Impact of dairy fat manipulation on endothelial function and lipid regulation in human aortic endothelial cells exposed to human plasma samples: an in vitro investigation from the RESET study.

PURPOSE: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo. METHODS: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed. RESULTS: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured. CONCLUSION: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.

Effect of dietary protein source and Saccharina latissima on nutritional and safety characteristics of milk.

BACKGROUND: Wheat distillers' grains (WDG) and seaweeds are recommended as alternative protein sources and enteric methane mitigators in dairy cow diets, respectively, but little is known about their impact on milk quality and safety. In the present study, 16 cows in four 4 × 4 Latin squares were fed isonitrogenous diets (50:50 forage:concentrate ratio), with rapeseed meal (RSM)-based or WDG-based concentrate (230 and 205 g kg-1 dry matter) and supplemented with or without Saccharina latissima. RESULTS: Replacement of RSM with WDG enhanced milk nutritional profile by decreasing milk atherogenicity (P = 0.002) and thrombogenicity (P = 0.019) indices and the concentrations of the nutritionally undesirable saturated fatty acids - specifically, lauric (P = 0.045), myristic (P = 0.022) and palmitic (P = 0.007) acids. It also increased milk concentrations of the nutritionally beneficial vaccenic (P < 0.001), oleic (P = 0.030), linoleic (P < 0.001), rumenic (P < 0.001) and α-linolenic (P = 0.012) acids, and total monounsaturated (P = 0.044), polyunsaturated (P < 0.001) and n-6 (P < 0.001) fatty acids. Feeding Saccharina latissima at 35.7 g per cow per day did not affect the nutritionally relevant milk fatty acids or pose any risk on milk safety, as bromoform concentrations in milk were negligible and unaffected by the dietary treatments. However, it slightly reduced milk concentrations of pantothenate. CONCLUSION: Feeding WDG to dairy cows improved milk fatty acid profiles, by increasing the concentrations of nutritionally beneficial fatty acids and reducing the concentration of nutritionally undesirable saturated fatty acids, while feeding seaweed slightly reduced pantothenate concentrations. However, when considering the current average milk intakes in the population, the milk compositional differences between treatments in this study appear relatively small to have an effect on human health. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

LC-MS/MS Bioanalysis of Radioligand Therapeutic Drug Candidate for Preclinical Toxicokinetic Assessment.

Radioligand therapy (RLT) has gained significant momentum in recent years in the diagnosis, treatment, and monitoring of cancers. In preclinical development, the safety profile of RLT drug candidate(s) is investigated at relatively low dose levels using the cold (non-radioactive, e.g., 175Lu) ligand as a surrogate of the hot (radioactive, e.g., 177Lu) one in the "ligand-linker-chelator" complex. The formulation of the test article used in preclinical safety studies contains a mixture of free ligand (i.e., ligand-linker-chelator without metal) and cold ligand (i.e., ligand-linker-chelator with non-radioactive metal) in a similar molar ratio as seen under the manufacturing conditions for the RLT drug for clinical use, where only a fraction of free ligand molecules chelate the radioactive metal to form a hot ligand. In this very first report of LC-MS/MS bioanalysis of RLT molecules in support of a regulated preclinical safety assessment study, a highly selective and sensitive LC-MS/MS bioanalytical method was developed for the simultaneous determination of free ligand (NVS001) and cold ligand (175Lu-NVS001) in rat and dog plasma. Several unexpected technical challenges in relation to LC-MS/MS of RLT molecules were successfully addressed. The challenges include poor assay sensitivity of the free ligand NVS001, formation of the free ligand (NVS001) with endogenous metal (e.g., potassium), Ga loss from the Ga-chelated internal standard during sample extraction and analysis, "instability" of the analytes at low concentrations, and inconsistent IS response in the extracted plasma samples. The methods were validated according to the current regulatory requirements in a dynamic range of 0.5-250 ng/mL for both the free and cold ligands using a 25 µL sample volume. The validated method was successfully implemented in sample analysis in support of regulated safety studies, with very good results from incurred sample reanalysis. The current LC-MS/MS workflow can be expanded to quantitative analysis of other RLTs in support of preclinical RLT drug development.

