Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial.

BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. FINDINGS: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group. CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease. TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.

An agent-based model for studying the temperature changes on environments exposed to magnetic fluid hyperthermia.

Magnetic fluid hyperthermia (MFH) is a technique whose results show promise in the treatment against cancer, but which still faces obstacles such as controlling the spatial distribution of temperature. The present study developed an agent-based model in order to simulate the temperature changes in an aqueous environment submitted to the magnetic fluid hyperthermia technique. The developed model was built with its parameters based on the clinical treatment protocol for glioblastoma multiforme (GBM). Using thermodynamic properties of magnetic fluid and tissues, we define a specific thermal parameter (α) and evaluate its influence, together with the intensity of the external magnetic field (H), on the dynamics of the temperature of the cancer environment. The temperature evolution generated by the model was in accordance with experimental results known from the subject literature. The parameters evaluation indicates that the temperature stabilization of the tumor environment during MFH treatment is due to the local interactions of energy diffusion, as well as indicating that the α-parameter is a key factor for controlling the temperature and heating speed.

Protective Effect of Betulin on Streptozotocin-Nicotinamide-Induced Diabetes in Female Rats.

Type 2 diabetes is characterized by hyperglycemia and a relative loss of ß-cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin-nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α-amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of ß-cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes.

Sargassum natans I Algae: An Alternative for a Greener Approach for the Synthesis of ZnO Nanostructures with Biological and Environmental Applications.

In this work, the influence of the Sargassum natans I alga extract on the morphological characteristics of synthesized ZnO nanostructures, with potential biological and environmental applications, was evaluated. For this purpose, different ZnO geometries were synthesized by the co-precipitation method, using Sargassum natans I alga extract as stabilizing agent. Four extract volumes (5, 10, 20, and 50 mL) were evaluated to obtain the different nanostructures. Moreover, a sample by chemical synthesis, without the addition of extract, was prepared. The characterization of the ZnO samples was carried out by UV-Vis spectroscopy, FT-IR spectroscopy, X-ray diffraction, and scanning electron microscopy. The results showed that the Sargassum alga extract has a fundamental role in the stabilization process of the ZnO nanoparticles. In addition, it was shown that the increase in the Sargassum alga extract leads to preferential growth and arrangement, obtaining well-defined shaped particles. ZnO nanostructures demonstrated significant anti-inflammatory response by the in vitro egg albumin protein denaturation for biological purposes. Additionally, quantitative antibacterial analysis (AA) showed that the ZnO nanostructures synthesized with 10 and 20 mL of extract demonstrated high AA against Gram (+) S. aureus and moderate AA behavior against Gram (-) P. aeruginosa, depending on the ZnO arrangement induced by the Sargassum natans I alga extract and the nanoparticles' concentration (ca. 3200 µg/mL). Additionally, ZnO samples were evaluated as photocatalytic materials through the degradation of organic dyes. Complete degradation of both methyl violet and malachite green were achieved using the ZnO sample synthesized with 50 mL of extract. In all cases, the well-defined morphology of ZnO induced by the Sargassum natans I alga extract played a key role in the combined biological/environmental performance.

Sequential Biorefining of Bioactive Compounds of High Functional Value from Calafate Pomace (Berberis microphylla) Using Supercritical CO2 and Pressurized Liquids.

A biorefinery process was developed for a freeze-dried pomace of calafate berries (Berberis microphylla). The process consisted of extraction of lipophilic components with supercritical CO2 (scCO2) and subsequent extraction of the residue with a pressurized mixture of ethanol/water (1:1 v/v). scCO2 extracted oil from the pomace, while pressurized liquid extraction generated a crude extract rich in phenols and a residue rich in fiber, proteins and minerals. Response surface analysis of scCO2 extraction suggested optimal conditions of 60 °C, 358.5 bar and 144.6 min to obtain a lipid extract yield of 11.15% (d.w.). The dark yellow oil extract contained a good ratio of ω6/ω3 fatty acids (1:1.2), provitamin E tocopherols (406.6 mg/kg), and a peroxide index of 8.6 meq O2/kg. Pressurized liquid extraction generated a polar extract with good phenolic content (33 mg gallic acid equivalents /g d.w.), anthocyanins (8 mg/g) and antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl test = 25 µg/mL and antioxidant activity = 63 µM Te/g). The extraction kinetics of oil by scCO2 and phenolic compounds were optimally adjusted to the spline model (R2 = 0.989 and R2 = 0.999, respectively). The solid extracted residue presented a fiber content close to cereals (56.4% d.w.) and acceptable values of proteins (29.6% d.w.) and minerals (14.1% d.w.). These eco-friendly processes valorize calafate pomace as a source of ingredients for formulation of healthy foods, nutraceuticals and nutritional supplements.

