Search

Despite the high morbidity and mortality of metastatic colorectal cancer (mCRC) in older patients, they have been underrepresented in clinical trials and their optimal treatment is yet to be determined. This open-label phase II study evaluated the benefits of panitumumab and capecitabine as a first-line chemotherapy regimen in older patients with wild-type [WT] RAS mCRC. Patients (≥70 years; ECOG≤2) received 3-week cycles of panitumumab (9 mg/kg on day 1) plus capecitabine (850 mg/m2 twice daily on days 1–14) until disease progression or unacceptable toxicity. Response was evaluated every 9 weeks according to RECIST_1.1. Outcome measures were: objective response rate (ORR), duration of response (DoR), time to response (TTR), progression (TTP) and treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. Twenty-seven patients (11 women; median age: 78 years; ECOG: 0 [26%], 1 [67%], 2 [7%]) were evaluated. Median follow-up was 17.7 months. Confirmed ORR (95%CI) was 44.4% (25.7–63.2), with 25.9% of patients achieving at least stable disease. Median (95%CI) DoR was 8.7 (5.5–10.4) months, and median TTR was 2.2 (1.9–2.8) months. Median TTP was 9.6 (4.8–11.5) months, with a median TTF of 5.2 (2.8–7.2) months. The median PFS was 7.5 (4.4–10.4) months, and the median OS was 23.7 (7.4–27.5) months. Seventeen (63%) patients reported panitumumab and/or capecitabine-related adverse events grade 3–4, with skin toxicity (18.5%) being the most common. Two (7.4%) deaths were treatment-related. This study suggests that panitumumab plus capecitabine is a safe and effective regimen in older patients with WT RAS mCRC. • Panitumumab has a low rate of immunogenicity compared with other antibodies against EGFR because of its fully human nature. • The combination of panitumumab and capecitabine was suggested to be effective in older patients with WT RAS mCRC. • The good tolerability and safety profile of the combination were in line to previous studies in older patients. • Panitumumab with capecitabine may provide an alternative to other anti-EGFR regimens in older patients with WT RAS mCRC. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most frequent and deadly tumours worldwide. However, the evidence that currently exists for the treatment of older adults is limited and is derived mainly from clinical trials in which older patients are poorly represented. In this article, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Group for the Treatment of Digestive Tumours (TTD), and the Spanish Multidisciplinary Group on Digestive Cancer (GEMCAD) reviews the existing scientific evidence for older patients (≥65 years old) with gastric cancer and establishes a series of recommendations that allow optimization of management during all phases of the disease. Geriatric assessment (GA) and a multidisciplinary approach should be fundamental parts of the process. In early stages, endoscopic submucosal resection or laparoscopic gastrectomy is recommended depending on the stage. In locally advanced stage, the tolerability of triplet regimens has been established; however, as in the metastatic stage, platinum- and fluoropyrimidine-based regimens with the possibility of lower dose intensity are recommended resulting in similar efficacy. Likewise, the administration of trastuzumab, ramucirumab and immunotherapy for unresectable metastatic or locally advanced disease is safe. Supportive treatment acquires special importance in a population with different life expectancies than at a younger age. It is essential to consider the general state of the patient and the psychosocial dimension. [ABSTRACT FROM AUTHOR]

