Effects of trace mineral amount and source on aspects of oxidative metabolism and responses to intramammary lipopolysaccharide challenge in midlactation dairy cows.

Trace minerals have important roles in immune function and oxidative metabolism; however, little is known about the relationships between supplementation level and source with outcomes in dairy cattle. Multiparous Holstein cows (n=48) beginning at 60 to 140 days in milk were utilized to determine the effects of trace mineral amount and source on aspects of oxidative metabolism and responses to intramammary lipopolysaccharide (LPS) challenge. Cows were fed a basal diet meeting National Research Council (NRC) requirements except for no added zinc (Zn), copper (Cu) or manganese (Mn). After a 4-week preliminary period, cows were assigned to one of four topdress treatments in a randomized complete block design with a 2×2 factorial arrangement of treatments: (1) NRC inorganic (NRC levels using inorganic (sulfate-based) trace mineral supplements only); (2) NRC organic (NRC levels using organic trace mineral supplements (metals chelated to 2-hydroxy-4-(methythio)-butanoic acid); (3) commercial inorganic (approximately 2×NRC levels using inorganic trace mineral supplements only; and (4) commercial organic (commercial levels using organic trace mineral supplements only). Cows were fed the respective mineral treatments for 6 weeks. Treatment effects were level, source and their interaction. Activities of super oxide dismutase and glutathione peroxidase in erythrocyte lysate and concentrations of thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) in plasma were measured as indices of oxidative metabolism. Effects of treatment on those indices were not significant when evaluated across the entire experimental period. Plasma immunoglobulin G level was higher in cows supplemented with organic trace minerals over the entire treatment period; responses assessed as differences of before and after Escherichia coli J5 bacterin vaccination at the end of week 2 of treatment period were not significant. Cows were administered an intramammary LPS challenge during week 5; during week 6 cows fed commercial levels of Zn, Cu and Mn tended to have higher plasma TAC and cows fed organic sources had decreased plasma TBARS. After the LPS challenge, the extent and pattern of response of plasma cortisol concentrations and clinical indices (rectal temperature and heart rate) were not affected by trace mineral level and source. Productive performance including dry matter intake and milk yield and composition were not affected by treatment. Overall, results suggest that the varying level and source of dietary trace minerals do not have significant short-term effects on oxidative metabolism indices and clinical responses to intramammary LPS challenge in midlactation cows.

Immune responses in lactating Holstein cows supplemented with Cu, Mn, and Zn as sulfates or methionine hydroxy analogue chelates.

The aim of this study was to compare effects of inorganic sulfate versus chelated forms of supplemental Cu, Mn, and Zn on milk production, plasma and milk mineral concentrations, neutrophil activity, and antibody titer response to a model vaccination. Holstein cows (n=25) were assigned in 2 cohorts based on calving date to a 12-wk randomized complete block design study. The first cohort consisted of 17 cows that had greater days in milk (DIM; mean of 77 DIM at the start of the trial) than the second cohort of 8 cows (32 DIM at the start of the trial). Diets were formulated to supplement 100% of National Research Council requirements of Cu, Mn, and Zn by either inorganic trace minerals (ITM) in sulfate forms or chelated trace minerals (CTM) supplied as metal methionine hydroxy analog chelates, without accounting for trace mineral contribution from other dietary ingredients. Intake and milk production were recorded daily. Milk composition was measured weekly, and milk Cu, Mn, and Zn were determined at wk 0 and 8. Plasma Cu and Zn concentrations and neutrophil activity were measured at wk 0, 4, 8, and 12. Neutrophil activity was measured by in vitro assays of chemotaxis, phagocytosis, and reactive oxygen species production. A rabies vaccination was administered at wk 8, and vaccine titer response at wk 12 was measured by both rapid fluorescent focus inhibition test and ELISA. Analyzed dietary Cu was 21 and 23mg/kg, Mn was 42 and 46mg/kg, and Zn was 73 and 94mg/kg for the ITM and CTM diets, respectively. No effect of treatment was observed on milk production, milk composition, or plasma minerals. Dry matter intake was reduced for CTM compared with ITM cows, but this was largely explained by differences in body weight between treatments. Milk Cu concentration was greater for CTM than ITM cows, but this effect was limited to the earlier DIM cohort of cows and was most pronounced for multiparous compared with primiparous cows. Measures of neutrophil function were unaffected by treatment except for an enhancement in neutrophil phagocytosis with the CTM treatment found for the later DIM cohort of cows only. Rabies antibody titer in CTM cows was 2.8 fold that of ITM cows as measured by ELISA, with a trend for the rapid fluorescent focus inhibition test. Supplementation of Cu, Mn, and Zn as chelated sources may enhance immune response of early lactation dairy cows compared with cows supplemented with inorganic sources.