Antibacterial and Anti-Inflammatory Properties of ZnO Nanoparticles Synthesized by a Green Method Using Sargassum Extracts.

The present work shows the synthesis of ZnO nanoparticles through a green method, using sargassum extracts, which provide the reducing and stabilizing compounds. The conditions of the medium in which the reaction was carried out was evaluated, that is, magnetic stirring, ultrasound assisted, and resting condition. UV-Vis, FTIR spectroscopy, and X-ray diffraction results confirmed the synthesis of ZnO with nanometric crystal size. The scanning electron microscopy analysis showed that the morphology and size of the particles depends on the synthesis condition used. It obtained particles between 20 and 200 nm in the sample without agitation, while the samples with stirring and ultrasound were 80 nm and 100 nm, respectively. ZnO nanoparticles showed antibacterial activity against Gram-positive S. aureus and Gram-negative P. aeruginosa. A quantitative analysis was performed by varying the concentration of ZnO nanoparticles. In all cases, the antibacterial activity against Gram-positives was greater than against Gram-negatives. Ultrasound-assisted ZnO nanoparticles showed the highest activity, around 99% and 80% for S. aureus and P. aeruginosa, respectively. Similar results were obtained in the study of the anti-inflammatory activity of ZnO nanoparticles; the ultrasound-assisted sample exhibited the highest percentage (93%), even above that shown by diclofenac, which was used as a reference. Therefore, the ZnO nanoparticles synthesized with sargassum extracts have properties that can be used safely and efficiently in the field of biomedicine.

Qigong Training Positively Impacts Both Posture and Mood in Breast Cancer Survivors With Persistent Post-surgical Pain: Support for an Embodied Cognition Paradigm.

Theories of embodied cognition hypothesize interdependencies between psychological well-being and physical posture. The purpose of this study was to assess the feasibility of objectively measuring posture, and to explore the relationship between posture and affect and other patient centered outcomes in breast cancer survivors (BCS) with persistent postsurgical pain (PPSP) over a 12-week course of therapeutic Qigong mind-body training. Twenty-one BCS with PPSP attended group Qigong training. Clinical outcomes were pain, fatigue, self-esteem, anxiety, depression, stress and exercise self-efficacy. Posture outcomes were vertical spine and vertical head angles in the sagittal plane, measured with a 3D motion capture system in three conditions: eyes open (EO), eyes open relaxed (EOR) and eyes closed (EC). Assessments were made before and after the Qigong training. The association between categorical variables (angle and mood) was measured by Cramer's V. In the EO condition, most participants who improved in fatigue and anxiety scales also had better vertical head values. For the EOR condition, a moderate correlation was observed between changes in vertical head angle and changes in fatigue scale. In the EC condition, most of the participants who improved in measures of fatigue also improved vertical head angle. Additionally, pain severity decreased while vertical spine angle improved. These preliminary findings support that emotion and other patient centered outcomes should be considered within an embodied framework, and that Qigong may be a promising intervention for addressing biopsychosocially complex interventions such as PPSP in BCSs.

Use of Tribulus terrestris and Lepidium meyenii extract in rats: reproductive, biochemical and body parameters.

The oral administration of Tribulus terrestris and Lepidium meyenii extracts on reproductive, biochemical and body parameters was evaluated in rats. Thirty-six male Wistar rats weighting 210 ± 18 g were divided into six experimental groups (n = 6). Each group received, daily for 28 days, different solutions: T. terrestris (100 mg/kg), L. meyenii (1 g/kg) and T. terrestris at doses of 75, 50 and 25 mg/kg combined with L. meyenii at doses of 0.25, 0.5 and 0.75 g/kg, respectively, and distilled water (control). T. terrestris increased (p < 0.05) the serum testosterone, regardless of dose. Combined use of the extracts increased (p < 0.05) the diameter of the epididymal duct and epididymis lumen. The combinations of T. terrestris (75 and 50 mg/kg) with L. meyenii increased (p < 0.05) the sperm concentration. There were no differences (p > 0.05) in the other semen characteristics; relative weight of organs; and serum levels of urea, creatinine, alanine and aspartate transaminase, gamma glutamyl transferase, cholesterol, triglycerides, glucose, follicle-stimulating hormone and luteinizing hormone. No histopathological changes were observed (p > 0.05). It is concluded that the association of T. terrestris and L. meyenii has positive effects on serum testosterone, sperm concentration and epididymal morphology, with no evidence of effects in the testis, liver, spleen and kidneys.

Physical activity and metabolic syndrome severity among older adults at cardiovascular risk: 1-Year trends.

BACKGROUND AND AIMS: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk. METHODS AND RESULTS: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time. CONCLUSION: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk.

Coenzyme Q10 and Cardiovascular Diseases.