Introduction The effect of surgery for metastases in patients with esophagogastric cancer is unknown, given the lack of randomized clinical trials; likewise, the criteria for selecting eligible patients remain to be determined. Methods This registry evaluates the results of patients with advanced adenocarcinoma of the stomach, distal esophagus, or gastro-esophageal junction from 32 centers. To assess selection criteria and prognostic factors, a state arrival extended Markov proportional hazards (PH) model was used. Results 1792 subjects were analyzed, 5% of whom (n = 92) underwent surgery for metastasis. The most common surgeries were peritoneal (29%), hepatic (24%), and distant lymph nodes (11%). Subjects chosen for metastasectomy had higher survival rates, HR 0.34 (95% CI, 0.06–0.80, p = 0.021). Patients who underwent surgery had a mOS since metastasectomy of 16.7 months (95% CI, 12.5–22.4). The 1- and 3-year relapse rates following R0 resection were 58% and 65%, respectively. Median time since R0 metastasectomy until relapse was 8.4 months (95% CI, 7.6–23.7). The 3-year OS after surgery was 30.6% (95% CI, 19.3–40.4). Duration of chemotherapy prior to surgery (months) increased mortality (HR 1.04 [95% CI, 1.01–1.07]), p = 0.009. The only significant interaction involved the use of anti-HER2 therapy. Conclusion The AGAMENON registry suggests that subjects with limited metastatic disease, selected on a clinical basis, can benefit from early surgeries. Prospective trials are needed to confirm these data. [ABSTRACT FROM AUTHOR]

Objective Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC. Materials and Methods We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008–2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥ 70 vs. <70 years. The fixed-margin method was used (hazard ratio [HR]<1.176) that corresponds to conserving at least 85% efficacy. Results: 33% (n = 489) of the cases analyzed were ≥ 70 years. Two-agent chemotherapies and combinations with oxaliplatin (48% vs. 29%) were used more often in the older patients, as were modified schedules and/or lower doses. Toxicity grade 3–4 was comparable in both groups, although when looking at any grade, there were more episodes of enteritis, renal toxicity, and fatigue in older patients. In addition, toxicity was a frequent cause for discontinuing treatment in older patients. The response rate was similar in both groups. After adjusting for confounding factors, the non-inferiority of OS associated with schedules administered to the older vs. younger subjects was confirmed: HR 1.02 (90% CI, 0.91–1.14), P (non inferiority) = 0.018, as well as progression-free survival: HR 0.97 (90% CI, 0.87–1.08), P(non-inferiority) = 0.001. Conclusion In this AGC registry, the use of chemotherapy with schedules adapted to patients ≥ 70 years provided efficacy that was not inferior to that seen in younger cases, with comparable adverse effects. [ABSTRACT FROM AUTHOR]

Objectives: There are no tools or biomarkers for a quantitative analysis of sarcopenia.Study Design: Cross-sectional study of the diagnosis of sarcopenia in 200 independent adults aged 70 years or over.Main Outcome Measures: Sarcopenia was defined as loss of muscle mass together with low strength and/or loss of physical performance. We considered different clinical parameters and assayed potential blood biomarkers (cell energetic metabolism, muscle performance, inflammation, infection and oxidative stress).Results: The prevalence of sarcopenia was 35.3% in women and 13.1% in men, and it was significantly associated with advanced age, a low functional performance in the lower extremities, deficient weekly consumption of kilocalories, risk of malnutrition, and drug use for the digestive system. A close relationship was found between sarcopenia, pre-frailty and depressed mood. With these confounding variables, we observed that products of lipid peroxidation were closely associated with sarcopenia in independent older adults (frail participants and those with severe dependence had been excluded from the sample). The best multivariate model proposed was able to predict 67.6% of the variance in sarcopenia, with a power of discrimination of 93.5%. Additional analyses considering lipid levels, fat mass, dyslipidemia, use of lipid-lowering drugs and hypertension confirmed this close association between lipid peroxidation and sarcopenia.Conclusions: Given the difficulty in the diagnosis of sarcopenia in clinical practice, we suggest the use of blood circulating products of lipid peroxidation as potential biomarkers for an early diagnosis of sarcopenia in independent older adults. [ABSTRACT FROM AUTHOR]

