Impact of oxidative stress SNPs and dietary antioxidant quality score on prostate cancer.

Purpose: To analyse the relation between antioxidant genotypes and Dietary Antioxidant Quality score (DAQs) effect on prostate cancer (PCa) risk and aggressiveness in a Spanish population.Methods: Men (N = 155 patients and 152 controls) with PSA values >4 ng/ml were enrolled in the project. DAQs were used considering the daily recommended intake for Spanish people (DRI). Genotyping of 5 SNPs rs662 (PON1), rs10432782 (SOD1), rs4880 (SOD2), rs17650792 (GPX1) and rs1001179 (CAT) were included for the analysis.Results: rs17650792 was statistically significant between case and controls subjects. When comparing D´Amico risk, we found that rs662 (CC), rs10432782 (G allele) and rs17650792 (GG) confer a protection. When testing SNP-antioxidant nutrients interactions, we found an intake of vitamin A and rs100179 (T carriers) and selenium and rs17650792 (G carriers) confers a protection of being in low risk classification.Conclusions: We reported by the first time a correlation between rs662 (PON1) and PCa aggressiveness.

Scattering of the Halo Nucleus

Angular distributions of the elastic, inelastic, and breakup cross sections of the halo nucleus ^{11}Be on ^{197}Au were measured at energies below (E_{lab}=31.9 MeV) and around (39.6 MeV) the Coulomb barrier. These three channels were unambiguously separated for the first time for reactions of ^{11}Be on a high-Z target at low energies. The experiment was performed at TRIUMF (Vancouver, Canada). The differential cross sections were compared with three different calculations: semiclassical, inert-core continuum-coupled-channels and continuum-coupled-channels ones with including core deformation. These results show conclusively that the elastic and inelastic differential cross sections can only be accounted for if core-excited admixtures are taken into account. The cross sections for these channels strongly depend on the B(E1) distribution in ^{11}Be, and the reaction mechanism is sensitive to the entanglement of core and halo degrees of freedom in ^{11}Be.

Primary Graft Dysfunction and Mortality Following Lung Transplantation: A Role for Proadrenomedullin Plasma Levels.

Primary graft dysfunction (PGD) after lung transplantation (LT) is a heterogeneous syndrome that comprises clinical presentations with diverse grades of severity. Proadrenomedullin (proADM) levels may be associated with PGD and may enhance its relationship with outcomes. We prospectively included 100 LT recipients. Plasma levels of proADM were measured at 24, 48 and 72 h after admission to the intensive care unit (ICU). We assessed their relationship with PGD grade and ICU mortality. Fifty patients (50%) presented grade 3 PGD at ICU admission. Twenty-two patients (22%) developed grade 3 PGD at 72 h, the only grade associated with higher mortality (odds ratio 6.84, 95% confidence interval [CI] 1.47-38.44). ProADM levels measured at 24 h (3.25 vs. 1.61 nmol/L; p = 0.016) and 72 h (2.17 vs. 1.35 nmol/L; p = 0.011) were higher in these patients than the rest of the population. When we added the individual predictive utility of grade 3 PGD at 72 h for ICU mortality (area under the curve [AUC] 0.72, 95% CI 0.53-0.90) to that of ProADM at 72 h, the predictive value of the model improved (AUC 0.81, 95% CI 0.65-0.97). Higher levels of proADM measured following LT are associated with grade 3 PGD at 72 h. ProADM enhances the association of this entity with mortality.

Characterisation of genetic structure of the Mayan population in Guatemala by autosomal STR analysis.

