Implications of supplementing mid-lactation multiparous Holstein cows fed high by-product low-forage diets with rumen-protected methionine and lysine in a commercial dairy.

Supplementation of rumen-protected amino acids may improve dairy cow performance but few studies have evaluated the implications of supplementing low-forage diets. Our objective was to evaluate the effects of supplementing rumen-protected methionine (Met) and lysine (Lys) on milk production and composition as well as on mammary gland health of mid-lactating Holstein cows from a commercial dairy farm feeding a high by-product low-forage diet. A total of 314 multiparous cows were randomly assigned to control (CON; 107 g of dry distillers' grains) or rumen-protected Met and Lys (RPML; 107 g dry distillers' grains + 107 g of RPML). All study cows were grouped in a single dry-lot pen and fed the same total mixed ration diet twice a day for a total of 7 weeks. Treatments were top-dressed on the total mix ration immediately after morning delivery with 107 g of dry distillers' grains for 1 week (adaptation period) and then with CON and RPML treatments for 6 weeks. Blood samples were taken from a subset of 22 cows per treatment to determine plasma AA (d 0 and 14) and plasma urea nitrogen and minerals (d 0, 14, and 42). Milk yield and clinical mastitis cases were recorded daily, and milk components were determined bi-weekly. Body condition score change was evaluated from d 0 to 42 of the study. Milk yield and components were analyzed by multiple linear regression. Treatment effects were evaluated at the cow level considering parity and milk yield and composition taken at baseline as a covariate in the models. Clinical mastitis risk was assessed by Poisson regression. Plasma Met increased (26.9 vs 36.0 µmol/L), Lys tended to increase (102.5 vs 121.1 µmol/L), and Ca increased (2.39 vs 2.46 mmol/L) with RPML supplementation. Cows supplemented with RPML had higher milk yield (45.4 vs 46.0 kg/d) and a lower risk of clinical mastitis (risk ratio = 0.39; 95% CI = 0.17-0.90) compared to CON cows. Milk components yield and concentrations, somatic cell count, body condition score change, plasma urea nitrogen, and plasma minerals other than Ca were not affected by RPML supplementation. Results suggest that RPML supplementation increases milk yield and decreases the risk of clinical mastitis in mid-lactation cows fed a high by-product low-forage diet. Further studies are needed to clarify the biological mechanisms for mammary gland responses to RPML supplementation.

TreeQTL: hierarchical error control for eQTL findings.

UNLABELLED: : Commonly used multiplicity adjustments fail to control the error rate for reported findings in many expression quantitative trait loci (eQTL) studies. TreeQTL implements a hierarchical multiple testing procedure which allows control of appropriate error rates defined relative to a grouping of the eQTL hypotheses. AVAILABILITY AND IMPLEMENTATION: The R package TreeQTL is available for download at http://bioinformatics.org/treeqtl CONTACT: sabatti@stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A randomized controlled comparison of integrative cognitive-affective therapy (ICAT) and enhanced cognitive-behavioral therapy (CBT-E) for bulimia nervosa.

BACKGROUND: The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, 'enhanced' cognitive-behavioral therapy (CBT-E). METHOD: Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat). RESULTS: Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different. CONCLUSIONS: ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.

Eating-related anxiety in individuals with eating disorders.

Although previous research has supported the importance of anxiety as an etiological and maintenance factor for eating disorders, the specific mechanisms are not well understood. The role of anxiety in the context of eating behavior is especially unclear. The purpose of this study was to identify anxiety-eliciting eating situations and anxiety management strategies patients use to mitigate anxiety experienced in the context of eating as determined by diagnostic groups and symptom patterns. Fifty-three eating disorder outpatients were administered the Eating and Anxiety Questionnaire (EAQ) and the Eating Disorder Diagnostic Scale. Ratings indicated significant anxiety in most eating situations, whereas management strategies were more limited yet regularly employed. Factor analysis of the EAQ revealed a 6-factor solution for anxiety management strategies and a 4-factor solution for anxiety-eliciting situations. These results indicate patients with eating disorders report high levels of anxiety associated with eating behaviors but utilize limited yet consistent anxiety management strategies. Effective intervention strategies for managing eating-related anxiety should be incorporated into treatment and may need to be specified for different diagnostic subgroups.

Cognitive-behavioral therapy for subthreshold bulimia nervosa: A case series.

