Variables with a negative impact on the quality of life of gays and lesbians in Spain: evaluation of homophobic and lesbophobic indicators to guide youth education.

Background: Despite the evidence about the negative impact of homophobic and lesbophobic attitudes on the quality of life of these individuals, the World Health Organisation (WHO) continues to report a lack of research and understanding regarding the health of gays and lesbians and LGTB people in general. There is a growing commitment in public health to understand and improve the health and well-being of LGTB people, and it is very important that professionals in social, educational and health care settings are adequately trained and informed to solve the problems that persist in this population. The aim of this study was to identify homophobic and lesbophobic attitudes in a Spanish youth population, analyzing the relationship of these attitudes with sociodemographic, cultural, political and personal variables. Methods: A descriptive, cross-sectional study was carried out with 325 young people aged 18-30 years. The information was collected through the Modern Homophobia Scale of Raja & Stokes, in which sociodemographic and sociocultural variables were also gathered. The data were analyzed and correlations were estimated. Results: The males showed a more negative attitude toward homosexual people compared to the females. The participants with a higher education level presented more positive attitudes toward homosexual people. Younger people with a heterosexual orientation had more negative attitudes toward homosexual people compared to those with a homosexual orientation. The participants with a stronger right-wing political tendency presented a greater percentage of negative attitudes toward LGTB people. Conclusion: Variables such as education level, sexual orientation and political ideology may have a significant influence on the attitudes toward homosexual men and/or lesbian women. Different results were obtained as a function of sex, thus it is important to consider the gender perspective in future studies that tackle this topic.

GPER binding site detection and description: A flavonoid-based docking and molecular dynamics simulations study.

Flavonoids, a phenolic compounds class widely distributed in the plant kingdom, have attracted much interest for their implications on several health and disease processes. Usually, the consumption of this type of compounds is approximately 1 g/d, primarily obtained from cereals, chocolate, and dry legumes ensuring its beneficial role in maintaining the homeostasis of the human body. In this context, in cancer disease prominent data points to the role of flavonoids as adjuvant treatment aimed at the regression of the disease. GPER, an estrogen receptor on the cell surface, has been postulated as a probable orchestrator of the beneficial effects of several flavonoids through modulation/inhibition of various mechanisms that lead to cancer progression. Therefore, applying pocket and cavity protein detection and docking and molecular dynamics simulations (MD), we generate, from a cluster composed of 39 flavonoids, crucial insights into the potential role as GPER ligands, of Puerarin, Isoquercetin, Kaempferol 3-O-glucoside and Petunidin 3-O-glucoside, aglycones whose sugar moiety delimits a new described sugar-acceptor sub-cavity into the cavity binding site on the receptor, as well as of the probable activation mechanism of the receptor and the pivotal residues involved in it. Altogether, our results shed light on the potential use of the aforementioned flavonoids as GPER ligands and for further evaluations in in vitro and in vivo assays to elucidate their probable anti-cancer activity.

The Autoxidized Mixture of (-)-Epicatechin Contains Procyanidins and Shows Antiproliferative and Apoptotic Activity in Breast Cancer Cells.

For this study, procyanidins generated through the autoxidation of (-)-epicatechin (Flavan-3-ol) under mildly acidic conditions (pH = 6.0) were characterized with ultra high-performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS/MS). Two procyanidins (types A and B) and a mix of oligomers were generated through the autoxidation of (-)-epicatechin. The antiproliferative activity of this mixture of procyanidins on MDA-MB-231, MDA-MB-436, and MCF-7 breast cancer cells was evaluated. The results indicate that the procyanidin mixture inhibited the proliferation of breast cancer cells, where the activity of the procyanidin mixture was stronger than that of (-)-epicatechin. Moreover, the mechanism underlying the antiproliferative activity of procyanidins was investigated. The resulting data demonstrate that the procyanidins induced apoptotic cell death in a manner selective to cancerous cells. In particular, they caused the activation of intrinsic and extrinsic apoptotic pathways in the breast cancer cells. The findings obtained in this study demonstrate that the generation of procyanidins in vitro by the autoxidation of (-)-epicatechin has potential for the development of anti-breast cancer agents.