Assessment of the reliability and validity of imaging measurements for patellofemoral instability: an updated systematic review.

OBJECTIVE: To provide an update on the reliability and validity of all radiological measures used to assess patients presenting with patellofemoral instability. METHODS: A search of the CINHAL, EMBASE, MEDLINE, and SCOPUS databases and the Cochrane library was conducted. All studies assessing the validity, reliability, sensitivity, and specificity of radiological measures of the patellofemoral joints of patients with patellofemoral instability from 2010 onwards were considered for inclusion. Discrimination validity, inter- and intra-observer reliability, and the sensitivity and specificity of specific imaging measures were evaluated. RESULTS: Seventy-three studies met the selection criteria and were included for analysis. We identified eight radiological measures in four categories with good reliability and validity: the tibial tubercle to trochlear groove distance, specific measures of patellar height (Blackburne-Peel index, Caton-Deschamps index and Insall-Salvati ratios), three measures of trochlear dysplasia (sulcus angle, trochlear depth, and lateral trochlear inclination), and the tibial tubercle to posterior cruciate ligament distance. No included studies examined the reliability and validity of patellofemoral instability ultrasound measures. CONCLUSION: Our updated review demonstrated good inter- and intra-observer reliability and discrimination validity for the tibial tubercle-trochlear groove distance, specific patellar height, and trochlear dysplasia measures on MRI. The tibial tubercle to posterior cruciate ligament distance, an indirect measure of rotational asymmetry, was a valid and reliable measure on MRI. Due to a lack of assessments across more than one study, there are a variety of proposed measures with insufficient evidence to determine their validity, reliability, sensitivity, and specificity.

Postprandial Fatty Acid Profile, but Not Cardiometabolic Risk Markers, Is Modulated by Dairy Fat Manipulation in Adults with Moderate Cardiovascular Disease Risk: The Randomized Controlled REplacement of SaturatEd fat in dairy on Total cholesterol (RESET) Study.

BACKGROUND: Chronic consumption of dairy products with an SFA-reduced, MUFA-enriched content was shown to impact favorably on brachial artery flow-mediated dilatation (FMD). However, their acute effect on postprandial cardiometabolic risk biomarkers requires investigation. OBJECTIVE: The effects of sequential high-fat mixed meals rich in fatty acid (FA)-modified or conventional (control) dairy products on postprandial FMD (primary outcome) and systemic cardiometabolic biomarkers in adults with moderate cardiovascular risk (≥50% above the population mean) were compared. METHODS: In a randomized crossover trial, 52 participants [mean ± SEM age: 53 ± 2 y; BMI (kg/m2) 25.9 ± 0.5] consumed a high-dairy-fat breakfast (0 min; ∼50 g total fat: modified: 25 g SFAs, 20 g MUFAs; control: 32 g SFAs, 12 g MUFAs) and lunch (330 min; ∼30 g total fat; modified: 15 g SFAs, 12 g MUFAs; control: 19 g SFAs, 7 g MUFAs). Blood samples were obtained before and until 480 min after breakfast, with FMD assessed at 0, 180, 300, and 420 min. Data were analyzed by linear mixed models. RESULTS: Postprandial changes in cardiometabolic biomarkers were comparable between the different dairy meals, with the exception of a tendency for a 4% higher AUC for the %FMD response following the modified-dairy-fat meals (P = 0.075). Plasma total lipid FA analysis revealed that incremental AUC responses were 53% lower for total SFAs, 214% and 258% higher for total cis-MUFAs (predominantly cis-9 18:1), and trans-18:1, respectively, following the modified relative to the control dairy meals (all P < 0.0001). CONCLUSIONS: In adults at moderate cardiovascular risk, acute consumption of sequential high-fat meals containing FA-modified dairy products had little impact on postprandial endothelial function or systemic cardiometabolic biomarkers, but a differential effect on the plasma total lipid FA profile, relative to conventional dairy fat meals.This trial was registered at clinicaltrials.gov as NCT02089035.