BACKGROUND: Currently, the Guatemalan population comprises genetically isolated groups due to geographic, linguistic and cultural factors. For example, Mayan groups within the Guatemala population have preserved their own language, culture and religion. These practices have limited genetic admixture and have maintained the genetic identity of Mayan populations. AIM: This study is designed to define the genetic structure of the Mayan-Guatemalan groups Kaqchiquel, K'iche', Mam and Q'eqchi' through autosomal short tandem repeat (STR) polymorphisms and to analyse the genetic relationships between them and with other Mayan groups. SUBJECTS AND METHODS: Fifteen STR polymorphisms were analysed in 200 unrelated donors belonging to the Kaqchiquel (n = 50), K'iche' (n = 50), Mam (n = 50) and Q'eqchi' (n = 50) groups living in Guatemala. Genetic distance, non-metric MDS and AMOVA were used to analyse the genetic relationships between population groups. RESULTS: Within the Mayan population, the STRs D18S51 and FGA were the most informative markers and TH01 was the least informative. AMOVA and genetic distance analyses showed that the Guatemalan-Native American populations are highly similar to Mayan populations living in Mexico. CONCLUSIONS: The Mayan populations from Guatemala and other Native American groups display high genetic homogeneity. Genetic relationships between these groups are more affected by cultural and linguistic factors than geographical and local flow. This study represents one of the first steps in understanding Mayan-Guatemalan populations, the associations between their sub-populations and differences in gene diversity with other populations. This article also demonstrates that the Mestizo population shares most of its ancestral genetic components with the Guatemala Mayan populations.

Recovering rhamnogalacturonan-I pectin from sugar beet pulp using a sequential ultrasound and microwave-assisted extraction: Study on extraction optimization and membrane purification.

This research focuses on the integrated recovery of rhamnogalacturonan-I (RG-I) pectin from sugar beet pulp (SBP). First, the extraction of RG-I pectin through sequential ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) was assessed. Optimization using a response surface methodology identified the optimal conditions as initial pH 4, 10 min of UAE, and 157 °C for MAE, achieving a 66.0 % recovery of pectooligosaccharides (POS). Additionally, purification through continuous diafiltration and concentration via ultrafiltration of the POS using membranes with different molecular weight cut-offs (MWCO) was explored. In contrast to previous research using discontinuous diafiltration, the use of continuous diafiltration allowed a decrease in the extract viscosity and obtained higher yields using a higher MWCO membrane. The refined RG-I pectin solids exhibited a high global yield (39-40 g pectin/100 g SBP), and high-methoxyl characteristics, as well as purity levels (70-80 %) similar to commercial prebiotics.

11Li Breakup on 208 at energies around the Coulomb barrier.

The inclusive breakup for the (11)Li + (208)Pb reaction at energies around the Coulomb barrier has been measured for the first time. A sizable yield of (9)Li following the (11)Li dissociation has been observed, even at energies well below the Coulomb barrier. Using the first-order semiclassical perturbation theory of Coulomb excitation it is shown that the breakup probability data measured at small angles can be used to extract effective breakup energy as well as the slope of B(E1) distribution close to the threshold. Four-body continuum-discretized coupled-channels calculations, including both nuclear and Coulomb couplings between the target and projectile to all orders, reproduce the measured inclusive breakup cross sections and support the presence of a dipole resonance in the (11)Li continuum at low excitation energy.

Efficient recovery and characterization of humic acids from municipal and manure composts: A comparative study.

The recovery of humic acids from low-quality compost obtained in municipal solid waste treatment plants provides opportunities for its valorization. This study compares the recovery and properties of the humic acids obtained from municipal mixed waste compost (MMWC) and manure compost. The effects of temperature, time, and KOH concentration on the ratio of humic acids in the extracted liquid and the content of organic carbon of the precipitates were investigated by response surface methodology. Optimal conditions were 30 °C and 24 h for both composts, with a KOH concentration of 0.53 M for MMWC and 0.25 M for manure compost. The manure compost provided a liquid extract richer in humic acids than MMWC (76.6 % vs. 33.7 %), but the precipitates presented similar organic carbon contents (38.1 % vs. 42.4 %). Regarding composition, both humic acids presented higher organic carbon and nitrogen contents than the composts used as feedstock. The extraction and further precipitation of humic acids reduced the concentration of heavy metals. Humic acids from manure compost have a slightly higher average molecular weight (2650 Da) than those from MMWC (1980 Da), while both present similar C/N ratios and degree of aromaticity. Most contaminants of emerging concern present in the original composts were not detected in the humic acids. Thus, it was demonstrated that MMWC constitutes an attractive source of humic acids with properties similar to those obtained from a high-quality compost and, therefore, with potential economic value.

