Search Results (42)

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical–pathological changes associated with EBOV disease in this model. Full article

There is evidence of perturbed microbial and host processes in the gastrointestinal tract of individuals with functional gastrointestinal disorders (FGID) compared to healthy controls. The faecal metabolome provides insight into the metabolic processes localised to the intestinal tract, while the plasma metabolome highlights the overall perturbances of host and/or microbial responses. This study profiled the faecal (n = 221) and plasma (n = 206) metabolomes of individuals with functional constipation (FC), constipation-predominant irritable bowel syndrome (IBS-C), functional diarrhoea (FD), diarrhoea-predominant IBS (IBS-D) and healthy controls (identified using the Rome Criteria IV) using multimodal LC-MS technologies. Discriminant analysis separated patients with the ‘all constipation’ group (FC and IBS-C) from the healthy control group and ‘all diarrhoea’ group (FD and IBS-D) from the healthy control group in both sample types. In plasma, almost all multimodal metabolite analyses separated the ‘all constipation’ or ‘all diarrhoea’ group from the healthy controls, and the IBS-C or IBS-D group from the healthy control group. Plasma phospholipids and metabolites linked to several amino acid and nucleoside pathways differed (p < 0.05) between healthy controls and IBS-C. In contrast, metabolites involved in bile acid and amino acid metabolism were the key differentiating classes in the plasma of subjects with IBS-D from healthy controls. Faecal lipids, particularly ceramides, diglycerides, and triglycerides, varied (p < 0.05) between healthy controls and the ‘all constipation’ group and between healthy controls and ‘all diarrhoea’ group. The faecal and plasma metabolomes showed perturbations between constipation, diarrhoea and healthy control groups that may reflect processes and mechanisms linked to FGIDs. Full article

Background: Age-related changes can lead to dietary insufficiency in older adults. The inclusion of high-quality, nutrient-dense foods such as ruminant milks can significantly improve health outcomes. However, many older adults worldwide do not meet daily milk intake recommendations because of digestive discomfort and health concerns. Ovine and caprine milks are increasingly popular for their perceived digestive and nutritional benefits. While preclinical studies suggest differences in milk digestion, human studies investigating acute postprandial responses remain inconclusive, and the impacts of sustained milk consumption remain uncertain. Objectives: Hence, we present a randomized controlled trial investigating how the sustained consumption of bovine, caprine, or ovine milk influences digestion, nutrition, and metabolism in older women. Methods: A total of 165 healthy older women were randomized to receive bovine, caprine, or ovine milk, or no milk, twice daily for 12 weeks. The primary outcome is the impact of milk consumption on digestive comfort assessed via the Gastrointestinal Syndrome Rating Scale (GSRS). Secondary outcomes include changes in nutrient intake, plasma amino acid and lipid appearance, bowel habits, the gut microbiota, cardiometabolic health, physical function, physical activity, sleep, mood, sensory perception, and emotional response. Conclusions: The findings could inform dietary recommendations for older women and facilitate the development of targeted functional food products. Full article

The global dairy market has been increasingly diversified with more dairy product offerings of milk products from different animal species. Meanwhile, milk powders remain the main exported dairy product format due to their ease of transportation. In this work, we studied the structural changes, protein hydrolysis and nutrient delivery during dynamic gastric digestion and small intestinal digestion of cow, goat and sheep milk reconstituted from commercial whole milk powders. The results show that the reconstituted milks digest similarly to processed fresh milk. The digestion behaviors of the three reconstituted ruminant milks are broadly similar (gastric coagulation, kinetics of gastric emptying of protein and fat and the high digestibility in the small intestine) with some differences, which are likely contributed by the processing history of the milk powders. The delivery of individual amino acids to the small intestine differed between the early and late stages of gastric digestion, which were primarily affected by the abundance of amino acids in caseins and whey proteins but also by the difference between milk types associated with their gastric coagulation behaviors. This work showed that powdered milk is similar to fresh processed milk in digestion behavior, and the inherent differences between ruminant milks can be modified by processing treatments. Full article