Behind the scenes: the changing roles of parents in the transition from child to adult diabetes service.

AIMS: To explore the experiences of young people and their carers during the transition from child to adult diabetes services. METHODS: Longitudinal qualitative case studies of young people and carers undergoing transition in five different diabetes services in the UK. RESULTS: When young people make the transition from child to adult diabetes services, it is assumed that they will also undergo a parallel transition away from dependence on parents to independent diabetes management. However, the lives of young people are characterized by interdependencies, which are facilitative of their diabetes management and which are not always reflected in healthcare policy and practice. This can lead to discontinuities of information and undermine mothers' ability to continue to support their child into young adulthood. Mothers also lose contact with the service at a time when they are undergoing developmental challenges of their own and need support in adjusting to a new existence. CONCLUSIONS: There is a clear need to develop service structures that recognize the continuing role played by mothers in the diabetes care of young adults.

Effects of feeding a dietary antioxidant in diets with oxidized fat on lactation performance and antioxidant status of the cow.

The objective of the study was to evaluate the effect of feeding the dietary antioxidant Agrado Plus (AOX; Novus International, St. Louis, MO) in diets that contained 2% fresh fat (FF) or oxidized fat (OF) on milk production and composition and antioxidant status of cows during mid to late lactation. Forty-four mid to late lactating primiparous cows housed in a tie-stall barn were fed a diet that contained 2% FF for 15 d as adaptation period and then randomly allocated to 1 of the 4 dietary treatments (FF, FF+AOX, OF, OF +AOX) for 6 wk. Feeding AOX increased dry matter intake, 3.5% fat-corrected milk, and milk fat yield, and decreased milk protein content but not yield. Feeding OF increased milk fat yield, but decreased dry matter intake and body weight gain. Milk fat composition changed with treatments: AOX increased cis 18:1 and decreased trans-11 18:1, whereas OF decreased trans-9 and trans-11 18:1 and cis-9, trans-11 18:2 in milk. Plasma antioxidant enzymes and status were affected by treatments. Feeding OF increased superoxidase dismutase activity but decreased plasma antioxidant status, whereas AOX supplementation increased glutathione peroxidase activity across fat types and increased the antioxidant status and superoxidase dismutase activity when feeding OF diets. It can be concluded that feeding AOX improved lactation performance and the antioxidant status of the cow across fat types, and feeding OF increased milk fat yield but decreased dry matter intake, body weight gain, and antioxidant status. The negative effects of feeding OF were partially alleviated by AOX.

Determining the methionine activity of Mintrex organic trace minerals in broiler chicks by using radiolabel tracing or growth assay.