Anticancer Activity of Sargassum fluitans Extracts in Different Cancer Cells.

BACKGROUND: The arrival of large quantities of Sargassum in the Mexican Caribbean Sea has generated major environmental, health and economic problems. Although Sargassum has been used in the generation of some commercial products, few studies have described its possible applications as a source of compounds with anticancer activity. OBJECTIVE: This study aimed to evaluate the antiproliferative effects of different Sargassum extracts on various cancer cell lines. Furthermore, LC/QTOF-MS was used to identify the compounds related to the antiproliferative effect. METHODS: First, determination of the seaweed was performed, and dichloromethane, chloroform and methanol extracts were obtained. The extracts were evaluated for their antiproliferative effects by MTT in breast (MDAMB- 231 and MCF-7), prostate (DU-145), lung (A549) and cervical (SiHa) cancer cell lines. Finally, LC/QTOFMS identified the compounds related to the antiproliferative effect. RESULTS: The authentication showed Sargassum fluitans as the predominant species. The extracts of dichloromethane and chloroform showed an antiproliferative effect. Interestingly, the fractionation of the chloroform extract showed two fractions (FC1 and FC2) with antiproliferative activity in MDA-MB-231, SiHa and A549 cancer cell lines. On the other hand, three fractions of dichloromethane extract (FD1, FD4 and FD5) also showed antiproliferative effects in the MDA-MB-231, MCF-7, SiHa and DU-145 cancer cell lines. Furthermore, LC/QTOF-MS revealed the presence of eight major compounds in FC2. Three compounds with evidence of anticancer activity were identified (D-linalool-3-glucoside, (3R,4S,6E,10Z)-3,4,7,11-tetramethyl-6,10-tridecadienal and alpha-tocotrienol). CONCLUSION: These findings showed that Sargassum fluitans extracts are a possible source of therapeutic agents against cancer and could act as scaffolds for new drug discovery.

Sustainable removal of nutrients (n and p) in a wastewater treatment plant, with eggshell (biocalcium).

Biological treatments have become insufficient to treat municipal wastewater with greater toxicity and excess nitrogen and phosphate species, thus affecting the organisms that consume the water. In this work, a process was implemented for the removal of nutrients through three stages: stage A, complete aeration (24 h, 43 months); stage B, decreased aeration (12 h, 17 months); and stage C, decreased aeration with biocalcium (12 h, 19 months). The addition of biocalcium from eggshell promoted the formation of flocks, which resulted in the removal of nitrites (61 %), nitrates (84 %), total nitrogen (57 %), total phosphorus (8.3 %), sedimentable solids (50 %), total suspended solids (69 %), BOD5 (76 %), helminth eggs (50 %) and fecal coliforms (54 %). The statistical analyses in the three stages indicated that there is a strong correlation between the concentration of fats and oils and the removal of sedimentable solids and total suspended solids, since these parameters were correlated by 97 and 89 %, respectively. Sedimentable solids were correlated with total suspended solids by 94 %, while nitrates and total nitrogen were correlated 92 %, which favors the removal of nutrients in wastewater. The increase in the concentration of nitrogen in the sludge in stage C generated a C:N ratio of 7.98. This ratio shows that the sludge is feasible for use as a mediator of soils and a biofertilizer because of the high contents of calcium, phosphorus and nitrogen. In addition, biocalcium promoted the precipitation of hydroxyapatite, struvite, calcite and quartz. In general, the three stages of the treatment contributed to the stabilization of the wastewater treatment plant (WWTP) in an efficient, economical, and safe way.

In Vitro Analysis of SARS-CoV-2 Spike Protein and Ivermectin Interaction.

