Dietary plant microRNAs as potential regulators of cellular cholesterol efflux.

AIM: Epidemiological evidence suggests adherence to vegetable-rich diets is associated to atheroprotective effects and bioactive components are most likely to play a relevant role. The notion of inter-kingdom regulation has opened a new research paradigm and perhaps microRNAs (miRNAs) from edible vegetables could influence consumer gene expression and lead to biological effects. We aimed to investigate the potential impact of broccoli-derived miRNAs on cellular cholesterol efflux in vitro. METHODS: Four miRNAs (miR159a, miR159b, miR166a and miR403) from Brassica oleracea var. italica (broccoli), a widely consumed cruciferous vegetable, were selected for further investigation, based on their high abundancy in this vegetable and their presence in other plants. Selected miRNAs were synthesized with a 3'-terminal 2'-O-methylation and their cellular toxicity, in vitro gastrointestinal resistance and cellular uptake were evaluated. Potential target genes within the mammalian transcriptome were assessed in silico following pathway analysis. In vitro cholesterol efflux was assessed in human THP-1-derived macrophages. RESULTS: miRNAs survival to in vitro GI digestion was around 1%, although some variation was seen between the four candidates. Cellular uptake by mammalian cells was confirmed, and an increase in cholesterol efflux was observed. Pathway analysis suggested these miRNAs are involved in biological processes related to phosphorylation, phosphatidylinositol and Wnt signaling, and to the insulin/IGF pathway. CONCLUSIONS: Health-promoting properties attributed to cruciferous vegetables, might be mediated (at least in part) through miRNA-related mechanisms.

Olive Oil Components as Novel Antioxidants in Neuroblastoma Treatment: Exploring the Therapeutic Potential of Oleuropein and Hydroxytyrosol.

In this review, we explored the therapeutic potential of oleuropein (OLE) and hydroxytyrosol (HT) in the treatment of neuroblastoma (NB). NB is an extracranial tumour that predominantly affects children aged between 17 and 18 months. Recurrence and drug resistance have emerged as the biggest challenges when treating NB, leading to a crucial need for new therapeutic approaches. Food of the Mediterranean Diet (MD) presents several health benefits, including that of cancer treatment. In this review, we emphasised olive oil since it is one of the main liquid ingredients of the MD. OLE is the principal phenolic compound that constitutes olive oil and is hydrolysed to produce HT. Considering that tumour cells produce increased amounts of reactive oxygen species, this review highlights the antioxidant properties of OLE and HT and how they could result in increased cellular antioxidant defences and reduced oxidative damage in NB cells. Moreover, we highlight that these phenolic compounds lead to apoptosis and cell cycle arrest, reduce the side effects caused by conventional treatments, and activate tumours that become dormant as a resistance mechanism. Future research should explore the effects of these compounds and other antioxidants on the treatment of NB in vivo.

Health impact of the Tajogaite volcano eruption in La Palma population (ISVOLCAN study): rationale, design, and preliminary results from the first 1002 participants.

BACKGROUND: The eruption of the Tajogaite volcano began on the island of La Palma on September 19, 2021, lasting for 85 days. This study aims to present the design and methodology of the ISVOLCAN (Health Impact on the Population of La Palma due to the Volcanic Eruption) cohort, as well as the preliminary findings from the first 1002 enrolled participants. METHODS: A prospective cohort study was conducted with random selection of adult participants from the general population, with an estimated sample size of 2600 individuals. The results of the first 857 participants are presented, along with a group of 145 voluntary participants who served as interveners during the eruption. Data on epidemiology and volcano exposure were collected, and participants underwent physical examinations, including anthropometry, blood pressure measurement, spirometry, and venous blood extraction for toxicological assessment. RESULTS: In the general population (n = 857), descriptive analysis revealed that the participants were mostly middle-aged individuals (50.8 ± 16.4), with a predominance of females. Before the eruption, the participants resided at a median distance of 6.7 km from the volcano in the Western region and 10.9 km in the Eastern region. Approximately 15.4% of the sample required evacuation, whose 34.8% returning to their homes on average after 3 months. A significant number of participants reported engaging in daily tasks involving cleaning of volcanic ash both indoors and outdoors. The most reported acute symptoms included ocular irritation, insomnia, mood disorders (anxiety-depression), and respiratory symptoms. Multivariate analysis results show that participants in the western region had a higher likelihood of lower respiratory tract symptoms (OR 1.99; 95% CI:1.33-2.99), depression and anxiety (OR 1.95; 95% CI:1.30-2.93), and insomnia (OR 2.03; 95% CI:1.33-3.09), compared to those in the eastern region. CONCLUSION: The ongoing follow-up of the ISVOLCAN cohort will provide valuable insights into the short, medium, and long-term health impact related to the material emitted during the Tajogaite eruption, based on the level of exposure suffered by the affected population.