Mintrex Zn, Mintrex Cu, and Mintrex Mn organic trace minerals contain 16% Zn, 15% Cu, and 13% Mn with 80, 78, and 76% 2-hydroxy-4-(methylthio)butanoic acid (HMTBA) by weight as the organic ligand, respectively. Our objective was to determine if HMTBA from Mintrex was fully available as a Met source. In experiment 1, thirty-six broilers (7 to 10 d old) were orally gavaged with methyl-(14)C-labeled HMTBA, either as free HMTBA (Alimet feed supplement) or Zn bis(-2-hydroxy-4-methylthiobutyrate) (Mintrex Zn). Radiolabel incorporation from either source into protein was measured as a marker of bioavailable Met activity. Results demonstrated that the HMTBA from Mintrex Zn was equally available as free HMTBA to support protein synthesis. In experiment 2, five hundred seventy-six 1-d-old broilers were allotted to 12 dietary treatments (TRT) for a 21-d growth assay. A TSAA-deficient diet containing 0.70% total TSAA (TRT 1) was supplemented with 0.05, 0.10, 0.15, and 0.20% free HMTBA (TRT 2 to 5) to establish the standard Met response curve. Treatment 6 was analogous to TRT 2 but had an additional 160 ppm Zn, 80 ppm Cu, and 160 ppm Mn as sulfates. Treatments 7 to 12 were identical to TRT 2 but supplemented with 40 or 160 ppm Zn from Mintrex Zn, 20 or 80 ppm Cu from Mintrex Cu, or 40 or 160 ppm Mn from Mintrex Mn, respectively. For TRT 1 through 6, growth performance increased due to increasing Met addition (P < 0.01) but not to increasing inorganic trace minerals. For Mintrex Zn, Cu, and Mn (TRT 7 to 12), there was a linear increase in cumulative gain:feed ratio (P < 0.04), and for Mintrex Zn and Mn, there was a linear increase in cumulative gain (P < 0.03) to increasing Mintrex addition. A 1-slope broken-line model was used to calculate bioavailable Met activity from Mintrex for comparison with actual intake values. Results indicated that HMTBA from Mintrex was fully available as a Met source.

Comparative in vitro and in vivo absorption of 2-hydroxy-4(methylthio) butanoic acid and methionine in the broiler chicken.

Poultry diets are typically supplemented with DL-2-hydroxy-4(methylthio) butanoic acid (HMTBA, or the hydroxy analog of methionine) or DL-methionine (DLM). Although HMTBA and DLM provide methionine activity, they are structurally distinct molecules with different physiological characteristics until they are converted to L-methionine. The relative rates of intestinal HMTBA vs. DLM absorption have been controversial, and it has been claimed that HMTBA is not fully absorbed. We measured the uptake of HMTBA and DLM in an in vitro everted intestinal slice model. Sections of intestinal slices (jejunum and ileum) were incubated with 0.1 to 50 mM HMTBA that was radiolabeled or DLM that was radiolabeled, and absorption was measured by scintillation counting. The HMTBA uptake was equal to or greater than DLM absorption in each tissue and at every time point with one exception. Furthermore, the rates of HMTBA absorption were always equal to or significantly greater than DLM uptake. In a separate in vivo experiment, absorption of HMTBA and L-methionine was monitored along the entire gastrointestinal (GI) tract. Broilers were fed commercial-type corn-soy diets supplemented with 0.21% HMTBA. Digesta was collected from crop, proventriculus, gizzard, duodenum, jejunum, ileum, large intestine, and cloaca and analyzed for the concentration of free HMTBA and free methionine in each compartment. These studies demonstrated that HMTBA is absorbed completely and along the entire GI tract, especially the upper GI tract. Furthermore, there was a higher concentration of free L-methionine than HMTBA in the digesta from every segment distal to the gizzard.

Achieving involvement: process outcomes from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.

BACKGROUND: A consulting method known as 'shared decision making' (SDM) has been described and operationalized in terms of several 'competences'. One of these competences concerns the discussion of the risks and benefits of treatment or care options-'risk communication'. Few data exist on clinicians' ability to acquire skills and implement the competences of SDM or risk communication in consultations with patients. OBJECTIVE: The aims of this study were to evaluate the effects of skill development workshops for SDM and the use of risk communication aids on the process of consultations. METHODS: A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. Half the consultations were randomly selected for audio-taping, of which 352 patients attended and were audio-taped successfully. After baseline, participating doctors were randomized to receive training in (i) SDM skills or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were allocated randomly to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations were audio-taped from each phase. Raters (independent, trained and blinded to study phase) assessed the audio-tapes using a validated scale to assess levels of patient involvement (OPTION: observing patient involvement), and to analyse the nature of risk information discussed. Clinicians completed questionnaires after each consultation, assessing perceived clinician-patient agreement and level of patient involvement in decisions. Multilevel modelling was carried out with the OPTION score as the dependent variable, and rater, consultation and clinician levels of data, standardized by rater within clinician. RESULTS: Following each of the interventions, the clinicians significantly increased their involvement of patients in decision making (OPTION score increased by 10.6 following risk communication training [95% confidence interval (CI) 7.9 -13.3; P < 0.001] and by 12.9 after SDM skill development (95% CI 10 -15.8, P < 0.001), a moderate effect size. The level of involvement achieved by the risk communication aids was significantly increased by the subsequent introduction of the skill development workshops (7.7 increase in OPTION score, 95% CI 3.4-12; P < 0.001). The alternative sequence (skills followed by risk communication aids) did not achieve this effect. The use of most risk information formats increased after the provision of specific risk communication aids (P < 0.001). Clinicians using the risk communication tools perceived significantly higher patient and clinician agreement on treatment (P < 0.001), patient satisfaction with information (P < 0.01), clinician satisfaction with decision (P < 0.01) and general overall satisfaction with the consultation (P < 0.001) than those who were exposed to SDM skill development workshops. CONCLUSIONS: These clinicians were able to acquire the skills to implement SDM competences and to use risk communication aids. Each intervention provided independent effects. Further progress towards greater patient involvement in health care decision making is possible, and skill development in this area should be incorporated into postgraduate professional development programmes.

Patient-based outcome results from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.

BACKGROUND: Shared decision-making (SDM) between professionals and patients is increasingly advocated from ethical principles. Some data are accruing about the effects of such approaches on health or other patient-based outcomes. These effects often vary substantially between studies. OBJECTIVE: Our aim was to evaluate the effects of training GPs in SDM, and the use of simple risk communication aids in general practice, on patient-based outcomes. METHODS: A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. After baseline, participating doctors were randomized to receive training in (i) SDM skills; or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were randomly allocated to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations took place in 'research clinics' to evaluate the effects of more time for consultations, compared with usual surgery time. Patient-based outcomes were assessed at exit from consultation and 1 month follow-up. These were: COMRADE instrument (principal measures; subscales of risk communication and confidence in decision), and a range of secondary measures (anxiety, patient enablement, intention to adhere to chosen treatment, satisfaction with decision, support in decision making and SF-12 health status measure). Multilevel modelling was carried out with outcome score as the dependent variable, and follow-up point (i.e. exit or 1 month later for each patient), patient and doctor levels of explanatory variables. RESULTS: No statistically significant changes in patient-based outcomes due to the training interventions were found: COMRADE risk communication score increased 0.7 [95% confidence interval (CI) -0.92 to 2.32] after risk communication training and 0.9 (95% CI -0.89 to 2.35) after SDM training; and COMRADE satisfaction with communication score increased by 1.0 (95% CI -1.1 to 3.1) after risk communication, and decreased by 0.6 (95% CI 2.7 to -1.5) after SDM training. Patients' confidence in the decision (2.1 increase, 95% CI 0.7-3.5, P < 0.01) and expectation to adhere to chosen treatments (0.7 increase, 95% CI 0.04-1.36, P < 0.05) were significantly greater among patients seen in the research clinics (when more time was available) compared with usual surgery time. Most outcomes deteriorated between exit and 1 month later. There was no interaction between intervention effects. CONCLUSION: Patients can be more involved in treatment decisions, and risks and benefits of treatment options can be explained in more detail, without adversely affecting patient-based outcomes. SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes, but the resources required to enhance these professional skills must also be taken into consideration. These data also indicate the benefits of extra consultation time.

Shared decision making: developing the OPTION scale for measuring patient involvement.

