Prospective study for the early detection of lung carcinoma in patients with HIV infection (GESIDA study 8815).

INTRODUCTION: Lung cancer (LC) screening detects tumors early. The prospective GESIDA 8815 study was designed to assess the usefulness of this strategy in HIV + people (PLHIV) by performing a low-radiation computed tomography (CT) scan. PATIENTS AND METHODS: 371 heavy smokers patients were included (>20 packs/year), >45 years old and with a CD4+ <200 mm3 nadir. One visit and CT scan were performed at baseline and 4 for follow-up time annually. RESULTS: 329 patients underwent the baseline visit and CT (CT0) and 206 completed the study (CT1 = 285; CT2 = 259; CT3 = 232; CT4 = 206). All were receiving ART. A total >8 mm lung nodules were detected, and 9 early-stage PCs were diagnosed (4 on CT1, 2 on CT2, 1 on CT3 and 2 on CT4). There were no differences between those who developed LC and those who did not in sex, age, CD4+ nadir, previous lung disease, family history, or amount of packets/year. At each visit, other pathologies were diagnosed, mainly COPD, calcified coronary artery and residual tuberculosis lesions. At the end of the study, 38 patients quit smoking and 75 reduced their consumption. Two patients died from LC and 16 from other causes (p = 0.025). CONCLUSIONS: The design of the present study did not allow us to define the real usefulness of the strategy. Adherence to the test progressively decreased over time. The diagnosis of other thoracic pathologies is very frequent. Including smokers in an early diagnosis protocol for LC could help to quit smoking.

Radon exposure and its influencing factors across 3,140 workplaces in Spain.

Indoor radon exposure increases the risk of lung cancer. Radon concentration in workplaces is regulated in EU countries, including Spain, based on a reference level of 300 Bq/m3. The objective of this study is to describe workplace radon exposure in Spain and its influencing factors. To do this, we collected long-term radon measurements with alpha track detectors in 3140 workplaces mainly located in radon prone areas. Radon concentration exceeded 300 Bq/m3 in 1 out of 5 workplaces. Median radon concentration was 107 Bq/m3 in radon prone areas, 28 Bq/m3 off radon prone areas, and 101 Bq/m3 globally for the complete sample. Our results indicate that excessive radon concentrations can be expected in radon prone areas at all floor levels, especially below ground. Floor level, working sector, and location significantly influence radon concentration. The highest radon concentrations were found in the Education & Culture sector, comprising schools, universities, libraries, or cultural centers. These results indicate that radon should no longer be considered a risk for marginal occupations, but a risk everyone has if located in a radon prone area. Immediate action, including radon testing and mitigation, is needed to protect workers in Spain against radon exposure. This is already mandatory since EU regulation for radon has been recently transposed in Spain. Competent authorities should enforce this regulation without further delay, and employers must address their responsibility and communicate with workers about this risk.

Pseudocereals: a novel source of biologically active peptides.

The interest in the research about underexploited foods has increased in the last two decades. Pseudocereals have been consumed by the ancient populations for hundreds of years. These plants that do not belong to the family of cereals, but that have properties and uses similar to them, stand out among underexploited foods. Some of the most representative species are quinoa, amaranth, chia and buckwheat. They do not contain gluten but high valued proteins and peptides can be obtained from them, as well as other nutritional and bioactive compounds such as flavonoids, phenolic acids, fatty acids, vitamins and minerals. Anticancer, antioxidant, anti-inflammatory, hypocholesterolemic and antihypertensive properties have been found and postulated for pseudocereals protein derived peptides. These interesting characteristics of pseudocereals are producing an increase of the relevance of these crops. The purpose of this work was to carry out an exhaustive revision of the scientific literature describing the biological activities of peptides and protein hydrolysates obtained from the most widely studied pseudocereals: quinoa, amaranth, chia and buckwheat.

Antioxidant Properties of Egg White Hydrolysate Prevent Mercury-Induced Vascular Damage in Resistance Arteries.