Delphi developed syllabus for the medical specialty of sport and exercise medicine: part 2.

Training in the medical specialty of sport and exercise medicine (SEM) is available in many, but not all countries. In 2015, an independent Delphi group, the International Syllabus in Sport and Exercise Medicine Group (ISSEMG), was formed to create a basic syllabus for this medical specialty. The group provided the first part of this syllabus, by identifying 11 domains and a total of 80 general learning areas for the specialty, in December 2017. The next step in this process, and the aim of this paper was to determine the specific learning areas for each of the 80 general learning areas. A group of 26 physicians with a range of primary medical specialty qualifications including, Sport and Exercise Medicine, Family Medicine, Internal Medicine, Cardiology, Rheumatology and Anaesthetics were invited to participate in a multiple round online Delphi study to develop specific learning areas for each of the previously published general learning areas. All invitees have extensive clinical experience in the broader sports medicine field, and in one or more components of sports medicine governance at national and/or international level. SEM, Family Medicine, Internal Medicine, Cardiology, Rheumatology and Anaesthetics were invited to participate in a multiple round online Delphi study to develop specific learning areas for each of the previously published general learning areas. All invitees have extensive clinical experience in the broader sports medicine field, and in one or more components of sports medicine governance at national and/or international level. The hierarchical syllabus developed by the ISSEMG provides a useful resource in the planning, development and delivery of specialist training programmes in the medical specialty of SEM.

A Delphi developed syllabus for the medical specialty of sport and exercise medicine.

Training in the medical specialty of sport and exercise medicine is now available in many, but not all countries. Lack of resources may be a barrier to the development of this important specialty field and the International Syllabus in Sport and Exercise Medicine Group was convened to reduce one potential barrier, the need to develop a syllabus. The group is composed of 17 sport and exercise medicine specialists residing in 12 countries (Australia, Canada, India, Ireland, Malaysia, the Netherlands, Qatar, South Africa, Sweden, Switzerland, the UK and USA). This paper presents the first phase of this project covering the domains and general learning areas of a specialist training syllabus in sport and exercise medicine.

Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial.

BACKGROUND: Dairy products are a major contributor to dietary SFA. Partial replacement of milk SFA with unsaturated fatty acids (FAs) is possible through oleic-acid rich supplementation of the dairy cow diet. To assess adherence to the intervention of SFA-reduced, MUFA-enriched dairy product consumption in the RESET (REplacement of SaturatEd fat in dairy on Total cholesterol) study using 4-d weighed dietary records, in addition to plasma phospholipid FA (PL-FA) status. METHODS: In a randomised, controlled, crossover design, free-living UK participants identified as moderate risk for CVD (n = 54) were required to replace habitually consumed dairy foods (milk, cheese and butter), with study products with a FA profile typical of retail products (control) or SFA-reduced, MUFA-enriched profile (modified), for two 12-week periods, separated by an 8-week washout period. A flexible food-exchange model was used to implement each isoenergetic high-fat, high-dairy diet (38% of total energy intake (%TE) total fat): control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA). RESULTS: Following the modified diet, there was a smaller increase in SFA (17.2%TE vs. 19.1%TE; p < 0.001) and greater increase in MUFA intake (15.4%TE vs. 11.8%TE; p < 0.0001) when compared with the control. PL-FA analysis revealed lower total SFAs (p = 0.006), higher total cis-MUFAs and trans-MUFAs (both p < 0.0001) following the modified diet. CONCLUSION: The food-exchange model was successfully used to achieve RESET dietary targets by partial replacement of SFAs with MUFAs in dairy products, a finding reflected in the PL-FA profile and indicative of objective dietary compliance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02089035 , date 05-01-2014.