Kiwifruit (KF) has shown neuroprotective potential in cell-based and rodent models by augmenting the capacity of endogenous antioxidant systems. This study aimed to determine whether KF consumption modulates the antioxidant capacity of plasma and brain tissue in growing pigs. Eighteen male pigs were divided equally into three groups: (1) bread, (2) bread + Actinidia deliciosa cv. ‘Hayward’ (green-fleshed), and (3) bread + A. chinensis cv. ‘Hort16A’ (yellow-fleshed). Following consumption of the diets for eight days, plasma and brain tissue (brain stem, corpus striatum, hippocampus, and prefrontal cortex) were collected and measured for biomarkers of antioxidant capacity, enzyme activity, and protein expression assessments. Green KF significantly increased ferric-reducing antioxidant potential (FRAP) in plasma and all brain regions compared with the bread-only diet. Gold KF increased plasma ascorbate concentration and trended towards reducing acetylcholinesterase activity in the brain compared with the bread-only diet. Pearson correlation analysis revealed a significant positive correlation between FRAP in the brain stem, prefrontal cortex, and hippocampus with the total polyphenol concentration of dietary interventions. These findings provide exploratory evidence for the benefits of KF constituents in augmenting the brain’s antioxidant capacity that may support neurological homeostasis during oxidative stress. Full article

An increasing number of dairy farmers in New Zealand (NZ) have adopted a once-a-day (OAD) milking production system, and little is known about the impact of this production system on milk protein composition. The objective of this study was to evaluate the effect of OAD milking on the protein composition in milk from individual cows. Milk was sampled in early, mid-, and late lactation from cows kept at Massey University farms Dairy No. 1 (OAD milking) and Dairy No. 4 (TAD milking) in Palmerston North, NZ. The yields of total milk and milk solids, the proximate composition, and the protein composition were determined. Results showed that OAD milking yielded less milk and milk solids than TAD milking. However, no significant differences in protein, fat, and lactose contents were found. While the proportions of total casein (CN), total whey proteins, αs1-CN, β-CN, and β-lactoglobulin were not affected by the milking frequency, milk from a OAD milking system contained higher proportions of αs2-CN and κ-CN and lower proportions of α-lactalbumin. These proteins also changed differently throughout the milking season in a OAD milking system than in a TAD milking system. These changes in the protein composition of the milk observed in a OAD milking system could have implications for its processing properties and product quality. Full article

This study investigated whether heat treatments (raw, 63 °C for 30 min, and 85 °C for 5 min) affect protein hydrolysis by endogenous enzymes in the milk of ruminants (bovine, ovine, and caprine) using a self-digestion model. Self-digestion consisted of the incubation for six hours at 37 °C of the ruminants’ milk. Free amino group concentration was measured by the o-phthaldialdehyde method, and peptide sequences were identified by chromatography-mass spectrometry. Results showed that heat treatments prior to self-digestion decreased the free NH₂ by 59% in bovine milk heated at 85 °C/5 min, and by 44 and 53% in caprine milk heated at 63 °C/30 min and 85 °C/5 min, respectively. However, after self-digestion, only new free amino groups were observed for the raw and heated at 63 °C/30 min milk. β-Casein was the most cleaved protein in the raw and heated at 63 °C/30 min bovine milk. A similar trend was observed in raw ovine and caprine milk. Self-digestion increased 6.8-fold the potential antithrombin peptides in the bovine milk heated at 63 °C/30 min. Enhancing bioactive peptide abundance through self-digestion has potential applications in the industry for functional products. Overall, heat treatments affected the free amino groups according to the species and heat treatment applied, which was reflected in the varying degrees of cleaved peptide bonds and peptides released during self-digestion. Full article