The spike (S) protein of SARS-CoV-2 is a molecular target of great interest for developing drug therapies against COVID-19 because S is responsible for the interaction of the virus with the host cell receptor. Currently, there is no outpatient safety treatment for COVID-19 disease. Furthermore, we consider it of worthy importance to evaluate experimentally the possible interaction of drugs (approved by the Food and Drug Administration) and the S, considering some previously in silico and clinical use. Then, the objective of this study was to demonstrate the in vitro interaction of ivermectin with S. The equilibrium dialysis technique with UV-Vis was performed to obtain the affinity and dissociation constants. In addition, the Drug Affinity Responsive Target Stability (DARTS) technique was used to demonstrate the in vitro interaction of S with ivermectin. The results indicate the interaction between ivermectin and the S with an association and dissociation constant of Ka = 1.22 µM-1 and Kd = 0.81 µM, respectively. The interaction was demonstrated in ratios of 1:50 pmol and 1:100 pmol (S: ivermectin) by the DARTS technique. The results obtained with these two different techniques demonstrate an interaction between S and ivermectin previously explored in silico, suggesting its clinical uses to stop the viral spread among susceptible human hosts.

In silico design and cell-based evaluation of two dual anti breast cancer compounds targeting Bcl-2 and GPER.

According to WHO statistics, breast cancer (BC) disease represents about 2.3 million diagnosed and 685,000 deaths globally. Regarding histological classification of BC, the Estrogen (ER) and Progesterone (PR) receptors negative-expression cancer, named Triple-Negative BC (TNBC), represents the most aggressive type of this disease, making it a challenge for drug discovery. In this context, our research group, applying a well-established Virtual Screening (VS) protocol, in addition to docking and molecular dynamics simulations studies, yielded two ligands identified as 6 and 37 which were chemically synthesized and evaluated on MCF-7 and MDA-MB-231 cancer cell lines. Strikingly, 37 assayed on MDA-MB-231 (a TNBC cell model) depicted an outstanding value of 18.66 µM much lower than 65.67 µM yielded by Gossypol Bcl-2 inhibitor whose main disadvantage is to produce multiple toxic effects. Highlighted above, enforce the premise of the computational tools to find new therapeutic options against the most aggressive forms of breast cancer, as the results herein showed.

Cocoa: a functional food that decreases insulin resistance and oxidative damage in young adults with class II obesity.

BACKGROUND/OBJECTIVES: Cocoa consumption is associated with health benefits due to its high content of polyphenols. However, the effects of short-term cocoa consumption remain unclear. We aimed to determine the effects generated by cocoa consumption (for 7 days) in young adults in normoweight and class II obesity. SUBJECTS/METHODS: Before-and-after study was carried out in normoweight (NW) (n = 15) and class II obesity (CIIO) (n = 15) young adults. The NW and CIIO participants consumed 25 and 39 g of cocoa, respectively, per day for 7 days. The effect of cocoa consumption was evaluated on the lipid profile, insulin resistance (IR), and inflammation. Oxidative damage was also examined by assessing the biomarkers of oxidative damage in plasma. In addition, recombinant human insulin was incubated with blood obtained from the participants, and the molecular damage to the hormone was analyzed. RESULTS: Cocoa consumption resulted in decreased low-density lipoprotein-cholesterol in both groups (P = 0.04), while the total cholesterol, high-density lipoprotein cholesterol, and triglycerides were maintained at the recommended levels. Initially, IR was detected in the CIIO group (homeostasis model assessment [HOMA] = 4.78 ± 0.4), which is associated with molecular damage to insulin. Interestingly, intervention with cocoa resulted in improved IR (HOMA = 3.14 ± 0.31) (P = 0.0018) as well as molecular damage to insulin. Finally, cocoa consumption significant decreased the arginase activity (P = 0.0249) in the CIIO group; this is a critical enzymatic activity in the inflammatory process associated with obesity. CONCLUSIONS: The short-term consumption of cocoa improves the lipid profile, exerts anti-inflammatory effects, and protects against oxidative damage. Results of this study indicate that cocoa consumption can potentially improve IR and restore a healthy redox status.

Hyperbaric oxygenation applied before or after mild or hard stress: effects on the redox state in the muscle tissue.