Consumer acceptance of dairy products with a saturated fatty acid-reduced, monounsaturated fatty acid-enriched content.

Agriculture-based reformulation initiatives, including oleic acid-rich lipid supplementation of the dairy cow diet, provide a novel means for reducing intake of saturated fatty acids (SFA) at a population level. In a blinded manner, this study evaluated the consumer acceptance of SFA-reduced, monounsaturated fatty acid-enriched (modified) milk, Cheddar cheese, and butter when compared with control and commercially available comparative samples. The effect of providing nutritional information about the modified cheese was also evaluated. Consumers (n = 115) rated samples for overall liking (appearance, flavor, and texture) using 9-point hedonic scales. Although no significant differences were found between the milk samples, the modified cheese was liked significantly less than a regular-fat commercial alternative for overall liking and liking of specific modalities and had a lower liking of texture score compared with the control cheese. The provision of health information significantly increased the overall liking of the modified cheese compared with tasting the same sample in a blinded manner. Significant differences were evident between the butter samples for overall liking and modalities of liking; all of the samples were significantly more liked than the commercial butter and sunflower oil spread. In conclusion, this study illustrated that consumer acceptance of SFA-reduced, monounsaturated fatty acid-enriched dairy products was dependent on product type. Future research should consider how optimization of the textural properties of fatty acid-modified (and fat-reduced) cheese might enhance consumer acceptance of this product.

Influence of ruminal methane on digesta retention and digestive physiology in non-lactating dairy cattle.

Enteric methane (CH4) production is a side-effect of herbivore digestion, but it is unknown whether CH4 itself influences digestive physiology. We investigated the effect of adding CH4 to, or reducing it in, the reticulorumen (RR) in a 4×4 Latin square experiment with rumen-fistulated, non-lactating cows, with four treatments: (i) control, (ii) insufflation of CH4 (iCH4), (iii) N via rumen fistula, (iv) reduction of CH4 via administration of bromochloromethane (BCM). DM intake (DMI), apparent total tract digestibility, digesta mean retention times (MRT), rumen motility and chewing activity, spot breath CH4 emission (CH4exhal, litre/kg DMI) as well as CH4 dissolved in rumen fluid (CH4RRf, µg/ml) were measured. Data were analysed using mixed models, including treatment (or, alternatively, CH4exhal or CH4RRf) and DMI relative to body mass0·85 (rDMI) as covariates. rDMI was the lowest on the BCM treatment. CH4exhal was highest for iCH4 and lowest for BCM treatments, whereas only BCM affected (reduced) CH4RRf. After adjusting for rDMI, CH4RRf had a negative association with MRT in the gastrointestinal tract but not in the RR, and negative associations with fibre digestibility and measures of rumination activity. Adjusting for rDMI, CH4exhal had additionally a negative association with particle MRT in the RR and a positive association with rumen motility. Thus, higher rumen levels of CH4 (CH4exhal or CH4RRf) were associated with shorter MRT and increased motility. These findings are tentatively interpreted as a feedback mechanism in the ruminant digestive tract that aims at mitigating CH4 losses by shortening MRT at higher CH4.

The effect of Asparagopsis taxiformis, Ascophyllum nodosum, and Fucus vesiculosus on ruminal methanogenesis and metagenomic functional profiles in vitro.

