM aged for 48 h (P = 0.91); however, when aged for 21 d, steers fed microalgae tended to produce LM with greater TBARS concentration compared to steers fed the control diet (P = 0.08). In conclusion, DHA-rich microalgae decreased DMI of steers, and increased n-3 fatty acids and beef oxidation in steaks aged for 21 d.

Background: Sex hormones may play important roles in sex-specific biological aging. In the study, we specifically examined associations between circulating sex hormone concentrations and leukocyte telomere length (TL)., Methods: A cross-sectional study was conducted among 1124 Black, 444 Hispanic, and 289 Asian/Pacific Islander women in the Women's Health Initiative Observational Cohort. Estradiol and testosterone concentrations were measured using electrochemiluminescence immunoassays; TL was measured using quantitative polymerase chain reaction., Results: Women in the study were aged 50-79 years. Estradiol concentrations were not significantly associated with TL in this sample. The associations between total and free testosterone and TL differed by race/ethnicity (P interaction  = 0.03 and 0.05 for total and free testosterone, respectively). Total and free testosterone concentrations were not associated with TL in Black and Hispanic women, whereas in Asian/Pacific Islander women their concentrations were inversely associated with TL (P trend  = 0.003 for both). These associations appeared robust in multiple subgroup analyses and multivariable models adjusted for potential confounding factors. In Asian/Pacific Islander women, a doubling of serum free and total testosterone concentrations was associated with a 202-bp shorter TL (95% confidence interval [CI] 51-353 bp) and 203-bp shorter TL (95% CI 50-355 bp), respectively., Conclusions: Serum estradiol concentrations were not associated with leukocyte TL in this large sample of postmenopausal women. Total and free testosterone concentrations were inversely associated with TL in Asian/Pacific Islander women, but not in Black and Hispanic women, although future studies to replicate our observations are warranted particularly to address potential ethnicity-specific relationships., (© 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Study Objective: To evaluate rates of presumptive anovulation in eumenorrheic adolescents and young adults with moderate to severe primary dysmenorrhea and those without primary dysmenorrhea., Design: Participants completed luteinizing hormone surge ovulation predictor test kits. Anovulatory cycles were defined by never receiving a positive result before the next menstrual period; participants were grouped as anovulatory if they experienced at least 1 anovulatory cycle during study participation. Participants rated daily level of menstrual pain on a 0-10 numeric rating scale., Setting: A university-based clinical research laboratory., Participants: Thirty-nine adolescents and young adults (ages 16-24) with primary dysmenorrhea and 52 age-matched control girls., Interventions and Main Outcome Measures: Rates of presumptive anovulation., Results: One hundred sixty-eight cycles were monitored, 29.8% (N = 50) of which were anovulatory (37.1% [39/105] vs 17.5% [11/63] of cycles in control and dysmenorrhea groups, respectively). During study participation, control girls were significantly more likely to have had at least 1 anovulatory cycle than were girls with primary dysmenorrhea (44.2% [23/52] vs 17.9% [7/39] of participants, respectively; P < .01). Cycle length and number of bleeding days between ovulatory and anovulatory cycles were similar. The primary dysmenorrhea group's maximum menstrual pain ratings did not differ between ovulatory and anovulatory cycles (4.77 and 4.36, respectively; P > .05)., Conclusion: Our data support previous findings of increased rates of ovulation in primary dysmenorrhea. However, menstruation after anovulatory cycles can be as painful as menstruation after ovulatory cycles. These data support the idea that regular menses do not necessarily indicate that a normal ovulatory cycle has occurred. Previous implications that ovulation is necessary for the development of substantial menstrual pain are incomplete., (Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the prevalence of MPZ mutations that cause Charcot Marie Tooth neuropathy type 1B (CMT1B) and activate the unfolded protein Response (UPR)., Background: CMT1B is caused by >200 heterozygous mutations in MPZ , the major protein in peripheral nerve myelin. Mutations Ser63del MPZ and Arg98Cys MPZ cause the mutant protein to be retained in the ER and activate the generally adaptive UPR. Treatments that modulate UPR activation have improved cellular and rodent models of CMT1B raising the possibility that other MPZ mutations that activate the UPR would also respond favorably to similar treatment. The prevalence of MPZ mutations that activate the UPR is unknown., Methods: We developed a dual luciferase reporter assay of Xbp1 splicing using stably transfected RT4 Schwann cells to assay the ability of cDNA constructs bearing 46 distinct MPZ mutations to activate the UPR. Constructs also carried an HA tag to permit detection of ER retention of mutant proteins. UPR activation and ER retention were correlated with clinical phenotypes., Results: Eighteen mutations demonstrated ER retention and UPR activation to a similar degree as Ser63del and Arg98Cys MPZ. Thirty-five of the mutations activated the UPR > 1.5 fold compared to that of wild-type MPZ. Correlation was high between firefly and Nano-luciferase reporters and between both reporters and ER localization. UPR activity did not correlate with clinical onset or severity., Conclusion: Many CMT1B causing mutations activate the UPR and may be susceptible to therapeutic efforts to facilitate UPR function.

