Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations

Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Bio-Inspired Watermarking Method for Authentication of Fundus Images in Computer-Aided Diagnosis of Retinopathy

Nowadays, medical imaging has become an indispensable tool for the diagnosis of some pathologies and as a health prevention instrument. In addition, medical images are transmitted over all types of computer networks, many of them insecure or susceptible to intervention, making sensitive patient information vulnerable. Thus, image watermarking is a popular approach to embed copyright protection, Electronic Patient Information (EPR), institution information, or other digital image into medical images. However, in the medical field, the watermark must preserve the quality of the image for diagnosis purposes. In addition, the inserted watermark must be robust both to intentional and unintentional attacks, which try to delete or weaken it. This work presents a bio-inspired watermarking algorithm applied to retinal fundus images used in computer-aided retinopathy diagnosis. The proposed system uses the Steered Hermite Transform (SHT), an image model inspired by the Human Vision System (HVS), as a spread spectrum watermarking technique, by leveraging its bio-inspired nature to give imperceptibility to the watermark. In addition, the Singular Value Decomposition (SVD) is used to incorporate the robustness of the watermark against attacks. Moreover, the watermark is embedded into the RGB fundus images through the blood vessel patterns extracted by the SHT and using the luma band of Y’CbCr color model. Also, the watermark was encrypted using the Jigsaw Transform (JST) to incorporate an extra level of security. The proposed approach was tested using the image public dataset MESSIDOR-2, which contains 1748 8-bit color images of different sizes and presenting different Diabetic Retinopathy (DR). Thus, on the one hand, in the experiments we evaluate the proposed bio-inspired watermarking method over the entire MESSIDOR-2 dataset, showing that the embedding process does not affect the quality of the fundus images and the extracted watermark, by obtaining average Peak Signal-to-Noise Ratio (PSNR) values higher to 53 dB for the watermarked images and average PSNR values higher to 32 dB to the extracted watermark for the entire dataset. Also, we tested the method against image processing and geometric attacks successfully extracting the watermarking. A comparison of the proposed method against state-of-the-art was performed, obtaining competitive results. On the other hand, we classified the DR grade of the fundus image dataset using four trained deep learning models (VGG16, ResNet50, InceptionV3, and YOLOv8) to evaluate the inference results using the originals and marked images. Thus, the results show that DR grading remains both in the non-marked and marked images

Steganography in Audio Files by Hermite Transform

This work proposes the use of the Hermite Transform (HT) for imprinting audio files with hidden information. One of the most important aspects of this kind of concealment derives from the amount of data that a host file (audio, images, data, or video) can hold. In this particular case, both the host and the hidden files are audio files. The amount of information that can be hiddenwith the suggested technique-occupies half the length of the host file. Furthermore, the use of the Hermite Transform on audio files helps improve the algorithm performance. Experimental results show that our proposal is efficient and effective, because the audio file concealment is imperceptible to human hearing. Performance of our proposal was assessed using correlation and peak signal to noise ratio. The results strengthen the effectiveness of the method

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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