Zebrafish Model Insights into Mediterranean Diet Liquids: Olive Oil and Wine.

In this review, we explored the potential of a zebrafish model to investigate the antioxidant effects of key components of the Mediterranean diet, namely, olive oil and wine, in the context of preventing age-related diseases, particularly cardiovascular conditions. This paper explores the spectrum of observational studies to preclinical investigations and ultimately converges toward potential translational insights derived from animal experimentation. This review highlights the potential and underutilization of zebrafish as an experimental model in this domain. We highlighted the genetic proximity of zebrafish to humans, offering a unique opportunity for translational insights into the health benefits of olive oil and wine. Indeed, we wanted to focus on the potential of zebrafish to elucidate the health benefits of olive oil and wine while calling for continued exploration to unlock its full potential to advance our knowledge of age-related disease prevention within the Mediterranean diet framework.

Irisin, in women and men: blood pressure, heart rate, obesity and insulin resistance.

Background: Irisin is a myokine that increases with leisure time physical activity (LTPA) and for which a cardiovascular protective role has been postulated. Our aim was to assess this role in the general population. Methods: A cross-sectional analysis was performed in a large randomly selected population sample (n=2298 women and 1529 men). Apart from age and sex, we record anthropometrics (blood pressure, heart rate, obesity), lifestyle (LTPA, smoking, alcohol), and biochemical measurements (irisin, lipid profile, insulin resistance). Correlations and regression multivariate models were used to analyze the association of irisin levels with the studied factors. Results: The variables more strongly and directly associated with irisin, adjusting the studied factors separately in women and men, were HOMA-2 (p=0.043 and p=0.001, respectively) and LTPA (p<0.001 and p=0.001, respectively). Also heart rate inversely (p=0.005 and p=0.002, respectively) and DBP directly (p<0.005 and p=0.045, respectively) were associated to irisin in both sexes. The waist/height ratio (p<0.001) was inversely associated to irisin only in women, and the alcohol drinking was directly associated (p=0.029) only in men. Conclusion: We provide new findings for irisin, such as its association with DBP and with heart rate; furthermore, in women irisin is associated to abdominal obesity, and in men is associated to the alcohol intake. We also corroborate the association of irisin with LTPA and insulin resistance. The associations detected point towards a protective role of irisin in the maintenance of cardiometabolic health.

Adherence to the Mediterranean diet and waist-to-hip ratio in middle-aged postmenopausal women are the main factors associated with semantic verbal fluency 12 years later.

Few studies have analized the effect of vascular risk factors and lifestyle habits affecting the middle age of postmenopausal women on later cognitive performance in old age. We have carried out an observational study to identify those factors and whether they differ from those acting in men. Postmenopausal women and males, both aged 40-60 years old at recruitment, from a community dwelling cohort were included. Data for this study were collected from the first visit at recruitment (2001 to 2005). Participants were interviewed with a questionnaire on their health-related antecedents and underwent a physical exam. The cohort was contacted again for a new presential visit between 2014 and 2015. A semantic verbal fluency test was included in this new visit protocol as a brief measure of cognition. Besides educational attainment, Mediterranean diet adherence 20th percentile (OR = 1.93; 95%CI = 1.07-3.47) and waist to hip ratio 80th percentile (OR = 1.81; 95%CI = 1.10-2,98) were the main factors associated to low semantic fluency performance in postmenopausal women, while declared diabetes mellitus (OR = 2.24; 95%CI = 1.16-4,33), HOMA 2 insulin resistance index (OR = 1.77; 95%CI =1.04-3,02), light physical activity in leisure time (OR = 0.41; 95%CI = 0.19-0,93) and recommended moderate to vigorous physical activity (OR = 2.09; 95%CI = 1.23-3.56) did in men. Factors in middle age that explain semantic verbal fluency in old age are different between postmenopausal women and men. Menopause related fat redistribution may be a precondition for other vascular risk factors. The effect of Mediterranean diet on cognition deserves new specific studies centered on postmenopausal women as group.