The ruminant-microorganism symbiosis is unique by providing high-quality food from fibrous materials but also contributes to the production of one of the most potent greenhouse gases-methane. Mitigating methanogenesis in ruminants has been a focus of interest in the past decades. One of the promising strategies to combat methane production is the use of feed supplements, such as seaweeds, that might mitigate methanogenesis via microbiome modulation and direct chemical inhibition. We conducted in vitro investigations of the effect of three seaweeds (Ascophyllum nodosum, Asparagopsis taxiformis, and Fucus vesiculosus) harvested at different locations (Iceland, Scotland, and Portugal) on methane production. We applied metataxonomics (16S rRNA gene amplicons) and metagenomics (shotgun) methods to uncover the interplay between the microbiome's taxonomical and functional states, methanogenesis rates, and seaweed supplementations. Methane concentration was reduced by A. nodosum and F. vesiculosus, both harvested in Scotland and A. taxiformis, with the greatest effect of the latter. A. taxiformis acted through the reduction of archaea-to-bacteria ratios but not eukaryotes-to-bacteria. Moreover, A. taxiformis application was accompanied by shifts in both taxonomic and functional profiles of the microbial communities, decreasing not only archaeal ratios but also abundances of methanogenesis-associated functions. Methanobrevibacter "SGMT" (M. smithii, M. gottschalkii, M. millerae or M. thaueri; high methane yield) to "RO" (M. ruminantium and M. olleyae; low methane yield) clades ratios were also decreased, indicating that A. taxiformis application favored Methanobrevibacter species that produce less methane. Most of the functions directly involved in methanogenesis were less abundant, while the abundances of the small subset of functions that participate in methane assimilation were increased. IMPORTANCE: The application of A. taxiformis significantly reduced methane production in vitro. We showed that this reduction was linked to changes in microbial function profiles, the decline in the overall archaeal community counts, and shifts in ratios of Methanobrevibacter "SGMT" and "RO" clades. A. nodosum and F. vesiculosus, obtained from Scotland, also decreased methane concentration in the total gas, while the same seaweed species from Iceland did not.

Transfer of polychlorinated, polybrominated and mixed-halogenated dioxins, furans and biphenyls, polychlorinated naphthalenes and alkanes, polycyclic aromatic hydrocarbons and chlorobenzenes to the milk of dairy cattle from controlled ingestion of industrial and municipal bioresources recycled to agricultural land.

Recycled bioresources (biosolids, compost-like-output, meat and bonemeal ash, poultry litter ash, paper sludge ash) were added to the feed of dairy cattle to simulate incidental ingestion from agricultural utilisation, to investigate the transfer of organic contaminants from the ingested materials to milk. The bioresources were blended with a loamy sand soil at agronomic rates to simulate a single application to land, which was added to the diet at 5 % of the total intake on a dry matter (DM) basis. Biosolids, and control treatments consisting of unamended soil, were also added directly to the feed at 5 % DM. The cattle were fed the bioresource amended diets for a target period of three to four weeks, depending on material, and monitoring continued for four weeks after treatment withdrawal. Milk samples were taken weekly with chemical analysis of selected samples for a range of organic contaminants including: polychlorinated, polybrominated and mixed-halogenated dioxins, furans and biphenyls, polychlorinated naphthalenes and alkanes (often called chlorinated paraffins), polycyclic aromatic hydrocarbons and chlorobenzenes. No statistically significant additional transfer of organic contaminants to the milk was detected due to the relatively low levels of contaminants present when the bioresources were incorporated with soil at agronomic rates. However, direct biosolids ingestion by cattle significantly increased the transfer of contaminants to milk in comparison to control animals. Although present in larger concentrations in biosolids than their chlorinated counterparts, the carry over rates and bioconcentration factors of brominated dioxins and furans were considerably smaller. Direct ingestion of biosolids resulted in most contaminants approaching, but not always completely reaching, steady state concentrations within the treatment feeding period, however, concentrations generally declined to control values within four-weeks after withdrawing the biosolids-amended diet.

Mineral concentrations in milk from cows fed seaweed (Saccharina latissima) under different basal protein supplementation.

Sixteen multiparous Holstein cows in four blocks of 4 × 4 Latin square over 4-week experimental periods were used to study the effects of seaweed (Saccharina latissima) supplement (with/without) and protein source (rapeseed meal (RSM)/wheat distiller's grain (WDG)) on milk mineral concentrations. Dietary treatments did not affect milk production and basic composition. Feeding seaweed slightly decreased milk Ca and Cu concentrations; whilst increased (by 3.3-fold) milk iodine (I) concentration, due to a higher dietary I supply. Substitution of WDG with RSM increased feed-to-milk transfer of Ca, Na, and Se and decreased that of Mg, P, Fe, and Mn; but only reduced milk Mn and I concentrations (the latter by 27 % as a potential result of increased glucosinolate intake). Seaweed supplement can improve milk I content when cows' I supply/availability is limited, but care should be taken to avoid excess milk I contents that may pose nutritional risks for young children.