The extent to which cognitive-behavioral therapy (CBT) is helpful in treating individuals with bulimic symptoms who do not meet full criteria for bulimia nervosa is unclear. The purpose of this investigation was to examine the potential efficacy of CBT for eating disorder individuals with bulimic symptoms who do not meet full criteria for bulimia nervosa. Twelve participants with subthreshold bulimia nervosa were treated in a case series with 20 sessions of CBT. Ten of the 12 participants (83.3%) completed treatment. Intent-to-treat abstinent percentages were 75.0% for objectively large episodes of binge eating (OBEs), 33.3% for subjectively large episodes of binge eating (SBEs), and 50% for purging at end of treatment. At one year follow-up, 66.7% were abstinent for OBEs, 41.7% for SBEs, and 50.0% for purging. The majority also reported improvements in associated symptoms. This case series provides support for the use of CBT with individuals with subthreshold bulimia nervosa.

Targeting parents for the treatment of pediatric obesity in boys with Duchenne muscular dystrophy: a case series.

Obesity is a major public health concern in children. Obesity occurs frequently in boys with Duchenne muscular dystrophy (DMD), complicating treatment and impairing functioning. Parent-focused interventions to facilitate weight loss have been successful in other pediatric samples but have not been studied with this population. The current investigation examined the feasibility and potential efficacy of parent-focused treatment to improve healthy eating and physical activity of parents and eating and weight in their sons with DMD. Three families participated in this case series. Resulting changes in body weight among boys with DMD were an outcome variable. Findings indicate inconsistent changes in boys' weight, decreases in parent weight, increases in healthy foods available in the home, and increases in children's perceived quality of life. Participant ratings of treatment suitability and satisfaction were generally favorable. These preliminary findings support the use of parent-focused psychoeducation for the treatment of obesity in children with DMD.

Examining a psychosocial interactive model of binge eating and vomiting in women with bulimia nervosa and subthreshold bulimia nervosa.

The current study tested a psychosocial interactive model of perfectionism, self-efficacy, and weight/shape concern within a sample of women with clinically significant bulimic symptoms, examining how different dimensions of perfectionism operated in the model. Individuals with bulimia nervosa (full diagnostic criteria or subthreshold) completed measures of bulimic symptoms, multidimensional perfectionism, self-efficacy, and weight/shape concern. Among those who were actively binge eating (n=180), weight/shape concern was associated with binge eating frequency in the context of high perfectionism (either maladaptive or adaptive) and low self-efficacy. Among those who were actively vomiting (n=169), weight/shape concern was associated with vomiting frequency only in the context of high adaptive perfectionism and low self-efficacy. These findings provide support for the value of this psychosocial interactive model among actively binge eating and purging samples and for the importance of considering different dimensions of perfectionism in research and treatment related to bulimia nervosa.

Self-help versus therapist-led group cognitive-behavioral treatment of binge eating disorder at follow-up.

OBJECTIVE: The purpose of this study was to evaluate the longer-term outcome of three group cognitive-behavioral therapy (CBT) delivery models for the treatment of binge eating disorder (BED). METHOD: Fifty-one participants were assigned to one of three conditions. In the therapist-led condition (TL; n = 16), a psychologist provided psychoeducational information for the first half hour and led a group discussion for the second half hour of each session. In the partial self-help condition (PSH; n = 19), participants viewed a 30-min psychoeducational videotape, followed by a therapist-led discussion. In the structured self-help condition (SSH; n = 16), participants watched a psychoeducational videotape and led their own discussion. RESULTS: Reductions in binge eating episodes and associated symptoms were observed for all three treatments at post, 1-month, 6-month, and 1-year follow-up, with no significant differences among the three conditions. DISCUSSION: These findings suggest that CBT for BED can be delivered successfully using videotape and a structured self-help group format and that improvements in binge eating are maintained up to 1 year follow-up.

Differences in DSM-III-R and DSM-IV diagnoses in eating disorder patients.

Two hundred eighty-eight eating disorder patients were administered the DSM-III-R Structured Clinical Interview (SCID) and the DSM-IV SCID for axis I and II. Concordance between DSM-III-R and DSM-IV was excellent for the axis I affective and anxiety disorders, bulimia nervosa, and substance abuse/dependence. It was also excellent for axis II paranoid, schizoid, borderline, and antisocial personality disorders. Agreement between the two nosological systems was lower for alcohol abuse/dependence with a kappa of.63. Kappas were also poor for the following personality disorders: schizotypal (.44), histrionic (.29), dependent (.54), obsessive-compulsive (.62) and not otherwise specified (.63). There was a substantial difference in the diagnosis of anorexia nervosa between DSM-III-R and DSM-IV. Fourteen patients were diagnosed with anorexia nervosa, binge/purge type, using DSM-IV criteria, while only six received the diagnoses of anorexia nervosa and bulimia nervosa using DSM-III-R criteria. Kappa was.49 and the percent agreement was 79%. While there are considerable areas of overlap in DSM-IV and DSM-III-R, there are also areas of substantial differences. Clinicians and researchers must be very cautious when attempting to compare data from the different nosologies.

