Effect of Palmitoylethanolamide Compared to a Placebo on the Gut Microbiome and Biochemistry in an Overweight Adult Population: A Randomised, Placebo Controlled, Double-Blind Study.

This study investigates the effects of palmitoylethanolamide (PEA) on the gut microbiome of overweight adults. Fifty-eight participants (twenty males, thirty-eight females) aged 18-65 years with a BMI range of 30-40 kg/m2 were recruited. Participants were randomised to receive PEA (n = 36) or a placebo (n = 22) for 12 weeks. Microbiota composition, richness, diversity, and metabolic functions, faecal short chain fatty acids and calprotectin, pathology markers, and health-related questionnaires were analysed throughout the 12 weeks of supplementation. PEA supplementation significantly reduced triglyceride levels and IL-2 concentrations. No significant differences were found in the overall microbiota composition between the groups, and microbiota richness and diversity remained consistent for both groups. Functional analysis demonstrated no differences in functional richness and diversity, but specific pathways were modified. PEA supplementation resulted in a decrease in the abundance of pathways related to aromatic compound degradation, NAD interconversion, and L-glutamate degradation, while pathways associated with molybdopterin biosynthesis and O-antigen building blocks exhibited increased abundance. Increased production of O-antigen results in smooth LPS associated with reduced pathogenic stealth and persistence. PEA supplementation may influence specific microbial species, metabolic pathways, and reduce serum triglyceride and IL-2 concentration, shedding light on the intricate relationship between PEA, the microbiome, and host health.

Effects of epicatechin on cardiovascular function in middle-aged diet-induced obese rat models of metabolic syndrome.

The current study aimed to investigate the cardiovascular effects of epicatechin, a flavonoid found in green tea and cocoa, in attenuating complications associated with metabolic syndrome in diet-induced obese rats. Male Wistar-Kyoto (WKY) rats aged 16 weeks were fed either standard rat chow or given a high-fat-high-carbohydrate (HFHC) diet for 20 weeks. Epicatechin treatment (5 mg/kg/d) was administered to a subset of WKY rats commencing at week 8 of the 20 week HFHC feeding period. Body weights, food, water and energy intakes, blood pressure, heart rate and glucose tolerance were measured throughout the treatment period. Oxidative stress and inflammatory markers, lipid levels, cardiac collagen deposition, cardiac electrical function, aortic and mesenteric vessel reactivity were examined after the treatment. Twenty weeks of HFHC feeding in WKY rats resulted in the development of metabolic syndrome indicated by the presence of abdominal obesity, dyslipidaemia, glucose intolerance and increased blood pressure. Epicatechin treatment was found to enhance the oxidative stress status in HFHC groups through an increase in serum nitric oxide levels and a decrease in 8-isoprostane concentrations. Furthermore, WKY-HFHC rats displayed a decrease in IL-6 levels. The lipid profiles in HFHC groups showed improvement, with a decrease in LDL-cholesterol and TAG and an increase in HDL-cholesterol levels observed in WKY-HFHC rats. However, epicatechin was not effective in preventing weight gain, glucose intolerance or hypertension in HFHC fed rats. Overall, the results of this study suggest that epicatechin has the potential to improve the underlying mechanisms associated with metabolic syndrome in obese rats.

Experiences of Rural and Metropolitan Background Applicants in Preparing for and Completing a Regionally Focused Multiple Mini-interview for Admission into a Regional Medical Program.

BACKGROUND: To better target rural background and rurally interested applicants during medical school admission, it is increasingly common for rural medical programs to include multiple mini-interview (MMI) scenarios designed to screen for rural interest. It remains unclear whether the inclusion of regionally/rurally focused MMI scenarios positively impacts the selection of rural background applicants and evidence is limited regarding why rural background applicants may perform worse on the MMI. Therefore, this study explored how rural and metropolitan applicants prepare for and perceive the MMI for admission to a regional medical pathway. METHODS: A mixed-methods survey was sent to provisional entry regional pathway medical school applicants who had completed an MMI. The survey was distributed before any offers of admission had been released. RESULTS: Rural applicants spent less time and money preparing for the MMI and felt less prepared (P < 0.05). However, time and money spent, and resources used to prepare were not associated with feeling more prepared (all P > 0.05). Respondents mostly felt that the MMI process aligned with their expectations (83%), is fair (64%), and helps a rural program select the most suitable applicants (61%). Rural applicants generally felt that they had an advantage over other applicants (61%) while most metropolitan applicants did not (23%; P = 0.002). DISCUSSION: Applicants to a regional medical pathway are generally supportive of the MMI process. It appears valuable for applicants to prepare for the MMI by understanding the format and requirements; however, investing substantial time and money does not underpin feeling better prepared. MMI scenarios which include a regional focus are perceived to advantage rural applicants.