Differences and similarities between COVID-19 related-headache and COVID-19 vaccine related-headache. A case-control study. / Diferencias y similitudes entre la cefalea relacionada con la COVID-19 y la cefalea relacionada con la vacuna de la COVID-19. Un estudio de casos y controles.

INTRODUCTION: Headache is a frequent symptom at the acute phase of coronavirus disease 2019 (COVID-19) and also one of the most frequent adverse effects following vaccination. In both cases, headache pathophysiology seems linked to the host immune response and could have similarities. We aimed to compare the clinical phenotype and the frequency and associated onset symptoms in patients with COVID-19 related-headache and COVID-19 vaccine related-headache. SUBJECTS AND METHODS: A case-control study was conducted. Patients with confirmed COVID-19 infection and COVID-19-vaccine recipients who experienced new-onset headache were included. A standardised questionnaire was administered, including demographic variables, prior history of headaches, associated symptoms and headache-related variables. Both groups were matched for age, sex, and prior history of headache. A multivariate regression analysis was performed. RESULTS: A total of 238 patients fulfilled eligibility criteria (143 patients with COVID-19 related-headache and 95 subjects experiencing COVID-19 vaccine related-headache). Patients with COVID-19 related-headache exhibited a higher frequency of arthralgia, diarrhoea, dyspnoea, chest pain, expectoration, anosmia, myalgia, odynophagia, rhinorrhoea, cough, and dysgeusia. Further, patients with COVID-19 related-headache had a more prolonged daily duration of headache and described the headache as the worst headache ever experienced. Patients with COVID-19 vaccine-related headache, experienced more frequently pain in the parietal region, phonophobia, and worsening of the headache by head movements or eye movements. CONCLUSION: Headache caused by SARS-CoV-2 infection and COVID-19 vaccination related-headache have more similarities than differences, supporting a shared pathophysiology, and the activation of the innate immune response. The main differences were related to associated symptoms.

TITLE: Diferencias y similitudes entre la cefalea relacionada con la COVID-19 y la cefalea relacionada con la vacuna de la COVID-19. Un estudio de casos y controles.Introducción. La cefalea es un síntoma frecuente en la fase aguda de la enfermedad por coronavirus 2019 (COVID-19) y también uno de los efectos adversos más comunes tras la vacunación. En ambos casos, la fisiopatología de la cefalea parece estar relacionada con la respuesta inmunitaria del huésped y podría presentar similitudes. Nuestro objetivo fue comparar el fenotipo clínico y la frecuencia de los síntomas asociados y los síntomas de inicio en pacientes con cefalea relacionada con la COVID-19 y cefalea relacionada con la vacuna de la COVID-19. Sujetos y métodos. Se realizó un estudio de casos y controles. Se incluyó a pacientes con infección confirmada por COVID-19 y receptores de la vacuna de la COVID-19 que experimentaron un nuevo inicio de cefalea. Se administró un cuestionario estandarizado que incluyó variables demográficas, antecedentes previos de cefaleas, síntomas asociados y variables relacionadas con la cefalea. Ambos grupos se emparejaron por edad, sexo y antecedentes previos de cefaleas. Se realizó un análisis de regresión multivariante. Resultados. Un total de 238 pacientes cumplieron con los criterios de elegibilidad (143 pacientes con cefalea relacionada con la COVID-19 y 95 sujetos con cefalea relacionada con la vacuna de la COVID-19). Los pacientes con cefalea relacionada con la COVID-19 presentaron una mayor frecuencia de artralgia, diarrea, disnea, dolor torácico, expectoración, anosmia, mialgia, odinofagia, rinorrea, tos y disgeusia. Además, los pacientes con cefalea relacionada con la COVID-19 experimentaron una duración diaria más prolongada de la cefalea y describieron la cefalea como la peor que habían experimentado. Los pacientes con cefalea relacionada con la vacuna de la COVID-19 experimentaron con más frecuencia dolor en la región parietal, fonofobia y empeoramiento de la cefalea por movimientos de la cabeza o de los ojos. Conclusión. La cefalea causada por la infección por el SARS-CoV-2 y la cefalea relacionada con la vacunación de la COVID-19 presentan más similitudes que diferencias, lo que respalda una fisiopatología compartida y la activación de la respuesta inmunitaria innata. Las principales diferencias estuvieron relacionadas con los síntomas asociados.