Incidence and case-fatality rate of stroke in General Villegas, Buenos Aires, Argentina. The EstEPA population study.

OBJECTIVES: Stroke epidemiology varies among different populations. The burden of stroke is high in low- and middle-income countries. Reliable population data is needed to assess the impact of stroke and to develop policies aimed to improve stroke care in our region. EstEPA is a population-based project assessing prevalence, incidence, mortality and burden of stroke in General Villegas Department, Buenos Aires, Argentina (pop=30,864 inhabitants). We determined incidence of stroke (first-ever and recurrent stroke) and stroke case-fatality rate from 2017 to 2020. METHODS: First-ever strokes, recurrent strokes and transient ischemic attacks were ascertained and case-fatality rate was obtained. Diagnoses were based on standard AHA/WHO definitions. Study population included all persons residing in General Villegas during the three-year period. Hospitals, households, nursing homes, death certificates and several overlapping sources were surveyed. RESULTS: We assessed 92,592 person-years. There were 155 cerebrovascular events aged 70 years (SD ± 13 years), of which 115 were first-ever strokes (74%), 21 recurrent strokes (13.5%) and 19 transient ischemic attacks (12.5%). The crude overall incidence rate of first-ever strokes was 124.2 per 100,000 population (86.9 per 100,000 [95% CI 58.5-115.2] when standardized by WHO World population and 109.7 per 100,000 [95% CI 89.7-129.8] when standardized by Argentine population) and 317.0 per 100,000 population in subjects older than 40 years. Case fatality rate at 30 days of first-ever strokes was 27%. CONCLUSION: In this population-based comprehensive stroke epidemiological study in Argentina, first-ever stroke incidence in an urban population was 124.2 per 100,000 population (86.9 per 100,000 adjusted by the WHO World population). This is lower than the incidence in other countries in the region and similar to a recent incidence study in Argentina. It is also comparable to reported incidence in most middle- and high-income countries. Stroke case-fatality rate was comparable to other population-based Latin-American studies.

The adult outcome of childhood quasi-autism arising following extreme institutional deprivation.

BACKGROUND: Rutter and colleagues' seminal observation that extended early life exposure to extreme institutional deprivation can result in what he termed quasi-autism (QA), informed both our understanding of the effects of adversity on development and the nature of autism. Here we provide the first detailed analysis of the adult outcomes of the group of institutionally deprived-then-adopted children identified as displaying QA. METHODS: Twenty-six adult adoptees identified with QA in childhood (Childhood QA+) were compared to 75 adoptees who experienced extended institutional deprivation (>6 months) but no QA (Childhood QA-), and 116 adoptees exposed to Low/No institutional deprivation. The outcomes were child-to-adult developmental trajectories of neuro-developmental symptoms (autism, attention-deficit/hyperactivity disorder (ADHD), disinhibited social engagement (DSE) and cognitive impairment), adult functioning, life satisfaction and mental health. RESULTS: Childhood QA+ was associated with elevated and persistent trajectories of broad-based autism-related difficulties, ADHD and DSE symptoms and low IQ, as well as adult mental health difficulties and functional impairment, including high rates of low educational attainment and unemployment. Life satisfaction and self-esteem were unaffected. Autism-related communication problems, in particular, predicted negative adult outcomes. Childhood QA+ was still associated with poor outcomes even when ADHD, DSE and IQ were controlled. CONCLUSIONS: Early and time-limited institutional deprivation has a critical impact on adult functioning, in part via its association with an early established and persistent variant of autism, especially related to communication difficulties. Apparent similarities and differences to non-deprivation related autism are discussed.

Digging into the admixture strata of current-day Canary Islanders based on mitogenomes.