The mechanism is unclear for the reported protective effect of hyperbaric oxygen preconditioning against oxidative stress in tissues, and the distinct effects of hyperbaric oxygen applied after stress. The trained mice were divided into three groups: the control, hyperbaric oxygenation preconditioning, and hyperbaric oxygenation applied after mild (fasting) or hard (prolonged exercise) stress. After preconditioning, we observed a decrease in basal levels of nitric oxide, tetrahydrobiopterin, and catalase despite the drastic increase in inducible and endothelial nitric oxide synthases. Moreover, the basal levels of glutathione, related enzymes, and nitrosative stress only increased in the preconditioning group. The control and preconditioning groups showed a similar mild stress response of the endothelial and neuronal nitric oxide synthases. At the same time, the activity of all nitric oxide synthase, glutathione (GSH) in muscle, declined in the experimental groups but increased in control during hard stress. The results suggested that hyperbaric oxygen preconditioning provoked uncoupling of nitric oxide synthases and the elevated levels of GSH in muscle during this study, while hyperbaric oxygen applied after stress showed a lower level of GSH but higher recovery post-exercise levels in the majority of antioxidant enzymes. We discuss the possible mechanisms of the redox response and the role of the nitric oxide in this process.

Dihydropyrazole-Carbohydrazide Derivatives with Dual Activity as Antioxidant and Anti-Proliferative Drugs on Breast Cancer Targeting the HDAC6.

Breast cancer (BC) is the most frequently diagnosed cancer and is the second-most common cause of death in women worldwide. Because of this, the search for new drugs and targeted therapy to treat BC is an urgent and global need. Histone deacetylase 6 (HDAC6) is a promising anti-BC drug target associated with its development and progression. In the present work, the design and synthesis of a new family of dihydropyrazole-carbohydrazide derivatives (DPCH) derivatives focused on HDAC6 inhibitory activity is presented. Computational chemistry approaches were employed to rationalize the design and evaluate their physicochemical and toxic-biological properties. The new family of nine DPCH was synthesized and characterized. Compounds exhibited optimal physicochemical and toxicobiological properties for potential application as drugs to be used in humans. The in silico studies showed that compounds with -Br, -Cl, and -OH substituents had good affinity with the catalytic domain 2 of HDAC6 like the reference compounds. Nine DPCH derivatives were assayed on MCF-7 and MDA-MB-231 BC cell lines, showing antiproliferative activity with IC50 at µM range. Compound 2b showed, in vitro, an IC50 value of 12 ± 3 µM on human HDAC6. The antioxidant activity of DPCH derivatives showed that all the compounds exhibit antioxidant activity similar to that of ascorbic acid. In conclusion, the DPCH derivatives are promising drugs with therapeutic potential for the epigenetic treatment of BC, with low cytotoxicity towards healthy cells and important antioxidant activity.

Platelet rich plasma and plasma rich in growth factors for split-thickness skin graft donor site treatment in the burn patient setting: A randomized clinical trial.

INTRODUCTION: Management of donor site morbidity in the setting of split thickness skin graft (STSG) is of crucial importance with no superior wound dressing described to date and the growing need of decreasing epithelializing time. The purpose of the study was to compare the standard of care using a hydrocolloid dressing to platelet rich plasma (PRP) and plasma rich in growth factors (PRGF) in order to determine its therapeutic potential in this setting. METHODS: A randomized clinical trial was conducted in which each patient served as its own control. PRGF was obtained by means of freeze-thaw out of the PRP from the subject of the study. Patients from the study had three donor sites and each donor site received either to PRP, PRGF or the standard of care, hydrocolloid. The main variable was time to epithelialization, and secondary variables subject to study were pain, quality of the scar, complications and cost. RESULTS: 20 patients were recruited with a total number of 60 donor sites to study. On the 8th post-operative day 55% and 45% of the sites treated with PRP and PRGF, respectively, complete epithelialization was observed as compared to 20% of the sites treated with hydrocolloid, statistical significance was achieved between the latter two (p = 0.036). The areas treated with PRP and PRGF received inferior values on the visual analog scale on post-op day 5 and 8 compared to hydrocolloid. Values on wound healing metrics were lower in the PRP when compared to hydrocolloid. No adverse effects were recorded. CONCLUSION: Donor site of STSG treated with PRP in the setting of the burn patient decreased time to epithelialization. In our study a better pain control and in scar quality was observed in both, the PRP and PRGF group.