Coenzyme Q10 (CoQ10), which plays a key role in the electron transport chain by providing an adequate, efficient supply of energy, has another relevant function as an antioxidant, acting in mitochondria, other cell compartments, and plasma lipoproteins. CoQ10 deficiency is present in chronic and age-related diseases. In particular, in cardiovascular diseases (CVDs), there is a reduced bioavailability of CoQ10 since statins, one of the most common lipid-lowering drugs, inhibit the common pathway shared by CoQ10 endogenous biosynthesis and cholesterol biosynthesis. Different clinical trials have analyzed the effect of CoQ10 supplementation as a treatment to ameliorate these deficiencies in the context of CVDs. In this review, we focus on recent advances in CoQ10 supplementation and the clinical implications in the reduction of cardiovascular risk factors (such as lipid and lipoprotein levels, blood pressure, or endothelial function) as well as in a therapeutic approach for the reduction of the clinical complications of CVD.

New device for active gastric mechanical stimulation.

BACKGROUND: Gastroparesis is a chronic stomach disorder and effective treatment is the aim of different strategies. Alternative therapies consist of an electrical stimulation of the stomach to evoke a response in the gastric activity. We present the development and in vivo application of an electromagnet system to induce a mechanical stimulus in the stomach aiming for gastric contractile responses. METHODS: The electromagnet system consisted of an implantable magnet and an external drive coil. We implanted the magnet at the greater curvature of the gastric body in rats. We applied an alternating current to the drive coils, inducing mechanical stimulation of the gastric wall. We measured the gastric contraction activity and gastric electrical activity in response to the stimulus using AC biosusceptometry and electrogastrography. Moreover, we used the phenol red to evaluate the stimulus effects on gastrointestinal transit. KEY RESULTS: The stimulus increased the spectral intensity and signal-to-noise ratio significantly of gastric contraction activity and gastric electrical activity. Furthermore, we found a lower phenol red retention in the stomach in rats without stimulus. No significant differences were found in frequency and root mean square amplitude. CONCLUSIONS & INFERENCES: We developed a new simple electromagnet system that evoked a contraction and gastric electrical response using a mechanical stimulus and decreased gastric emptying time. The system is an accessible tool and may contribute to gastroparesis studies in animals.

Consumption of caffeinated beverages and kidney function decline in an elderly Mediterranean population with metabolic syndrome.

It remains unclear whether caffeinated beverages could have deleterious renal effects in elderly population with underlying comorbid conditions. We investigated the associations between coffee, tea, or caffeine intake and 1-year changes in glomerular filtration rate (eGFR) in a large Spanish cohort of overweight/obese elderly with metabolic syndrome (MetS). This prospective analysis includes 5851 overweight/obese adults (55-75 years) with MetS from the PREDIMED-Plus study. We assessed coffee, tea, and caffeine consumption from a validated food-frequency questionnaire and creatinine-based eGFR using the Chronic Kidney Disease Epidemiology Collaboration equation. Multivariate-adjusted regression models were applied to test associations between baseline coffee, tea, or caffeine intake and 1-year eGFR changes. Caffeinated coffee (> 2 cups/day) and tea (at least 1 cup/day) drinkers had 0.88 and 0.93 mL/min/1.73 m2 greater eGFR decrease respectively, compared to those with less than 1 cup/day of coffee consumption or non-tea drinkers. Furthermore, caffeinated coffee consumption of > 2 cups/day was associated with 1.19-fold increased risk of rapid eGFR decline > 3 mL/min/1.73 m2 (95% CI 1.01-1.41). Similarly, individuals in the highest (median, 51.2 mg/day) tertile of caffeine intake had a 0.87 mL/min/1.73 m2 greater eGFR decrease. Decaffeinated coffee was not associated with eGFR changes. In conclusion, higher consumption of caffeinated coffee, tea, and caffeine was associated with a greater 1-year eGFR decline in overweight/obese adults with MetS.

Biosaline agriculture: an agronomic proposal for onion (Allium cepa L.) production.

NOVELTY STATEMENT: The onion crop with brackish irrigation but accompanied by halophytes is productive, so halophytoremediation is an excellent agronomic proposal for areas where there is poor quality water used for irrigation.

MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study.

BACKGROUND AND AIM: The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. METHODS: All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. RESULTS: Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. CONCLUSION: Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease. CLINICAL TRIALS NUMBER: NCT00924937.

