Trend analysis and prediction of seasonal changes in milk composition from a pasture-based dairy research herd.

The composition of seasonal pasture-produced milk is influenced by stage of lactation, animal genetics, and nutrition, which affects milk nutritional profile and processing characteristics. The objective was to study the effect of lactation stage (early, mid, and late lactation) and diet on milk composition in an Irish spring calving dairy research herd from 2012 to 2020 using principal component and predictive analytics. Crude protein, casein, fat, and solids increased from 2012 to 2020, whereas lactose concentration peaked in 2017, then decreased. Based on seasonal data from 2013 to 2016, forecasting models were successfully created to predict milk composition for 2017 to 2020. The diet of cows in this study is dependent upon grass growth rates across the milk production season, which in turn, are influenced by weather patterns, whereby extreme weather conditions (rainfall and temperature) were correlated with decreasing grass growth and increasing nonprotein nitrogen levels in milk. The study demonstrates a significant change in milk composition since 2012 and highlights the effect that seasonal changes such as weather and grass growth have on milk composition of pasture-based systems. The potential to forecast milk composition at different stages of lactation benefits processers by facilitating the optimization of in-process and supply logistics of dairy products.

Parental And Clinician Views Of Consent In Neonatal Research.

AIM: To determine parental and clinician views of the informed consent process in neonatal research. METHODS: A questionnaire-based study on the informed consent process. Two questionnaires were developed and distributed to parents and clinicians over a four-month period. RESULTS: Thirty-four parents (79%) surveyed had consented their baby to a research study. The majority of clinicians (72%) had a preference for antenatal provision of information. A desire to help future babies (97%, n=32) and a belief that their baby's healthcare would directly benefit (72%, n=28) were primary reasons for consenting. The majority (76% n=28) of parents were not in favour of a waiver of consent. However twenty clinicians (56%) agreed that a waiver of consent may be appropriate in neonatal research. Thirty-one (86%) clinicians rated GCP training as important. DISCUSSION: Parents are generally supportive of neonatal research. Good clinical practice training is essential for clinicians involved in neonatal research.

Body dysmorphic disorder in patients undergoing septorhinoplasty surgery: should we be performing routine screening?

OBJECTIVE: Body dysmorphic disorder (BDD) is defined as having a preoccupation with a perceived flaw in one's appearance, which appears slight to others and significantly interferes with a person's functioning. When undetected in septorhinoplasty patients, it will often lead to poor outcomes. DESIGN: We performed a prospective cohort study to determine the prevalence of BDD in our patients and whether surgical correction could be considered. SETTING AND PARTICIPANTS: We recruited 34 patients being considered for septorhinoplasty in a tertiary referral rhinology clinic and a control group of 50 from the otology clinic giving a total of 84. MAIN OUTCOME MEASURES: Participants completed the Body Dysmorphic Disorder Questionnaire (BDDQ), the sino-nasal outcome test-23 (SNOT-23) and underwent nasal inspiratory peak flow (NIPF). Those found to be at high risk for BDD were referred to a clinical psychologist. RESULTS: Of the septorhinoplasty patients, 11 (32%) were high risk for BDD. Following psychological assessment, 7 (63%) patients were felt to be unsuitable for surgery and were offered psychological therapy. SNOT-23 scores were significantly higher in the BDD group indicating a negative impact on quality of life. NIPF readings were not significantly different in the BDD group compared to the control group. CONCLUSIONS: The BDDQ is a valid tool for identifying patients at risk of BDD. A close working relationship with clinical psychology has been advantageous to help the selection process of candidates for surgery when there is a high risk of BDD.

Modelling the effects of orange pomace using response surface design for gluten-free bread baking.

The development of gluten-free bread creates many challenges; producing bread that will match the properties of its wheat counterpart can be difficult. Fruit by-products are know from literature to contain a high level of dietary fibre which could improve the bread properties and fibre contents of gluten-free bread. Therefore, a mathematical design was created; three variables were identified from preliminary tests (water (85-100% flour weight, OP 0-8% flour weight and proofing time 35-100 min) as being crucial in the development of acceptable bread. Results illustrated longer proofing times (p<0.05) and lower orange pomace levels (OP) (p<0.001) produced a bread with a greater specific volume. OP had the most significant (p<0.0001) effect on hardness at 2h and 24h post-baking. The optimised formulation was calculated to contain 5.5% OP, 94.6% water and a proofing time of 49 min. Total fibre content of the control bread (2.1%) was successfully increased t o 3.9% in the OP containing bread. Substituting gluten-free flours with orange pomace flour can help improve the total dietary intake of a coeliac while not negating on the quality properties of the bread.