Milk structural assemblies (e.g., casein micelles) occur naturally and can be altered during processing, and this may influence the milk’s nutritional properties. Heat treatment of dairy ensures microbiological safety and extends shelf-life. Both pasteurisation and ultra-high temperature (UHT) processing are known to alter natural structural assemblies, but despite widespread use, only four human studies have addressed how heat treatment affects nutrient delivery. In vitro, animal, and human models have all shown more rapid nutrient release or appearance from UHT vs. pasteurised milk, with altered gastric emptying rate proposed as a mechanism. We hypothesised that differences in bovine milk structural assemblies arising from different processing methods would speed up gastric emptying and nutrient delivery following consumption of UHT relative to pasteurised milk. A randomised double-blind crossover trial assessed gastric emptying rate (using magnetic resonance imaging measuring gastric content volume) over 3 h and plasma amino acid appearance (using ultra-performance liquid chromatography) over 5 h following 500 mL of each milk in healthy women (n = 20). Gastric electrical activity was measured using body surface gastric mapping, and abdominal distension using stretch sensors. The time to empty 25% of the stomach contents was greater following UHT vs. pasteurised milk (45 ± 4 vs. 33 ± 4 min p < 0.05). While gastric content remained greater for longer following UHT milk, the incremental area under the curve of plasma essential amino acids was greater than pasteurised milk (55324 ± 3809 vs. 36598 ± 5673 μmol·min·L⁻¹ p < 0.05). The greater amino acid appearance following UHT milk aligns with more rapid release of proteins from the gastric curd observed in vitro, yet the greater gastric content volume implies gastric content composition (e.g., solid vs. liquid) is an important determinant of nutrient release. Dairy processing using different heat treatments, which induced structural modifications, impacted gastric emptying and plasma amino acid appearance, with implications for appetite regulation and nutrient utilisation for metabolism. Full article

Amino acids are important in several biochemical pathways as precursors to neurotransmitters which impact biological processes previously linked to functional gastrointestinal disorders (FGIDs). Dietary protein consumption, metabolic host processes, and the gut microbiome can influence the plasma concentration of amino acids and neurotransmitters, and their uptake by tissues. The aim of this analysis was to quantify 19 proteogenic and 4 non-proteogenic amino acids and 19 neurotransmitters (including precursors and catabolites, herein referred to as neurotransmitters) to ascertain if their circulating concentrations differed between healthy participants and those with FGIDs. Plasma proteogenic and non-proteogenic amino acids and neurotransmitters were measured using ultra-performance liquid chromatography and liquid chromatography–mass spectrometry, respectively, from 165 participants (Rome IV: irritable bowel syndrome (IBS-constipation, IBS-diarrhea), functional constipation, functional diarrhea, and healthy controls). There were significant differences (p < 0.05) in pairwise comparisons between healthy controls and specific FGID groups for branched-chain amino acids (BCAAs), ornithine, and alpha-aminobutyric acid. No other significant differences were observed for the neurotransmitters or any other amino acids analyzed. Multivariate and bivariate correlation analyses between proteogenic and non-proteogenic amino acids and neurotransmitters for constipation (constipation (IBS-C and functional constipation) and phenotypes diarrhea (IBS-D and functional diarrhea)) and healthy controls suggested that associations between BCAAs, 5-hydroxytryptophan, and kynurenine in combination with tyrosine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylacetic acid and associations with gamma-aminobutyric acid, glutamate, asparagine, and serine are likely disrupted in FGID phenotypes. In conclusion, although correlations were evident between some proteogenic and non-proteogenic amino acids and neurotransmitters, the results showed minor concentration differences in plasma proteogenic and non-proteogenic amino acids, amino acid-derived metabolites, and neurotransmitters between FGID phenotypes and healthy controls. Full article

Chronic constipation is highly prevalent worldwide and may be managed with two green or three gold kiwifruit daily. It is unknown whether a smaller standard serve of gold kiwifruit (two daily) is as effective in constipation management. The study aimed to improve chronic constipation with two gold kiwifruit and psyllium in lieu of a placebo daily over four weeks. Adult participants (18–65 years) with functional constipation (FC, n = 11), constipation-predominant irritable bowel syndrome (IBS-C, n = 13), and healthy controls (n = 32) were block-randomized to the treatment order: gold kiwifruit (2/day) or psyllium (fiber-matched, 7.5 g/day) for four weeks, followed by four weeks washout before crossover. Outcomes included alterations of Gastrointestinal Symptom Rating Scale (GSRS) domains and weekly complete spontaneous bowel movements (CSBM) as part of a larger study. Both interventions reduced GSRS constipation domain scores in all subjects compared to baseline values (p = 0.004). All participants reported significantly more weekly CSBM (p = 0.014). Two gold kiwifruit decreased straining (p = 0.021). Two gold kiwifruit daily are as effective as fiber-matched psyllium in treating constipation in adults and should be considered as a treatment option. Full article