Aim: We investigated the antioxidant protective power of egg white hydrolysate (EWH) against the vascular damage induced by mercury chloride (HgCl2) exposure in resistance arteries. Methods: Male Wistar rats received for 60 days: (I) intramuscular injections (i.m.) of saline and tap water by gavage - Untreated group; (II) 4.6 µg/kg of HgCl2 i.m. for the first dose and subsequent doses of 0.07 µg/kg/day and tap water by gavage - HgCl2 group; (III) saline i.m. and 1 g/kg/day of EWH by gavage - EWH group, or (IV) the combination of the HgCl2 i.m. and EWH by gavage - EWH + HgCl2 group. Blood pressure (BP) was indirectly measured and dose-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), and noradrenaline (NE) were assessed in mesenteric resistance arteries (MRA), as in situ production of superoxide anion, nitric oxide (NO) release, vascular reactive oxygen species (ROS), lipid peroxidation, and antioxidant status. Results: Egg white hydrolysate prevented the elevation in BP and the vascular dysfunction after HgCl2 exposure; restored the NO-mediated endothelial modulation and inhibited the oxidative stress and inflammatory pathways induced by HgCl2. Conclusion: Egg white hydrolysate seems to be a useful functional food to prevent HgCl2-induced vascular toxic effects in MRA.

Physical and Psychological Effects Related to Food Habits and Lifestyle Changes Derived from Covid-19 Home Confinement in the Spanish Population.

As a consequence of COVID-19, millions of households have suffered mobility restrictions and changes in their lifestyle over several months. The aim of this study is to evaluate the effects of COVID-19 home confinement on the food habits, lifestyle and emotional balance of the Spanish population. This cross-sectional study used data collected via an anonymous online questionnaire during the month before lockdown finished in Spain, with a total of 675 participants. 38.8% of the respondents experienced weight gain while 31.1% lost weight during confinement. The increase in body weight was positively correlated with age (Rs = 0.14, p < 0.05) and BMI (Rs = 0.20, p < 0.05). We also identified that 39.7% reported poorer quality sleep, positively correlated with BMI (Rs = -0.18, p < 0.05) and with age (Rs = -0.21, p < 0.05). 44.7% of the participants had not performed physical exercise during confinement with differences by sex (p < 0.05), by age (p < 0.05), by BMI (p < 0.05) and by sleep quality (p < 0.05). According to an emotional-eater questionnaire, 21.8% and 11% were classified as an emotional eater or a very emotional eater, respectively. We emphasize the importance of adopting a healthy lifestyle, as the COVID-19 pandemic is ongoing.

Characterization of Novel Synthetic Polyphenols: Validation of Antioxidant and Vasculoprotective Activities.

Antioxidant compounds, including polyphenols, have therapeutic effects because of their anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. They play important roles in protecting the cardiovascular and neurological systems, by having preventive or protective effects against free radicals produced by either normal or pathological metabolism in such systems. For instance, resveratrol, a well-known potent antioxidant, has a counteracting effect on the excess of reactive oxygen species (ROS) and has a number of therapeutic benefits, like anti-inflammatory, anti-cancer and cardioprotective activities. Based on previous work from our group, and on the most frequent OH substitutions of natural polyphenols, we designed two series of synthetically accessible bis-polyhydroxyphenyl derivatives, separated by amide or urea linkers. These compounds exhibit high antioxidant ability (oxygen radical absorbance capacity (ORAC) assay) and interesting radical scavenging activity (RSA) values (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and α,α-diphenyl-ß-picrylhydrazyl (DPPH) tests). Some of the best polyphenols were evaluated in two biological systems, endothelial cells (in vitro) and whole aorta (ex vivo), highly susceptible for the deleterious effects of prooxidants under different inflammatory conditions, showing protection against oxidative stress induced by inflammatory stimuli relevant in cardiovascular diseases, i.e., Angiotensin II and IL-1ß. Selected compounds also showed strong in vivo antioxidant properties when evaluated in the model organism Saccharomyces cerevisiae.

Efficacy and safety of dorsal penile nerve block before collagenase of clostridium histolyticum injections in peyronie's disease patients: Results from a prospective pilot study.

