Antioxidant and Immune-Related Implications of Minerals in COVID-19: A Possibility for Disease Prevention and Management

Since the coronavirus disease 2019 (COVID-19) pandemic appeared, both governments and the scientific community have focused their efforts on the search for prophylactic and therapeutic alternatives in order to reduce its effects. Vaccines against SARS-CoV-2 have been approved and administered, playing a key role in the overcoming of this situation. However, they have not reached the whole world population, and several doses will be needed in the future in order to successfully protect individuals. The disease is still here, so other strategies should be explored with the aim of supporting the immune system before and during the infection. An adequate diet is certainly associated with an optimal inflammatory and oxidative stress status, as poor levels of different nutrients could be related to altered immune responses and, consequently, an augmented susceptibility to infections and severe outcomes derived from them. Minerals exert a wide range of immune-modulatory, anti-inflammatory, antimicrobial, and antioxidant activities, which may be useful for fighting this illness. Although they cannot be considered as a definitive therapeutic solution, the available evidence to date, obtained from studies on similar respiratory diseases, might reflect the rationality of deeper investigations of the use of minerals during this pandemic

Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms

This manuscript was supported by the Vicerrectorado de Investigacion y Transferencia of University of Granada, "Programa de Estimulacion a la Investigacion".Since the appearance of the coronavirus disease 2019 (COVID-19) and its announcement as a global pandemic, the search for prophylactic and therapeutic options have become a priority for governments and the scientific community. The approval of several vaccines against SARS-CoV-2 is being crucial to overcome this situation, although the victory will not be achieved while the whole population worldwide is not protected against the virus. This is why alternatives should be studied in order to successfully support the immune system before and during a possible infection. An optimal inflammatory and oxidative stress status depends on an adequate diet. Poor levels of several nutrients could be related to an impaired immune response and, therefore, an increased susceptibility to infection and serious outcomes. Vitamins exert a number of anti-microbial, immunomodulatory, anti-inflammatory, and antioxidant activities, which can be of use to fight against this and several other diseases (especially vitamin D and C). Even though they cannot be considered as a definitive therapeutic option, in part owing to the lack of solid conclusions from well-designed clinical trials, currently available evidence from similar respiratory diseases may indicate that it would be rational to deeply explore the use of vitamins during this global pandemic.Vicerrectorado de Investigacion y Transferencia of University of Granada, "Programa de Estimulacion a la Investigacion

The Role of Endocrine Disrupting Chemicals in Gestation and Pregnancy Outcomes

This research was funded by the Plan Propio de Investigación de la Universidad de Granada of Spain (grant number PP2022.PP-07). J.M.T. and M.P.-J. are grateful to the Ph.D. Excellence Program “Nutrición y Ciencias de los Alimentos” from the University of Granada. J.M.T. was supported by an FPU contract with grant reference FPU21/04865 funded by the Ministry of Education of Spain.Endocrine disrupting chemicals (EDCs) are exogenous substances widely disseminated both in the environment and in daily-life products which can interfere with the regulation and function of the endocrine system. These substances have gradually entered the food chain, being frequently found in human blood and urine samples. This becomes a particularly serious issue when they reach vulnerable populations such as pregnant women, whose hormones are more unstable and vulnerable to EDCs. The proper formation and activity of the placenta, and therefore embryonic development, may get seriously affected by the presence of these chemicals, augmenting the risk of several pregnancy complications, including intrauterine growth restriction, preterm birth, preeclampsia, and gestational diabetes mellitus, among others. Additionally, some of them also exert a detrimental impact on fertility, thus hindering the reproductive process from the beginning. In several cases, EDCs even induce cross-generational effects, inherited by future generations through epigenetic mechanisms. These are the reasons why a proper understanding of the reproductive and gestational alterations derived from these substances is needed, along with efforts to establish regulations and preventive measures in order to avoid exposition (especially during this particular stage of life).Universidad de Granada PP2022.PP-07Ministry of Education of Spain FPU21/0486

Basal VEGF-A and ACE Plasma Levels of Metastatic Colorectal-Cancer Patients Have Prognostic Value for First-Line Treatment with Chemotherapy Plus Bevacizumab

