The Gut Microbiota and Their Metabolites in Human Arterial Stiffness

Aim: Gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs) have vasodilator properties in animal and human ex vivo arteries. However, the role of the gut microbiota and SCFAs in arterial stiffness in humans is still unclear. Here we aimed to determine associations between the gut microbiome, SCFA and their G-protein coupled sensing receptors (GPCRs) in relation to human arterial stiffness. / Methods: Ambulatory arterial stiffness index (AASI) was determined from ambulatory blood pressure (BP) monitoring in 69 participants from regional and metropolitan regions in Australia (55.1% women; mean, 59.8± SD, 7.26 years of age). The gut microbiome was determined by 16S rRNA sequencing, SCFA levels by gas chromatography, and GPCR expression in circulating immune cells by real-time PCR. / Results: There was no association between metrics of bacterial α and β diversity and AASI or AASI quartiles in men and women. We identified two main bacteria taxa that were associated with AASI quartiles: Lactobacillus spp. was only present in the lowest quartile, while Clostridium spp. was present in all quartiles but the lowest. AASI was positively associated with higher levels of plasma, but not faecal, butyrate. Finally, we identified that the expression of GPR43 (FFAR2) and GPR41 (FFAR3) in circulating immune cells were negatively associated with AASI. / Conclusions: Our results suggest that arterial stiffness is associated with lower levels of the metabolite-sensing receptors GPR41/GPR43 in humans, blunting its response to BP-lowering metabolites such as butyrate. The role of Lactobacillus spp. and Clostridium spp., as well as butyrate-sensing receptors GPR41/GPR43, in human arterial stiffness needs to be determined

Liver transplantation for colorectal liver metastasis: Survival without recurrence can be achieved

info:eu-repo/semantics/publishedVersio

Regional differences in self-reported screening, prevalence and management of cardiovascular risk factors in Switzerland

In Switzerland, health policies are decided at the local level, but little is known regarding their impact on the screening and management of cardiovascular risk factors (CVRFs). We thus aimed at assessing geographical levels of CVRFs in Switzerland. Swiss Health Survey for 2007 (N = 17,879). Seven administrative regions were defined: West (Leman), West-Central (Mittelland), Zurich, South (Ticino), North-West, East and Central Switzerland. Obesity, smoking, hypertension, dyslipidemia and diabetes prevalence, treatment and screening within the last 12 months were assessed by interview. After multivariate adjustment for age, gender, educational level, marital status and Swiss citizenship, no significant differences were found between regions regarding prevalence of obesity or current smoking. Similarly, no differences were found regarding hypertension screening and prevalence. Two thirds of subjects who had been told they had high blood pressure were treated, the lowest treatment rates being found in East Switzerland: odds-ratio and [95% confidence interval] 0.65 [0.50-0.85]. Screening for hypercholesterolemia was more frequently reported in French (Leman) and Italian (Ticino) speaking regions. Four out of ten participants who had been told they had high cholesterol levels were treated and the lowest treatment rates were found in German-speaking regions. Screening for diabetes was higher in Ticino (1.24 [1.09 - 1.42]). Six out of ten participants who had been told they had diabetes were treated, the lowest treatment rates were found for German-speaking regions. In Switzerland, cardiovascular risk factor screening and management differ between regions and these differences cannot be accounted for by differences in populations' characteristics. Management of most cardiovascular risk factors could be improved

Bone marrow haematopoiesis in patients with COVID-19

AIMS Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection broadly affects organ homeostasis, including the haematopoietic system. Autopsy studies are a crucial tool for investigation of organ-specific pathologies. Here we perform an in-depth analysis of the impact of severe coronavirus disease 2019 (COVID-19) on bone marrow haematopoiesis in correlation with clinical and laboratory parameters. METHODS AND RESULTS Twenty-eight autopsy cases and five controls from two academic centres were included in the study. We performed a comprehensive analysis of bone marrow pathology and microenvironment features with clinical and laboratory parameters and assessed SARS-CoV-2 infection of the bone marrow by quantitative polymerase chain reaction (qPCR) analysis. In COVID-19 patients, bone marrow specimens showed a left-shifted myelopoiesis (19 of 28, 64%), increased myeloid-erythroid ratio (eight of 28, 28%), increased megakaryopoiesis (six of 28, 21%) and lymphocytosis (four of 28, 14%). Strikingly, a high proportion of COVID-19 specimens showed erythrophagocytosis (15 of 28, 54%) and the presence of siderophages (11 of 15, 73%) compared to control cases (none of five, 0%). Clinically, erythrophagocytosis correlated with lower haemoglobin levels and was more frequently observed in patients from the second wave. Analysis of the immune environment showed a strong increase in CD68+ macrophages (16 of 28, 57%) and a borderline lymphocytosis (five of 28, 18%). The stromal microenvironment showed oedema (two of 28, 7%) and severe capillary congestion (one of 28, 4%) in isolated cases. No stromal fibrosis or microvascular thrombosis was found. While all cases had confirmed positive testing of SARS-CoV-2 in the respiratory system, SARS-CoV-2 was not detected in the bone marrow by high-sensitivity PCR, suggesting that SARS-CoV-2 does not commonly replicate in the haematopoietic microenvironment. CONCLUSIONS SARS-CoV-2 infection indirectly impacts the haematological compartment and the bone marrow immune environment. Erythrophagocytosis is frequent and associated with lower haemoglobin levels in patients with severe COVID-19