Mycotoxins produced by fungal species commonly contaminate livestock feedstuffs, jeopardizing their health and diminishing production. Citrinin (CIT) and ochratoxin A (OTA) are mycotoxins produced by Penicillium spp. and commonly co-occur. Both CIT and OTA can modulate immune response by inhibiting cell proliferation and differentiation, altering cell metabolism, and triggering programmed cell death. The objective of this study was to determine the effects of sublethal exposure (i.e., the concentration that inhibited cell proliferation by 25% (IC 25 )) to CIT, OTA or CIT + OTA on the bovine macrophage transcriptome. Gene expression was determined using the Affymetrix Bovine Genome Array. After 6 h of exposure to CIT, OTA or CIT + OTA, the number of differentially expressed genes (DEG), respectively, was as follows: 1471 genes (822 up-regulated, 649 down-regulated), 5094 genes (2611 up-regulated, 2483 down-regulated) and 7624 genes (3984 up-regulated, 3640 down-regulated). Of these, 179 genes (88 up-regulated, 91 down-regulated) were commonly expressed between treatments. After 24 h of exposure to CIT, OTA or CIT + OTA the number of DEG, respectively, was as follows: 3230 genes (1631 up-regulated, 1599 down-regulated), 8558 genes (4167 up-regulated, 4391 down-regulated), and 10,927 genes (6284 up-regulated, 4643 down-regulated). Of these, 770 genes (247 up-regulated, 523 down-regulated) were commonly expressed between treatments. The categorization of common biological functions and pathway analysis suggests that the IC 25 of both CIT and OTA, or their combination, induces cellular oxidative stress, a slowing of cell cycle progression, and apoptosis. Collectively, these effects contribute to inhibiting bovine macrophage proliferation., Competing Interests: The authors declare no conflict of interest.

G Protein-Coupled Receptors (GPCRs) are transmembrane (TM) proteins that span the cell membrane seven times, and contain intracellular and extracellular domains, comprised of connecting loops, as well as terminal extension sequences. GPCRs bind ligands within their transmembrane and/or extracellular domains. Ligand binding elicits conformational changes that initiate downstream intracellular signaling events through arrestins and G proteins. GPCRs play central roles in many physiological processes, from sensory to neurological, cardiovascular, endocrine, and reproductive functions. This paper strives to provide an entry point to current GPCR science, and to identify visual approaches to communicate select aspects of GPCR structure and function with clarity and accuracy. The overall GPCR structure, primary sequence and the implications of sequence for membrane topology, ligand binding and helical rearrangements accompanying activation are considered and discussed in the context of visualization strategies, including two-dimensional topological diagrams, three-dimensional representations, and common errors that arise from these representations.

Angus × Simmental cows ( = 48, BW = 594 kg, BCS = 5.26, age = 2.7) pregnant with male fetuses were used to determine the effect of selenium source during the last 80 d of gestation and first 108 d of lactation on progeny feedlot performance. At 203 d of gestation, cows were blocked by BW, breed composition, and calf sire and randomly allotted to 1 of 3 treatments: no supplemental Se, 3 mg/d inorganic Se (sodium selenite), and 3 mg/d organic Se (Sel-plex). Maternal diets were formulated to contain 10.4% CP and 0.90 Mcal/kg NE during gestation and 12.1% CP and 1.01 Mcal/kg NE during lactation. Basal diets contained 0.07 and 0.11 mg/kg Se for gestation and lactation diets, respectively. Diets were fed daily as a total mixed ration, and no additional Se, 3 mg/d Se as sodium selenite, or 3 mg/d Se as Sel-Plex were top-dressed daily. Treatment diets were fed through 108 d postpartum (DPP). At 108 DPP cow-calf pairs were commingled until weaning at 210 DPP. At 28 d postweaning, steers ( = 47, BW = 301 kg) were placed in individual pens and fed a diet formulated to provide 13.9% CP and 1.24 Mcal/kg NE. No supplemental Se was fed; however, basal Se concentration was 0.10 mg/kg. The diet was delivered as a total mixed ration once daily. Steers were slaughtered at a target BW of 625 kg. Steers from cows supplemented with organic Se tended to enter the feedlot heavier ( = 0.06) than steers from cows supplemented with inorganic Se. There was no difference in ADG among treatments ( ≥ 0.73), but steers from organic Se cows tended to spend fewer days on feed compared to steers from inorganic Se cows ( = 0.09). Steers from organic Se cows had a greater overall DMI compared to steers from inorganic Se cows ( = 0.04), but there was no difference in overall G:F ( = 0.49). Dressing percentage was greater for steers from cows fed no Se compared with steers from cows fed either inorganic or organic Se ( = 0.03). Maternal Se source had no effect on HCW, back fat, percentage KPH, LM area, yield grade, marbling score, or quality grade distribution ( ≥ 0.17) of progeny. In conclusion, maternal supplementation with organic Se appears to have a long-term benefit on intake of steer progeny and may result in improvements in growth that could decrease days on feed.

Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog 18 F-fluoro-6-thia heptadecanoic acid ( 18 F-FTHA) and glucose analog 18 F-fluorodeoxyglucose ( 18 F-FDG) under normal or fasting conditions. We also used 18 F-fluorodihydrorotenol ( 18 F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimate the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18 F-FDHROL wash-in rate constant ( P = .1) and distribution volume ( P = .1), significantly higher 18 F-FDG myocardial influx rate constant ( P = 4×10 -8 ), and significantly lower 18 F-FTHA myocardial influx rate constant ( P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18 F-FDHROL wash-in rate constant ( P = 5×10 -6 ) and distribution volume ( P = 3×10 -8 ), significantly higher 18 F-FDG myocardial influx rate constant ( P = 3×10 -8 ), and a higher trend of 18 F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011-2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH.