Plastic pollution constitutes an environmental problem in the Canary Islands nowadays. Nevertheless, studies evaluating the impact of plastics on its avifauna are still scarce. Gastrointestinal tracts of 88 birds belonging to 14 species were studied for the presence of plastics. Moreover, their livers were analyzed for the determination of bromodiphenyl ethers (BDEs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs). Among Cory's shearwaters (n = 45), the frequency of occurrence of plastic ingestion was considerably high (88.89 %). This species had the highest mean value of items (7.22 ± 5.66) and most of them were compatible with lines derived from fishing gear. PCBs and PAHs were detected in all of the samples and OCPs in the great majority of them (98.86 %). Our results highlight the problems that plastic debris (mainly for seabirds) and organic pollutants pose to these species. • Plastic ingestion and hepatic chemical pollutants were studied in 88 birds of 14 species. • High frequency of plastic ingestion in Calonectris borealis and Oceanodroma castro and lower in Larus michahellis. • High proportion of plastics derived from fishing gear. • Detection of PCBs and PAHs in all birds. [ABSTRACT FROM AUTHOR]

International Public Health authorities recommend biomonitoring studies to assess the exposure to chemicals in the general population. The aim of the present study was to analyze the blood concentrations of a total 360 pollutants, including 230 pesticides in current or recent use, 59 persistent organochlorine pollutants (POPs), 11 anticoagulant rodenticides and 60 pharmaceutical active compounds (PhACs), in a cohort of 403 subjects from Cape Verde. The study was performed in the frame of the Pesticide Residues in Vegetables of the Macaronesia project (PERVEMAC-II). A total of 60 out of 360 toxic compounds (16.7%) were detected, at least, in one participant. The three most frequently detected substances were p,p'-DDE (100%), phenanthrene (94.0%) and hexachlobenzene (35.9%). 2-Phenylphenol and imidacloprid were detected in 29.0 and 14.4% of the population. The three substances with the highest serum concentrations were PhACs: naproxen (249.1 ng/mL), metronidazole (115.6 ng/mL) and acetaminophen (25.2 ng/mL). Median blood concentration of p,p'-DDE, HCB and phenanthrene were 1.87, 0.08 and 0.36 ng/mL. Blood concentrations of POPs were influenced by age, although both gender and body mass index may exert an influence in the presence of these substances. Lifestyle has an effect on the concentration of these substances, especially in terms of dietary habits. Both the frequency of detection and the concentration of the studied substances are similar to those of other biomonitored populations. This is the first biomonitoring study carried out in Cape Verde. Our results may be useful for the implementation of public health measures by the competent authorities. [Display omitted] • 360 pollutants were analyzed in blood from 403 subjects from Cape Verde. • 16.7% of toxic elements were detected/quantified. • p,p'-DDE, phenanthrene and HCB were the 3 most frequently detected substances. • Lifestyle has an effect on the concentration of these substances. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress plays an essential role in triggering many cellular processes including programmed cell death. Proving a relationship between apoptosis and reactive oxygen species has been the goal of numerous studies. Accumulating data point to an essential role for oxidative stress in the activation of autophagy. The term autophagy encompasses several processes including not only survival or death mechanisms, but also pexophagy, mitophagy, ER-phagy or ribophagy, depending of which organelles are targeted for specific autophagic degradation. However, whether the outcome of autophagy is survival or death and whether the initiating conditions are starvation, pathogens or death receptors, reactive oxygen species are invariably involved. The role of antioxidants in the regulation of these processes, however, has been sparingly investigated. Among the known antioxidants, melatonin has high efficacy and, in both experimental and clinical situations, its protective actions against oxidative stress are well documented. Beneficial effects against mitochondrial dysfunction have also been described for melatonin; thus, this indoleamine seems to be linked to mitophagy. The present review focuses on data and the most recent advances related to the role of melatonin in health and disease, on autophagy activation in general, and on mitophagy in particular. [Copyright &y& Elsevier]