Influences on gum feeding in primates

This chapter reviews the factors that may affect patterns of gum feeding by primates. These are then examined for mixed-species troops of saddleback (S. fuscicollis) and mustached (S. mystax) tamarins. An important distinction is made between gums produced by tree trunks and branches as a result of damage and those produced by seed pods as part of a dispersal strategy as these may be expected to differ in their biochemistry. Feeding on fruit and Parkia seed pod exudates was more prevalent in the morning whereas other exudates were eaten in the afternoon. This itinerary may represent a deliberate strategy to retain trunk gums in the gut overnight, thus maximising the potential for microbial fermentation of their β-linked oligosaccharides. Both types of exudates were eaten more in the dry than the wet season. Consumption was linked to seasonal changes in resource availability and not the tamarins’ reproductive status pro-viding no support for the suggestion that gums are eaten as a pri-mary calcium source in the later stages of gestation and lactation. The role of availability in determining patterns of consumption is further supported by the finding that dietary overlap for the trunk gums eaten was greater between species within mixed-species troops within years than it was within species between years. These data and those for pygmy marmosets (Cebuella pygmaea) suggest that patterns of primate gummivory may reflect the interaction of prefer-ence and availability for both those able to stimulate gum production and those not

Brake response time before and after total knee arthroplasty: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Although the numbers of total knee arthroplasty (TKA) are increasing, there is only a small number of studies investigating driving safety after TKA. The parameter 'Brake Response Time (BRT)' is one of the most important criteria for driving safety and was therefore chosen for investigation.</p> <p>The present study was conducted to test the hypotheses that patients with right- or left-sided TKA show a significant increase in BRT from pre-operative (pre-op, 1 day before surgery) to post-operative (post-op, 2 weeks post surgery), and a significant decrease in BRT from post-op to the follow-up investigation (FU, 8 weeks post surgery). Additionally, it was hypothesized that the BRT of patients after TKA is significantly higher than that of healthy controls.</p> <p>Methods</p> <p>31 of 70 consecutive patients (mean age 65.7 +/- 10.2 years) receiving TKA were tested for their BRT pre-op, post-op and at FU. BRT was assessed using a custom-made driving simulator. We used normative BRT data from 31 healthy controls for comparison.</p> <p>Results</p> <p>There were no significant increases between pre-op and post-op BRT values for patients who had undergone left- or right-sided TKA. Even the proportion of patients above a BRT threshold of 700 ms was not significantly increased postop. Controls had a BRT which was significantly better than the BRT of patients with right- or left-sided TKA at all three time points.</p> <p>Conclusion</p> <p>The present study showed a small and insignificant postoperative increase in the BRT of patients who had undergone right- or left-sided TKA. Therefore, we believe it is not justified to impair the patient's quality of social and occupational life post-surgery by imposing restrictions on driving motor vehicles beyond an interval of two weeks after surgery.</p

Computational analysis suggests that virulence of Chromobacterium violaceum might be linked to biofilm formation and poly-NAG biosynthesis

Groups of genes that produce exopolysaccharide with a N-acetyl-D-glucosamine monomer are in the genome of several pathogenic bacteria. Chromobacterium violaceum, an opportunistic pathogen, has the operon hmsHFR-CV2940, whose proteins can synthesize such polysaccharide. In this work, multiple alignments among proteins from bacteria that synthesize such polysaccharide were used to verify the existence of amino acids that might be critical for pathogen activity. Three-dimensional models were generated for spatial visualization of these amino acid residues. The analysis carried out showed that the protein HmsR preserves the amino acids D135, D228, Q264 and R267, considered critical for the formation of biofilms and, furthermore, that these amino acids are close to each other. The protein HmsF of C. violaceum preserves the residues D86, D87, H156 and W115. It was also shown that these residues are also close to each other in their spatial arrangement. For the proteins HmsH and CV2940 there is evidence of conservation of the residues R104 and W94, respectively. Conservation and favorable spatial location of those critical amino acids that constitute the proteins of the operon indicates that they preserve the same enzymatic function in biofilm synthesis. This is an indicator that the operon hmsHFR-CV2940 is a possible target in C. violaceum pathogenicity

Microbial Interventions to Control and Reduce Blood Pressure in Australia (MICRoBIA): rationale and design of a double-blinded randomised cross-over placebo controlled trial

Background: Hypertension is a prevalent chronic disease worldwide that remains poorly controlled. Recent studies support the concept that the gut microbiota is involved in the development of hypertension and that dietary fibre intake may act through the gut microbiota to lower blood pressure (BP). Resistant starch is a type of prebiotic fibre which is metabolised by commensal bacteria in the colon to produce short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. Previous work in pre-clinical models provides strong evidence that both prebiotic fibre as well as SCFAs (i.e. postbiotics) can prevent the development of hypertension. The aim of this clinical trial is to determine if acetylated and butyrylated modified resistant starch can decrease BP of hypertensive individuals via the modulation of the gut microbiota and release of high levels of SCFAs.Methods: This is a phase IIa double-blinded, randomised, cross-over, placebo controlled trial. Participants are randomly allocated to receive either a diet containing 40 g/day of the modified resistant starch or placebo (corn starch or regular flour) for 3 weeks on each diet, with a 3-week washout period between the two diets. BP is measured in the office, at home, and using a 24-h ambulatory device. Arterial stiffness is measured using carotid-to-femoral pulse wave velocity. Our primary endpoint is a reduction in ambulatory daytime systolic BP. Secondary endpoints include changes to circulating cytokines, immune markers, and modulation to the gut microbiome.Discussion: The findings of this study will provide the first evidence for the use of a combination of pre- and postbiotics to lower BP in humans. The results are expected at the end of 2021