Reversal of nonstructural protein 3-specific CD4(+) T cell dysfunction in patients with persistent hepatitis C virus infection.

Hepatitis C virus (HCV)-specific T cell responses are essential for HCV control, and chronic infection is characterized by functionally altered antigen-specific T cells. It has been proposed that the early inactivation of specific CD4(+) T cell responses may be involved in establishment of HCV persistence. We have investigated whether HCV-specific CD4(+) T cells dysfunction can be reversed in vitro. Nonstructural protein 3 (NS3) and core-specific CD4(+) T cells from eight chronically infected and eight spontaneously resolved HCV individuals were selected through transient CD154 (CD40 ligand) expression, and their functional profile (IFN-γ, IL-2, TNF-α, IL-10 and IL-4 production by enzyme-linked immunospot assay, cytometric bead array and intracellular cytokine staining, and proliferation by carboxy-fluorescein diacetate succinimidyl ester dilution assay) was determined both ex vivo and after in vitro expansion of sorted CD154-expressing cells in the absence of specific antigen in IL-7/IL-15-supplemented medium. Ex vivo bulk CD4(+) T cells from chronic patients expressed CD154 in most cases, albeit at lower frequencies than those of resolved patients (0.11%vs 0.41%; P = 0.01), when stimulated with NS3, but not core, although they had a markedly impaired capacity to produce IL-2 and IFN-γ. Antigen-free in vitro expansion of NS3-specific CD154(+) cells from chronic patients restored IFN-γ and IL-2 production and proliferation to levels similar to those of patients with spontaneously resolved infection. Hence, NS3-specific CD4(+) T cell response can be rescued in most chronic HCV patients by in vitro expansion in the absence of HCV-specific antigen. These results might provide a rationale for adoptive immunotherapy.

Improved limit on direct α decay of the Hoyle state.

The current evaluation of the triple-α reaction rate assumes that the α decay of the 7.65 MeV, 0+ state in 12C, commonly known as the Hoyle state, proceeds sequentially via the ground state of 8Be. This assumption is challenged by the recent identification of two direct α-decay branches with a combined branching ratio of 17(5)%. If correct, this would imply a corresponding reduction in the triple-α reaction rate with important astrophysical consequences. We have used the 11B(3He,d) reaction to populate the Hoyle state and measured the decay to three α particles in complete kinematics. We find no evidence for direct α-decay branches, and hence our data do not support a revision of the triple-α reaction rate. We obtain an upper limit of 5×10(-3) on the direct α decay of the Hoyle state at 95% C.L., which is 1 order of magnitude better than a previous upper limit.

Do halo nuclei follow Rutherford elastic scattering at energies below the barrier? The case of 11Li.

The first measurement of the elastic scattering of the halo nucleus 11Li and its core 9Li on 208Pb at energies near the Coulomb barrier is presented. The 11Li+208Pb elastic scattering shows a strong reduction with respect to the Rutherford cross section, even at energies well below the barrier and down to very small scattering angles. This drastic change of the elastic differential cross section observed in 11Li+208Pb is the consequence of the halo structure of 11Li, as it is not observed in the elastic scattering of its core 9Li at the same energies. Four-body continuum-discretized coupled-channels calculations, based on a three-body model of the 11Li projectile, are found to explain the measured angular distributions and confirm that the observed reduction is mainly due to the strong Coulomb coupling to the dipole states in the low-lying continuum of 11Li. These calculations suggest the presence of a low-lying dipole resonance in 11Li close to the breakup threshold.

Genetic identification of missing persons: DNA analysis of human remains and compromised samples.