Inhibition of forskolin-induced sensitisation of frog skin nociceptors by the cyclic AMP-dependent protein kinase A antagonist H-89.

The role of cAMP and protein kinase A (PKA) in nociceptor sensitisation has been studied in frog skin in vitro. Multifibre nerve responses during noxious heating were enhanced by adding forskolin, an agent that elevates cAMP. H-89, a PKA antagonist, blocked the increased responses due to forskolin, but did not affect baseline responses. Thus, cAMP appears to act via PKA when sensitising nociceptors in frog skin.

Effect of a bicycle safety program and free bicycle helmet distribution on the use of bicycle helmets by elementary school children.

OBJECTIVE: Each year in the United States, 300,000 children are treated in emergency departments for bicycle injuries; one third have head injuries. The purpose of this study was to determine the effectiveness of educational interventions and free helmet distribution in increasing the use of helmets by elementary school children. METHODS: Self-report questionnaires on the use of bicycle helmets were used for students at two elementary schools (n = 1610). Testing was done both before and after the administration of a bicycle safety program and the distribution of free helmets. Pretest and posttest answers were then compared for changes in helmet use. RESULTS: Helmet usage increased significantly after the bicycle safety program, from 38% to 46% overall (p < 0.005). Children who were given free helmets were significantly more likely to wear their helmets (61.4%) than children who already owned helmets (43.4%) (p > 0.016). Children who attended the school in which free helmets were distributed showed a significant increase in helmet use (p < 0.01), whereas those at the school that had a safety program alone did not show a significant increase (p > 0.17). DISCUSSION: The results of this study suggest that bicycle safety programs and free helmet distribution may increase the consistent use of helmets in elementary school children.

The effects of co-administration of benzhexol on the peripheral pharmacokinetics of oral levodopa in young volunteers.

1. The effects of benzhexol on the absorption and pharmacokinetics of an oral dose of levodopa have been studied in 10 young healthy volunteers. Subjects were given a suspension of levodopa (250 mg) 90 min after either benzhexol (5 mg) or placebo in a randomized cross over design with doses separated by at least 1 week; on each occasion carbidopa was given 1 h before and 5 h after the dose of levodopa. Soluble paracetamol and radiolabelled DTPA were given with the levodopa as markers of gastric emptying. 2. Most subjects showed two peaks in the levodopa plasma concentration-time curve on the placebo day, with the second minor peak occurring 1-2 h after the dose. After benzhexol administration all subjects showed two or more peak levodopa concentrations in plasma. Benzhexol administration caused a significant decrease in the maximum concentration (43%; P < 0.05) of the initial peak and an increase (22%; P < 0.1) in the maximum concentration of the second peak. This change in absorption profile caused by benzhexol significantly altered the ratios of the second peak compared with the initial peak for both the maximum concentrations (P < 0.02) and for the AUC values (P < 0.05). Benzhexol administration did not affect the total AUC of levodopa (7.30 +/- 1.09 vs 7.19 +/- 1.26 micrograms ml-1 h; means +/- s.d.). 3. The plasma concentration-time curves for paracetamol showed similar profiles to those for levodopa and the ratios of the peak concentrations and AUC values for the second peak compared with the initial peak were increased significantly by benzhexol administration (P < 0.05). The total AUC of paracetamol was not affected by benzhexol administration (39.4 +/- 8.2 vs 40.0 +/- 8.9 micrograms ml-1 h; mean +/- s.d.) 4. Benzhexol altered the gastric emptying profile, shown by gamma-scintigraphy, with a reduced extent of initial emptying prior to the establishment of the plateau which is characteristic of levodopa administration in the fasting state. In consequence the ratio of the second to the initial phase of emptying was significantly higher (P < 0.01) following benzhexol treatment. 5. Benzhexol reduces the initial phase of gastric emptying after a dose of levodopa so that there is a decrease in the initial peak and a greater proportion of the dose is absorbed subsequently following the second phase of gastric emptying which occurs approximately 1 h later. Theoretically, this altered concentration-time profile could be an advantage for some patients with Parkinson's disease.

The effect of selegiline on the peripheral pharmacokinetics of levodopa in young volunteers.

The plasma pharmacokinetics of levodopa were studied in eight healthy young subjects following an i.v. infusion of 50 mg over 5 min. Subjects were studied on two occasions in random order following treatment with carbidopa; on one occasion they were pretreated with selegiline (four doses of 10 mg over the preceding 3 days) and on the other with a placebo. The mean plasma concentration-time curves on each occasion were essentially superimposable and there were no significant differences in any calculated pharmacokinetic parameter. Selegiline does not significantly alter the distribution or elimination of levodopa from plasma.