Abstract: The Syrian hamster Harderian gland (HG) displays a huge porphyrins metabolism with sexual dimorphism. Even in male Syrian hamsters with much lower porphyrins concentration than female HG, this activity is higher than in the liver. The damage derived from constant porphyrin production, displayed by reactive oxygen species, forces the gland to develop mechanisms that allow it to continue with its normal physiology. The survival strategy of the Harderian gland is mainly based on autophagic processes that are considered as a constant renovation system. Our results show different autophagy mechanisms in Syrian hamster HG, macroautophagy and other lysosomal‐like processes such as chaperone‐mediated autophagy, depending on sex and probably related to oxidative stress status. This chapter describes the methods used by us to characterize the autophagic processes that are being physiologically developed by this organ under normal conditions. [Copyright &y& Elsevier]

Effects of δ-aminolevulinic acid (ALA) and melatonin were investigated in the female Syrian hamster Harderian gland. This is an organ physiologically exposed to strong oxidative stress due to the highest porphyrinogenic rates known in nature. Enzyme activities of porphyrin biosynthesis and of antioxidative protection, oxidative protein modification, and histological integrity were studied. In the porphyrin biosynthetic pathway, ALA and melatonin acted synergistically by downregulating ALA synthase (ALA-S) and stimulating product formation from ALA; the combination of ALA and melatonin suppressed ALA-S activity, down to about 1% of that in controls. While ALA effects on porphyrinogenesis can be interpreted in terms of homeostasis, melatonin’s actions may be seen in relation to seasonality and/or reduction of oxidative stress. Among antioxidant enzymes, superoxide dismutase (SOD) and glutathione reductase (GR) activities were diminished by ALA, presumably due to the vulnerability of their active centers to free radicals, whereas melatonin moderately increased SOD. Both ALA and melatonin strongly stimulated catalase (CAT), thereby counteracting the oxidative stress induced by ALA and its metabolites. Nevertheless, exogenous ALA caused a strong net rise in protein carbonyl and considerable damage of tissue. When given together with ALA, melatonin antagonized these effects and largely protected the integrity of glandular structures. [Copyright &y& Elsevier]

• Standard reflectance hyperspace vs -log reflectance hyperspace. • Deep learning-based vs linear-based unmixing algorithms. • Unmixing performed in the SWIR range. • Combined metric for pigment identification. • Application to a painting with inscription "Boceto di Pablo Veronese" on the back. Hyperspectral imaging has recently consolidated as a useful technique for pigment mapping and identification, although it is commonly supported by additional non-invasive analytical methods. Since it is relatively rare to find pure pigments in aged paintings, spectral unmixing can be helpful in facilitating pigment identification if suitable mixing models and endmember extraction procedures are chosen. In this study, a subtractive mixing model is assumed, and two approaches are compared for endmember extraction: one based on a linear mixture model, and the other, nonlinear and Deep-Learning based. Two spectral hyperspaces are used: the spectral reflectance (R hyperspace) and the -log(R) hyperspace, for which the subtractive model becomes additive. The performance of unmixing is evaluated by the similarity of the estimated reflectance to the measured data, and pigment identification accuracy. Two spectral ranges (400 to 1000 nm and 900 to 1700 nm) and two objects (a laboratory sample and an aged painting, both on copper) are tested. The main conclusion is that unmixing in the -log(R) hyperspace with a linear mixing model is better than for the non-linear model in R hyperspace, and that pigment identification is generally better in R hyperspace, improving by merging the results in both spectral ranges. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Few studies have evaluated the relationship between morphological and functional characteristics of the masticatory apparatus in young subjects. Thus, the aim of this study was to evaluate masticatory performance (MP), maximal bite force (BF), orthodontic treatment need and orofacial dysfunction in children and adolescents. Design: The sample consisted of 316 subjects of both genders, with an age range 6–16years divided into 4 groups: early mixed, intermediate mixed, late mixed and permanent dentition. MP was evaluated by the individual''s ability to comminute a chewable test material in order to determine median particle size (X 50) and distribution of particles in different sieves (“b”). BF was determined using a digital gnatodynamometer with fork strength of 10mm. Orofacial function and orthodontic treatment need were screened using the Nordic Orofacial Test-Screening (NOT-S) protocol and Index of Orthodontic Treatment Need (IOTN), respectively. The results were submitted to descriptive statistics, normality test, analysis of variance and stepwise multiple linear regression to test relationship between MP and studied independent variables. Results: Variance of X 50 and b between groups was statistically significant. But evaluation of variables that significantly contributed to MP variation showed that age, body mass index (BMI), BF and the presence of sleep bruxism were negatively related to X 50 and the NOT-S clinical exam scores showed a positive relationship with X 50. Conclusion: In the studied sample, age, BMI, BF and the presence of sleep bruxism were related to better MP; but the increase in NOT-S scores was significantly related to poorer MP. [Copyright &y& Elsevier]