The intraplaque injection of collagenase from Clostridium Histolyticum (CCH) was established as an effective therapeutic alternative for selected patients with Peyronie's disease (PD). There is no consensus on the use of pre-procedure anaesthesia. The aim of this pilot study was to assess the efficacy and safety of dorsal penile block before CCH injections in reducing procedure related pain. The treatment protocol described in the IMPRESS trials was adopted. The first injection of the first cycle was given without anaesthesia, while the second after penile block. After the administration of each injection, the pain related to the procedure was evaluated with the Wong-Baker-FACES® -Pain-Rating-Scale. Thirty patients were included. Mean age 56.7 (SD: 9.61) years. Mean basal penile curvature 59.37º (SD: 18.26). The mean pain value related to the procedure measured after the first injection of the first cycle (without anaesthesia) was 5.4 (SD: 2.13), while after the second injection (with anaesthesia) was 2.5 (SD: 1.92), (p < .001). The treatment was more painful in patients with dorsal plaques (mean:6.2) than in patients with lateral plaques (mean: 4.35) (p = .01). We can conclude that penile block before CCH injection in patients with PD seems an effective and safe measure to decrease the pain related to the procedure.

Cadmium exposure activates NADPH oxidase, renin-angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage.

Exposure to high concentrations of cadmium (Cd), widely used in many industries and found in air, food and contaminated water, is not uncommon. Cd damages the cardiovascular system, but the vascular mechanisms involved are not fully understood. This study investigated the mechanisms involved in cardiovascular damage after exposure to high Cd concentrations. Three-month-old male Wistar rats were treated intraperitoneally for 14 days with distilled water (Untreated group) or 1 mg/kg cadmium chloride (Cd group). We investigated the systolic blood pressure (SBP) and vascular reactivity of mesenteric resistance arteries (MRA) and the aorta by analysing contractile and relaxation responses in the absence and presence of the endothelium; we also evaluated pathways involved in vascular tone regulation. Superoxide anion production, COX-2 protein expression and in situ detection of COX-2, AT-1, and NOX-1 were evaluated. Oxidative status, creatinine level and angiotensin-converting enzyme (ACE) activity in plasma were also evaluated. Fourteen-day exposure to a high Cd concentration induced hypertension associated with vascular dysfunction in MRA and the aorta. In both vessels, there was increased participation of cyclooxygenase 2 (COX2), angiotensin II type 1 (AT1) receptor and NOX1. MRA also presented endothelial dysfunction, denoted by impaired acetylcholine-mediated relaxation. All vascular changes were accompanied by increased reactive oxygen species production and COX2, NOX1 and AT1 receptor expression in vascular tissue. Overall, high Cd concentrations induced cardiovascular damage: hypertension, endothelial dysfunction and vascular damage in conductance and resistance arteries, NADPH oxidase, renin-angiotensin system and COX2 pathway activation.

Bioactive Peptides and Hydrolysates from Egg Proteins as a New Tool for Protection Against Cardiovascular Problems.

The aim of the present work is to review the potential beneficial effects of dietary supplementation with bioactive egg protein hydrolysates or peptides on cardiometabolic changes associated with oxidative stress. The development of nutritionally improved food products designed to address specific health concerns is of particular interest because many bioactive food compounds can be potentially useful in various physiological functions such as for reducing oxidative stress. The results presented suggest that egg hydrolysates or derived peptides could be included in the diet to prevent and/or reduce some cardiometabolic complications associated with oxidative stress-related diseases.

Egg white hydrolysates improve vascular damage in obese Zucker rats by its antioxidant properties.

Metabolic Syndrome (MS) is related to increased risk of early death due to cardiovascular complications, among others. Dietary intervention has been suggested as the safest and most cost-effective alternative for treatment of those alterations in patients with MS. The aim of this study was to investigate the effects of different egg white hydrolysates (HEW1 and HEW2) in obese Zucker rats, focus on the development of cardiovascular complications. Blood pressure, heart rate, basal cardiac function and vascular reactivity in aorta and mesenteric resistance arteries were evaluated. Reactive oxygen species production by dihydroethidium-emitted fluorescence, NOX-1 mRNA levels by qRT-PCR, angiotensin-converting enzyme activity by fluorimetry and kidney histopathology were also analysed. Both hydrolysates improve the endothelial dysfunction occurring in resistance arteries. Additionally, HEW2 reduced vascular oxidative stress. PRACTICAL APPLICATIONS: Egg white is a good source of bioactive peptides, some of them with high antioxidant activity. They may be used as functional foods ingredients and could serve as an alternative therapeutic option to decrease some Metabolic Syndrome-related complications. This study suggests that these hydrolysates could be an interesting non-pharmacological tool to control cardiovascular complications related to Metabolic Syndrome.

