The Australian multidomain approach to reduce dementia risk by protecting brain health with lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55–79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. DISCUSSION: The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Highlights: Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study. The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative. AU-ARROW\u27s primary outcome measure is change in a global composite cognitive score. Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests. Leading to development of an innovative treatment plan to reduce cognitive decline

Physicochemical and rheological characterization of honey from Mozambique

[EN] Obtaining information about honey from Mozambique is the first step towards the economic and nutritional exploitation of this natural resource. The aim of this study was to evaluate physicochemical (moisture, hydroxymethylfurfural ¿HMF¿, electrical conductivity, Pfund colour, CIE L*a*b* colour and sugars) and rheological parameters elastic modulus G0 , loss modulus G00 and complex viscosity h*) obtained at different temperatures (from 10 to 40 C). All the physicochemical parameters were in agreement with the international regulations. Most of the honey samples were classed as honeydew honey since they were dark and had conductivity values above 0.800 mS/cm. The moduli G0, G00 and h* decreased with increasing temperature. G 0 and G00 were strongly influenced by the applied frequency, whereas h* did not depend on this parameter, demonstrating Newtonian behaviour. An artificial neural network (ANN) was applied to predict the rheological parameters as a function of temperature, frequency and chemical composition. A multilayer perceptron (MLP) was found to be the best model for G00 and h*(r2 > 0.950), while probabilistic neural network (PNN) was the best for G0(r2 ¿ 0.758). Sensitivity testing showed that in the case of G00 and G0 frequency and moisture were the most important factors whereas for h* they were moisture and temperature.The authors thank the Ministerio de Ciencia e Tecnologia Ensino Superior e Tecnico Profissional de Mocambique (Project: HEST "Ensino Superior, Ciencia e Tecnologia") and Universidade Pedagogica de Mocambique-Nampula for the grant awarded to Fernando Tanleque Alberto.Escriche Roberto, MI.; Alberto, FJT.; Visquert Fas, M.; Oroian, M. (2017). Physicochemical and rheological characterization of honey from Mozambique. LWT - Food Science and Technology. 86:108-115. doi:10.1016/j.lwt.2017.07.053S1081158

Ketone bodies mediate alterations in brain energy metabolism and biomarkers of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia. AD is a progressive neurodegenerative disorder characterized by cognitive dysfunction, including learning and memory deficits, and behavioral changes. Neuropathology hallmarks of AD such as amyloid beta (Aβ) plaques and neurofibrillary tangles containing the neuron-specific protein tau is associated with changes in fluid biomarkers including Aβ, phosphorylated tau (p-tau)-181, p-tau 231, p-tau 217, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL). Another pathological feature of AD is neural damage and hyperactivation of astrocytes, that can cause increased pro-inflammatory mediators and oxidative stress. In addition, reduced brain glucose metabolism and mitochondrial dysfunction appears up to 15 years before the onset of clinical AD symptoms. As glucose utilization is compromised in the brain of patients with AD, ketone bodies (KBs) may serve as an alternative source of energy. KBs are generated from the β-oxidation of fatty acids, which are enhanced following consumption of ketogenic diets with high fat, moderate protein, and low carbohydrate. KBs have been shown to cross the blood brain barrier to improve brain energy metabolism. This review comprehensively summarizes the current literature on how increasing KBs support brain energy metabolism. In addition, for the first time, this review discusses the effects of ketogenic diet on the putative AD biomarkers such as Aβ, tau (mainly p-tau 181), GFAP, and NFL, and discusses the role of KBs on neuroinflammation, oxidative stress, and mitochondrial metabolism

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Time-series NARX feedback neural network for forecasting impedance cardiography ICG missing points : a predictive model

One of the crucial steps in assessing hemodynamic parameters using impedance cardiography (ICG) is the detection of the characteristic points in the dZ/dt ICG complex, especially the X point. The most often estimated parameters from the ICG complex are stroke volume and cardiac output, for which is required the left ventricular pre-ejection time. Unfortunately, for beat-to-beat calculations, the accuracy of detection is affected by the variability of the ICG complex subtypes. Thus, in this work, we aim to create a predictive model that can predict the missing points and decrease the previous work percentages of missing points to support the detection of ICG characteristic points and the extraction of hemodynamic parameters according to several existing subtypes. Thus, a time-series non-linear autoregressive model with exogenous inputs (NARX) feedback neural network approach was implemented to forecast the missing ICG points according to the different existing subtypes. The NARX was trained on two different datasets with an open-loop mode to ensure that the network is fed with correct feedback inputs. Once the training is satisfactory, the loop can be closed for multi-step prediction tests and simulation. The results show that we can predict the missing characteristic points in all the complexes with a success rate ranging between 75% and 88% in the evaluated datasets. Previously, without the NARX predictive model, the successful detection rate was 21%–30% for the same datasets. Thus, this work indicates a promising method and an accuracy increase in the detection of X, Y, O, and Z points for both datasets

Simultaneous Recording of ICG and ECG Using Z-RPI Device with Minimum Number of Electrodes

Impedance cardiography (ICG) is a noninvasive method for monitoring mechanical function of the heart with the use of electrical bioimpedance measurements. This paper presents the feasibility of recording an ICG signal simultaneously with electrocardiogram signal (ECG) using the same electrodes for both measurements, for a total of five electrodes rather than eight electrodes. The device used is the Z-RPI. The results present good performance and show waveforms presenting high similarity with the different signals reported using different electrodes for acquisition; the heart rate values were calculated and they present accurate evaluation between the ECG and ICG heart rates. The hemodynamics and cardiac parameter results present similitude with the physiological parameters for healthy people reported in the literature. The possibility of reducing number of electrodes used for ICG measurement is an encouraging step to enabling wearable and personal health monitoring solutions

Systematic variability in ICG recordings results in ICG complex subtypes : steps towards the enhancement of ICG characterization

The quality of an impedance cardiography (ICG) signal critically impacts the calculation of hemodynamic parameters. These calculations depend solely on the identification of ICG characteristic points on the ABEXYOZ complex. Unfortunately, contrary to the relatively constant morphology of the PQRST complex in electrocardiography, the waveform morphology of ICG data is far from stationary, which causes difficulties in the accuracy of the automated detection of characteristic ICG points. This study evaluated ICG recordings obtained from 10 volunteers. The results indicate that there are several different waveforms for the ABEXYOZ complex; there are up to five clearly distinct waveforms for the ABEXYOZ complex in addition to those that are typically reported. The differences between waveform types increased the difficulty of detecting ICG points. To accurately detect all ICG points, the ABEXYOZ complex should be analyzed according to the corresponding waveform type