Abstract: This work focuses on the study of paper and textiles used in the binding of a series of manuscripts that share some specific characteristics that lead us to speculate on the possibility of a transitional codicological typology from the Arabic to the Christian book in Al-Andalus during the 15th century. The books we analyzed belong to the collection of the Historical Archive of Malaga, the Archive of Sacromonte Abbey, in Granada, the School of Arabic Studies and the Library of P.P. Escolapios, also in Granada. Paper physical study was performed by microscopic and spectroscopic techniques. A routine and objective method, Fourier Transform Infrared (FTIR) spectroscopy, was employed and proved to be a useful technique for the characterization of cellulosic fibres, main component of paper from the boards and the envelope flap pasteboards, and the fabric lining from the cover. The results of our research will help us to date, identify and study the evolution of the techniques, proving that the materials and innovations of the Italian paper manufacturing processes were perfectly known in the south of modern day Spain, before the Christian Reconquest. [Copyright &y& Elsevier]

The apple cultivar, known for its adaptability and diverse varieties, has been extensively utilized for cider production, particularly in climatically suitable regions. Cider, an age-old alcoholic beverage derived from fermenting apple juice, is gaining popularity, especially among younger generations. Despite this trend, comprehensive knowledge regarding the toxicological profile of ciders remains limited, leaving room for potential chemical contaminants from raw ingredients or production methods. To address this gap, we conducted an unprecedented study analyzing sixty-eight cider samples from the Spanish market, encompassing both traditional ciders and newly developed apple-based flavored drinks referred to as "ciders." Our investigation focused on pesticide residues, elemental profiles, and mycotoxin residues. In a groundbreaking approach, our study integrated the analysis of 225 pesticide residues, 50 Persistent Organic Pollutants (POPs), 11 mycotoxins (AFB1, AFB2, AFG1, AFG2, DON, FB1, FB2, H-2, HT-2, OTA, PAT, and ZEN), and a total of 50 elements. Pesticide residues were identified using GCMSMS and LCMSMS, elemental composition determined via ICPMS, and mycotoxins analyzed using LCMSMS. The significance of our research lies in addressing the dearth of toxicological analyses of ciders, despite their burgeoning global consumption and production. For pesticide residues and elemental composition, our results underwent statistical processing, revealing distinct differences between the elemental profiles of traditional ciders and "ciders." Additionally, disparities were observed between cider and other low-alcohol fermented beverages like wines and beers. Concentrations of most pesticide residues and elements in the cider samples were deemed non-toxic, falling below allowable limits established by international organizations for other beverages such as water or wine. However, certain elements, notably Br and Pb in traditional ciders, raised potential concerns. Our findings underscore the necessity of establishing regulatory limits for pesticide residues, potentially hazardous elements, and mycotoxins in cider, a regulatory framework currently lacking on a global scale. • Knowledge about the toxicological profile of ciders is rather scarce. • 68 ciders were analyzed for pesticides, mycotoxins, POPs and elemental composition. • The concentrations of pesticides, POPs and mycotoxins can be considered as safe. • Some elements in traditional ciders were potentially problematic, including Br and Pb. • MRLs for pesticides, toxic elements and mycotoxins should be set for cider. [ABSTRACT FROM AUTHOR]