Egg White Hydrolysate: A new putative agent to prevent vascular dysfunction in rats following long-term exposure to aluminum.

Aluminum (Al) is toxic for humans and animals. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against cardiovascular changes in rats exposed to both high and low dietary levels of Al. Indeed, EWH has been previously shown to improve cardio metabolic dysfunctions induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl3 at a dose of 8.3 mg/kg b.w. during 60 days) with or without EWH treatment (1 g/kg/day); Group 2) High aluminum level (AlCl3 at a dose of 100 mg/kg b.w. during 42 days) with or without EWH treatment. After Al treatment, rats co-treated with EWH did not show vascular dysfunction or increased blood pressure as was observed in non EWH-cotreated animals. Indeed, co-treatment with EWH prevented the following effects observed in both aorta and mesenteric arteries: the increased vascular responses to phenylephrine (Phe), the decreased ACh-induced relaxation, the reduction on endothelial modulation of vasoconstrictor responses and the nitric oxide bioavailability, as well as the increased reactive oxygen species production from NAD(P)H oxidase. Altogether, our results suggest that EWH could be used as a protective agent against the harmful vascular effects after long term exposure to Al.

Management of atherogenic dyslipidemia in the primary care setting in Spain.

AIM: To describe the management of atherogenic dyslipidemia (AD) in routine clinical practice in the Primary Care (PC) setting in Spain. METHODS: Observational, descriptive, cross-sectional study based on a structured questionnaire designed for this study and addressed to PC physicians. The questionnaire content was based on a literature review and was validated by 3 experts in AD. RESULTS: A total of 1029 PC physicians participated in the study. 96.99% indicated that AD is determinant for cardiovascular risk, even if LDL-C levels are appropriate. 88.43% evaluated residual cardiovascular risk in their clinical practice, however, only 27.89% of them evaluated it in secondary prevention. Regarding diagnosis, 82.22% reported that TC, TG, HDL-C and non-HDL-C are essential measures when evaluating AD. Almost all physicians reported that they can request fractionated cholesterol to assess HDL-C and LDL-C, however 3.69% could not. Physicians (95.63%) considered that the first step in AD treatment should be diet, regular exercise, smoking cessation and pharmaceutical treatment, if necessary. 19.1% agreed partially or completely that gemfibrozil is the most suitable fibrate to associate with statins. 74.83% completely agreed that fenofibrate is the most suitable fibrate to combine with statins. CONCLUSIONS: Physicians have access to general Spanish guidelines and recommendations associated with AD management, however, it is necessary to continue rising awareness about the importance of early detection and optimal control of AD to reduce patients' cardiovascular risk.

1-(2',5'-Dihydroxyphenyl)-3-(2-fluoro-4-hydroxyphenyl)-1-propanone (RGM079): A Positive Allosteric Modulator of α7 Nicotinic Receptors with Analgesic and Neuroprotective Activity.

Acetylcholine α7 nicotinic receptors are widely expressed in the brain, where they are involved in the central processing of pain as well as in neuropsychiatric, neurodegenerative, and inflammatory processes. Positive allosteric modulators (PAMs) show the advantage of allowing the selective regulation of different subtypes of acetylcholine receptors without directly interacting with the agonist binding site. Here, we report the preparation and biological activity of a fluoro-containing compound, 1-(2',5'-dihydroxyphenyl)-3-(2-fluoro-4-hydroxyphenyl)-1-propanone (8, RGM079), that behaves as a potent PAM of the α7 receptors and has a balanced pharmacokinetic profile and antioxidant properties comparable or even higher than well-known natural polyphenols. In addition, compound RGM079 shows neuroprotective properties in Alzheimer's disease (AD)-toxicity related models. Thus, it causes a concentration-dependent neuroprotective effect against the toxicity induced by okadaic acid (OA) in the human neuroblastoma cell line SH-SY5Y. Similarly, in primary cultures of rat cortical neurons, RGM079 is able to restore the cellular viability after exposure to OA and amyloid peptide Aß1-42, with cell death almost completely prevented at 10 and 30 µM, respectively. Finally, compound RGM079 shows in vivo analgesic activity in the complete Freund's adjuvant (CFA)-induced paw inflammation model after intraperitoneal administration.