High-resolution isotope-dilution mass spectrometry using metabolism of isotope-labeled compounds: application to drug metabolites.

RATIONALE: Herein we describe a generic quantitative method using high-resolution, isotope-dilution (HRID) metabolism of isotope-labeled compounds and apply it to the analysis of drug metabolites (DMs) in human plasma. Metabolites (drug) in Safety Testing (MIST) application was one goal. METHODS: Testosterone (T) and diclofenac (D) were chosen for mass defect characteristics. T, [(14)C]T, [(13)C(3)]T, D, [(14)C]D, and [(13)C(6)]D were metabolized separately in vitro to produce test metabolites. Liquid chromatography/radioactivity monitoring (LC/RAM) analysis was used to determine the concentration of the test metabolites in the incubates. The incubates containing 6ß-hydroxy-T (6ßHT), [(13)C(3)]6ßHT, 4'-hydroxy-D (4'HD) and [(13)C(6)]4'HD were used to make standard curves. Plasma samples were prepared by 'dilute-and-shoot' and analyzed by LC/MS using SCIEX 5000 and Thermo Orbitrap instrumentation. RESULTS: Human hepatic microsomes and the S9 fraction produced between 2-6 µM ß-hydroxy-T and 4'-hydroxy-D at 60 min starting with 10 µM parent drug as determined by LC/RAM. It was assumed that the amounts of [(13)C(3)]6ßHT and [(13)C(6)]4'HD produced were similar. Dilutions and standard curves were prepared in human plasma. Analysis of the DMs by LC/MS/MS and LC/HRMS exhibited linear responses over a useable range. CONCLUSIONS: HRID with metabolism of an isotope-labeled compound reduces the number of analytical variables considerably. Metabolism of the parent drug to DMs represents a simpler alternative quantitative method compared with traditional approaches. The method will have useful applications for evaluating MIST situations.

Dissipation of glyphosate and aminomethylphosphonic acid in water and sediment of two Canadian prairie wetlands.

Glyphosate [N-(phosphonomethyl)glycine] is the active ingredient of several herbicide products first registered for use in 1974 under the tradename Roundup. The use of glyphosate-based herbicides has increased dramatically over the last two decades particularly in association with the adoption of glyphosate-tolerant crops. Glyphosate has been detected in a range of surface waters but this is the first study to monitor its fate in prairie wetlands situated in agricultural fields. An ephemeral wetland (E) and a semi-permanent wetland (SP) were each divided into halves using a polyvinyl curtain. One half of each wetland was fortified with glyphosate with the added mass simulating an accidental direct overspray. Glyphosate dissipated rapidly in the water column of the two prairie wetlands studied (DT(50) values of 1.3 and 4.8 d) which may effectively reduce the impact of exposure of aquatic biota to the herbicide. Degradation of glyphosate to its major metabolite aminomethylphosphonic acid (AMPA) and sorption of the herbicide to bottom sediment were more important pathways for the dissipation of glyphosate from the water column than movement of the herbicide with infiltrating water. Presently, we are not aware of any Canadian guidelines for glyphosate residues in sediment of aquatic ecosystems. Since a substantial portion of glyphosate entering prairie wetlands will become associated with bottom sediments, particularly in ephemeral wetlands, guidelines would need to be developed to assess the protection of organisms that spend all or part of their lifecycle in sediment.

Kidnapping intergroup young: an alternative strategy to maintain group size in the group-living pied babbler (Turdoides bicolor).

