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Clinical studies have previously established the role of olive products in cardiovascular disease (CVD) prevention, whilst the identification of the responsible constituents for the beneficial effects is still pending. We sought to assess and compare the cardioprotective potential of oleuropein (OL), hydroxytyrosol (HT), oleocanthal (OC) and oleanolic Acid (OA), regarding Ischemia/Reperfusion Injury (IRI) and CVD risk factors alleviation. The scope of the study was to design a potent and safe combinatorial therapy for high-cardiovascular-risk patients on a bench-to-bedside approach. We evaluated the IRI-limiting potential of 6-weeks treatment with OL, HT, OC or OA at nutritional doses, in healthy and metabolic syndrome (MS)-burdened mice. Three combinatorial regimens were designed and the mixture with preponderant benefits (OL-HT-OC, Combo 2), including infarct sparing and antiglycemic potency, compared to the isolated compounds, was further investigated for its anti-atherosclerotic effects. In vivo experiments revealed that the combination regimen of Combo 2 presented the most favorable effects in limiting infarct size and hyperglycemia, which was selected to be further investigated in the clinical setting in Chronic Coronary Artery Syndrome (CCAS) patients. Cardiac function, inflammation markers and oxidative stress were assessed at baseline and after 4 weeks of treatment with the OL-HT-OC supplement in the clinical study. We found that OL, OC and OA significantly reduced infarct size in vivo compared to Controls. OL exhibited antihyperglycemic properties and OA attenuated hypercholesterolemia. OL-HT-OA, OL-HT-OC and OL-HT-OC-OA combination regimens were cardioprotective, whereas only OL-HT-OC mitigated hyperglycemia. Combo 2 cardioprotection was attributed to apoptosis suppression, enhanced antioxidant effects and upregulation of antioxidant enzymes. Additionally, it reduced atherosclerotic plaque extent in vivo. OL-HT-OC supplement ameliorated cardiac, vascular and endothelial function in the small-scale clinical study. Conclusively, OL-HT-OC combination therapy exerts potent cardioprotective, antihyperglycemic and anti-atherosclerotic properties in vivo, with remarkable and clinically translatable cardiovascular benefits in high-risk patients.

Global rates of adolescent obesity have led the World Health Organization to consider the disease a pandemic that needs focus. In search of new anti-obesity agents, Crocus sativus, popularly known as saffron, is a nutraceutical agent, praised for its beneficial effects. The study aimed to investigate the possible effect of Kozanis saffron administration on weight management of obese prediabetic adolescents. Seventy-four obese prediabetic adolescents participated in a double-blind placebo-controlled trial of three arms, randomly assigned to receive either Kozanis saffron (n = 25, 60 mg/day), metformin (n = 25, 1000 mg/day) or a placebo (n = 24), for twelve weeks. Anthropometry, glycemic markers and lipid profiles were investigated at baseline and post-intervention. Saffron supplementation significantly reduced the weight z-score, BMI, BMI z-score and waist circumference (WC) of obese adolescents; however, this reduction was less significant compared to the effect of metformin. Metformin administration offered a significantly more profound improvement in anthropometry compared to saffron administration. Saffron administration also provided significant improvements in weight, weight z-scores, BMI values, BMI z-scores and WCs compared to the placebo. Saffron supplementation failed to change any glycemic marker, but provided a significant reduction in fasting triglyceride levels and also a significant increase in fasting HDL levels. Saffron Kozanis constitutes a promising nutraceutical option for adolescents and children with obesity and prediabetes in need of weight management.

Periodontitis is a microbially-induced inflammation of the periodontium that is characterized by the destruction of the periodontal ligament (PDL) and alveolar bone and constitutes the principal cause of teeth loss in adults. Periodontal tissue regeneration can be achieved through guided tissue/bone regeneration (GTR/GBR) membranes that act as a physical barrier preventing epithelial infiltration and providing adequate time and space for PDL cells and osteoblasts to proliferate into the affected area. Electrospun nanofibrous scaffolds, simulating the natural architecture of the extracellular matrix (ECM), have attracted increasing attention in periodontal tissue engineering. Carrageenans are ideal candidates for the development of novel nanofibrous GTR/GBR membranes, since previous studies have highlighted the potential of carrageenans for bone regeneration by promoting the attachment and proliferation of osteoblasts. Herein, we report the development of bi- and tri-layer nanofibrous GTR/GBR membranes based on carrageenans and other biocompatible polymers for the regeneration of periodontal tissue. The fabricated membranes were morphologically characterized, and their thermal and mechanical properties were determined. Their periodontal tissue regeneration potential was investigated through the evaluation of cell attachment, biocompatibility, and osteogenic differentiation of human PDL cells seeded on the prepared membranes.