Soluble Biomarkers with Prognostic and Predictive Value in Advanced Non-Small Cell Lung Cancer Treated with Immunotherapy.

Numerous targeted therapies have been evaluated for the treatment of non-small cell lung cancer (NSCLC). To date, however, only a few agents have shown promising results. Recent advances in cancer immunotherapy, most notably immune checkpoint inhibitors (ICI), have transformed the treatment scenario for these patients. Although some patients respond well to ICIs, many patients do not benefit from ICIs, leading to disease progression and/or immune-related adverse events. New biomarkers capable of reliably predicting response to ICIs are urgently needed to improve patient selection. Currently available biomarkers-including programmed death protein 1 (PD-1) and its ligand (PD-L1), and tumor mutational burden (TMB)-have major limitations. At present, no well-validated, reliable biomarkers are available. Ideally, these biomarkers would be obtained through less invasive methods such as plasma determination or liquid biopsy. In the present review, we describe recent advances in the development of novel soluble biomarkers (e.g., circulating immune cells, TMB, circulating tumor cells, circulating tumor DNA, soluble factor PD-L1, tumor necrosis factor, etc.) for patients with NSCLC treated with ICIs. We also describe the potential use of these biomarkers as prognostic indicators of treatment response and toxicity.

A moderate intensity exercise program improves physical function and oxidative damage in older women with and without sarcopenic obesity.

BACKGROUND AND OBJECTIVES: The excess of body fat and muscle mass loss in adulthood results in sarcopenic obesity, which is associated with disability and poor physical condition. A relationship among obesity, sarcopenia and oxidative stress also has been established. These aspects limit a good muscle function which is crucial in the independence of older women with and without sarcopenic obesity. This study had as objective to design a moderate intensity exercise program for older women with sarcopenic obesity, and to examine its effects on oxidative damage and physical function. We hypothesized that the exercise program will reduce oxidative damage and to improve the physical function of older women with sarcopenic obesity. METHODS: Thirty healthy women (68 ± 5.05 years old) and 30 women with sarcopenic obesity (68.06 ± 5.75 years old) from the Integral Development of the Family rest home participated in the evaluation. The participants underwent evaluations of body composition, physical fitness (timed up-and-go [TUG] test, reaction time, gait speed, flexibility and muscle strength) and oxidative stress (oxidative damage to lipid and protein as well as evaluation of the antioxidant system) before and after of moderate intensity exercise program. The program consisted of warm-up, flexibility; aerobic exercises of moderate intensity (VO2 max and HR max between 60% and 70%); isotonic exercises of low intensity with progressive weight (250 g of initial weight, with increase every two weeks until reaching 750 g of final weight) and global stretching at the end of each section. The program was monitored on a personal basis and undertaken three times a week over three months. RESULTS: In both groups, the program induced a five-fold increase in muscle strength, an increase in flexibility and improvement of fragility parameters (TUG and gait speed) (P ≤ 0.001, respectively). Furthermore, this exercise program decreased oxidative damage and increased antioxidant defense (P ≤ 0.001) to a greater extent in the sarcopenic group. CONCLUSION: It was concluded that moderate intensity exercise is an effective approach to promote changes in body composition, physical fitness and to reduce oxidative damage in older women with and without sarcopenic obesity. These findings might have important implications for the prevention or treatment of sarcopenic obesity in older people.

A Novel Dynamic Three-Level Tracking Controller for Mobile Robots Considering Actuators and Power Stage Subsystems: Experimental Assessment.