Perindopril prevents development of obesity and hypertension in middle aged diet-induced obese rat models of metabolic syndrome.

AIMS: The therapeutic properties of anti-hypertensive medications that extend beyond blood pressure lowering have started to become important clinical targets in recent years. This study aimed to assess the cardioprotective effects of perindopril in attenuating complications associated with metabolic syndrome in diet induced obese rats. MAIN METHODS: Male Wistar-Kyoto (WKY) rats aged 16 weeks were fed either standard rat chow (SC) or given a high-fat-high-carbohydrate (HFHC) diet for 20 weeks. Perindopril treatment (1 mg/kg/day) was administered to a subset of WKY rats commencing at week 8 of the 20 week HFHC feeding period. Body weights, food, water and energy intakes, blood pressure, heart rate and glucose tolerance were measured throughout the treatment period. Oxidative stress and inflammatory markers, lipid levels, cardiac collagen deposition, vascular function, aortic and cardiac electrical function were examined after the treatment. KEY FINDINGS: WKY rats developed metabolic syndrome after 20 weeks of HFHC feeding, evidenced by the presence of abdominal obesity, dyslipidaemia, glucose intolerance and hypertension. Perindopril treatment prevented the development of obesity and hypertension in WKY-HFHC. Perindopril improved blood lipid profiles in HFHC rats with decreases in LDL cholesterol, triglycerides and total cholesterol. Type I collagen levels were decreased in WKY-HFHC rats along with decreases in left ventricle mass. Perindopril treated rats also showed improved cardiac electrical function indicated by decreases in action potential at 90 % of repolarisation in WKY-HFHC rats. SIGNIFICANCE: These results show that perindopril has a profound effect on preventing the development of metabolic syndrome in animals fed a HFHC diet.

Rapid growth of antimicrobial resistance: the role of agriculture in the problem and the solutions.

The control of infectious diseases has always been a top medical priority. For years during the so-called antibiotic era, we enjoyed prolonged life expectancy and the benefits of superior pathogen control. The devastating failure of the medical system, agriculture and pharmaceutical companies and the general population to appreciate and safeguard these benefits is now leading us into a grim post-antibiotic era. Antimicrobial resistance (AMR) refers to microorganisms becoming resistant to antibiotics that were designed and expected to kill them. Prior to the COVID-19 pandemic, AMR was recognised by the World Health Organization as the central priority area with growing public awareness of the threat AMR now presents. The Review on Antimicrobial Resistance, a project commissioned by the UK government, predicted that the death toll of AMR could be one person every 3 seconds, amounting to 10 million deaths per year by 2050. This review aims to raise awareness of the evergrowing extensiveness of antimicrobial resistance and identify major sources of this adversity, focusing on agriculture's role in this problem and its solutions. KEYPOINTS: • Widespread development of antibiotic resistance is a major global health risk. • Antibiotic resistance is abundant in agricultural produce, soil, food, water, air and probiotics. • New approaches are being developed to control and reduce antimicrobial resistance.

Phytogenic supplement containing menthol, carvacrol and carvone ameliorates gut microbiota and production performance of commercial layers.

Consumer push towards open and free-range production systems makes biosecurity on farms challenging, leading to increased disease and animal welfare issues. Phytogenic products are increasingly becoming a viable alternative for the use of antibiotics in livestock production. Here we present a study of the effects of commercial phytogenic supplement containing menthol, carvacrol and carvone on intestinal microbiota of layer hens, microbial functional capacity, and intestinal morphology. A total of 40,000 pullets were randomly assigned to two sides of the experimental shed. Growth performance, mortality, egg production and egg quality parameters were recorded throughout the trial period (18-30 weeks of age). Microbial community was investigated using 16S amplicon sequencing and functional difference using metagenomic sequencing. Phytogen supplemented birds had lower mortality and number of dirty eggs, and their microbial communities showed reduced richness. Although phytogen showed the ability to control the range of poultry pathogens, its action was not restricted to pathogenic taxa, and it involved functional remodelling the intestinal community towards increased cofactor production, heterolactic fermentation and salvage and recycling of metabolites. The phytogen did not alter the antimicrobial resistance profile or the number of antibiotic resistance genes. The study indicates that phytogenic supplementation can mimic the action of antibiotics in altering the gut microbiota and be used as their alternative in industry-scale layer production.