The circulation of SARS-CoV-2 omicron BA.4 and BA.5 subvariants with enhanced transmissibility and capacity for immune evasion resulted in a recent pandemic wave that began in April–May of 2022. We performed a statistical phylogeographic study that aimed to define the cross-border transmission patterns of BA.4 and BA.5 at the earliest stages of virus dispersal. Our sample included all BA.4 and BA.5 sequences that were publicly available in the GISAID database through mid-May 2022. Viral dispersal patterns were inferred using maximum likelihood phylogenetic trees with bootstrap support. We identified South Africa as the major source of both BA.4 and BA.5 that migrated to other continents. By contrast, we detected no significant export of these subvariants from Europe. Belgium was identified as a major hub for BA.4 transmission within Europe, while Portugal and Israel were identified as major sources of BA.5. Western and Northern European countries exhibited the highest rates of cross-border transmission, as did several popular tourist destinations in Southern and Central/Western Europe. Our study provides a detailed map of the early dispersal patterns of two highly transmissible SARS-CoV-2 omicron subvariants at a time when there was an overall relaxation of public health measures in Europe.

Our study aims to describe the global distribution and dispersal patterns of the SARS-CoV-2 Omicron subvariants. Genomic surveillance data were extracted from the CoV-Spectrum platform, searching for BA.1*, BA.2*, BA.3*, BA.4*, and BA.5* variants by geographic region. BA.1* increased in November 2021 in South Africa, with a similar increase across all continents in early December 2021. BA.1* did not reach 100% dominance in all continents. The spread of BA.2*, first described in South Africa, differed greatly by geographic region, in contrast to BA.1*, which followed a similar global expansion, firstly occurring in Asia and subsequently in Africa, Europe, Oceania, and North and South America. BA.4* and BA.5* followed a different pattern, where BA.4* reached high proportions (maximum 60%) only in Africa. BA.5* is currently, by Mid-August 2022, the dominant strain, reaching almost 100% across Europe, which is the first continent aside from Africa to show increasing proportions, and Asia, the Americas, and Oceania are following. The emergence of new variants depends mostly on their selective advantage, translated as enhanced transmissibility and ability to invade people with existing immunity. Describing these patterns is useful for a better understanding of the epidemiology of the VOCs’ transmission and for generating hypotheses about the future of emerging variants.