The identification of factors that respond to anti-angiogenic therapy would represent a significant advance in the therapeutic management of metastatic-colorectal-cancer (mCRC) patients. We previously reported the relevance of VEGF-A and some components of the renin–angiotensin-aldosterone system (RAAS) in the response to anti-angiogenic therapy in cancer patients. Therefore, this prospective study aims to evaluate the prognostic value of basal plasma levels of VEGF-A and angiotensin-converting enzyme (ACE) in 73 mCRC patients who were to receive bevacizumab-based therapies as a first-line treatment. We found that high basal VEGF-A plasma levels were significantly associated with worse overall survival (OS) and progression-free survival (FPS). On the other hand, low ACE levels were significantly associated with poor OS. Importantly, a simple scoring system combining the basal plasma levels of VEGF-A and ACE efficiently stratified mCRC patients, according to OS, into high-risk or low-risk groups, prior to their treatment with bevacizumab. In conclusion, our study supports that VEGF-A and ACE may be potential biomarkers for selecting those mCRC patients who will most benefit from receiving chemotherapy plus bevacizumab treatment in first-line therapy. Additionally, our data reinforce the notion of a close association between the RAAS and the anti-angiogenic response in cancer

Article Ubiquinol Short-Term Supplementation Prior to Strenuous Exercise Improves Physical Performance and Diminishes Muscle Damage

The benefits of physical exercise on health are diminished when it is non-planned, strenuous, or vigorous, which causes an increase in oxygen consumption and production of free radicals, particularly serious at the muscular level. Ubiquinol could help achieve an antioxidant, anti-inflammatory, and ergogenic effect. The aim of this study is to evaluate whether a supplementation of ubiquinol during a short period could have a positive effect on muscle aggression, physical performance, and fatigue perception in non-elite athletes after high intensity circuit weight training. One hundred healthy and well-trained men, (firemen of the Fire Department of Granada) were enrolled in a placebocontrolled, double-blinded, and randomized study, and separated into two groups: the placebo group (PG, n = 50); and the ubiquinol group (UG, n = 50), supplemented with an oral dose. Before and after the intervention, data related to the number of repetitions, muscle strength, and perceived exertion, as well as blood samples were collected. An increase was observed in the UG regarding average load and repetitions, revealing an improvement in muscle performance. Ubiquinol supplementation also reduced muscle damage markers, showing a protective effect on muscle fibers. Therefore, this study provides evidence that ubiquinol supplementation improves muscle performance and prevents muscle damage after strenuous exercise in a population of well-trained individuals who are not elite athletes.FPU contract with grant reference FPU21/04865Ministry of Education of Spai

The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly inflammatory microenvironment and liquid biopsy has emerged as a promising tool for the noninvasive analysis of this tumor. In this study, plasma was obtained from 58 metastatic PDAC patients, and neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), circulating cell-free DNA (cfDNA) concentration, and circulating RAS mutation were determined. We found that NLR was significantly associated with both overall survival (OS) and progression-free survival. Remarkably, NLR was an independent risk factor for poor OS. Moreover, NLR and PLR positively correlated, and combination of both inflammatory markers significantly improved the prognostic stratification of metastatic PDAC patients. NLR also showed a positive correlation with cfDNA levels and RAS mutant allelic fraction (MAF). Besides, we found that neutrophil activation contributed to cfDNA content in the plasma of metastatic PDAC patients. Finally, a multi-parameter prognosis model was designed by combining NLR, PLR, cfDNA levels, RAS mutation, RAS MAF, and CA19-9, which performs as a promising tool to predict the prognosis of metastatic PDAC patients. In conclusion, our study supports the idea that the use of systemic inflammatory markers along with circulating tumor-specific markers may constitute a valuable tool for the clinical management of metastatic PDAC patients

Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer

Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients’ outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients

Daytime and nighttime aerosol optical depth implementation in CÆLIS

The University of Valladolid (UVa, Spain) has managed a calibration center of the AErosol RObotic NETwork (AERONET) since 2006. The CÆLIS software tool, developed by UVa, was created to manage the data generated by AERONET photometers for calibration, quality control and data processing purposes. This paper exploits the potential of this tool in order to obtain products like the aerosol optical depth (AOD) and Ångström exponent (AE), which are of high interest for atmospheric and climate studies, as well as to enhance the quality control of the instruments and data managed by CÆLIS. The AOD and cloud screening algorithms implemented in CÆLIS, both based on AERONET version 3, are described in detail. The obtained products are compared with the AERONET database. In general, the differences in daytime AOD between CÆLIS and AERONET are far below the expected uncertainty of the instrument, ranging in mean differences between −1.3×10−4 at 870 nm and 6.2×10−4 at 380 nm. The standard deviations of the differences range from 2.8×10−4 at 675 nm to 8.1×10−4 at 340 nm. The AOD and AE at nighttime calculated by CÆLIS from Moon observations are also presented, showing good continuity between day and nighttime for different locations, aerosol loads and Moon phase angles. Regarding cloud screening, around 99.9 % of the observations classified as cloud-free by CÆLIS are also assumed cloud-free by AERONET; this percentage is similar for the cases considered cloud-contaminated by both databases. The obtained results point out the capability of CÆLIS as a processing system. The AOD algorithm provides the opportunity to use this tool with other instrument types and to retrieve other aerosol products in the future. This research has been supported by the Spanish Ministry of Science and Innovation (grant no. RTI2018-097864-B-I00) and the European Union's Horizon 2020 research and innovation program (grant no. 871115).The authors gratefully thank AERONET and PHOTONS teams for the collaboration and support. The authors thank the Spanish Ministry of Science, Innovation and Universities for the support through the ePOLAAR project (RTI2018-097864-B-I00). This research has been supported by the Spanish Ministry of Science and Innovation (grant no. RTI2018-097864-B-I00) and the European Union's Horizon 2020 research and innovation program (grant no. 871115)