The milk fat globule membrane (MFGM) appears to play an important role in infant neurocognitive development; however, its mechanism(s) of action remains unclear. This study aimed to investigate the role of a dietary MFGM supplement on the lipid profiles of different neonatal brain regions. Ten-day-old male piglets (4–5 kg) were fed unsupplemented infant formula (control, n = 7) or an infant formula supplemented with low (4%) or high (8%) levels of MFGM (n = 8 each) daily for 21 days. Piglets were then euthanized, and brain tissues were sectioned. Untargeted liquid chromatography-mass spectrometry lipidomics was performed on the cerebellum, hippocampus, prefrontal cortex, and the rest of the brain. The analyses identified 271 and 171 lipids using positive and negative ionization modes, respectively, spanning 16 different lipid classes. MFGM consumption did not significantly alter the lipidome in most brain regions, regardless of dose, compared to the control infant formula. However, 16 triacylglyceride species were increased in the hippocampus (t-test, p-value < 0.05) of the high-supplemented piglets. Most lipids (262 (96.7%) and 160 (93.6%), respectively) differed significantly between different brain regions (ANOVA, false discovery rate corrected p-value < 0.05) independent of diet. Thus, this study highlighted that dietary MFGM altered lipid abundance in the hippocampus and detected large differences in lipid profiles between neonatal piglet brain regions. Full article

Emerging evidence suggests that consuming two New Zealand green kiwifruit (Actinidia deliciosa cv. Hayward) daily for four weeks may improve sleep quality. The subjective and objective acute responses and underlying physiological responses are unknown. The current study aimed to investigate the acute effects of fresh and dried green kiwifruit compared to a water control on sleep quality and mood measures, and concentration of urinary serotonin and melatonin metabolites. In a randomised, single-blind crossover study, 24 men (age: 29 ± 1 years old, body mass index (BMI): 24 ± 1 kg/m²) with either poor or good sleep quality were recruited. They consumed an evening standardised meal with one of three treatments; (i) two fresh green kiwifruit (without skin); (ii) 32 g dried green kiwifruit powder (including the skin; equivalent to two fresh fruit) mixed with water; or (iii) a water control, on three separate nights separated by 6–8 days. The subjective (Leeds Sleep Evaluation Questionnaire, Stanford sleepiness scale) and objective (actigraphy) sleep quality, mood (profile of mood states), and 5-Hydroxyindoleacetic acid [5-HIAA] and 6-Sulfatoxymelatonin concentrations in morning urine were determined. In poor sleepers, ease of awakening improved 24% after dried kiwifruit (p = 0.005) and trended to improve after fresh kiwifruit (p = 0.052), compared to the control. Good sleepers trended towards improved ratings of getting to sleep with fresh kiwifruit (p = 0.053) and no improvement after dried (p > 0.1) compared to control. Regardless of sleeper type, compared to control, both fresh and dried kiwifruit treatments trended (p < 0.1) toward improved esteem and total mood disturbances. Furthermore, after dried kiwifruit, ratings of morning alertness (p = 0.012), behaviour following wakening and vigour were higher (p < 0.05) compared to control. Both kiwifruit treatments increased urinary concentrations of the serotonin metabolite 5-HIAA (+1.56 ± 0.4 ng/g (fresh) p = 0.001, +1.30 ± 0.4 ng/g (dried) p = 0.004) compared to the control (4.32 ± 0.4 ng/g). This study is the first to demonstrate that a single evening intake of kiwifruit improves aspects of sleep quality and mood. Full article

This study reports the role played by the mutation status of Uveal Melanoma (UM) in relation to hepatic metastatic patterns as seen on imaging modalities. Radiological images were obtained from 123 patients treated at the Erasmus Medical Center Rotterdam or the Rotterdam Eye Hospital. Radiological images were derived from either computed tomography or magnetic resonance imaging. Hepatic metastatic patterns were classified by counting the number of metastases found in the liver. Miliary metastatic pattern (innumerable small metastases in the entire liver) was analyzed separately. Mutation status was determined in 85 patients. Median disease-free survival (DFS) and survival with metastases differed significantly between each of the metastatic patterns (respectively, p = 0.009, p < 0.001), both in favor of patients with less hepatic metastases. The mutation status of the primary tumor was not correlated with any hepatic tumor profiles (p = 0.296). Of the patients who had a solitary metastasis (n = 18), 11 originated from a primary BAP1-mutated tumors and one from a primary SF3B1-mutated tumor. Of the patients who had a miliary metastasis pattern (n = 24), 17 had a primary BAP1-mutated tumor and two had a primary SF3B1-mutated tumor. Chromosome 8p loss was significantly more in patients with more metastases (p = 0.045). Moreover, the primary UMs of patients with miliary metastases harbored more chromosome 8p and 1p loss, compared to patients with single solitary metastasis (p = 0.035 and p = 0.026, respectively). In conclusion, our study shows that there is an inverse correlation of the number of metastasis with the DFS and metastasized survival, indicating separate growth patterns. We also revealed that the number and type of metastases is irrelevant to the prognostic mutation status of the tumor, showing that both BAP1- and SF3B1-mutated UM can result in solitary and miliary metastases, indicating that other processes lay ground to the different metastatic patterns. Full article

A high protein intake at old age is important for muscle protein synthesis, however, this could also trigger protein oxidation with the potential risk for DNA damage. The aim of this study was to investigate whether an increased protein intake at recommended level or well above would affect DNA damage or change levels of reduced (GSH) and oxidised glutathione (GSSG) in community-dwelling elderly subjects. These analyses were performed in two randomized intervention studies, in Austria and in New Zealand. In both randomized control trials, the mean protein intake was increased with whole foods, in the New Zealand study (n = 29 males, 74.2 ± 3.6 years) to 1.7 g/kg body weight/d (10 weeks intervention; p < 0.001)) in the Austrian study (n = 119 males and females, 72.9 ± 4.8 years) to 1.54 g/kg body weight/d (6 weeks intervention; p < 0.001)). In both studies, single and double strand breaks and as formamidopyrimidine—DNA glycosylase-sensitive sites were investigated in peripheral blood mononuclear cells or whole blood. Further, resistance to H₂O₂ induced DNA damage, GSH, GSSG and CRP were measured. Increased dietary protein intake did not impact on DNA damage markers and GSH/GSSG levels. A seasonal-based time effect (p < 0.05), which led to a decrease in DNA damage and GSH was observed in the Austrian study. Therefore, increasing the protein intake to more than 20% of the total energy intake in community-dwelling seniors in Austria and New Zealand did not increase measures of DNA damage, change glutathione status or elevate plasma CRP. Full article

Bile acids are metabolites involved in nutrient absorption and signaling with levels influenced by dietary intake, metabolic processes, and the gut microbiome. We aimed to quantify 23 bile acids in fecal samples to ascertain if concentrations differed between healthy participants and those with functional gut disorders. Fecal bile acids were measured using liquid chromatography-mass spectrometry (LC-MS) in the COMFORT (The Christchurch IBS cohort to investigate mechanisms for gut relief and improved transit) cohort of 250 participants with Rome IV IBS (IBS-constipation (C), IBS-diarrhea (D), IBS-mixed (M)), functional gut disorders (functional constipation (FC), functional diarrhea (FD)) and healthy controls (FC n = 35, FD n = 13, IBS-C n = 24, IBS-D n = 52, IBS-M n = 29, and control n = 97). Dietary information was recorded to ascertain three-day dietary intake before fecal samples were collected. Fecal bile acid concentrations, predominantly primary bile acids, were significantly different between all functional gut disorder participants and healthy controls (CDCA p = 0.011, CA p = 0.003) and between constipation (FC + IBS-C) and diarrhea (FD + IBS-D) groups (CDCA p = 0.001, CA p = 0.0002). Comparison of bile acids between all functional groups showed four metabolites were significantly different, although analysis of combined groups (FC + IBS-C vs. FD + IBS-D) showed that 10 metabolites were significantly different. The bile acid profiles of FD individuals were similar to those with IBS-D, and likewise, those with FC were similar to IBS-C. Individuals with a diarrhea phenotype (FD + IBS-D) had higher concentrations of bile acids compared to those with constipation (FC + IBS-C). Bile acid metabolites distinguish between individuals with functional gut disorders and healthy controls but are similar in constipation (or diarrhea) whether classified as IBS or not. Full article