Gender and RYR1 gene mutation might have an effect on the muscle metabolic characteristics and on the animal's stress at slaughter, which could influence the process of muscle-to-meat conversion. Forty-eight pigs were distributed in a design including two factors: sex (male/female) and RYR1 genotype (NN/Nn). At slaughter, physiological blood biomarkers and muscle proteome were analyzed and carcass and meat quality traits were registered. Females had higher serum levels of glucose, urea, C-reactive protein “CRP”, Pig-MAP and glutation-peroxidase “GPx” and lower levels of lactate, showed faster muscle pH decline and higher meat exudation. RYR1 mutation increased serum creatinine, creatine kinase and CRP and decreased GPx. The proteomic study highlighted significant effects of gender and RYR1 genotype on proteins related to fibre composition, antioxidant defense and post mortem glycolytic pathway, which correlate to differences of meat quality. This study provides interesting information on muscle biomarkers of the ultimate meat quality that are modulated by the animal's individual susceptibility to stress at slaughter. [ABSTRACT FROM AUTHOR]

Sarcopenia is the gradual loss of skeletal muscle mass, strength and quality associated with aging. Changes in body composition, especially in skeletal muscle and fat mass are crucial steps in the development of chronic diseases. We studied the effect of overweight on skeletal muscle tissue in elderly people without reaching obesity to prevent this extreme situation. Overweight induces a progressive protein breakdown reflected as a progressive withdrawal of anabolism against the promoted catabolic state leading to muscle wasting. Protein turnover is regulated by a network of signaling pathways. Muscle damage derived from overweight displayed by oxidative and endoplasmic reticulum (ER) stress induces inflammation and insulin resistance and forces the muscle to increase requirements from autophagy mechanisms. Our findings showed that failure of autophagy in the elderly deprives it to deal with the cell damage caused by overweight. This insufficiently efficient autophagy leads to an accumulation of p62 and NBR1, which are robust markers of protein aggregations. This impaired autophagy affects myogenesis activity. Depletion of myogenic regulatory factors (MRFs) without links to variations in myostatin levels in overweight patients suggest a possible reduction of satellite cells in muscle tissue, which contributes to declined muscle quality. This discovery has important implications that improve the understanding of aged-related atrophy caused by overweight and demonstrates how impaired autophagy is one of the main responsible mechanisms that aggravate muscle wasting. Therefore, autophagy could be an interesting target for therapeutic interventions in humans against muscle impairment diseases. [ABSTRACT FROM AUTHOR]

Defects in meat quality such as dark, firm and dry (DFD) beef have been related to high levels of oxidative stress that produce cellular alterations that may affect to the process of meat quality acquisition. Despite the important role of endoplasmic reticulum (ER) in the cellular response to oxidative stress, its function in the muscle-to-meat conversion process has not yet been studied. In this study, differences in muscular antioxidant defense and the unfolded protein response (UPR) of the ER in CONTROL (normal pH 24) and dark, firm, and dry (DFD, pH 24 ≥ 6.2) beef at 24 h post-mortem were analyzed to understand the changes in the muscle-to-meat conversion process related to meat quality defects. DFD meat showed poor quality, lower antioxidant activity (P < 0.05) and higher UPR activation (P < 0.05), which indicates higher oxidative stress what could partly explain the occurrence of meat quality defects. Therefore, the biomarkers of these cellular processes (IRE1α, ATF6α, and p-eIF2α) are putative biomarkers of meat quality. • Oxidative stress negatively affects meat quality traits. • DFD beef showed lower antioxidant activity at 24 h post-mortem. • Higher endoplasmic reticulum response to stress was found in DFD beef. • Biomarkers of these cellular processes can be putative biomarkers of meat quality. [ABSTRACT FROM AUTHOR]