Ileum transcriptional response to prolonged supplementation with phytogenic product containing menthol, carvacrol and carvone.

Pathogen control is a critical issue in the layer industry. Plant-based natural products are firmly replacing the undesirable use of antibiotics in animal production. The poultry industry embraced the opportunity to distance itself from the negative public perception of antibiotic use. In this study, we investigated the effects of a phytogenic product comprising of menthol, carvacrol and carvone on ileum gene expression profile in layers after 16 weeks of continual supplementation. Phytogen supplementation increased endocytosis and autophagy while showing significant predicted cardiovascular protective effects. Statistical comparison with over 100,000 manually curated and comparably reanalysed public datasets suggests that the phytogen effects are highly significantly comparable with transcriptomic effects of clinical antibiotics doxycycline and geldanamycin, and that phytogen can reverse transcriptomic effects of a range of viral diseases and malaria. Our data confirmed the hypothesis that similarly to the original essential oil type antimicrobial constituents of phytogenic products, there may be a range of benefits unrelated to their critical antimicrobial action, contributing to improved bird welfare.

Effect of different intensities of physical activity on cardiometabolic markers and vascular and cardiac function in adult rats fed with a high-fat high-carbohydrate diet.

BACKGROUND: Physical activity (PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat high-carbohydrate (HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training (LIT), and high-intensity interval training (HIIT) on cardiometabolic markers and vascular and cardiac function in HFHC-fed adult rats. METHODS: Twelve-week-old Wistar rats were randomly allocated to 4 groups (12 rats/group): control (CTL), sedentary (SED), LIT, and HIIT. Biometric indices, glucose and lipid control, inflammatory and oxidative stress markers, vascular reactivity, and cardiac electrophysiology of the experimental groups were examined after 12 weeks of HFHC-diet feeding and PA interventions. RESULTS: The SED group had slower cardiac conduction (p = 0.0426) and greater thoracic aortic contractile responses (p < 0.05) compared with the CTL group. The LIT group showed improved cardiac conduction compared with the SED group (p = 0.0003), and the HIIT group showed decreased mesenteric artery contractile responses compared with all other groups and improved endothelium-dependent mesenteric artery relaxation compared with the LIT group (both p < 0.05). The LIT and HIIT groups had lower visceral (p = 0.0057 for LIT, p = 0.0120 for HIIT) and epididymal fat (p < 0.0001 for LIT, p = 0.0002 for HIIT) compared with the CTL group. CONCLUSION: LIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation, mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.

(-)-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats.

(−)-Epicatechin (E) is a flavanol found in green tea and cocoa and has been shown to attenuate tumour necrosis factor alpha (TNF-α)-mediated inflammation, improve nitric oxide levels, promote endothelial nitric oxide synthase (eNOS) activation and inhibit NADPH oxidase. This study investigated the effect of 28 days of low epicatechin dosing (1 mg/kg/day) on the cardiovascular function of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Wistar rats (n = 120, 8 weeks of age) underwent uninephrectomy and were randomised into four groups (uninephrectomy (UNX), UNX + E, DOCA, DOCA + E). DOCA and DOCA + E rats received 1% NaCl drinking water along with subcutaneous injections of 25 mg deoxycorticosterone-acetate (in 0.4 mL of dimethylformamide) every fourth day. UNX + E and DOCA + E rats received 1 mg/kg/day of epicatechin by oral gavage. Single-cell micro-electrode electrophysiology, Langendorff isolated-heart assessment and isolated aorta and mesenteric organ baths were used to assess cardiovascular parameters. Serum malondialdehyde concentration was used as a marker of oxidative stress. Myocardial stiffness was increased and left ventricular compliance significantly diminished in the DOCA control group, and these changes were attenuated by epicatechin treatment (p < 0.05). Additionally, the DOCA + E rats showed significantly reduced blood pressure and malondialdehyde concentrations; however, there was no improvement in left ventricular hypertrophy, electrophysiology or vascular function. This study demonstrates the ability of epicatechin to reduce blood pressure, prevent myocardial stiffening and preserve cardiac compliance in hypertrophied DOCA-salt rat hearts.

Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies.