Both inter- and intragroup interactions can be important influences on behaviour, yet to date most research focuses on intragroup interactions. Here, we describe a hitherto relatively unknown behaviour that results from intergroup interaction in the cooperative breeding pied babbler: kidnapping. Kidnapping can result in the permanent removal of young from their natal group. Since raising young requires energetic investment and abductees are usually unrelated to their kidnappers, there appears no apparent evolutionary advantage to kidnapping. However, kidnapping may be beneficial in species where group size is a critically limiting factor (e.g. for reproductive success or territory defence). We found kidnapping was a highly predictable event in pied babblers: primarily groups that fail to raise their own young kidnap the young of others, and we show this to be the theoretical expectation in a model that predicts kidnapping to be facultative, only occurring in those cases where an additional group member has sufficient positive impact on group survival to compensate for the increase in reproductive competition. In babblers, groups that failed to raise young were also more likely to accept extragroup adults (hereafter rovers). Groups that fail to breed may either (i) kidnap intergroup young or (ii) accept rovers as an alternative strategy to maintain or increase group size. This article is part of the theme issue 'Intergroup conflict across taxa'.

Sensitive LC-MS/MS quantification of unconjugated maytansinoid DM4 and its metabolite S-methyl-DM4 in human plasma.

Aim: To report the development and validation of an LC-MS/MS method for the simultaneous determination of unconjugated payload DM4 and its metabolite S-methyl-DM4 in human plasma. Methodology: A workflow of protein precipitation followed by reduction and solid phase extraction was employed to remove antibody-maytansinoid conjugates from plasma matrix, release DM4 from endogenous conjugates, and generate a clean sample extract for analysis, respectively. Sodium adduct species of both analytes were selected for multiple reaction monitoring to meet the assay sensitivity requirement in liquid chromatography with tandem mass spectrometry. Conclusion: The method was fully validated for a dynamic range of 0.100-50.0 ng/ml for both analytes along with desired stability and acceptable incurred sample reanalysis.

Methane Reduction Potential of Brown Seaweeds and Their Influence on Nutrient Degradation and Microbiota Composition in a Rumen Simulation Technique.

This study aimed to investigate the effects of two brown Icelandic seaweed samples (Ascophyllum nodosum and Fucus vesiculosus) on in vitro methane production, nutrient degradation, and microbiota composition. A total mixed ration (TMR) was incubated alone as control or together with each seaweed at two inclusion levels (2.5 and 5.0% on a dry matter basis) in a long-term rumen simulation technique (Rusitec) experiment. The incubation period lasted 14 days, with 7 days of adaptation and sampling. The methane concentration of total gas produced was decreased at the 5% inclusion level of A. nodosum and F. vesiculosus by 8.9 and 3.6%, respectively (P < 0.001). The total gas production was reduced by all seaweeds, with a greater reduction for the 5% seaweed inclusion level (P < 0.001). Feed nutrient degradation and the production of volatile fatty acids and ammonia in the effluent were also reduced, mostly with a bigger effect for the 5% inclusion level of both seaweeds, indicating a reduced overall fermentation (all P ≤ 0.001). Microbiota composition was analyzed by sequencing 16S rRNA amplicons from the rumen content of the donor cows, fermenter liquid and effluent at days 7 and 13, and feed residues at day 13. Relative abundances of the most abundant methanogens varied between the rumen fluid used for the start of incubation and the samples taken at day 7, as well as between days 7 and 13 in both fermenter liquid and effluent (P < 0.05). According to the differential abundance analysis with q2-ALDEx2, in effluent and fermenter liquid samples, archaeal and bacterial amplicon sequence variants were separated into two groups (P < 0.05). One was more abundant in samples taken from the treatment without seaweed supplementation, while the other one prevailed in seaweed supplemented treatments. This group also showed a dose-dependent response to seaweed inclusion, with a greater number of differentially abundant members between a 5% inclusion level and unsupplemented samples than between a 2.5% inclusion level and TMR. Although supplementation of both seaweeds at a 5% inclusion level decreased methane concentration in the total gas due to the high iodine content in the seaweeds tested, the application of practical feeding should be done with caution.