Model for the three-dimensional structure of vitronectin: predictions for the multi-domain protein from threading and docking.

The structure of vitronectin, an adhesive protein that circulates in high concentrations in human plasma, was predicted through a combination of computational methods and experimental approaches. Fold recognition and sequence-structure alignment were performed using the threading program PROSPECT for each of three structural domains, i.e., the N-terminal somatomedin B domain (residues 1-53), the central region that folds into a four-bladed beta-propeller domain (residues 131-342), and the C-terminal heparin-binding domain (residues 347-459). The atomic structure of each domain was generated using MODELLER, based on the alignment obtained from threading. Docking experiments between the central and C-terminal domains were conducted using the program GRAMM, with limits on the degrees of freedom from a known inter-domain disulfide bridge. The docked structure has a large inter-domain contact surface and defines a putative heparin-binding groove at the inter-domain interface. We also docked heparin together with the combined structure of the central and C-terminal domains, using GRAMM. The predictions from the threading and docking experiments are consistent with experimental data on purified plasma vitronectin pertaining to protease sensitivity, ligand-binding sites, and buried cysteines.

Combining pharmacotherapy and psychotherapy in the treatment of patients with eating disorders.

The available treatment literature supports a role for medication management in the treatment of both AN and BN. The data on BN are clearer and suggest that antidepressant therapy--fluoxetine being the drug most widely studied--is superior to treatment with placebo but less effective than CBT alone, with one such study suggesting that the combination may provide optimal treatment. Specific recommendations as to when to add or not add antidepressants to CBT have been made, although the rules suggested here have yet to be empirically tested. Although the data on AN are much more limited, information available suggests a lack of efficacy for SSRIs in patients with AN at low weight and considerable use for SSRIs when used in combination with psychotherapy for patients with AN following weight recovery. Where do we go from here? Several pressing issues require careful study. First, in the case of patients with AN, can other agents, in particular the new atypical antipsychotics, be useful in treating patients when they are at low weight? In terms of relapse prevention, can the available findings indicating a role for antidepressants in relapse prevention be replicated, and, if so, can predictor variables that are associated with antidepressant response be identified? In the case of BN, clinicians need to know more about the best possible way to sequence interventions. It has been proposed to add medication to CBT early in treatment if the response to CBT alone is thought to be inadequate. However, other models should be considered, such as stepped-care models in which self-help manuals are used in conjunction with medications. The advantage of these interventions is they could be made more widely available than CBT, which requires a specialist's care. Also, several other new agents, such as sibutramine, which is a drug with serotonin and norepinephrine reuptake inhibition effects, should be tested empirically in subjects with BN, given their pharmacologic profiles.

Association between puberty and disordered eating, body image, and other psychological variables.

OBJECTIVE: To examine associations between puberty and disordered eating, body image, and other psychological variables. METHOD: Females were grouped into three categories of age at puberty onset (Study 1; N = 267) as well as three categories of self-perception of prepubertal weight (Study 2; N = 222). Participants in both studies were matched on current body mass index (BMI) across categories. RESULTS: Females who perceived themselves to be overweight prior to puberty scored significantly higher on measures of disordered eating, body dissatisfaction, asceticism, drive for thinness, impulse regulation, interoceptive awareness, and perfectionism. They also perceived their current body figure to be larger when compared with those who believed they were average or underweight prior to puberty. Age at puberty onset was not significantly associated with disordered eating, body dissatisfaction, depression, or self-esteem. However, females who entered puberty at an earlier age scored higher on measures of asceticism, drive for thinness, impulse regulation, and social insecurity. They also chose a more slender ideal body figure than those who entered at an older age. DISCUSSION: Females who believe they are overweight prior to puberty may be at risk for the development of disordered eating, body image dissatisfaction, and related problems. Age at puberty onset is not a consistent risk factor of pathological eating.

Full-length and truncated forms of vitronectin provide insight into effects of proteolytic processing on function.

A genetic polymorphism in the vitronectin allele directs the production of two distinct forms of the 459 amino acid glycoprotein. A methionine present at position 381 favors production of the single-chain form of vitronectin, while threonine at this position increases the susceptibility of vitronectin to cleavage just beyond its heparin-binding domain at residue 379. This reaction gives rise to a disulfide-bonded, two-chain form of vitronectin. In order to investigate the functional significance of the vitronectin polymorphism, the baculovirus system has been used to express recombinant full-length vitronectin and a truncated form of the molecule that represents the 62-kDa fragment of two-chain vitronectin. Both forms of vitronectin bind and neutralize heparin anticoagulant activity. The proteins also bind PAI-1 and stabilize its active conformation. These experiments suggest that the C-terminal 80 amino acids do not confer a functional difference in the two allelic variants. Immunoassays and gel filtration experiments indicate that both full-length and truncated recombinant forms of vitronectin are multimeric. Together with other reports from this laboratory, these results provide information regarding the primary binding sites for two vitronectin ligands and further define regions that may be involved in multimerization of the protein.

Weight loss and gender: an examination of physician attitudes.

OBJECTIVE: The purpose of this study was to investigate physician attitudes toward the treatment of overweight and obese individuals and to evaluate potential gender differences in treatment recommendations. RESEARCH METHODS AND PROCEDURES: A survey describing several hypothetical patients was sent to 700 randomly selected physicians; 209 (29.9%) returned the survey. Two versions of the questionnaire (one for men and one for women) described three hypothetical patients at three levels of body mass index (BMI) (32, 28, and 25 kg/m(2)). One-half of the physicians received a version of the questionnaire describing the patients as women, and one-half received a version describing the patients as men. Respondents answered questions about attitudes toward treatment and specific interventions and referrals they would view as appropriate. RESULTS: Physicians were more likely to encourage women with a BMI of 25 kg/m(2) to lose weight than men with the same BMI, and indicated that they would suggest more treatment referrals for women than men. Men with a BMI of 32 kg/m(2) were more likely to be encouraged to lose weight than women with the identical BMI. Physicians were more likely to encourage weight loss and see treatment referrals as appropriate for patients with higher BMIS: DISCUSSION: This study indicates that physicians treat male and female patients differently, with physicians more likely to encourage weight loss and provide referrals for women with a BMI of 25 kg/m(2) than for men with an identical BMI and less likely to encourage weight loss for women than men with a BMI of 32 kg/m(2).

Effect of body image and self-image on women's sexual behaviors.

OBJECTIVES: To evaluate the relationship between women's body image, self-image, and sexual behaviors; to determine the effect of body image on personal and sex variables; and to identify factors that contribute to more frequent and greater comfort with sex. METHOD: A magazine survey that included items about body image, self-image, and sexual behaviors was completed by 3,627 women. RESULTS: Women more satisfied with body image reported more sexual activity, orgasm, and initiating sex, greater comfort undressing in front of their partner, having sex with the lights on, trying new sexual behaviors, and pleasing their partner sexually than those dissatisfied. Positive body image was inversely related to self-consciousness and importance of physical attractiveness, and positively related to relationships with others and overall satisfaction. Body image was predictive only of one's comfort undressing in front of partner and having sex with lights on. Overall satisfaction was predictive of frequency of sex, orgasm, and initiating sex, trying new sexual behaviors, and confidence in giving partner sexual pleasure. DISCUSSION: Results indicate that overall self-image and body image are significant predictors of sexual activity. Directions for future research are discussed.

Test-retest reliability of the eating disorder examination.

OBJECTIVE: The purpose of this investigation was to determine the test-retest reliability of the Eating Disorder Examination (EDE). METHOD: This study examined the test-retest and interrater reliability of the EDE in 20 adult women with a range of eating disorder symptoms. Trained assessors administered the EDE to participants on two separate occasions, ranging from 2 to 7 days apart. RESULTS: Test-retest correlations were.7 or greater for all subscales and measures of eating disorder behaviors except for subjective bulimic episodes and subjective bulimic days. Interrater reliability was uniformly high with correlations above.9. DISCUSSION: Results provide further support for the reliability of the EDE, but suggest that smaller binge episodes may not be reliable indicators of eating pathology.

Predictors of treatment outcome for binge eating disorder.

OBJECTIVE: The purpose of this study was to identify predictors of short-term treatment outcome for individuals with binge eating disorder (BED). METHOD: Fifty women who met DSM-IV criteria for BED were enrolled in a manual-based group cognitive-behavioral therapy that consisted of fourteen 1-hr sessions over an 8-week period. Baseline measures included the frequency of self-reported binge eating from the Eating Behaviors-IV (EB-IV), severity of binge eating and dietary restraint using the Binge Eating Scale (BES) and Three-Factor Eating Questionnaire (TFEQ), depressive symptoms as assessed by the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS), and self-esteem as measured by the Rosenberg Self-Esteem Questionnaire (RSEQ). RESULTS: Logistic regression analyses indicated that the baseline frequency of self-reported episodes of binge eating that were objectively large predicted the likelihood of such episodes at the end of treatment. No variables predicted the likelihood of binge eating episodes that were objectively and subjectively large at the conclusion of treatment. DISCUSSION: This study indicates that the frequency of binge eating episodes at baseline is predictive of outcome status at the end of treatment, suggesting that meaningful prognostic factors in BED are identifiable.