Egg White Hydrolysate as a functional food ingredient to prevent cognitive dysfunction in rats following long-term exposure to aluminum.

Aluminum (Al), which is omnipresent in human life, is a potent neurotoxin. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against changes in cognitive function in rats exposed to both high and low levels of Al. Indeed, EWH has been previously shown to improve the negative effects induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl3 at a dose of 8.3 mg/kg b.w. during 60 days) with or without EWH treatment (1 g/kg/day); Group 2) High aluminum level (AlCl3 at a dose of 100 mg/kg b.w. during 42 days) with or without EWH treatment (1 g/kg/day). After 60 or 42 days of exposure, rats exposed to Al and EWH did not show memory or cognitive dysfunction as was observed in Al-treated animals. Indeed, co-treatment with EWH prevented catalepsy, hippocampal oxidative stress, cholinergic dysfunction and increased number of activated microglia and COX-2-positive cells induced by Al exposure. Altogether, since hippocampal inflammation and oxidative damage were partially prevented by EWH, our results suggest that it could be used as a protective agent against the detrimental effects of long term exposure to Al.

Inhibitor of Differentiation-1 Sustains Mutant KRAS-Driven Progression, Maintenance, and Metastasis of Lung Adenocarcinoma via Regulation of a FOSL1 Network.

Because of the refractory nature of mutant KRAS lung adenocarcinoma (LUAD) to current therapies, identification of new molecular targets is essential. Genes with a prognostic role in mutant KRAS LUAD have proven to be potential molecular targets for therapeutic development. Here we determine the clinical, functional, and mechanistic role of inhibitor of differentiation-1 (Id1) in mutant KRAS LUAD. Analysis of LUAD cohorts from TCGA and SPORE showed that high expression of Id1 was a marker of poor survival in patients harboring mutant, but not wild-type KRAS. Abrogation of Id1 induced G2-M arrest and apoptosis in mutant KRAS LUAD cells. In vivo, loss of Id1 strongly impaired tumor growth and maintenance as well as liver metastasis, resulting in improved survival. Mechanistically, Id1 was regulated by the KRAS oncogene through JNK, and loss of Id1 resulted in downregulation of elements of the mitotic machinery via inhibition of the transcription factor FOSL1 and of several kinases within the KRAS signaling network. Our study provides clinical, functional, and mechanistic evidence underscoring Id1 as a critical gene in mutant KRAS LUAD and warrants further studies of Id1 as a therapeutic target in patients with LUAD. SIGNIFICANCE: These findings highlight the prognostic significance of the transcriptional regulator Id1 in KRAS-mutant lung adenocarcinoma and provide mechanistic insight into how it controls tumor growth and metastasis.

Small Library of Triazolyl Polyphenols Correlating Antioxidant Activity and Stability with Number and Position of Hydroxyl Groups.

Polyphenolic compounds have attracted much interest because of their antioxidant properties and multiple applications, from food or cosmetic preservatives to free radical scavengers as therapeutic agents. Inspired by common OH substitutions in natural products, here we describe a small library of 1,2,3-triazoles disubstituted with polyphenol groups at 1,4-positions, in an attempt to correlate the number and position of hydroxyl groups in the aromatic rings with the antioxidant activity. Some compounds from this library exhibit strong radical scavenging activities in the oxygen radical absorbance capacity assay, similar to or even higher than resveratrol and other well-kwon flavonoids. The antioxidant activity for selected compounds was confirmed in vitro through the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) test and in vivo by a Saccharomyces cerevisiae model organism assay. The activity depends on the number and position of the hydroxyl groups, with compounds bearing a 2″5″-hydroxyl substituents on the phenyl ring at position 4 showing the best antioxidant values. The presence of two quinone-forming phenolic groups at the same molecule is behind the instability of some of these compounds in aqueous media.