Effect of fat-reformulated dairy food consumption on postprandial flow-mediated dilatation and cardiometabolic risk biomarkers compared with conventional dairy: a randomized controlled trial.

BACKGROUND: Longer-term consumption of SFA-reduced, MUFA-enriched dairy products has been reported to improve fasting flow-mediated dilatation (FMD). Yet, their impact on endothelial function in the postprandial state warrants investigation. OBJECTIVES: The aim was to compare the impact of a fatty acid (FA) modified with a conventional (control) dairy diet on the postprandial %FMD (primary outcome) and systemic cardiometabolic responses to representative meals, and retrospectively explore whether treatment effects differ by apolipoprotein E (APOE) or endothelial NO synthase (eNOS) Glu298Asp gene polymorphisms. METHODS: In a crossover-design randomized controlled study, 52 adults with moderate cardiovascular disease risk consumed dairy products [38% of total energy intake (%TE) from fat: FA-modified (target: 16%TE SFAs; 14%TE MUFAs) or control (19%TE SFAs; 11%TE MUFAs)] for 12 wk, separated by an 8-wk washout. Blood sampling and FMD measurements (0-480 min) were performed pre- and postintervention after sequential mixed meals that were representative of the assigned dairy diets (0 min, ∼50 g fat; 330 min, ∼30 g fat). RESULTS: Relative to preintervention (∆), the FA-modified dairy diet and meals (treatment) attenuated the increase in the incremental AUC (iAUC), but not AUC, for the %FMD response observed with the conventional treatment (-135 ± 69% vs. +199 ± 82% × min; P = 0.005). The ∆ iAUC, but not AUC, for the apoB response decreased after the FA-modified treatment yet increased after the conventional treatment (-4 ± 3 vs. +3 ± 3 mg/mL × min; P = 0.004). The ∆ iAUC decreased for plasma total SFAs (P = 0.003) and trans 18:1 (P < 0.0001) and increased for cis-MUFAs (P < 0.0001) following the conventional relative to the FA-modified treatment. No treatment × APOE or eNOS genotype interactions were evident for any outcome. CONCLUSIONS: This study provides novel insights into the longer-term effects of FA-modified dairy food consumption on postprandial cardiometabolic responses.

Insights into the complexity of presentation and management of patients: the Sport and Exercise Physician's perspective.

OBJECTIVES: Sport and Exercise Physicians represent a relatively new specialty focusing on exercise in complex diseases including musculoskeletal diseases. Our objective was to describe the characteristics, type and complexity of patient presentations, their management strategies and referral information in Australian practice. METHODS: A cross-sectional study including a cohort of 11 senior Sport and Exercise Physicians in Australia studied all new patient consultations within an 8-week period. Data were analysed relating to presentation, referral source, follow-up referrals, and patient management strategies. RESULTS: Data from 419 patients were recorded. The majority, 97% (n=406), had musculoskeletal conditions, 53% (n=222) had one or more associated comorbidities and 47% (n=195) had ongoing symptoms for >12 months. Most patients, 82% (n=355), were referred by general practitioners. Prior consultations included physiotherapy 72% (n=301) and orthopaedic 20% (n=85). A multidisciplinary network of referrals from Sport and Exercise Physicians was observed, including 210 referrals to 9 allied health specialities and 61 referrals to 17 medical specialities. Over 74% (n=311) of patients received exercise-based intervention as part of the treatment plan, including 57% (n=240) physician managed exercise interventions. CONCLUSION: Our work shines a light on the nature and complexity of the role of Sport and Exercise Physicians in an Australian practice context. Findings will assist in implementing measures to promote patient care at the community level in managing musculoskeletal conditions. Sport and exercise medicine stakeholders and government policy makers can use this information in developing appropriate programmes to support patients and create integrated sport and exercise medicine services for the community.