Effect of gut microbiome modulation on muscle function and cognition:the PROMOTe randomised controlled trial

Studies suggest that inducing gut microbiota changes may alter both musclephysiology and cognitive behaviour. Gut microbiota may play a role in bothanabolic resistance of older muscle, and cognition. In this placebo controlleddouble blinded randomised controlled trial of 36 twin pairs (72 individuals),aged ≥60, each twin pair are block randomised to receive either placebo orprebiotic daily for 12 weeks. Resistance exercise and branched chain aminoacid (BCAA) supplementation is prescribed to all participants. Outcomes arephysical function and cognition. The trial is carried out remotely using videovisits, online questionnaires and cognitive testing, and posting of equipmentand biological samples. The prebiotic supplement is well tolerated and resultsin a changed gut microbiome [e.g., increased relative Bifidobacterium abundance].There is no significant difference between prebiotic and placebo forthe primary outcome of chair rise time (β=0.579; 95% CI −1.080-2.239p = 0.494). The prebiotic improves cognition (factor score versus placebo(β = −0.482; 95% CI,−0.813, −0.141; p = 0.014)). Our results demonstrate thatcheap and readily available gut microbiome interventions may improve cognitionin our ageing population. We illustrate the feasibility of remotelydelivered trials for older people, which could reduce under-representation ofolder people in clinical trials. ClinicalTrials.gov registration: NCT04309292

Il nome e il sangue secondo Quinto Smirneo. Riprese e trasformazioni di un motivo del duello eroico

The aim of this essay is to examine the rules of duelling in Greek epic poetry from Homer and Arctinus to Quintus Smyrnaeus, within the perspective of composition by theme, which make it possible to identify heroes' ancestry as a specific motif of the epic duel

Pioglitazone Improves Myocardial Blood Flow and Glucose Utilization in Nondiabetic Patients With Combined Hyperlipidemia A Randomized, Double-Blind, Placebo-Controlled Study

ObjectivesThis study’s aim was to examine whether treatment with pioglitazone, added to conventional lipid-lowering therapy, would improve myocardial glucose utilization (MGU) and blood flow (MBF) in nondiabetic patients with familial combined hyperlipidemia (FCHL).BackgroundThiazolidinediones were found to improve insulin sensitivity and MGU in type 2 diabetes and MBF in Mexican Americans with insulin resistance. Familial combined hyperlipidemia is a complex genetic disorder conferring a high risk of premature coronary artery disease, characterized by high serum cholesterol and/or triglyceride, low high-density lipoprotein (HDL) cholesterol, and insulin resistance.MethodsWe undertook a randomized, double-blind, placebo-controlled study in 26 patients with FCHL, treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, followed by 45 mg daily for 12 weeks. Positron emission tomography was used to measure MBF at rest and during adenosine-induced hyperemia and MGU during euglycemic hyperinsulinemic clamp at baseline and after treatment.ResultsWhereas no change was observed in the placebo group after treatment, patients receiving pioglitazone showed a significant increase in whole body glucose disposal (3.93 ± 1.59 mg/kg/min to 5.24 ± 1.65 mg/kg/min; p = 0.004) and MGU (0.62 ± 0.26 μmol/g/min to 0.81 ± 0.14 μmol/g/min; p = 0.0007), accompanied by a significant improvement in resting MBF (1.11 ± 0.20 ml/min/g to 1.25 ± 0.21 ml/min/g; p = 0.008). Furthermore, in the pioglitazone group HDL cholesterol (+28%; p = 0.003) and adiponectin (+156.2%; p = 0.0001) were increased and plasma insulin (−35%; p = 0.017) was reduced.ConclusionsIn patients with FCHL treated with conventional lipid-lowering therapy, the addition of pioglitazone led to significant improvements in MGU and MBF, with a favorable effect on blood lipid and metabolic parameters. (A study to investigate the effect of pioglitazone on whole body and myocardial glucose uptake and myocardial blood flow/coronary vasodilator reserve in patients with familial combined hyperlipidaemia; http://www.controlled-trials.com/mrct/trial/230761/ISRCTN78563659; ISRCTN78563659

Antibodies to Leptospira among blood donors in higher-risk areas of Australia: Possible implications for transfusion safety

BACKGROUND: Leptospirosis is one of the most common bacterial zoonoses worldwide, and clinical manifestations range from asymptomatic infection to acute febrile illness, multi-organ failure and death. Asymptomatic, acute bacteraemia in a blood donor provides a potential for transfusion-transmission, although only a single such case from India has been recorded. Human leptospirosis is uncommon in developed countries; however, the state of Queensland in Australia has one of the highest rates among developed countries, especially after increased rainfall. This study examined the prevalence of antibodies to Leptospira spp. in blood donors residing in higher-risk areas of Australia, to evaluate the appropriateness of current blood safety guidelines. MATERIALS AND METHODS: Plasma samples collected from blood donors residing in higher-risk areas of Australia during 2009 and 2011 were included in the study. All samples were tested for the presence of antibodies to 22 leptospiral serovars using the microscopic agglutination test. RESULT: No sample had antibody titres suggestive of a current or recent infection, however, seven samples (1.44%, 95% CI: 0.38-2.50%) had titres suggestive of a past infection. DISCUSSION: This study provides data that may support the appropriateness of current relevant donor selection policies in Australia. Given that the risk profile for leptospirosis is expanding and that the infection is likely to become more prevalent with climate change, this disease may become more of a concern for transfusion safety in the futur