BACKGROUND: A systematic review has shown that no measures of the extent to which healthcare professionals involve patients in decisions within clinical consultations exist, despite the increasing interest in the benefits or otherwise of patient participation in these decisions. AIMS: To describe the development of a new instrument designed to assess the extent to which practitioners involve patients in decision making processes. DESIGN: The OPTION (observing patient involvement) scale was developed and used by two independent raters to assess primary care consultations in order to evaluate its psychometric qualities, validity, and reliability. STUDY SAMPLE: 186 audiotaped consultations collected from the routine clinics of 21 general practitioners in the UK. METHOD: Item response rates, Cronbach's alpha, and summed and scaled OPTION scores were calculated. Inter-item and item-total correlations were calculated and inter-rater agreements were calculated using Cohen's kappa. Classical inter-rater intraclass correlation coefficients and generalisability theory statistics were used to calculate inter-rater reliability coefficients. Basing the tool development on literature reviews, qualitative studies and consultations with practitioner and patients ensured content validity. Construct validity hypothesis testing was conducted by assessing score variation with respect to patient age, clinical topic "equipoise", sex of practitioner, and success of practitioners at a professional examination. RESULTS: The OPTION scale provided reliable scores for detecting differences between groups of consultations in the extent to which patients are involved in decision making processes in consultations. The results justify the use of the scale in further empirical studies. The inter-rater intraclass correlation coefficient (0.62), kappa scores for inter-rater agreement (0.71), and Cronbach's alpha (0.79) were all above acceptable thresholds. Based on a balanced design of five consultations per clinician, the inter-rater reliability generalisability coefficient was 0.68 (two raters) and the intra-rater reliability generalisability coefficient was 0.66. On average, mean practitioner scores were very similar (and low on the overall scale of possible involvement); some practitioner scores had more variation around the mean, indicating that they varied their communication styles to a greater extent than others. CONCLUSIONS: Involvement in decision making is a key facet of patient participation in health care and the OPTION scale provides a validated outcome measure for future empirical studies.

The relative effectiveness of 2-hydroxy-4-(methylthio) butanoic acid and DL-methionine in young swine.

We compared the effectiveness of 2-hydroxy-4-(methylthio) butanoic acid (HMB) and DL-methionine (DLM) as sources of L-methionine activity in methionine-deficient primary cultures of pig liver cells and methionine-deficient early-weaned pigs. Viable hepatocytes were obtained from minced pig liver and maintained in a high density, differentiated, nonproliferation cell culture system. Culture medium was supplemented with HMB, DLM, or L-methionine, and cells were pulse-dosed with L-[14C(U)]leucine for 24 h to determine the level of protein synthesis. Leucine incorporation per milligram of protein indicated a six-to eightfold increase in protein synthesis (P < .01) with methionine levels between 5 and 10 microM, regardless of source of methionine activity. Two 24-pen replicate methionine dose titrations were conducted with 95 early-weaned commercial crossbred pigs. The pelleted corn, dried whey, and porcine plasma basal diet contained 1.5% lysine, .23% methionine, and .48% cystine and was supplemented with 0, .05, or .10% methionine activity as DLM or HMB for 21 d. There was a 134, 104, and 61% increase (P < .01) in cumulative ADG for each successive week on study with a 30 and 19% improvement in feed/gain (P < .01) after 7 and 14 d. Performance responses due to source of methionine activity did not differ and slope ratio potency determinations (gain vs intake of methionine source) of HMB vs DLM indicated a 119, 111, and 95% relative activity for cumulative weekly performance. These results support the hypothesis that HMB and DLM provide equimolar levels of methionine activity in swine.

Effect of intermittent periods of high environmental temperature on broiler performance responses to sources of methionine activity.

The objective of these experiments was to study the effect of intermittent high temperature (IHT) on performance of broilers fed different sources of methionine activity. Two 20-d experiments were conducted in which individually caged 28-d-old cockerels were exposed to a 5-d period of constant high temperature (HT, 30 to 32 C) followed by an equal period of thermoneutral (TN) temperatures (22 C) with the 10-d temperature cycle repeated twice. Birds held at 22 C were TN controls. Grower diets contained 3,275 kcal/kg ME and 20% CP and were supplemented with either 2-hydroxy-4-(methylthio)butanoic acid (HMB, Alimet Feed Supplement) or DL-Met up to a maximum of .88 to .90% total sulfur amino acids (TSAA). In Experiment 1, gain:feed but not average daily gain was greater (P < .05) for HMB than DL-Met birds subjected to IHT (.451 vs .413, respectively), but no treatment differences were observed for TN birds. Results of Experiment 2 demonstrated a linear response to HMB and DL-Met dose in TN (P < .01); however, only HMB-supplemented birds responded similarly in IHT (P < .01). These results are consistent with lower availability of DL-Met as a result of IHT. In vitro experiments indicated that capacity for uptake of DL-Met into intestinal epithelial cells was reduced in heat-stressed birds. Uptake of D-Met was more severely affected than was L-Met. Consequently, a third performance experiment compared the ability of D-Met and L-Met to support growth under conditions of HT. The results indicated that the effect of HT on broiler performance was mediated through reduced utilization of D-Met.