Human identification has made great strides over the past 2 decades due to the advent of DNA typing. Forensic DNA typing provides genetic data from a variety of materials and individuals, and is applied to many important issues that confront society. Part of the success of DNA typing is the generation of DNA databases to help identify missing persons and to develop investigative leads to assist law enforcement. DNA databases house DNA profiles from convicted felons (and in some jurisdictions arrestees), forensic evidence, human remains, and direct and family reference samples of missing persons. These databases are essential tools, which are becoming quite large (for example the US Database contains 10 million profiles). The scientific, governmental and private communities continue to work together to standardize genetic markers for more effective worldwide data sharing, to develop and validate robust DNA typing kits that contain the reagents necessary to type core identity genetic markers, to develop technologies that facilitate a number of analytical processes and to develop policies to make human identity testing more effective. Indeed, DNA typing is integral to resolving a number of serious criminal and civil concerns, such as solving missing person cases and identifying victims of mass disasters and children who may have been victims of human trafficking, and provides information for historical studies. As more refined capabilities are still required, novel approaches are being sought, such as genetic testing by next-generation sequencing, mass spectrometry, chip arrays and pyrosequencing. Single nucleotide polymorphisms offer the potential to analyze severely compromised biological samples, to determine the facial phenotype of decomposed human remains and to predict the bioancestry of individuals, a new focus in analyzing this type of markers.

Liquid fertilizer production from organic waste by conventional and microwave-assisted extraction technologies: Techno-economic and environmental assessment.

The use of mineral fertilizers in agriculture has significantly increased to support the growing global food demand. Organic fertilizers are produced from renewable waste materials to overcome the drawbacks of inorganic fertilizers. The development of novel production processes of organic fertilizers entails a significant advance towards the circular economy that reincorporates waste materials into the production cycle. In this work, the economic and environmental feasibility of an industrial plant with a treatment capacity of 300 kg/h of organic waste for the production of liquid fertilizers has been performed. Two extraction technologies (conventional and microwave) and two solvents (water and alkaline) have been compared to select the most sustainable and profitable scenario for scaling-up. The extraction process consists of 2 steps: extraction followed by a concentration stage (necessary only if water extraction is applied). The resolution of the mass balances shows that the fertilizer production under alkaline conditions is ten times higher than for water-based extraction. The economic analysis demonstrated that the total investment cost of microwave technology (>3.5 M€) is three times higher compared to the conventional extraction technology (<1.5 M€), mainly due to the higher complexity of the equipment. These facts directly impact the minimum selling price, because the fertilizers obtained by conventional extraction with alkaline solvent would have a lower selling price (about 1 €/L). As for environmental assessment, the indicators show that the environmental impact produced by water-based extraction is higher than alkaline-solvent extraction, mainly due to the necessity of a concentration stage of the liquid extract to meet the requirements of European regulations. In view of the results obtained in the economic and environmental evaluation, it could be concluded that the most favourable scenario for scaling up the production of liquid fertilizers from organic waste is the conventional extraction under alkaline conditions.

Genetic variants of antioxidant enzymes and environmental exposures as molecular biomarkers associated with the risk and aggressiveness of bladder cancer.