The conquest of the Canary Islands by Europeans began at the beginning of the 15th century and culminated in 1496 with the surrender of the aborigines. The collapse of the aboriginal population during the conquest and the arrival of settlers caused a drastic change in the demographic composition of the archipelago. To shed light on this historical process, we analyzed 896 mitogenomes of current inhabitants from the seven main islands. Our findings confirm the continuity of aboriginal maternal contributions and the persistence of their genetic footprints in the current population, even at higher levels (>60% on average) than previously evidenced. Moreover, the age estimates for most autochthonous founder lineages support a first aboriginal arrival to the islands at the beginning of the first millennium. We also revealed for the first time that the main recognizable genetic influences from Europe are from Portuguese and Galicians.

The Effect of the Extra Virgin Olive Oil Minor Phenolic Compound 3',4'-Dihydroxyphenylglycol in Experimental Diabetic Kidney Disease.

The aim of this study was to analyze the possible nephroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7-7.8% reduction in DHPG-treated rats), as well as 38-56% reduction in urinary protein excretion and 22-46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson's coefficient 0.68-0.74), antinitrosative (Pearson's coefficient 0.83), and prostacyclin production regulator (Pearson's coefficient 0.75) effects.

Olive oil and wine as source of multi-target agents in the prevention of Alzheimer disease.

Olive oil and wine are consumed daily worldwide, and they constitute the fundamental pillars of the healthy Mediterranean diet. Polyphenolic compounds, naturally present in both olive oil and wine, are responsible for their beneficial properties. Current studies have shown the neuroprotective effects of polyphenols independently of their well-known antioxidant action. In this work, we have focused on reviewing the protective effect of polyphenols from extra virgin olive oil and wine in Alzheimer´s disease (AD), to emphasise that both foods could be a possible therapeutic tool. Beneficial effects have been described in ß-aggregation, neurofibrillary tangles, autophagy and mitochondrial function, as well as in cerebral insulin resistance. Furthermore, to date, a harmful dose has not been described. Both pre-clinical and clinical works demonstrate that polyphenols act on neuropathological and cognitive disorders of AD, preventing or stopping the onset of this devastating disease. However, there are certain limitations in these studies, since it is very difficult to research diseases that lead to cognitive impairment. Although all the findings obtained are very encouraging, more studies should be carried out investigating the use of the polyphenols from olive oil and wine as therapeutic agents in the progression of AD. Therefore, more longitudinal studies in humans with a homogeneous cohort of patients are necessary to corroborate the efficacy of these nutraceuticals, as well as determine the most appropriate dose for this purpose.

Tunneled catheter-related bacteremia in hemodialysis patients: incidence, risk factors and outcomes. A 14-year observational study.

BACKGROUND: Tunneled catheter-related bacteremia represents one of the major complications in patients on hemodialysis, and is associated with increased morbidity and mortality. This study aimed to evaluate the incidence of tunneled catheter-related bacteremia and, secondly, to identify possible factors involved in the first episode of bacteremia. METHODS: This is a retrospective study of all tunneled catheters inserted between 1 January, 2005 and 31 December, 2019. Data on patients with a tunneled catheter were analyzed for comorbidities, catheter characteristics, microbiological culture results and variables related to the first episode of bacteremia. Patient outcomes were also assessed. RESULTS: In the 14-year period under study, 406 tunneled catheters were implanted in 325 patients. A total of 85 cases of tunneled catheter-related bacteremia were diagnosed, resulting in an incidence of 0.40 per 1000 catheter days (81.1% after 6 months of implantation). The predominant microorganisms isolated were Gram-positive organisms: Staphylococcus epidermidis (48.4%); Staphylococcus aureus (28.0%). We found no significant differences in time to catheter removal for infections or non-infection-related reasons. The jugular vein, the Palindrome® catheter, and being the first vascular access were protective factors for the first episode of bacteremia. The 30-day mortality rate from the first tunneled catheter-related bacteremia was 8.7%. CONCLUSIONS: The incidence of bacteremia in our study was low and did not seem to have a relevant impact on catheter survival. S. epidermidis was the most frequently isolated microorganism, followed by S. aureus. We identified Palindrome® catheter, jugular vein, and being the first vascular access as significant protective factors against tunneled catheter-related bacteremia.

Resistin as a risk factor for all-cause (and cardiovascular) death in the general population.