Frequência Alfa na meditação Gurdjieff / Alpha Frequency in Gurdjieff Meditation

Introdução: a meditação é uma prática que visa regular o estado mental e as emoções, podendo induzir a estados alterados de consciência. Dentre inúmeras técnicas de meditação, o trabalho proposto por George I. Gurdjieff, inclui práticas voltadas para o recolhimento da atenção e o equilíbrio entre a atividade do corpo, da mente e do sentimento. Estudos realizados com eletroencefalografia (EEG), avaliando o estado meditativo em geral, demonstraram um padrão cerebral caracterizado pelo aumento da amplitude dos ritmos eletroencefalográficos alfa e teta, bem como diferenças na atividade alfa entre a meditação e o relaxamento. Entretanto, isto não está caracterizado em meditadores da linha de G.I. Gurdjieff, que praticam, além de meditações sentadas, exercícios corporais acompanhados de uma música própria e exercícios de atenção durante a vida diária. Objetivo: comparar a atividade cerebral da frequência alfa durante os estágios de meditação e relaxamento e avaliar as diferenças entre as regiões frontal, central e occipital nesses dois estados, em meditadores experientes do grupo Gurdjieff, de Salvador-Bahia-Brasil. Metodologia: a coleta da atividade cerebral dos 8 voluntários foi realizada através do EEG. O protocolo de coleta adotado foi de 6 minutos de relaxamento e 12 minutos de meditação. Resultados: foi encontrado aumento significativo da potência alfa durante a meditação, quando comparada ao relaxamento. As regiões frontal e central não apresentaram diferenças entre si para a potência alfa, enquanto a região occipital apresentou aumento da potência alfa em comparação com as regiões frontal e central. Existe um aumento da densidade de alfa durante a meditação em todas as regiões cerebrais testadas, com maior densidade na região occipital. Conclusão: A frequência alfa comporta-se de forma diferente durante a meditação, comparada ao relaxamento, com um aumento da densidade de potência durante o estado meditativo em todas as regiões avaliadas, sendo a região occipital a que apresentou maior potência.

Introduction: meditation is a practice that aims to regulate the mental state and emotions, and can induce altered states of consciousness. Among numerous meditation techniques, the work proposed by George I. Gurdjieff, includes an attempt to balance activities from the body, the mind and the feelings. Studies conducted with electroencephalography (EEG), evaluating the meditative tate, demonstrated a brain pattern characterized by increased alpha and theta amplitude, as well as differences in alpha activity between meditation and relaxation. However, this is not characterized in Gurdjieff meditators, which practice beyond sitted meditations, body exercises with music, and attentional exercises during everyday life. Objective: comparing the brain activity of the alpha power during the meditation and relaxation stages and evaluate the differences between the frontal, central and occipital regions in these two states, in experienced meditators from the Gurdjieff group, in Salvador-Bahia-Brazil. Methodology: the data collection of the brain activity from 8 volunteers was performed by EEG. The collection protocol adopted was 6 minutes of relaxation and 12 minutes of meditation. Results: a significant increase in alpha power was found during meditation, when compared to relaxation. The frontal and central regions showed no differences between them for alpha power, while the occipital region showed an increase in alpha power compared to the frontal and central regions. Conclusion: the alpha frequency behaves differently during meditation, compared to relaxation, with an increase in alpha density during the meditative state in all evaluated regions, with the occipital region being the most potent.

Coenzyme Q10 Supplementation for the Reduction of Oxidative Stress: Clinical Implications in the Treatment of Chronic Diseases.

Apart from its main function in the mitochondria as a key element in electron transport, Coenzyme Q10 (CoQ10) has been described as having multiple functions, such as oxidant action in the generation of signals and the control of membrane structure and phospholipid and cellular redox status. Among these, the most relevant and most frequently studied function is the potent antioxidant capability of its coexistent redox forms. Different clinical trials have investigated the effect of CoQ10 supplementation and its ability to reduce oxidative stress. In this review, we focused on recent advances in CoQ10 supplementation, its role as an antioxidant, and the clinical implications that this entails in the treatment of chronic diseases, in particular cardiovascular diseases, kidney disease, chronic obstructive pulmonary disease, non-alcoholic fatty liver disease, and neurodegenerative diseases. As an antioxidant, CoQ10 has proved to be of potential use as a treatment in diseases in which oxidative stress is a hallmark, and beneficial effects of CoQ10 have been reported in the treatment of chronic diseases. However, it is crucial to reach a consensus on the optimal dose and the use of different formulations, which vary from ubiquinol or ubiquinone Ubisol-Q10 or Qter®, to new analogues such as MitoQ, before we can draw a clear conclusion about its clinical use. In addition, a major effort must be made to demonstrate its beneficial effects in clinical trials, with a view to making the implementation of CoQ10 possible in clinical practice.

"Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study".

OBJECTIVE: The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. DESIGN: Parallel pilot randomized open label, double-masked clinical trial. SETTING: University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) PARTICIPANTS: 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). PROCEDURES: All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. RESULTS: Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002-0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. CONCLUSION: Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

Analytical Technology in Nutrition Analysis.

The great challenge facing humanity in the coming decades is to secure food for the 9 [...].

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study.

Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membrane-camouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe2O4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (tmax), as well as changes in DE and tmax due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.