The current review clarifies the cardiometabolic health effects of high-intensity interval training (HIIT) in adults. A systematic search (PubMed) examining HIIT and cardiometabolic health markers was completed on 15 October 2015. Sixty-five intervention studies were included for review and the methodological quality of included studies was assessed using the Downs and Black score. Studies were classified by intervention duration and body mass index classification. Outcomes with at least 5 effect sizes were synthesised using a random-effects meta-analysis of the standardised mean difference (SMD) in cardiometabolic health markers (baseline to postintervention) using Review Manager 5.3. Short-term (ST) HIIT (<12 weeks) significantly improved maximal oxygen uptake (VO2 max; SMD 0.74, 95% CI 0.36 to 1.12; p<0.001), diastolic blood pressure (DBP; SMD -0.52, 95% CI -0.89 to -0.16; p<0.01) and fasting glucose (SMD -0.35, 95% CI -0.62 to -0.09; p<0.01) in overweight/obese populations. Long-term (LT) HIIT (≥12 weeks) significantly improved waist circumference (SMD -0.20, 95% CI -0.38 to -0.01; p<0.05), % body fat (SMD -0.40, 95% CI -0.74 to -0.06; p<0.05), VO2 max (SMD 1.20, 95% CI 0.57 to 1.83; p<0.001), resting heart rate (SMD -0.33, 95% CI -0.56 to -0.09; p<0.01), systolic blood pressure (SMD -0.35, 95% CI -0.60 to -0.09; p<0.01) and DBP (SMD -0.38, 95% CI -0.65 to -0.10; p<0.01) in overweight/obese populations. HIIT demonstrated no effect on insulin, lipid profile, C reactive protein or interleukin 6 in overweight/obese populations. In normal weight populations, ST-HIIT and LT-HIIT significantly improved VO2 max, but no other significant effects were observed. Current evidence suggests that ST-HIIT and LT-HIIT can increase VO2 max and improve some cardiometabolic risk factors in overweight/obese populations.

Light-intensity and high-intensity interval training improve cardiometabolic health in rats.

Physical activity has the potential to reduce cardiometabolic risk factors but evaluation of different intensities of physical activity and the mechanisms behind their health effects still need to be fully established. This study examined the effects of sedentary behaviour, light-intensity training, and high-intensity interval training on biometric indices, glucose and lipid metabolism, inflammatory and oxidative stress markers, and vascular and cardiac function in adult rats. Rats (12 weeks old) were randomly assigned to 1 of 4 groups: control (CTL; no exercise), sedentary (SED; no exercise and housed in small cages to reduce activity), light-intensity trained (LIT; four 30-min exercise bouts/day at 8 m/min separated by 2-h rest period, 5 days/week), and high-intensity interval trained (HIIT, four 2.5-min work bouts/day at 50 m/min separated by 3-min rest periods, 5 days/week). After 12 weeks of intervention, SED had greater visceral fat accumulation (p < 0.01) and slower cardiac conduction (p = 0.04) compared with the CTL group. LIT and HIIT demonstrated beneficial changes in body weight, visceral and epididymal fat weight, glucose regulation, low-density lipoprotein cholesterol, total cholesterol, and mesenteric vessel contractile response compared with the CTL group (p < 0.05). LIT had significant improvements in insulin sensitivity and cardiac conduction compared with the CTL and SED groups whilst HIIT had significant improvements in systolic blood pressure and endothelium-independent vasodilation to aorta and mesenteric artery compared with the CTL group (p < 0.05). LIT and HIIT induce health benefits by improving traditional cardiometabolic risk factors. LIT improves cardiac health while HIIT promotes improvements in vascular health.

Effects of Light Intensity Activity on CVD Risk Factors: A Systematic Review of Intervention Studies.

The effects of light intensity physical activity (LIPA) on cardiovascular disease (CVD) risk factors remain to be established. This review summarizes the effects of LIPA on CVD risk factors and CVD-related markers in adults. A systematic search of four electronic databases (PubMed, Academic Search Complete, SPORTDiscus, and CINAHL) examining LIPA and CVD risk factors (body composition, blood pressure, glucose, insulin, glycosylated hemoglobin, and lipid profile) and CVD-related markers (maximal oxygen uptake, heart rate, C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and tumor necrosis factor receptors 1 and 2) published between 1970 and 2015 was performed on 15 March 2015. A total of 33 intervention studies examining the effect of LIPA on CVD risk factors and markers were included in this review. Results indicated that LIPA did not improve CVD risk factors and CVD-related markers in healthy individuals. LIPA was found to improve systolic and diastolic blood pressure in physically inactive populations with a medical condition. Reviewed studies show little support for the role of LIPA to reduce CVD risk factors. Many of the included studies were of low to fair study quality and used low doses of LIPA. Further studies are needed to establish the value of LIPA in reducing CVD risk.