Angus × Simmental cows ( = 48; BW = 595 ± 17.4 kg, BCS = 5.26 ± 0.05, and age = 2.3 ± 0.07 yr), pregnant with male fetuses, were used to determine the effect of Se source during the last 80 d of gestation and first 108 d of lactation on cow and calf performance. At 203 d in gestation, cows were blocked by BW, breed composition, age, and calf sire and randomly allotted to organic Se, inorganic Se, or no Se treatments. Diets contained corn silage, corn stover, haylage, dried distillers' grains with solubles, and minerals and were formulated to contain 10.4% CP and 0.90 Mcal/kg NEg during gestation and 12.1% CP and 1.01 Mcal/kg NEg during lactation. Diets were fed daily as a total mixed ration and none, 3 mg/d Se as sodium selenite, or 3 mg/d Se as Sel-Plex were top-dressed daily. At 68 d postpartum (DPP), milk production was calculated using the weigh-suckle-weigh procedure and a milk sample was collected to determine composition. At 108 DPP, cow-calf pairs were commingled until weaning at 210 DPP. Cow BW and BCS ( ≥ 0.56) did not differ between treatments at any time point during the study. Milk production, milk fat, and total solids ( ≥ 0.38) did not differ among treatments. Milk protein tended to increase in cows fed inorganic Se compared with cows fed organic Se ( = 0.07) and milk lactose tended to be greatest in cows fed organic Se ( = 0.10). Conception to AI and overall pregnancy rates did not differ between treatments ( ≥ 0.39). Calf weights and ADG did not differ through 108 DPP ( ≥ 0.77) or for the preweaning period ( ≥ 0.33). Plasma Se concentration was adequate for all cows and did not differ among treatments for cows ( ≥ 0.37) or calves ( ≥ 0.90). Liver Se concentrations in cows fed inorganic or organic Se were greater than in control cows ( < 0.01). Longissimus muscles biopsies taken from progeny at 108 DPP also did not differ between treatments ( = 0.45). In conclusion, dietary Se source did not affect cow performance, milk production, or reproductive efficiency. Organic Se decreased milk protein and increased milk lactose but did not alter preweaning performance of progeny from Se-adequate cows.

Objective: To determine effects of a microalgae nutritional product on insulin sensitivity in horses., Animals: 8 healthy mature horses. PROCEDURES :Horses (n = 4/group) received a basal diet without (control diet) or with docosahexaenoic acid-rich microalgae meal (150 g/d) for 49 days (day 0 = first day of diet). On day 28, an isoglycemic hyperinsulinemic clamp procedure was performed. Horses then received dexamethasone (0.04 mg/kg/d) for 21 days. On day 49, the clamp procedure was repeated. After a 60-day washout, horses received the alternate diet, and procedures were repeated. Plasma fatty acid, glucose, and insulin concentrations and glucose and insulin dynamics during the clamp procedure were measured on days 28 and 49. Two estimates of insulin sensitivity (reciprocal of the square root of the insulin concentration and the modified insulin-to-glucose ratio for ponies) were calculated., Results: Baseline glucose and insulin concentrations or measures of insulin sensitivity on day 28 did not differ between horses when fed the control diet or the basal diet plus microalgae meal. On day 49 (ie, after dexamethasone administration), the microalgae meal was associated with lower baseline insulin and glucose concentrations and an improved modified insulin-to-glucose ratio for ponies, compared with results for the control diet., Conclusions and Clinical Relevance: Although the microalgae meal had no effect on clamp variables following dexamethasone treatment, it was associated with improved plasma glucose and insulin concentrations and insulin sensitivity estimates. A role for microalgae in the nutritional management of insulin-resistant horses warrants investigation.

Using exome sequencing in an individual with Charcot-Marie-Tooth disease (CMT) we have identified a mutation in the X-linked dystrophin-related protein 2 (DRP2) gene. A 60-year-old gentleman presented to our clinic and underwent clinical, electrophysiological and skin biopsy studies. The patient had clinical features of a length dependent sensorimotor neuropathy with an age of onset of 50 years. Neurophysiology revealed prolonged latencies with intermediate conduction velocities but no conduction block or temporal dispersion. A panel of 23 disease causing genes was sequenced and ultimately was uninformative. Whole exome sequencing revealed a stop mutation in DRP2, c.805C>T (Q269*). DRP2 interacts with periaxin and dystroglycan to form the periaxin-DRP2-dystroglycan complex which plays a role in the maintenance of the well-characterized Cajal bands of myelinating Schwann cells. Skin biopsies from our patient revealed a lack of DRP2 in myelinated dermal nerves by immunofluorescence. Furthermore electron microscopy failed to identify Cajal bands in the patient's dermal myelinated axons in keeping with ultrastructural pathology seen in the Drp2 knockout mouse. Both the electrophysiologic and dermal nerve twig pathology support the interpretation that this patient's DRP2 mutation causes characteristic morphological abnormalities recapitulating the Drp2 knockout model and potentially represents a novel genetic cause of CMT., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of NEFL Glu396Lys mutation on the expression and assembly of neurofilaments (NFs) in cutaneous nerve fibers of patients with Charcot-Marie-Tooth disease type 2E (CMT2E)., Methods: A large family with CMT2E underwent clinical, electrophysiologic, and skin biopsy studies. Biopsies were processed by indirect immunofluorescence (IF), electron microscopy (EM), and Western blot analysis., Results: The clinical features demonstrated intrafamilial phenotypic variability, and the electrophysiologic findings revealed nerve conductions that were either slow or in the intermediate range. All patients had reduced or absent compound muscular action potential amplitudes. Skin biopsies showed axons labeled with the axonal markers protein gene product 9.5 and α-tubulin, but not with NFs. The results of Western blot analysis were consistent with those of IF, showing reduced or absent NFs and normal expression of α-tubulin. EM revealed clusters of regenerated fibers, in absence of myelin sheath abnormalities. Both IF and EM failed to show NF aggregates in dermal axons. The morphometric analysis showed a smaller axonal caliber in patients than in controls. The study of the nodal/paranodal architecture demonstrated that sodium channels and Caspr were correctly localized in patients with CMT2E., Conclusions: Decrease in NF abundance may be a pathologic marker of CMT2E. The lack of NF aggregates, consistent with prior studies, suggests that they occur proximally leading to subsequent alterations in the axonal cytoskeleton. The small axonal caliber, along with the normal molecular architecture of nodes and paranodes, explain the reduced velocities detected in patients with CMT2E. Our results also demonstrate that skin biopsy can provide evidence of pathologic and pathogenic abnormalities in patients with CMT2E., (© 2015 American Academy of Neurology.)