Mutations of an active site threonyl residue promote beta elimination and other side reactions of the enediol intermediate of the ribulosebisphosphate carboxylase reaction.

The side chain of residue threonine 65 within the active site of ribulosebisphosphate carboxylase participates in a network of hydrogen bonds and ionic interactions involving the phosphate moiety attached to C-1 of the substrate. This residue was replaced with serine, alanine, and valine in the enzyme from Synechococcus PCC 6301. The mutant enzymes were stable, expressed abundantly by Escherichia coli, and retained the ability to form gel-filterable complexes with the reaction-intermediate analog, 2'-carboxyarabinitol-1,5-bisphosphate. The substitutions reduced the kcat/Km(CO2) (where kcat is the substrate-saturated turnover rate) of the enzyme from 17- to 340-fold with the more radical substitutions causing more severe reductions. The CO2/O2 specificity also deteriorated progressively, the valine replacement causing a 2.3-fold reduction. In concert with these changes, a compound tentatively identified as 1-deoxy-D-glycero-2,3-pentodiulose-5-phosphate, the product of beta elimination of the 2,3-enediol(ate) intermediate of the catalytic reaction, appeared among the reaction products in progressively increasing amounts. In the case of the valine substitution, it comprised 13% of the ribulose bisphosphate consumed. The mutant enzymes also partitioned more of their reaction flux to pentulose bisphosphate isomers of ribulose bisphosphate. By contrast, the diversion of carboxylated product to pyruvate, as a result of beta elimination of the three-carbon aci-carbanion intermediate of the carboxylation reaction, was ameliorated by the replacements, the valine mutant showing a 5-fold improvement in this parameter. These observations focus attention on a geometric conflict which exists between the requirements for stabilization of the 5-carbon enediol(ate) and 3-carbon aci-carbanion intermediates. This conflict must be resolved by a change in the angle of the C-1/bridge oxygen bond during each catalytic cycle. The network of hydrogen bonds involving the side chain of threonine 65 must play a crucial role in facilitating reaction of the enediol(ate) with the gaseous substrate and in shepherding this subsequent movement.

Enantioselective pharmacokinetics of ethotoin in humans following single oral doses of the racemate.

Racemic ethotoin (1000 mg) was administered orally as a single dose to six healthy adult volunteers. Blood samples were collected at appropriate times for 120 h following the dose. Ethotoin was quantified enantio-selectively in plasma using a novel chiral column HPLC procedure. One of the enantiomers of the chiral metabolite, 5-phenylhydantoin, was also quantified in the HPLC method. The Cmax and AUC0-infinity values for (+)-(S)-ethotoin were significantly greater than those for (-)-(R)-ethotoin (ratio of mean AUC0-infinity values 0.88), but the elimination half-lives of the isomers were virtually identical [12.35 +/- 5.15 h for (-)-(R)-ethotoin; 12.28 +/- 5.34 h for (+)-(S)-ethotoin]. Parameters derived from AUC0-infinity (Cl0/F and V(area)/F) also differed slightly between the isomers. The data were interpreted as indicating a small difference in the absorption of the two isomers; it seemed unlikely, in terms of the identical elimination rates, that their metabolic profiles would differ greatly. The 5-phenylhydantoin was eliminated with a significantly longer half-life (18.69 +/- 6.11 h) than that of ethotoin. Enantioselectivity in the pharmacokinetics of ethotoin is therefore a minor issue.

Enantioselective binding of mephobarbital to plasma proteins.

The enantioselective protein binding of mephobarbital (MPB) was investigated in human plasma and human serum albumin solutions by equilibrium dialysis. A small but statistically significant difference was observed in the in vitro plasma protein binding of the enantiomers; (S)-MPB was approximately 59% bound and (R)-MPB approximately 67% bound. The binding to albumin [(S)-MPB: approximately 29% bound, and (R)-MPB: approximately 41% bound] was less than to plasma proteins but showed somewhat greater enantioselectivity, suggesting that albumin binding is a major source of the enantioselectivity in plasma. The effects of MPB concentration, of varying enantiomeric concentration ratio, and of phenobarbital on the enantioselective binding of MPB were studied. The effect of age was also investigated by measuring the binding in plasma from 8 young (18-25 yr) and 8 elderly (greater than 60 yr) male subjects who took single doses of MPB. The results were in close agreement with the in vitro binding data, and the binding of both enantiomers was marginally but significantly lower in the young compared with the elderly subjects. These differences in binding were consistent with previously observed pharmacokinetic differences between the two subject groups.