A continuity of care programme for women at risk of preterm birth in the UK : process evaluation of a hybrid randomised controlled pilot trial

BACKGROUND: The development and evaluation of specific maternity care packages designed to address preterm birth remains a public health priority. We aim to evaluate the implementation, context, and potential mechanisms of action, of a new care pathway that combined midwifery continuity of care with a specialist obstetric clinic for women at risk of preterm birth (POPPIE) in London (UK). METHODS: We did a multiphase mixed method triangulation evaluation nested within a hybrid type 2, randomised controlled trial in London (United Kingdom). Pregnant women with identified risk factors for preterm birth were eligible for trial participation and randomly assigned (1:1) to either midwifery continuity of care linked to a specialist obstetric clinic (POPPIE group) or standard maternity care. The primary outcome was a composite of appropriate and timely interventions for the prevention and/or management of preterm labour and birth, analysed according to intention to treat. Clinical and process outcome data were abstracted from medical records and electronic data systems, and coded by study team members, who were masked to study group allocation. Implementation data were collected from meeting records and key documents, postnatal surveys (n = 164), semi-structured interviews with women (n = 30), healthcare providers and stakeholders (n = 24) pre-, mid and post implementation. Qualitative and quantitative data from meeting records and key documents were examined narratively. Qualitative data from interviews were analysed using three thematic frameworks: Proctor’s (for implementation outcomes: appropriateness, adoption, feasibility, acceptability, fidelity, penetration, sustainability), the Consolidated Framework for Implementation Research (for determinants of implementation), and published program theories of continuity models (for potential mechanisms). Data triangulation followed a convergent parallel and pragmatic approach which brought quantitative and qualitative data together at the interpretation stage. We averaged individual implementation measures across all domains to give a single composite implementation strength score which was compared to the primary outcome. RESULTS: Between May 9, 2017, and Sep 30, 2018, 553 women were assessed for eligibility and 334 were enrolled with less than 6% of loss to follow up (169 were assigned to the POPPIE group; 165 were to the standard group). There was no difference in the primary outcome (POPPIE group 83·3% versus standard group 84·7%; risk ratio 0·98 [95% CI 0·90 to 1·08]). Appropriateness and adoption: The introduction of the POPPIE model was perceived as a positive fundamental change for local maternity services. Partnership working and additional funding were crucial for adoption. Fidelity: More than 75% of antenatal and postnatal visits were provided by a named or partner midwife, and a POPPIE midwife was present in more than 80% of births. Acceptability: Nearly 98% of women who responded to the postnatal survey were very satisfied with POPPIE model. Quantitative fidelity and acceptability results were supported by the qualitative findings. Penetration and sustainability: Despite delays (likely associated with lack of existing continuity models at the hospital), the model was embedded within established services and a joint decision was made to sustain and adapt the model after the trial (strongly facilitated by national maternal policy on continuity pathways). Potential mechanisms of impact identified included e.g. access to care, advocacy and perceptions of safety and trust. There was no association between implementation measures and the primary outcome. CONCLUSIONS: The POPPIE model of care was a feasible and acceptable model of care that was implemented with high fidelity and sustained in maternity services. Larger powered trials are feasible and needed in other settings, to evaluate the impact and implementation of continuity programmes in other communities affected by preterm birth and women who experience social disadvantage and vulnerability. TRIAL REGISTRATION: UKCRN Portfolio Database (prospectively registered, 24 April 2017): 31951. ISRCTN registry (retrospectively registered, 21 August 2017): ISRCTN37733900

Placental magnetic resonance imaging in chronic hypertension: A case-control study

Introduction We aimed to explore the use of magnetic resonance imaging (MRI) in vivo as a tool to elucidate the placental phenotype in women with chronic hypertension. Methods In case-control study, women with chronic hypertension and those with uncomplicated pregnancies were imaged using either a 3T Achieva or 1.5T Ingenia scanner. T2-weighted images, diffusion weighted and T1/T2* relaxometry data was acquired. Placental T2*, T1 and apparent diffusion coefficient (ADC) maps were calculated. Results 129 women (43 with chronic hypertension and 86 uncomplicated pregnancies) were imaged at a median of 27.7 weeks’ gestation (interquartile range (IQR) 23.9–32.1) and 28.9 (IQR 26.1–32.9) respectively. Visual analysis of T2-weighted imaging demonstrated placentae to be either appropriate for gestation or to have advanced lobulation in women with chronic hypertension, resulting in a greater range of placental mean T2* values for a given gestation, compared to gestation-matched controls. Both skew and kurtosis (derived from histograms of T2* values across the whole placenta) increased with advancing gestational age at imaging in healthy pregnancies; women with chronic hypertension had values overlapping those in the control group range. Upon visual assessment, the mean ADC declined in the third trimester, with a corresponding decline in placental mean T2* values and showed an overlap of values between women with chronic hypertension and the control group. Discussion A combined placental MR examination including T2 weighted imaging, T2*, T1 mapping and diffusion imaging demonstrates varying placental phenotypes in a cohort of women with chronic hypertension, showing overlap with the control group