New insights into the size and stoichiometry of the plasminogen activator inhibitor type-1.vitronectin complex.

Plasminogen activator inhibitor-type 1 (PAI-1) is the primary inhibitor of endogenous plasminogen activators that generate plasmin in the vicinity of a thrombus to initiate thrombolysis, or in the pericellular region of cells to facilitate migration and/or tissue remodeling. It has been shown that the physiologically relevant form of PAI-1 is in a complex with the abundant plasma glycoprotein, vitronectin. The interaction between vitronectin and PAI-1 is important for stabilizing the inhibitor in a reactive conformation. Although the complex is clearly significant, information is vague regarding the composition of the complex and consequences of its formation on the distribution and activity of vitronectin in vivo. Most studies have assumed a 1:1 interaction between the two proteins, but this has not been demonstrated experimentally and is a matter of some controversy since more than one PAI-1-binding site has been proposed within the sequence of vitronectin. To address this issue, competition studies using monoclonal antibodies specific for separate epitopes confirmed that the two distinct PAI-1-binding sites present on vitronectin can be occupied simultaneously. Analytical ultracentrifugation was used also for a rigorous analysis of the composition and sizes of complexes formed from purified vitronectin and PAI-1. The predominant associating species observed was high in molecular weight (M(r) approximately 320,000), demonstrating that self-association of vitronectin occurs upon interaction with PAI-1. Moreover, the size of this higher order complex indicates that two molecules of PAI-1 bind per vitronectin molecule. Binding of PAI-1 to vitronectin and association into higher order complexes is proposed to facilitate interaction with macromolecules on surfaces.

Type 1 plasminogen activator inhibitor binds to fibrin via vitronectin.

Type 1 plasminogen activator inhibitor (PAI-1), the primary inhibitor of tissue-type plasminogen activator (t-PA), circulates as a complex with the abundant plasma glycoprotein, vitronectin. This interaction stabilizes the inhibitor in its active conformation In this report, the effects of vitronectin on the interactions of PAI-1 with fibrin clots were studied. Confocal microscopic imaging of platelet-poor plasma clots reveals that essentially all fibrin-associated PAI-1 colocalizes with fibrin-bound vitronectin. Moreover, formation of platelet-poor plasma clots in the presence of polyclonal antibodies specific for vitronectin attenuated the inhibitory effects of PAI-1 on t-PA-mediated fibrinolysis. Addition of vitronectin during clot formation markedly potentiates PAI-1-mediated inhibition of lysis of (125)I-labeled fibrin clots by t-PA. This effect is dependent on direct binding interactions of vitronectin with fibrin. There is no significant effect of fibrin-associated vitronectin on fibrinolysis in the absence of PAI-1. The binding of PAI-1 to fibrin clots formed in the absence of vitronectin was characterized by a low affinity (K(d) approximately 3.5 micrometer) and rapid loss of PAI-1 inhibitory activity over time. In contrast, a high affinity and stabilization of PAI-1 activity characterized the cooperative binding of PAI-1 to fibrin formed in the presence of vitronectin. These findings indicate that plasma PAI-1.vitronectin complexes can be localized to the surface of fibrin clots; by this localization, they may modulate fibrinolysis and clot reorganization.

Utilization of empirically supported psychotherapy treatments for individuals with eating disorders: A survey of psychologists.

OBJECTIVE: The purpose of this study was to assess the primary methods used by psychotherapists in treating individuals with eating disorders and to determine the extent to which certain empirically supported psychotherapies (i.e., cognitive behavioral therapy [CBT] and interpersonal psychotherapy [IPT]) are used in clinical settings. METHOD: Surveys developed for this study were sent to 500 psychologists randomly selected from a list of all licensed doctoral-level psychologists in an upper midwestern state. RESULTS: Despite the findings that CBT techniques were reported to be frequently used, most respondents identified something other than CBT or IPT as their primary theoretical approach. In addition, the majority of respondents indicated not having received training in the use of manual-based, empirically supported treatment approaches for working with individuals with eating disorders, although most reported a desire to obtain such training. CONCLUSIONS: Although commonly referred to as the "treatments of choice" in research literature, manual-based, empirically supported approaches to working with individuals with eating disorders has not received adequate dissemination.