Aerosol characterization at the Saharan AERONET site Tamanrasset

More than 2 years of columnar atmospheric aerosol measurements (2006–2009) at the Tamanrasset site (22.79° N, 5.53° E, 1377 m a.s.l.), in the heart of the Sahara, are analysed. Aerosol Robotic Network (AERONET) level 2.0 data were used. The KCICLO (K is the name of a constant and ciclo means cycle in Spanish) method was applied to a part of the level 1.5 data series to improve the quality of the results. The annual variability of aerosol optical depth (AOD) and Ångström exponent (AE) has been found to be strongly linked to the convective boundary layer (CBL) thermodynamic features. The dry-cool season (autumn and winter) is characterized by a shallow CBL and very low mean turbidity (AOD ~ 0.09 at 440 nm, AE ~ 0.62). The wet-hot season (spring and summer) is dominated by high turbidity of coarse dust particles (AE ~ 0.28, AOD ~ 0.39 at 440 nm) and a deep CBL. The aerosol-type characterization shows desert mineral dust as the prevailing aerosol. Both pure Saharan dust and very clear sky conditions are observed depending on the season. However, several case studies indicate an anthropogenic fine mode contribution from the industrial areas in Libya and Algeria. The concentration weighted trajectory (CWT) source apportionment method was used to identify potential sources of air masses arriving at Tamanrasset at several heights for each season. Microphysical and optical properties and precipitable water vapour were also investigated.The AERONET sun photometer at Tamanrasset has been calibrated within AERONET-EUROPE TNA supported by the PHOTONS and RIMA networks and partially financed by the European Community – Research Infrastructure Action under the Seventh Framework Programme (FP7/2007-2013) “Capacities” specific programme for Integrating Activities, ACTRIS grant agreement no. 262254. Financial support from the Spanish MINECO (projects CGL2011-23413, CGL2012-33576 and CGL2012-37505) is also gratefully acknowledged. J. M. Baldasano and S. Basart acknowledge the Supercomputación y eCiencia project (CSD2007-0050) from the Consolider-Ingenio 2010 and Severo Ochoa (SEV-2011-00067) programs of the Spanish Government

Rationale and design of the Concordance study between FFR and iFR for the assessment of lesions in the left main coronary artery. The ILITRO-EPIC-07 Trial

Introduction and objectives: Patients with left main coronary artery (LMCA) stenosis have been excluded from the trials that support the non-inferiority of the instantaneous wave-free ratio (iFR) compared to the fractional flow reserve (FFR) in the decision-making process of coronary revascularization. This study proposes to prospectively assess the concordance between the two indices in LMCA lesions and to validate the iFR cut-off value of 0.89 for clinical use. Methods: National, prospective, and observational multicenter registry of 300 consecutive patients with intermediate lesions in the LMCA (angiographic stenosis, 25% to 60%. A pressure gudiewire study and determination of the RFF and the iFR will be performed: in the event of a negative concordant result (FFR > 0.80/iFR > 0.89), no treatment will be performed; in case of a positive concordant result (FFR 0.80/iFR 0.89), an intravascular echocardiography will be performed and revascularization will be delayed if the minimum lumen area is > 6 mm(2). The primary clinical endpoint will be a composite of cardiovascular death, LMCA lesion-related non-fatal infarction or need for revascularization of the LMCA lesion at 12 months. Conclusions: Confirm that an iFR-guided decision-making process in patients with intermediate LMCA stenosis is clinically safe and would have a significant clinical impact. Also, justify its systematic use when prescribing treatment in these potentially high-risk patients