Serum resistin is a pro-inflammatory cytokine that has been described as a risk factor associated with mortality in several clinical sets including type 2 diabetes. Mortality studies in the general population are needed to find out the risk of death associated to this cytokine. In a follow-up study of a cohort of adult population (n = 6636) in Spain over a period of fifteen years (447 deaths/102,255 person-years), serum resistin measurements and death records were obtained. The risks of all-cause deaths, and deaths from cardiovascular and oncological diseases were estimated. Hazard ratios (HR) and its confidence intervals (CI) were calculated using multivariable Cox models, adjusting the effect of 11 traditional risk factors. The risk of all-cause mortality among participants exposed to the highest quintile of resistin was always higher than among those in the lowest quintile (HR varied between 1.55 when smoking was the adjusted factor [95% CI 1.17-2.05], and 1.68 when the adjusted factor was physical activity [95% CI 1.27-2.21]). The maximally adjusted model, accounting for the effect of all traditional factors, corroborated this higher risk of all-cause mortality among people in the highest resistin quintile (HR = 1.52; 95% CI 1.13-2.05). The effect of resistin was even higher for cardiovascular deaths (HR = 2.14; 95% CI 1.13-4.06), being exceeded only by suffering diabetes (HR = 3.04; 95% CI 1.98-4.69) or previous acute coronary syndrome (HR = 3.67; 95% CI 2.18-6.18). This findings corroborate the role of resistin as a risk factor for all-cause (and cardiovascular) death in the general population.

Irisin is more strongly associated with leisure-time physical activity than resistin and high-density lipoprotein cholesterol are.

Obectives: Irisin is a myokine with a potential role in cardiometabolic diseases, but previous studies have described inconsistencies between serum irisin and physical activity (PA). Our aim was to analyze the relationship between serum irisin and leisure-time PA (LTPA) in a large sample of the general adult population, and secondarily, to evaluate its relationship with two PA-related biomarkers (HDL cholesterol and resistin). Design: A cross-sectional study was nested in the "CDC of the Canary Islands" cohort participants (n = 3827, 18-75 years, 60% women). Methods: PA was collected by administering the Minnesota leisure-time physical activity questionnaire, and physical examination and blood tests (irisin, resistin, HDL-cholesterol) were performed. Results: Irisin inversely correlated with BMI (p < 0.001 in women) and resistin (p = 0.038 in women, p = 0.004 in men), and directly with HDL cholesterol (p < 0.001in women). There was a direct association of irisin with leisure-time and energy expenditure in light, moderate and vigorous LTPA, which was stronger in women than men. The distribution of leisure-time and PA variables across irisin quintiles showed a significant trend, except for light LPTA in men. Adjusting for age, sex and BMI, the association of irisin with leisure-time and LTPA variables was stronger than the association of these variables with resistin and HDL cholesterol, reaching the strongest association for irisin with the 80th percentile of time of LTPA (OR = 2.57; 95% CI = 2.00-3.31). Conclusions: There is a direct and independent association between serum irisin levels and LTPA in the general adult population, which is stronger than other biomarkers of PA. Findings on exercise-related irisin support the possibility of irisin health benefits.

Developing CIRdb as a catalog of natural genetic variation in the Canary Islanders.

The current inhabitants of the Canary Islands have a unique genetic makeup in the European diversity landscape due to the existence of African footprints from recent admixture events, especially of North African components (> 20%). The underrepresentation of non-Europeans in genetic studies and the sizable North African ancestry, which is nearly absent from all existing catalogs of worldwide genetic diversity, justify the need to develop CIRdb, a population-specific reference catalog of natural genetic variation in the Canary Islanders. Based on array genotyping of the selected unrelated donors and comparisons against available datasets from European, sub-Saharan, and North African populations, we illustrate the intermediate genetic differentiation of Canary Islanders between Europeans and North Africans and the existence of within-population differences that are likely driven by genetic isolation. Here we describe the overall design and the methods that are being implemented to further develop CIRdb. This resource will help to strengthen the implementation of Precision Medicine in this population by contributing to increase the diversity in genetic studies. Among others, this will translate into improved ability to fine map disease genes and simplify the identification of causal variants and estimate the prevalence of unattended Mendelian diseases.

Individual body mass and length dataset for over 12,000 fish from Iberian streams.