Effect of heat stress on 2-hydroxy-4-(methylthio)butanoic acid and DL-methionine absorption measured in vitro.

The objective of the present experiments was to determine the biochemical basis for preliminary chick performance data, which indicate an ameliorative effect of 2-hydroxy-4-(methylthio)butanoic acid (HMB) when compared with DL-methionine (DLM) fed during hot conditions. In vitro passage of HMB or DLM across intact segments of small intestine from either control (thermoneutral, TN) or heat-stressed (HS) birds was used as a model for intestinal absorption. For DLM placed in the lumen, appearance in the outside buffer was reduced when using intestine from HS birds compared with tissue from TN birds. In contrast, the appearance of HMB in the outside buffer was greater using HS intestine, resulting in a substrate by environment interaction (P < .01). Slices of everted small intestine from TN and HS birds were used to study epithelial uptake of methyl labeled 14C-DLM by three transport pathways: diffusion, carrier-specific energy- and sodium-independent uptake (ESI), and carrier-specific energy- and sodium-dependent uptake (ESD). Correcting for extracellular volume, total epithelial uptake of 14C-DLM (diffusion plus ESI plus ESD) was reduced by 34% in HS intestine (P < .05). Energy-dependent uptake was observed to decrease by 87% in HS (P < .05). Energy-independent uptake was increased (136%, HS versus TN, P < .05), but not enough to compensate for the decrease in ESD uptake. Intestinal transport systems for glucose and leucine were also observed to change during HS, suggesting a role for cellular transport changes in the performance reduction associated with HS.

Audit of pre-employment health assessment in the National Health Service.

Seventeen (77 per cent) of the 22 NHS occupational health departments in the West Midlands Region replied to a postal questionnaire about pre-employment health assessment. In only 5 departments (29 per cent) was the decision whether to interview and examine a prospective employee dependent on the results of a self-administered questionnaire. All departments were asked how many prospective employees had been screened and how many rejected/restricted over a 2 week period. Departments which interviewed/examined all prospective employees tended to have higher rejection/restriction rates than departments operating a selective policy: 6 (2.6 per cent) out of 232 versus 16 (1.4 per cent) out of 1140, relative risk 1.6, 95 per cent confidence interval 0.8 to 3.4, P = 0.31. In departments which did not automatically interview/examine prospective employees, the median proportion seen by nurses was 56 per cent, and by doctors was only 12 per cent. Within one NHS Region we have documented wide variation in what constitutes a pre-employment health assessment. A selective approach would release a significant amount of occupational health staff time.

Brain-stem dysfunction in autism. Results of vestibular stimulation.

Responses to vestibular stimulation can, under well-controlled experimental conditions, provide a measure of brain-stem function. Autistic children had significantly longer time constants during the primary nystagmus response and significantly fewer beats during the secondary response than normal children when stimulated with constant angular acceleration in complete darkness. These findings could not be attributed to gross differences in arousal, to developmental retardation, to associated clinical conditions, or to either the influence of vision or habituation. Rather, they are suggestive of a neurophysiologic dysfunction, perhaps involving the brain stem, and may be an expression of the process that underlies those autistic behaviors that suggest faulty modulation of sensory input and motor output. Brain-stem centers modulate both general sensory input and motor excitation and may play a role in the elaboration of the more complex adaptive and motivated behaviors that are also disturbed in autism.