Background Switch maintenance is an effective strategy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Pazopanib is an oral, multi-targeted tyrosine kinase inhibitor (TKI). EORTC 08092 evaluated pazopanib given as maintenance treatment following standard first line platinum-based chemotherapy in patients with advanced NSCLC. Methods Patients with non-progressive disease after 4–6 cycles of chemotherapy were randomised to receive either pazopanib 800 mg/day or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival and secondary end-points were progression-free survival (PFS) and safety. Results A total of 600 patients were planned to be randomised. The trial was prematurely stopped following an early interim analysis, after 102 patients were randomised to pazopanib ( n = 50) or placebo ( n = 52). Median age was 64 years in both arms. Median overall survival was 17.4 months for pazopanib and 12.3 months for placebo (adjusted hazard ratio (HR) 0.72 [95% confidence interval (CI) 0.40–1.28]; p = 0.257). Median PFS was 4.3 months versus 3.2 months (HR 0.67, [95% CI 0.43–1.03], p = 0.068). PFS rates at 4 months were 56% and 45% respectively. The majority of treatment-related adverse events (AEs) were grade 1–2. Grade 3–4 AEs (pazopanib versus placebo) were hypertension (38% versus 8%), neutropenia (8% versus 0%), and elevated SGPT (6% versus 0%). Of the patients randomised to pazopanib, 22% withdrew due to a treatment-related AE. Conclusions Switch maintenance with pazopanib following platinum-based chemotherapy in advanced NSCLC patients had limited side-effects. This study was stopped due to lack of efficacy by stringent criteria for PFS at a futility interim analysis. [ABSTRACT FROM AUTHOR]

• Western diet enhanced spatial memory and impaired behavorial flexibility in male rats. • Maternal separation or Western diet independently increased the metabolic capacity of the hippocampus and prefrontal cortex. • Western diet interacted with early-life stress decreasing levels of brain oxidative stress. • Western diet and maternal separation partially compensated their adverse effects on spatial memory. Prolonged daily intake of Western-type diet rich in saturated fats and sugars, and exposure to early life stress have been independently linked to impaired neurodevelopment and behaviour in animal models. However, sex-specific effects of both environmental factors combined on spatial learning and memory, behavioural flexibility, and brain oxidative capacity have still not been addressed. The current study aimed to evaluate the impact of maternal and postnatal exposure to a high-fat and high-sugar diet (HFS), and exposure to early life stress by maternal separation in adult male and female Wistar rats. For this purpose, spatial learning and memory and behavioural flexibility were evaluated in the Morris water maze, and regional brain oxidative capacity and oxidative stress levels were measured in the hippocampus and medial prefrontal cortex. Spatial memory, regional brain oxidative metabolism, and levels of oxidative stress differed between females and males, suggesting sexual dimorphism in the effects of a HFS diet and early life stress. Males fed the HFS diet performed better than all other experimental groups independently of early life stress exposure. However, behavioural flexibility evaluated in the spatial reversal leaning task was impaired in males fed the HFS diet. In addition, exposure to maternal separation or the HFS diet increased the metabolic capacity of the prefrontal cortex and dorsal hippocampus in males and females. Levels of oxidative stress measured in the latter brain regions were also increased in groups fed the HFS diet, but maternal separation seemed to dampen regional brain oxidative stress levels. Therefore, these results suggest a compensatory effect resulting from the interaction between prolonged exposure to a HFS diet and early life stress. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress has been reported to increase during aging and conditions of hypoxia. Although low oxygen saturation has a key role in the development of several age-related diseases, the underlying mechanisms are still unknown. We analyzed the relationship between aging and hypoxia by examining oxidative stress and inflammation-related cytokines. We collected blood samples from three volunteer experimental groups, consisting of one group of normoxic middle-aged people and two groups of individuals older than 75years, which comprised a subgroup of normoxic subjects and another with oxyhemoglobin saturation lower than 95% (hypoxic). Our results showed a fall in antioxidant defenses in older people with hypoxia. TNF-α, the first element in the cytokine cascade, was significantly increased in the aged population, implying that aging is accompanied by a gradual increase in this inflammatory biomarker. IL-6 was not associated with aging, but it was highly elevated under hypoxia conditions in elderly subjects. Thus, these parameters could be used as biological markers of different inflammatory processes triggered by oxidative stress induced by a decrease in antioxidant defenses in the elderly population, with TNF-α as an indicator of chronic processes, such as aging, and IL-6 as a marker for acute responses, such as hypoxia. [Copyright &y& Elsevier]