We provide a unique fish individual body size dataset collected from our own sampling and public sources in north-eastern Spain. The dataset includes individual body size measures (fork length and mass) of 12,288 individuals of 24 fish species within 10 families collected at 118 locations in large rivers and small streams. Fish were caught by one-pass electrofishing following European standard protocols. The fish dataset has information on the local instream conditions including climatic variables (i.e., temperature and precipitation), topography (i.e., altitude), nutrient concentration (i.e., total phosphorus and nitrates), and the IMPRESS values (a measure of cumulative human impacts in lotic ecosystems). The potential uses of this new fish dataset are manifold, including developing size-based indices to further estimate the ecological status of freshwater ecosystems, allometric models, and analysis of variation in body size structure along environmental gradients.

Control of Vascular Risk Factors and Response to Stroke Symptoms in Argentina During the COVID-19 Quarantine. The SIFHON-COVID Population Survey.

Background and Objectives: In preparation for the suspected influx of COVID-19 patients, many healthcare systems reduced or discontinued provision of "non-urgent" care. This decision had potential impact on stroke prevention and management. We conducted a large population survey to assess the effect of mandatory social isolation on routine health controls, emergency consultations and other stroke care-related behaviors of the population during the pandemic. Methods: We distributed multiple-choice anonymous questionnaires through the institutional email database and through the email database of clients of a beverage delivery company. Most respondents resided in the metropolitan area of Buenos Aires. This is the area where the infection rates were highest and restriction measures were hardest. The survey assessed demographic characteristics and actual and potential behaviors of people regarding medical checkups, risk factors control, medication provision and response to onset of symptoms consistent with stroke or TIA. Surveys were sent during May 2020, the strictest period of the quarantine in Argentina. Results: A total of 10,303 questionnaires were completed. Thirty-seven percent of the respondents were older than 60 years, 74% were women and 16% lived alone. Vascular risk factors were present in 39% of the individuals. Seventy-six percent did not continue with their regular medical checkups during the mandatory social and preventive isolation, 21% had difficulty obtaining medical prescriptions and only 38% considered that health institutions had implemented reliable safety measures to avoid exposure to COVID-19. When asked about response in case of onset of stroke symptoms, 9% would not consult given the context of the pandemic. Six percent reported having had symptoms consistent with stroke or TIA but only 35% went to a hospital. The vast majority of the respondents said they were awaiting for the end of the quarantine to resume their usual medical care. Conclusions: The implementation of a quarantine may have some serious adverse effects on the prevention, diagnosis and treatment of stroke. These undesirable aspects should be taken into consideration in the planning, communication and implementation of health policies.

Neuroprotective Effect of 3',4'-Dihydroxyphenylglycol in Type-1-like Diabetic Rats-Influence of the Hydroxytyrosol/3',4'-dihydroxyphenylglycol Ratio.

The aim of this study was to assess the possible neuroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenol from extra virgin olive oil (EVOO), in an experimental model of diabetes and whether this effect is modified by the presence of another EVOO polyphenol, hydroxytyrosol (HT). The neuroprotective effect was assessed in a hypoxia-reoxygenation model in brain slices and by quantifying retinal nerve cells. The animals were distributed as follows: (1) normoglycemic rats (NDR), (2) diabetic rats (DR), (3) DR treated with HT (5 mg/kg/day p.o.), (4) DR treated with DHPG (0.5 mg/kg/day), or (5) with 1 mg/kg/day, (6) DR treated with HT plus DHPG 0.5 mg/kg/day, or (7) HT plus 1 mg/kg/day p.o. DHPG. Diabetic animals presented higher levels of oxidative stress variables and lower numbers of neuronal cells in retinal tissue. The administration of DHPG or HT reduced most of the oxidative stress variables and brain lactate dehydrogenase efflux (LDH) as an indirect index of cellular death and also reduced the loss of retinal cells. The association of DHPG+HT in the same proportions, as found in EVOO, improved the neuroprotective and antioxidant effects of both polyphenols.

Pathological and clinical features of multiple cancers and lung adenocarcinoma: a multicentre study.

OBJECTIVES: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes. METHODS: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups. RESULTS: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008). CONCLUSIONS: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern.