Search Results (66)

Background/Objectives: Non-ablative stereotactic body radiation therapy (SBRT) is commonly employed for locally advanced pancreatic cancer (LAPC) using computed tomography-guided radiotherapy (CTgRT) without online adaptive radiation therapy (oART). The safe delivery of ablative SBRT has been demonstrated using stereotactic magnetic resonance-guided online adaptive radiation therapy (SMART). We performed an in silico comparison of non-adapted CTgRT versus SMART to better understand the potential benefit of oART for ablative pancreatic SBRT. Methods: We retrospectively evaluated original and daily adapted SMART plans that were previously delivered for 20 consecutive LAPC cases (120 total plans across all patients) treated on a 0.35 T MR-linac prescribed to 50 Gy (gross disease) and 33 Gy (elective sites) simultaneously in five fractions. Six comparative CTgRT plans for each patient (one original, five daily treatment) were retrospectively generated with the same prescribed dose and planning parameters as the SMART plans assuming no oART availability. The impact of daily anatomic changes on CTgRT and SMART plans without oART was evaluated across each treatment day MRI scan acquired for SMART. Results: Ninety percent of cases involved the pancreatic head. No statistically significant differences were seen between CTgRT and SMART with respect to target coverage. Nearly all (96%) fractions planned on either CT or MRI platforms exceeded at least one GI organ at risk (OAR) constraint without oART. Significant differences favoring SMART over non-adaptive CTgRT were observed for the duodenum V35 Gy ≤ 0.5 cc (34.2 vs. 41.9 Gy, p = 0.0035) and duodenum V40 Gy ≤ 0.03 cc (37 vs. 52.5 Gy, p = 0.0006) constraints. Stomach V40 Gy trended towards significance favoring SMART (37 vs. 40.3 Gy, p = 0.057) while no significant differences were seen. Conclusions: This is the first study that quantifies the frequency and extent of GI OAR constraint violations that would occur during ablative five-fraction SBRT using SMART vs. CTgRT. GI OAR constraint violations are expected for most fractions without oART whereas all constraints can be achieved with oART. As such, these data suggest that oART should be required for ablative five-fraction pancreatic SBRT. Full article

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

Effective clinical reasoning is essential for veterinary medical education, particularly in managing complex cases. This review explores strategies for learning clinical reasoning by veterinary medical learners, using a case example of mastitis to illustrate key concepts. Clinical reasoning encompasses cognitive, metacognitive, social, and situational activities, yet the literature on practical applications in veterinary education remains limited. The review discusses various stages of clinical reasoning, including data collection, problem representation, differential diagnosis, and management planning. It emphasizes the importance of integrating client-centered care and iterative evaluation into the clinical decision-making process. Key learning strategies include facilitation in using the domains of clinical reasoning—concepts, data collection, and analysis, taking action, and reflection on encounters. This review highlights best practices such as forward and backward reasoning, reflective practice, and the use of practical examples to enhance learners’ diagnostic accuracy and patient outcomes. The insights provided aim to enhance the training of veterinary learners, ensuring they can navigate day 1 as well as complex cases with improved diagnostic accuracy and patient outcomes. Full article

Individuals living in rural areas often face challenges in accessing healthcare, increasing their risk of poor health outcomes. Farmers, a sub-population in rural areas, are particularly vulnerable to mental health issues and suicide, yet they exhibit low rates of help-seeking behavior. The aim of our study was to develop an in-depth understanding of the issues influencing mental help-seeking among farmers living in rural areas from the perspectives of healthcare providers, as well as to explore the strategies providers use to navigate through these issues to effectively engage with this vulnerable population. Methods: We used a descriptive phenomenological approach to understand healthcare providers’ perspectives, experiences, and approaches to providing mental healthcare to farmer clients in rural areas. Semi-structured interviews were conducted with 21 participants practicing in Canada between March and May 2023. Results: Our analysis yielded five thematic areas: (1) ensuring accessibility, (2) establishing relatability, (3) addressing stoicism and stigma, (4) navigating dual roles, and (5) understanding community trauma. Conclusions: Healthcare service delivery for farmers is multifaceted. This study fills a gap in knowledge by translating these data to inform an evidence-based model and a list of recommendations for implementing agriculturally informed practices in rural areas. Full article

Despite efforts to increase childhood vaccination coverage in the Democratic Republic of the Congo (DRC), approximately 20% of infants have not started their routine immunization schedule (zero-dose). The present study aims to evaluate the relative influence of geospatial access to health facilities and caregiver perceptions of vaccines on the vaccination status of children in rural DRC. Pooled data from two consecutive nationwide immunization surveys conducted in 2022 and 2023 were used. Geographic accessibility was assessed based on travel time from households to their nearest health facility using the AccessMod 5 model. Caregiver attitudes to vaccination were assessed using the survey question “How good do you think vaccines are for your child?” We used logistic regression to assess the relationship between geographic accessibility, caregiver attitudes toward vaccination, and their child’s vaccination status. Geographic accessibility to health facilities was high in rural DRC, with 88% of the population living within an hour’s walk to a health facility. Responding that vaccines are “Bad, Very Bad, or Don’t Know” relative to “Very Good” for children was associated with a many-fold increased odds of a zero-dose status (ORs 69.3 [95%CI: 63.4–75.8]) compared to the odds for those living 60+ min from a health facility, relative to <5 min (1.3 [95%CI: 1.1–1.4]). Similar proportions of the population fell into these two at-risk categories. We did not find evidence of an interaction between caregiver attitude toward vaccination and travel time to care. While geographic access to health facilities is crucial, caregiver demand appears to be a more important driver in improving vaccination rates in rural DRC. 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

Background: High dietary fibre (DF) intake may have beneficial effects on gastrointestinal and brain interactions. Bread is an ideal vehicle to incorporate grain fibre to increase DF content. To date, no studies have explored the association between a habitual intake of bread fortified with unique grain fibre and gastrointestinal symptoms, general wellbeing, and mental health. Objective: To determine whether a four-week intake of bread fortified with unique grain fibre (thrice the amount of DF than control bread) improves subjective gastrointestinal symptoms, general wellbeing, and mental health compared to baseline and white toast (control bread) in healthy adults with low DF intake. Methods: A four-week, two-armed, placebo-controlled, double-blinded, randomised crossover study separated by a two-week washout period was conducted. Fifty-six participants with low DF intake (<18 g/day for females, <22 g/day for males) consumed three (females)/four (males) slices of fortified bread daily for four weeks then control bread and vice versa. Before and after each intervention phase, the participants completed seven self-reported questionnaires: the Gastrointestinal Symptom Rating Scale, Patient-Reported Outcome Measurement Information System-Anxiety and Depression Short Forms 8a, World Health Organisation Well-Being Index, Warwick-Edinburgh Mental Wellbeing Scales, Multidimensional Fatigue Inventory Short Form, and the Subjective Vitality Scale. Results: Fifty-five participants completed all of the questionnaires before and after each intervention. The preliminary and blinded results showed no significant changes (all p > 0.05) in gastrointestinal symptoms, general wellbeing, and mental health following intervention and between interventions. Discussion: With thrice the amount of DF, the unique grain fibre-fortified bread did not cause gastrointestinal symptoms nor did it worsen general wellbeing and mental health in healthy adults with low DF intake. Encouraging the consumption of unique grain fibre-fortified bread could still be an acceptable and effective method to improve DF intake in a healthy adult population with low DF intake. Trial Registration: ACTRN12622000884707. 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

The relationship between the microbiota profile and exposure to stress is not well understood. Therefore, we used a rat model of unpredictable chronic mild stress (UCMS) to investigate this relationship. Depressive-like behaviors were measured in Female Sprague Dawley rats using the sucrose preference test and the Porsolt swim test. Anxiety-like behaviors were measured with the light–dark box test. Fecal corticosterone, cecal microbiota (composition and organic acids), plasma gut permeability (lipopolysaccharide-binding protein, LBP) and plasma inflammation (12 cytokines) markers were measured. Atypical behaviors were observed in female rats following UCMS, but no depressive-like behaviors were observed. Circulating concentrations of cytokines granulocyte-macrophage colony-stimulating factor and cytokine-induced neutrophil chemoattractant 1 were higher in UCMS-exposed female rats; plasma LBP and cecal organic acid levels remained unchanged. Our results reflect a resilient and adaptive phenotype for female SD rats. The relative abundance of taxa from the Clostridiales order and Desulfovibrionaceae family did, however, correlate both positively and negatively with anxiety-like behaviors and plasma cytokine concentrations, regardless of UCMS exposure, supporting the brain-to-gut influence of mild anxiety with a microbiota profile that may involve inflammatory pathways. 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