In order to solve the trajectory tracking task in a wheeled mobile robot (WMR), a dynamic three-level controller is presented in this paper. The controller considers the mechanical structure, actuators, and power stage subsystems. Such a controller is designed as follows: At the high level is a dynamic control for the WMR (differential drive type). At the medium level is a PI current control for the actuators (DC motors). Lastly, at the low level is a differential flatness-based control for the power stage (DC/DC Buck power converters). The feasibility, robustness, and performance in closed-loop of the proposed controller are validated on a DDWMR prototype through Matlab-Simulink, the real-time interface ControlDesk, and a DS1104 board. The obtained results are experimentally assessed with a hierarchical tracking controller, recently reported in literature, that was also designed on the basis of the mechanical structure, actuators, and power stage subsystems. Although both controllers are robust when parametric disturbances are taken into account, the dynamic three-level tracking controller presented in this paper is better than the hierarchical tracking controller reported in literature.

Medium- and long-range transport events of Alnus pollen in western Mediterranean.

Alnus pollen has been frequently detected in the atmosphere of different airborne sampling sites of Southern Spain. However, Alnus sp. populations are very scarce and fragmented in the area, being restricted to a few river valleys in the southwest, and other further away regions of the Iberian Peninsula. This leads to think that the airborne pollen detected could be mainly the result of a medium- or long-distant transport. So, the aim of this study was to characterize the annual patterns of airborne Alnus pollen detected at three different locations of Malaga province, as well as to determine its possible origin, the pollen dispersion potential of these Alnus isolated populations, and their possible reproductive connectivity. Pollen sampling was conducted by means of three Hirst-type volumetric pollen traps. Samples were mounted and counted following the recommendations of the Spanish Aerobiology Network and the European Aeroallergen Society. The possible pollen sources were detected by means of a combination of meteorological information and backward air trajectories analysis. A high inter-annual variability in the annual pollen integrals was found in all the stations, favouring certain meteorological conditions a long-range transport and, therefore, causing the high concentrations detected in some specific days. Alnus pollen seems to have a heterogeneous origin with prevalence of the long-distant transport, which would suggest a possible reproductive connection among distant populations.

Targeting Breast Cancer Cells with G4 PAMAM Dendrimers and Valproic Acid Derivative Complexes.

BACKGROUND: Our research group has developed some Valproic Acid (VPA) derivatives employed as anti-proliferative compounds targeting the HDAC8 enzyme. However, some of these compounds are poorly soluble in water. OBJECTIVE: Employed the four generations of Polyamidoamine (G4 PAMAM) dendrimers as drug carriers of these compounds to increase their water solubility for further in vitro evaluation. METHODS: VPA derivatives were subjected to Docking and Molecular Dynamics (MD) simulations to evaluate their affinity on G4 PAMAM. Then, HPLC-UV/VIS, 1H NMR, MALDI-TOF and atomic force microscopy were employed to establish the formation of the drug-G4 PAMAM complexes. RESULTS: The docking results showed that the amide groups of VPA derivatives make polar interactions with G4 PAMAM, whereas MD simulations corroborated the stability of the complexes. HPLC UV/VIS experiments showed an increase in the drug water solubility which was found to be directly proportional to the amount of G4 PAMAM. 1H NMR showed a disappearance of the proton amine group signals, correlating with docking results. MALDI-TOF and atomic force microscopy suggested the drug-G4 PAMAM dendrimer complexes formation. DISCUSSION: In vitro studies showed that G4 PAMAM has toxicity in the micromolar concentration in MDAMB- 231, MCF7, and 3T3-L1 cell lines. VPA CF-G4 PAMAM dendrimer complex showed anti-proliferative properties in the micromolar concentration in MCF-7 and 3T3-L1, and in the milimolar concentration in MDAMB- 231, whereas VPA MF-G4 PAMAM dendrimer complex didn't show effects on the three cell lines employed. CONCLUSION: These results demonstrate that G4 PAMAM dendrimers are capableof transporting poorly watersoluble aryl-VPA derivate compounds to increase its cytotoxic activity against neoplastic cell lines.