Abstract Objectives Tissue hypoxia is the main cause of multi-organ dysfunction in sepsis. However, effective pharmacological treatments to combat sepsis-induced tissue hypoxia are not available. Emerging experimental and clinical evidence reveals an evolutionary conserved action of thyroid hormone (TH) to adapt injured tissue to hypoxic conditions via its action on p38 MAPK, Akt signaling pathways. In addition, TH has favorable effects on the immune system and viral load in infected tissue. Non-Thyroid Illness Syndrome is common in sepsis, acute myocardial infarction and trauma and is associated with increased mortality. Thus, TH may be a novel treatment in the setting of critical illness due to viral infection in which hypoxia prevails. The present study aims to address the efficacy and safety of acute administration of triiodothyronine (T3) in critically ill COVID-19 infected patients requiring mechanical respiratory support or Extra Corporeal Membrane Oxygenation (ECMO). Trial design This study is a phase II, parallel, 2-arm (1:1 ratio), multi-centre, prospective, randomized, double-blind, placebo controlled trial. Participants Male and female patients aged over 18 years old who are diagnosed with pulmonary infection due to COVID-19, admitted to Intensive Care Unit and requiring mechanical ventilation or ECMO will be enrolled in this trial. Patients will be excluded in cases of pregnancy, severe systemic disease with life expectancy less than 6 months, participation in another trial of an investigational drug or device, corticosteroid and/or sympathomimetic use before initiation of treatment. All data will be collected in electronic CRF files. Participants will start to be recruited from the ICU center of “ATTIKO” University Hospital in Greece. We aim to include two more clinical sites in the trial one from Greece and one from Germany Intervention and comparator Intervention: T3 Solution for injection 10 μg/ml. The dose administered will be 0.8g/kg i.v. bolus and will be followed by an infusion of 0.113g. kg-1.h-1 i.v. for 48 hours (therapeutic dose). After the first 48h, a maintenance dose will be administered corresponding to 50% of the therapeutic dose (0.057g. kg-1.h-1 i.v.). Drug administration will stop after successful weaning or end of follow up (maximum 30 days). Comparator: Placebo with composition and dosage identical apart from the active substance. Main outcomes The primary outcome assessed in the present study will be the percentage of patients successfully weaned after 30 days of follow-up. Successful weaning is defined as no requirement for ventilatory support after extubation (mechanical support) or support from ECMO for 48 hours. Randomisation An allocation sequence to one of the groups will be prepared by the Sponsor of the study. A 1:1 treatment allocation will be adopted. An electronic CRF will be used incorporating IWRS in order to assure proper randomization and unblinding in emergency cases. The representative of the sponsor will get a copy of randomization codes. The information of the randomization codes will then be locked in the database until the time at which an interim analysis or final analysis is performed. Blinding (masking) Participants, caregivers, and all investigators assessing the outcomes will be blinded to group assignment. Numbers to be randomised (sample size) The sample size of 60 patients (that indicates 30 subjects for each group) will have 84% power to detect the estimated difference between the two study groups. The criterion for significance (alpha) has been set at 0.05 and the test is 2-tailed. Trial Status Protocol number T3inj-02/ThySupport, version 03, May 11, 2020. The trial is not recruiting yet. The trial will start recruitment June 18th 2020. Estimated recruitment will finish June 18th, 2021. Trial registration Triiodothyronine for the Treatment of Critically Ill Patients With COVID-19 Infection (Thy-Support), ClinicalTrials.gov Identifier: NCT04348513, date of trial registration: April 16, 2020, EudraCT Identifier: 2020-001623-13, date of trial registration: April 22, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Hot flashes are considered the most bothersome complaint during menopause. Although hormone therapy is an effective option to relieve hot flashes, it has been associated with significant side effects. The aim of our study is to suggest a novel combination of different plant extracts with distinct mechanisms of action against hot flashes. We selected the rhizome of Glycyrrhiza glabra L. (Fabaceae), the rhizome of Actaea racemosa L. (Ranunculaceae), the aerial parts of Hypericum perforatum L. (Hypericaceae) to produce extracts rich in bioactive phytochemicals and the seed oil of Oenothera biennis L. (Onagraceae). We investigated their estrogenic and antioxidant potential and their inhibitory effect against prostaglandin D2 receptor 1 (DP1) as a novel mechanistic pathway for vasodilation in hot flashes, alone or in combination. The phytochemical footprint of the extracts was analyzed using HPLC-PDA and UPLC-HRMS. We observed that the tested extracts possess different mechanisms of action. A. racemosa exerts a beneficial activation of the estrogen receptor, H. perforatum possesses the highest antioxidant capacity and the seed oil of O. biennis inhibits the DP1 receptor. The triple combination in the optimal doses pertains to efficacy against all three mechanisms of action, serves as a multitarget plant-based therapy and could serve as a novel strategy for the alleviation of hot flashes in postmenopausal women.

Some emergent SARS-CoV-2 variants raise concerns due to their altered biological properties. For both B.1.1.7 and B.1351 variants, named as variants of concern (VOC), increased transmissibility was reported, whereas B.1.351 was more resistant to multiple monoclonal antibodies (mAbs), as well as convalescent and vaccination sera. To test this hypothesis, we examined the proportion of VOC over time across different geographic areas where the two VOC, B.1.1.7 and B.1.351, co-circulate. Our comparative analysis was based on the number of SARS-CoV-2 sequences on GISAID database. We report that B.1.1.7 dominates over B.1.351 in geographic areas where both variants co-circulate and the B.1.1.7 was the first variant introduced in the population. The only areas where B.1.351 was detected at higher proportion were South Africa and Mayotte in Africa, where this strain was associated with increased community transmission before the detection of B.1.1.7. The dominance of B.1.1.7 over B.1.351 could be important since B.1.351 was more resistant to certain mAbs, as well as heterologous convalescent and vaccination sera, thus suggesting that it may be transmitted more effectively in people with pre-existing immunity to other VOC. This scenario would lessen the effectiveness of vaccine and urge the need to update them with new strains.