The recent volcanic eruption on the island of La Palma has aroused the concern of banana producers and consumers, given that in its area of influence there are thousands of hectares of banana plantations with an annual production of about 100 million kilos for export. Since volcanoes are one of the main natural sources of heavy metal contamination, we sampled bananas from the affected area and determined the concentrations of 50 elements (Ag, Al, As, Au, Ba, Be, Bi, Cd, Ce, Co, Cr, Cu, Cu, Dy, Er, Eu, Fe, Ga, Gd, Hg, Ho, In, La, Lu, Mn, Mo, Nb, Nd, Ni, Os, Pb, Pd, Pm, Pr, Pt, Sb, Sc, Se, Sm, Sn, Sr, Ta, Tb, Th, Ti, Tl, Tm, U, Y, Yb and Zn). The levels of 36 elements were elevated but the washing implemented after the eruption can remove a good part. After the washout, bananas have elevated levels of Fe, Al, Ti, V, Ba, Pb, most of the rare earth elements, Mo, and Co. In all cases, except Mo, the elevation is much higher in the peel than in the flesh. In the case of Mo, the elevation in banana flesh would translate into a higher nutritional intake of this trace element, which could represent up to 35% of the daily nutritional requirements. Exposure to toxic or potentially toxic elements, does not represent a health risk, since would not exceed 5% of the tolerable daily intake, even in the worst-case scenario. [Display omitted] • Volcano bananas contain more molybdenum, capable of providing 35% of the RDI. • Washing the bunch can remove most of the toxic elements deposited on the bananas. • Concentrations of Mo, Co, Pb, Fe, Al, Ti, V, and REE were increased in the flesh of volcano bananas. • The banana skin accumulates much higher concentrations of toxic elements than the flesh. • In the worst-case scenario, they would provide less than 5% of the tolerable daily intakes of toxic elements. [ABSTRACT FROM AUTHOR]

Effects of the prooxidant δ-aminolevulinic acid (ALA) and the antioxidant melatonin (MEL) were investigated in the male Syrian hamster Harderian gland (HG). Rodent Harderian glands are highly porphyrogenic organs, which may be used as model systems for studying damage by δ-aminolevulinic acid and its metabolites, as occurring in porphyrias. Chronic administration of δ-aminolevulinic acid (2 weeks) markedly decreased activities of the porphyrogenic enzymes δ-aminolevulinate synthase (ALA-S) and δ-aminolevulinate dehydratase (ALA-D) and of the antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR) and catalase (CAT), whereas porphobilinogen deaminase (PBG-D) remained unaffected. This treatment led to increased lipid peroxidation (LPO) and oxidatively modified protein (protein carbonyl) as well as to morphologically apparent tissue damage. Melatonin also caused decreases in δ-aminolevulinate synthase, δ-aminolevulinate dehydratase, superoxide dismutase, glutathione reductase and catalase. Despite lower activities of antioxidant enzymes, lipid peroxidation and protein carbonyl were markedly diminished. The combination of δ-aminolevulinic acid and melatonin led to approximately normal levels of δ-aminolevulinate dehydratase, glutathione reductase, catalase and protein carbonyl, and to rises in superoxide dismutase and porphobilinogen deaminase activities; lipid peroxidation remained even lower than in controls and the appearance of the tissue revealed a protective influence of melatonin. These results suggest that melatonin may have profound effects on the oxidant status of the Harderian gland. [Copyright &y& Elsevier]