Inherited neuropathies known collectively as Charcot-Marie-Tooth disease are one of the most common inherited neurological conditions affecting ∼1 in 2500 people. A heterogenous disorder, CMT is divided into subtypes based on the pattern of inheritance and also by neurophysiological studies. Despite the clinical similarities among patients with demyelinating CMT, it is recognized that this group of disorders is both genetically and phenotypically heterogenous. Understanding the pathogenesis of these disorders requires an intimate knowledge of normal myelin development and homeostasis. Improvements in genetic testing techniques over the last 20 years have contributed majorly to the identification of specific genes, proteins, and molecular pathways that are providing the basis for understanding the disease processes and developing rational approaches to therapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aims/hypothesis: The aim of this work was to investigate the prospective relationship between low birthweight (LBW) and type 2 diabetes risk later in life and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2 diabetes risk., Methods: We measured baseline plasma concentrations of various type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790 controls in the Women's Health Initiative-Observational Study. Self-report birthweights of the participants were recorded. The total effect of LBW on type 2 diabetes risk was partitioned into effects that were mediated by a specific biomarker and effects that were not mediated by this biomarker, using counterfactual model-based mediation analysis., Results: LBW was significantly associated with increased risk of type 2 diabetes. Compared with women with birthweight 3.63-4.54 kg, women with LBW (<2.72 kg) had a multivariable-adjusted OR of 2.15 (95% CI, 1.54, 3.00). Insulin resistance (indicated by HOMA-IR) mediated 47% of the total effect. Decreased sex hormone-binding globulin (SHBG) concentration accounted for 24%, elevated E-selectin concentration accounted for 25% and increased systolic blood pressure accounted for 8% of the total effect of LBW on type 2 diabetes risk. (Due to interactions among different mediators, the sum of each individual mediator's contribution could exceed 100%, without an upper limit.), Conclusions/interpretation: LBW is directly predictive of higher risk of type 2 diabetes later in life. The effect of LBW on type 2 diabetes risk seems mainly mediated by insulin resistance, which is further explained by circulating levels of SHBG and E-selectin and systolic blood pressure. The study provides potential risk stratification in a population at greater risk of developing type 2 diabetes.

The objective was to study the effect of maternal supplementation with a yeast cell wall-based product containing a mannan-rich fraction (MRF) during gestation and lactation on piglet intestinal gene expression. First parity sows were fed experimental gestation and lactation diets with or without MRF (900 mg/kg). After farrowing, piglets were fostered within treatment, as necessary. Sow and litter production performance data were collected until weaning. On day 10 post farrowing, jejunum samples from piglets were collected for gene expression analysis using the Affymetrix Porcine GeneChip array. Most performance parameters did not differ between the treatments. However, protein (P<0.01), total solids less fat (P<0.03) and the concentration of immunoglobulin G (IgG) in milk were greater (P<0.05) in the MRF-supplemented group. Gene expression results using hierarchical clustering revealed an overall dietary effect. Further analysis elucidated activation of pathways involved in tissue development, functioning and immunity, as well as greater cell proliferation and less migration of cells in the jejunum tissue. In conclusion, feeding the sow MRF during pregnancy and lactation was an effective nutritional strategy to bolster colostrum and milk IgG that are essential for development of piglet immune system and gut. In addition, the gene expression patterns affected by the passive immunity transfer showed indicators that could benefit animal performance long term.

Objective: GNE myopathy is a rare recessive myopathy associated with inclusion bodies on muscle biopsy. The clinical phenotype is associated with distal muscle weakness with quadriceps sparing. Most of the current information on GNE myopathy has been obtained through studies of Jewish and Japanese patient cohorts carrying founder mutations in the GNE gene. However, little is known about GNE myopathy in Europe where the prevalence is thought to be very low., Methods: Patients were referred through the National Specialist Commissioning Team service for limb-girdle muscular dystrophies at Newcastle (UK). All patients harbouring mutations in the GNE gene were recruited for our study. Detailed clinical and genetic data as well as muscle MRIs and muscle biopsies were reviewed., Results: We identified 26 patients harbouring mutations in the GNE gene. Two previously reported mutations (c.1985C>T, p.Ala662Val and c.1225G>T, p.Asp409Tyr) were prevalent in the Scottish, Northern Irish and Northern English populations; with 90% of these patients carrying at least one of the two mutations. Clinically, we confirmed the homogenous pattern of selective quadriceps sparing but noted additional features like asymmetry of weakness at disease onset., Conclusions: GNE myopathy is an important diagnosis to consider in patients presenting with distal leg muscle weakness. We report, for the first time, two common mutations in the north of Britain and highlight the broader spectrum of clinical phenotypes. We also propose that the prevalence of GNE myopathy may be underestimated due to the frequent absence of rimmed vacuoles in the muscle biopsy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Reasons for Performing the Study: Dexamethasone is an anti-inflammatory drug commonly used in equine medicine. Insulin sensitivity decreases with prolonged dexamethasone administration, but little information is available about the duration of this side effect after long-term treatment ends., Objectives: To determine how long it takes for blood glucose, insulin and markers of insulin sensitivity to return to normal ranges after extended dexamethasone treatment has ceased., Study Design: Experimental study., Methods: Eight healthy, mature, mixed-breed horses received 0.04 mg/kg bwt/day oral dexamethasone for 21 days. Blood samples were taken weekly during dexamethasone treatment (Days -21, -14 and -7). Following the final dose of dexamethasone on Day 0, blood samples were taken on Days 1-6, 8, 10, 12, 15 and 22. Day -21 represents baseline or normal blood predexamethasone., Results: On Day 1, plasma glucose and insulin concentrations and the modified insulin-to-glucose ratio (a proxy for pancreatic β cell responsiveness) were higher and the reciprocal of the square root of insulin (a proxy for the estimate of insulin sensitivity) was lower, in comparison with Day -21 values. Blood glucose concentrations dropped and returned to Day -21 values by Day 2. Insulin concentrations remained elevated until Day 3. Values for the modified insulin-to-glucose ratio decreased and returned to Day -21 concentrations by Day 4. Values for the reciprocal of the square root of insulin did not return to Day -21 values until Day 15., Conclusions: These results indicate that, in contrast to blood glucose concentrations, which return to normal quickly (within 2 days after treatment ends), the pancreatic insulin-secreting response has a delayed recovery., (© 2014 EVJ Ltd.)

Introduction: We explored the modified Rankin scale (mRS) as a tool to quantitate disability in myasthenia gravis (MG). Our aim was to correlate patients' perception of their disability with that of the care provider and determine its relationship with other MG-related scores., Methods: We evaluated 107 MG patients at 2 neurological centers. Patients were assessed over the telephone before and after clinic visits using the 15-item Myasthenia Gravis Quality-of-Life index (MG-QOL15) and mRS. At the clinic, patients were assessed using the MG-QOL15, MG Composite (MGC), and mRS., Results: The MG-QOL15 correlated with the MGC, mRS, and assessors' scores of patients. Assessors' perception of disease burden was in line with that of the patients' scoring. MG-QOL15 scores obtained over the telephone were consistent with those obtained in the clinic. Scores were generally higher in patients receiving steroids at >5 mg/day and in those receiving or seeking benefits., Conclusion: The MG-QOL15 and mRS are useful for estimating disability in MG., (Copyright © 2014 Wiley Periodicals, Inc.)

The objective of this study was to evaluate the relationship between hepatic mitochondrial function and residual feed intake (RFI) in growing beef cattle. In Trial 1, RFI was measured in 29 Angus heifers (initial BW = 258.0 ± 24.9 kg) from divergent IGF-I selection lines created at the Eastern Agricultural Research Station (The Ohio State University) fed a grain-based diet (calculated ME = 2.85 Mcal/kg DM). In Trial 2, RFI was measured in 119 Santa Gertrudis steers (initial BW = 308.4 ± 28.1 kg) fed a roughage-based diet (calculated ME = 2.21 Mcal/kg DM). At the end of the RFI measurement period, cattle in Trial 1 (n = 7 low RFI and n = 7 high RFI) and in Trial 2 (n = 6 low RFI and n = 8 high RFI) with measures of RFI exceeding 0.5 (Trial 1) or 1.0 (Trial 2) SD from the mean RFI were selected to measure mitochondrial function. Overall ADG, DMI, and RFI were 1.19 ± 0.15, 9.31 ± 1.12, and 0.00 ± 0.63 kg/d and 0.83 ± 0.16, 9.48 ± 1.00, and 0.00 ± 0.86 kg/d in Trial 1 and 2, respectively. Cattle with low RFI consumed 13 and 24% less (P < 0.05) DM and had 14 and 56% greater (P < 0.05) G:F than cattle with high RFI in Trial 1 and 2, respectively, even though ADG and BW were similar (P > 0.10). In Trial 1, cattle with low RFI tended (P = 0.06) to have greater state 3 respiration rates than cattle with high RFI, but state 3 respiration rates were similar (P > 0.10) between cattle with low and high RFI in Trial 2. In both trials, cattle with low RFI had greater (P < 0.05) acceptor control ratios than their high RFI counterparts. The respiratory control ratio tended (P = 0.09) to be greater for cattle with low RFI compared with high RFI cattle in Trial 1, but no difference (P > 0.10) was observed in Trial 2. Proton-leak kinetics were similar (P > 0.05) between cattle with low and high RFI in both trials. These data suggest that ADP has greater control of oxidative phosphorylation in liver mitochondrial of cattle with low RFI compared to their high RFI counterparts.

Objective: Short sleep duration induces hormonal perturbations contributing to hyperphagia, insulin resistance, and obesity. The majority of these studies are conducted in young adults. This analysis in a large (n = 769) sample of postmenopausal women (median age 63 years) sought to (a) confirm that sleep duration and sleep quality are negatively correlated with circulating leptin concentrations and (b) to examine the relationship between self-reported sleep, dietary energy intake, and diet quality, as well as, investigate the role of leptin in these associations., Methods: Sleep duration/quality, insomnia, and dietary intake were determined via self-report. Blood samples were collected following an overnight fast to assess serum leptin concentration. All analyses were adjusted for total body fat mass., Results: Women reporting ≤6 hr sleep/night had lower serum leptin concentrations than those reporting ≥8 hr sleep (P = 0.04). Furthermore, those with ≤6 hr sleep/night reported higher dietary energy intake (P = 0.01) and lower diet quality (P = 0.04) than the reference group (7 hr sleep/night). Women sleeping ≥8 hr also reported lower diet quality than the reference group (P = 0.02). Importantly, serum leptin did not confound these associations., Conclusions: These results provide evidence that sleep duration is inversely associated with serum leptin and dietary energy intake in postmenopausal women., (Copyright © 2013 The Obesity Society.)

Autoantibodies are infrequently detected in the sera of patients with the demyelinating form of Guillain-Barré syndrome most commonly encountered in the Western world, despite abundant circumstantial evidence suggesting their existence. We hypothesised that antibody specificities reliant on the cis interactions of neighbouring membrane glycolipids could explain this discrepancy, and would not have been detected by traditional serological assays using highly purified preparations of single gangliosides. To assess the frequency of glycolipid complex antibodies in a Western European cohort of patients GBS we used a newly developed combinatorial glycoarray methodology to screen against large range of antigens (11 gangliosides, 8 other single glycolipids and 162 heterodimeric glycolipid complexes). Serum samples of 181 patients from a geographically defined, Western European cohort of GBS cases were analysed, along with 161 control sera. Serum IgG binding to single gangliosides was observed in 80.0% of axonal GBS cases, but in only 11.8% of cases with demyelinating electrophysiology. The inclusion of glycolipid complexes increased the positivity rate in demyelinating disease to 62.4%. There were 40 antigens with statistically significantly increased binding intensities in GBS as compared to healthy control sera. Of these, 7 complex antigens and 1 single ganglioside also produced statistically significantly increased binding intensities in GBS versus neurological disease controls. The detection of antibodies against specific complexes was associated with particular clinical features including disease severity, requirement for mechanical ventilation, and axonal electrophysiology. This study demonstrates that while antibodies against single gangliosides are often found in cases with axonal-type electrophysiology, antibodies against glycolipid complexes predominate in cases with demyelinating electrophysiology, providing a more robust serum biomarker than has ever been previously available for such cases. This work confirms the activation of the humoral immune system in the dysimmune disease process in GBS, and correlates patterns of antigen recognition with different clinical features.

Alterations in nutrient intake in the avian neonatal posthatch period can impact development, performance, and metabolism in adulthood. Very little is known about how mineral levels during the post-hatch period affect or “program” gene expression patterns later in life. The objective of this study was to determine the effect of post-hatch (0 to 96 h) dietary mineral supplementation on performance, tissue mineral content, and intestinal gene expression profiles in 21-day-old broiler chicks. One-day-old chicks were randomly assigned to one of two treatment groups consisting of N (organic Zn, Cu, and Mn provided at 100 % of recommendations (National Research Council 1994)) and/or L (organic Zn, Cu, and Mn provided at 20 % of recommendations (National Research Council 1994)) diets fed in two intervals (days 1–4, days 5–21) as follows: (1)N–Lor (2)L–L. Performance parameters did not differ between treatments except that body weight gain was greater (P < 0.05) in L–L birds than N–L birds over the experimental period. Bone mineral content was similar for both treatments at day 21. Intestinal gene expression profiling was examined using the Affymetrix GeneChip Chicken genome array. Ingenuity pathway analysis revealed differences in gene expression profiles between N and L treatments at day 5. At day 21, profiles were unique between N–L and L–L, suggesting that the diet fed until day 4 had an impact on gene expression patterns at day 21 even when birds were fed the same diets day 5–day 21. In this study, we demonstrated that diets fed for the 96 h post-hatch had long-term effects on gene expression, providing unique information as to why post-hatch diets are so important for the longterm bird health and productivity.

Unlabelled: Myocardial metabolic and perfusion imaging is a vital tool for understanding the physiologic consequences of heart failure. We used PET imaging to examine the longitudinal kinetics of (18)F-FDG and 14(R,S)-(18)F-fluoro-6-thia-heptadecanoic acid ((18)F-FTHA) as analogs of glucose and fatty acid (FA) to quantify metabolic substrate shifts with the spontaneously hypertensive rat (SHR) as a model of left ventricular hypertrophy (LVH) and failure. Myocardial perfusion and left ventricular function were also investigated using a newly developed radiotracer (18)F-fluorodihydrorotenol ((18)F-FDHROL)., Methods: Longitudinal dynamic electrocardiogram-gated small-animal PET/CT studies were performed with 8 SHR and 8 normotensive Wistar-Kyoto (WKY) rats over their life cycle. We determined the myocardial influx rate constant for (18)F-FDG and (18)F-FTHA (Ki(FDG) and Ki(FTHA), respectively) and the wash-in rate constant for (18)F-FDHROL (K1(FDHROL)). (18)F-FDHROL data were also used to quantify left ventricular ejection fraction (LVEF) and end-diastolic volume (EDV). Blood samples were drawn to independently measure plasma concentrations of glucose, insulin, and free fatty acids (FFAs)., Results: Ki(FDG) and Ki(FTHA) were higher in SHRs than WKY rats (P < 3 × 10(-8) and 0.005, respectively) independent of age. A decrease in Ki(FDG) with age was evident when models were combined (P = 0.034). The SHR exhibited higher K1(FDHROL) (P < 5 × 10(-6)) than the control, with no age-dependent trends in either model (P = 0.058). Glucose plasma concentrations were lower in SHRs than controls (P < 6 × 10(-12)), with an age-dependent rise for WKY rats (P < 2 × 10(-5)). Insulin plasma concentrations were higher in SHRs than controls (P < 3 × 10(-3)), with an age-dependent decrease when models were combined (P = 0.046). FFA levels were similar between models (P = 0.374), but an increase with age was evident only in SHR (P < 7 × 10(-6))., Conclusion: The SHR exhibited alterations in myocardial substrate use at 8 mo characterized by increased glucose and FA utilizations. At 20 mo, the SHR had LVH characterized by decreased LVEF and increased EDV, while simultaneously sustaining higher glucose and similar FA utilizations (compared with WKY rats), which indicates maladaptation of energy substrates in the failing heart. Elevated K1(FDHROL) in the SHR may reflect elevated oxygen consumption and decreased capillary density in the hypertrophied heart. From our findings, metabolic changes appear to precede mechanical changes of LVH progression in the SHR model.

1. The addition of yeast cell wall (YCW) mannan fractions or low concentrations of antibiotics to the diet of broilers positively affects gut health by improving intestinal cell morphology and improves feed efficiency and performance; however the exact mechanisms are unclear. Based on these production responses, the objective of this study was to compare the effects of supplementing YCW and bacitracin methylene disalicylate (BMD) in the diet on mRNA levels in the jejunum of 6-week-old broilers. 2. Dietary treatments were a maize-soya control diet and the control diet with the addition of YCW or BMD. Birds (n = 7) from each dietary treatment were randomly selected and killed at d 42. Whole jejunum (with serosa) samples were collected for RNA isolation. Gene expression analysis was performed using the AffymetrixGeneChip Chicken Genome Array (Santa Clara, CA, USA). 3. Supplementation with YCW resulted in 928 genes that were significantly changed (456 down-regulated, 472 up-regulated) and supplementation with BMD resulted in 857 genes that significantly changed (408 down-regulated, 449 up-regulated). In addition, 316 genes were significantly changed by both YCW and BMD (146 down-regulated, 170 up-regulated). 4. BMD increased the expression of genes involved in lipid and carbohydrate metabolism and decreased expression of genes associated with T-helper cell pathways. Gene expression profiles from birds fed on diets containing YCW showed changes on a genomic level that correspond to slower gut cell turnover and therefore increased energy preservation for growth. 5. In conclusion, supplementation with BMD or YCW had similar influences on the number of differentially expressed genes in the jejunum. Biological functions common to both YCW and BMD with positive activation scores included antiviral response and antimicrobial response. Genes that were affected by BMD or YCW classified into both different and common biological functions and pathways related to improved metabolism and health in the jejunum.

Background: Measurement of anti-GM1 IgM antibodies in multifocal motor neuropathy (MMN) sera is confounded by relatively low sensitivity that limits clinical usefulness. Combinatorial assay methods, in which antibodies react to heteromeric complexes of two or more glycolipids, are being increasingly applied to this area of diagnostic testing., Methods: A newly developed combinatorial glycoarray able to identify antibodies to 45 different heteromeric glycolipid complexes and their 10 individual glycolipid components was applied to a randomly selected population of 33 MMN cases and 57 normal or disease controls. Comparison with an enzyme-linked immunosorbent assay (ELISA) was conducted for selected single glycolipids and their complexes., Results: By ELISA, 22/33 MMN cases had detectable anti-GM1 IgM antibodies, whereas 19/33 MMN samples were positive for anti-GM1 antibodies by glycoarray. Analysis of variance (anova) revealed that of the 55 possible single glycolipids and their 1:1 complexes, antibodies to the GM1:galactocerebroside (GM1:GalC) complex were most significantly associated with MMN, returning 33/33 MMN samples as positive by glycoarray and 29/33 positive by ELISA. Regression analysis revealed a high correlation in absolute values between ELISA and glycoarray. Receiver operator characteristic analysis revealed insignificantly different diagnostic performance between the two methods. However, the glycoarray appeared to offer slightly improved sensitivity by identifying antibodies in four ELISA-negative samples., Conclusions: The use of combinatorial glycoarray or ELISA increased the diagnostic sensitivity of anti-glycolipid antibody testing in this cohort of MMN cases, without significantly affecting specificity, and may be a useful assay modification for routine clinical screening., (© 2012 The Author(s) European Journal of Neurology © 2012 EFNS.)

Spermatogenesis is a tightly regulated, selenium-dependent process. Nutritional deficiencies, including Se, have been associated with decreased fertility. During Se depletion, testes preferentially retain Se while other tissues are depleted. This study was aimed at evaluating the effect of Se source (inorganic or organic yeast derived) on testes weight, Se content, and gene expression. At 17 weeks of age, roosters were randomly assigned to one of three treatments: basal diet (control), basal diet + 0.3 mg organic Se/kg organic yeast-derived Se (YS; Sel-Plex®, Alltech Inc.), or basal diet + 0.3 mg inorganic Se /kg inorganic Se as sodium selenite (SS). At 40 weeks of age, seven roosters from each treatment were euthanized and testes removed. Testes weight did not differ between treatments, but Se content was greater (P ≤ 0.01) in YS than SS and control. Testicular differential gene expression profiling was accomplished using the Affymetrix Genechip® chicken genome array. Ingenuity® pathway analysis revealed that Se supplementation, regardless of source, results in the up-regulation of genes governing cell structure/morphology. The enrichment of such pathways was greater with YS than SS. These expression patterns suggest that aside from playing a role in antioxidant defense, Se, especially in the organic YS form, is useful for maintaining testicular cell structure.

Glycolipid-protein interactions are increasingly recognised as critical to numerous and diverse biological processes, including immune recognition, cell-cell signalling, pathogen adherence, and virulence factor binding. Previously, such carbohydrate-lectin interactions have been assessed in vitro largely by assaying protein binding against purified preparations of single glycolipids. Recent observations show that certain disease-associated autoantibodies and other lectins bind only to complexes formed by two different gangliosides. However, investigating such 1:1 glycolipid complexes can prove technically arduous. To address this problem, we have developed a semi-automated system for assaying lectin binding to large numbers of glycolipid complexes simultaneously. This employs an automated thin-layer chromatography sampler. Single glycolipids and their heterodimeric complexes are prepared in microvials. The autosampler is then used to print reproducible arrays of glycolipid complexes onto polyvinylidene difluoride membranes affixed to glass slides. A printing density of 300 antigen spots per slide is achievable. Following overnight drying, these arrays can then be probed with the lectin(s) of interest. Detection of binding is by way of a horseradish peroxidase-linked secondary antibody driving a chemiluminescent reaction rendered on radiographic film. Image analysis software can then be used to measure signal intensity for quantification.

Selenium (Se) content of feedstuffs is dependent on the Se level of the soil. Even though Se in grass and forage crops is primarily present in organic forms, Se is commonly supplemented in cattle diets in an inorganic (sodium selenite) form in geographic regions where Se soil concentrations are low. The purpose of this study was to answer two important questions about inorganic (ISe) vs organic (OSe) forms of dietary supplementation of Se (3 mg/day) to growing beef heifers (0.5 kg/day): (1) what would the effect of supplementing Se with an equal blend of ISe:OSe (Mix) have on Se tissue concentrations and (2) how long does it take for the greater assimilation with OSE to occur and stabilize? A long-term (224 day) Se dietary supplementation trial was conducted with serial sampling performed (days 28, 56, 112, and 224) to determine the length of time required to achieve Se supplement (OSE, Mix, and ISe)-dependent changes in Se assimilation in blood fractions and liver tissue. Forty maturing Angus heifers were fed a corn silage-based diet for 98 days with no Se supplementation, and then a cracked corn/cottonseed hull-based diet (basal diet) without Se supplementation for 74 days. Liver biopsies were taken for Se analysis, and heifers were fed the same diet for another 14 days. Heifers were assigned (n = 10) to one of four Se treatment groups such that basal liver Se contents were stratified among groups, and then fed enough of the basal diet (0.08 mg Se per day) and a mineral-vitamin mix that provided 0.16 (control) or 3.0 mg Se per day in ISe (sodium selenite), OSe (Sel-Plex(®)), or Mix (1:1 ISe:OSe) form to support 0.5 kg/day growth for 224 days. More Se was found in whole blood, red blood cells, serum, and liver of Mix and OSe heifers than ISe heifers, and all were greater than control. Se content either increased until day 56 then was stable (liver and plasma), or was stable until day 56 (whole blood) or day 112 (red blood cells) and then increased steadily through day 224, for all supplemental Se treatments. These data indicate that a 1:1 mix (1.5 mg Se:1.5 mg Se) of supplemental ISe and OSe is equal to 3 mg/day OSe supplementation and greater than 3 mg/day ISe supplementation. The data also indicate that Se levels stabilized in liver and plasma by 56 to 112 days whereas whole blood and red blood cell concentrations were still increasing through 224 days of supplementation, regardless of the form of supplemental Se.

Background: There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[(125)I]iodorotenone ((125)I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of (123)I-ZIROT in an intact large-animal model., Methods and Results: The (123)I-ZIROT was administered during adenosine A(2A) agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, (123)I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. (123)I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At (123)I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial (123)I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or (99m)Tc-sestamibi from previous studies using a similar model. Furthermore, the (123)I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09)., Conclusions: The ability of (123)I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.

The presence of oligoclonal bands of IgG (OCB) in cerebrospinal fluid (CSF) is used to establish a diagnosis of multiple sclerosis (MS), but their specificity has remained an enigma since its first description over forty years ago. We now report that the use of lipid arrays identifies heteromeric complexes of myelin derived lipids as a prominent target for this intrathecal B cell response., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Selenium (Se) is an essential component of at least 25 selenoproteins involved in a multitude of physiological functions, including reproduction. However, relatively little is known about the mechanisms by which Se exerts its physiological effects in reproductive tissue. The objective of this study was to compare the effect of long-term inorganic Se (sodium selenite, SS) and organic yeast-derived Se (Sel-Plex(®), SP) supplementations on tissue Se content and gene expression patterns in the oviduct of broiler-breeder hens. Hens were randomly assigned at 6 weeks of age to one of the three treatments: basal semi-purified diet (control), basal diet+0.3 ppm Se as SP or basal diet+0.3 ppm Se as SS. At 49 weeks, oviduct tissue from hens randomly selected from each treatment (n=7) was analyzed for Se content and gene expression profiles using the Affymetrix Chicken genome array. Gene expression data were evaluated using GeneSpring GX 10.0 (Silicon Genetics, Redwood, CA) and Ingenuity Pathways Analysis software (Ingenuity Systems, Redwood City, CA). Oviduct Se concentration was greater with Se supplementation compared with the control (P≤0.05) but did not differ between SS- and SP-supplemented groups. Gene expression analysis revealed that the quantity of gene transcripts associated with energy production and protein translation were greater in the oviduct with SP but not SS supplementation. Targets up-regulated by SP, but not SS, included genes encoding several subunits of the mitochondrial respiratory complexes, ubiquinone production and ribosomal subunits. SS hens showed a decrease in transcripts of genes involved in respiratory complexes, ATP synthesis and protein translation and metabolism in oviduct relative to control hens. In this study, although tissue Se concentrations did not differ between hens fed SS- and SP-supplemented diets, expression patterns of genes involved in energy production and protein synthesis pathways differed between treatments. These variations may partially explain the differences in reproductive performance reported in hens fed different forms of Se., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, (123)I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of (123)I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.

Previous study indicated that inclusion of an algae-based antioxidant as an antioxidative agent [EconomasE, Alltech, Nicholasville, KY; EcoE] significantly reduced the amount of vitamin E (VE) required in broiler diets without compromising performance and meat quality. To assess the mechanisms related to the VE-saving activity of EcoE, as well as other potential functions related to EcoE and VE supplementation, we analyzed gene expression profiles of breast muscle from broilers fed a control diet, the control diet + 50 IU of VE/kg, the control diet + 100 IU of VE/kg, or the control diet + 200 g of EcoE/ton. Evaluation of the serum antioxidant capacity indicated that dietary supplementation of either a high level of VE (50 or 100 IU of VE/kg) or EcoE significantly improved bird antioxidant status. Analysis of gene expression profiles indicated that expression of 542 genes of the breast muscle were altered (P < 0.05, fold change >1.2) by dietary treatments, of which a significant part were commonly regulated by EcoE and VE (especially the control diet + 50 IU of VE/kg). In addition to the process of cellular oxidation, gene ontology analysis indicated the involvement of EcoE and VE on cell morphology, skeletal and muscular system development and function, immune response, and multiple metabolic processes, including lipid, carbohydrate, and drug metabolism. Results of this experiment indicate that the biological roles of high VE, including its activity as an antioxidant, can be greatly mimicked at the transcriptional level by EcoE, and they suggest a relationship of functional redundancy between VE and EcoE in the broiler diets.

Glycolipids act as receptors for a wide range of antibodies, lectins and microbes. It has long been recognised that the local topography of glycolipids in the plasma membrane is critical to these recognition events, although the biological basis for this has been relatively under-investigated. Within the last five years, emerging evidence indicates that hetero-dimeric clusters of different glycolipids can form highly distinct and specific epitopes for antibody and lectin binding. The initial observation that these ganglioside complexes (GSC) could either dramatically enhance or equally well inhibit the binding of neuropathy sera has now been reproduced for a number of other lectins, including siglecs and bacterial toxins. Here we review the initial discovery of GSC as antibody binding domains and the subsequent studies delineating their broader functional importance. Potential mechanisms underlying these effects are considered, although much remains to be investigated and explained. However, the implications for this field are potentially widespread, ranging from glycoarray design, structural biology and membrane biophysics, through to the biological consequences of glycolipid complex organisation in plasma membranes.