Aluminum exposure for 60days at an equivalent human dietary level promotes peripheral dysfunction in rats.

Aluminum (Al) is a neurotoxic associated with a number of chronic human diseases. We investigated the effects of Al exposure at doses similar to human dietary levels and at a high level exposure to Al on the peripheral nervous system. Wistar male rats were divided into two major groups and received orally: 1) First group - Low level - rats were subdivided and treated for 60days: a) Control - received ultrapure water; b) AlCl3 - received Al at 8.3mg/kg body weight (bw) for 60days; and 2) Second group - High level - rats were subdivided and treated for 42days: C) Control - received ultrapure water through oral gavage; d) AlCl3 - received Al at 100mg/kg bw for 42days. Von Frey hair test, plantar test, the presence of catalepsy and the spontaneous motor activity were investigated. Reactive oxygen species, lipid peroxidation and total antioxidant capacity, immunohistochemistry to investigate the nerve inflammation and, the specific presence of Al in the sciatic nerve fibers were investigated. Al exposure at a representative human dietary level promotes the development of mechanical allodynia, catalepsy, increased inflammation in the sciatic nerve, systemic oxidative stress and, is able to be retained in the sciatic nerve. The effects of low-dose Al were similar to those found in rats exposed to Al at a dose much higher (100mg/kg). Our findings suggest that Al may be considered toxic for the peripheral nervous system, thus inducing peripheral dysfunction.

Egg white-derived peptides prevent cardiovascular disorders induced by mercury in rats: Role of angiotensin-converting enzyme (ACE) and NADPH oxidase.

The study aimed to investigate the effects of egg white hydrolysate (EWH) on vascular disorders induced by mercury (Hg). For this, male Wistar rats were treated for 60days: Untreated (saline, i.m.); Mercury (HgCl2, i.m., 1st dose 4.6µg/kg, subsequent doses 0.07µg/kg/day); Hydrolysate (EWH, gavage, 1g/kg/day); Hydrolysate-Mercury. Systolic (SBP) and diastolic (DBP) blood pressure measurement and vascular reactivity experiments in aorta were performed. We analyzed endothelial dependent and independent vasodilator responses and vasoconstrictor response to phenylephrine (Phe) in absence and presence of endothelium, a NOS inhibitor, a NADPH oxidase inhibitor, the superoxide dismutase, a non-selective COX inhibitor, a selective COX-2 inhibitor, an AT-1 receptors blocker. In situ superoxide anion production, SOD-1, NOX-4, p22phox, COX-2 and AT-1 mRNA levels and NOX-1 protein expression were performed in aorta while the determination of angiotensin converting enzyme (ACE) activity was measured in plasma. As results, EWH prevented the increase in SBP and Phe responses and the endothelial dysfunction elicited by Hg, which was related to decreased ACE activity and NOX activation by EWH and, subsequently, alleviated ROS production and improved NO bioavailability in aorta. In conclusion, EWH could be considered as alternative or complementary treatment tools for Hg-induced cardiovascular damage.

Aluminum exposure for 60days at human dietary levels impairs spermatogenesis and sperm quality in rats.

Concerns about environmental aluminum (Al) and reproductive health have been raised. We investigated the effects of Al exposure at a human relevant dietary level and a high level exposure to Al. Experiment 1 (Lower level) rats were treated orally for 60 days: a) controls - ultrapure water; b) aluminum at 1.5mg/kg bw/day and c) aluminum at 8.3mg/kg bw/day. Experiment 2 (High level) rats were treated for 42 days: a) controls - ultrapure water; b) aluminum at 100mg/kg bw/day. Al decreased sperm count, daily sperm production, sperm motility, normal morphological sperm, impaired testis histology; increased oxidative stress in reproductive organs and inflammation in testis. Our study shows the specific presence of Al in the germinative cells and, that low concentrations of Al in testes (3.35µg/g) are sufficient to impair spermatogenesis and sperm quality. Our findings provide a better understanding of the reproductive health risk of Al.