Bladder cancer (BC) is one of the top 10 most common tumours worldwide; however, no molecular markers are currently available for tumour management and follow-up. BC could benefit from molecular biomarkers in environmental disease, which provide mechanistic understanding of individual susceptibility to exposure-related cancers and allow characterizing genetic alterations in the molecular pathway for malignancy. This case-control study performed a molecular analysis in 99 BC and 125 controls. Buccal swabs were collected to assess SNPs in eleven genes coding for xenobiotic detoxification enzymes, cellular antioxidant defences, and hormone synthesis and signalling (NAT2 (rs1801280), GPX1 (rs1050450 and rs17650792), TXNRD1 (rs7310505), PRDX3 (rs3740562), PON1 (rs662), SOD1 (rs10432782), SOD2 (rs4880), CAT (rs1001179), CYP17A1 (rs743572) and ESR1 (rs746432)). A structured questionnaire was administered to study participants to assess environmental and dietary chemical exposures. Several miRNAs associated with BC and detoxification/antioxidant pathways were analysed in a subsample of the study population, including miR-93-5p, miR-221-3p, miR-126, miR-27a-3p, miR-193b, and miR-193a-5p. Levels of selected environmental pollutants (polycyclic aromatic hydrocarbons and endocrine disrupting chemicals) were determined in urine from a subsample of BC cases and controls. We found that CYP17A1, CAT, SOD1, ESR1, PON1, and GPX1 (rs17650792) were associated with BC risk. Furthermore, exposure to smoke and/or dust, and alcohol intake were identified as risk factors for BC. Increased urinary levels of benzo[a]pyrene and bisphenol A were observed in BC patients relative to controls, along with an increased expression of miR-193b, miR-27a and miR-93-5p in BC. Nevertheless, further studies with a larger sample size are warranted to confirm these exploratory results. This study also shows that the combination of genetic markers (PON1 and CYP17A1) and miRNA (miR-221-3p and miR-93-5p) open a new scenario in the use of non-invasive biomarkers in the stratification of BC to guide personalized medicine, which is extremely urged in the current clinical setting.

The role of prostate-specific antigen in light of new scientific evidence: An update in 2020. / Papel del antígeno prostático específico ante las nuevas evidencias científicas, una nueva actualización en 2020.

OBJECTIVE: To review and update the latest scientific evidence gathered in recent years regarding prostate-specific antigen (PSA) for better implementation into routine clinical practice. EVIDENCE ACQUISITION: Analysis of the available evidence on the current role of PSA, based on the experience of an expert panel in the subject under analysis. EVIDENCE SYNTHESIS: Currently, PSA cannot be considered only as a guide for the presence or absence of prostate cancer. This determination can also help the urologist to decide on the most convenient treatment for a patient with benign prostatic hypertrophy (BPH) as a criterion for disease progression, and it can also suggest the suspicious existence of a prostatic tumor when there is PSA rise of>0.3 ng/ml over the level reached 6 months after having initiated treatment with 5-alpha-reductase inhibitor. However, the limits of this PSA rise with derivatives of alternative 5-alpha-reductase (5-ARI) inhibitors to dutasteride are controversial. Moreover, PSA is a key factor for the follow-up of patients with prostate adenocarcinoma at any stage who have received treatment (surgery, radiotherapy or focal therapies, hormone therapy), it acts as a guide to identify biochemical recurrence, to suspect the existence of local or distant recurrence, as well as to propose or discard adjuvant treatments. Finally, the role of PSA as a screening tool has been recently reinforced, demonstrating increased mortality rates or the existence of more aggressive cases of prostate cancer in those countries where the use of this tool has declined. CONCLUSIONS: We present new data about the current role of PSA in the management of patients treated for BPH and/or prostate cancer that should be implemented into routine clinical practice, with special emphasis on the relevant role of this biomarker in the screening and follow-up of prostate cancer, as well as in the progression of BPH in dutasteride treatment.

Ideal conditions of microwave-assisted acid pretreatment of sugarcane straw allow fermentative butyric acid production without detoxification step.

Sugarcane straw (SCS) was pretreated with dilute sulfuric acid assisted by microwave to magnify fermentable sugars and to minimize the concentration of inhibitors in the hydrolysates. The optimum conditions for maximum recovery of sugars were 162 °C and 0.6% (w/v) H2SO4. The low level of inhibitors, such as acetate (2.9 g/L) and total phenolics (1.4 g/L), in the SCS slurry from the pretreatment stage allowed the enzymatic hydrolysis and fermentation steps to occur without detoxification. Besides consuming the total sugar content (31.0 g/L), Clostridium beijerinckii Br21 was able to use acetate from the SCS hydrolysate, to give butyric acid at high conversion factor (0.49 g of butyric acid /g of sugar). The optimized pretreatment conditions spared acid, time, and the detoxification stage, making bio-butyric acid production from SCS extremely attractive.

Role of IGF2 in the Study of Development and Evolution of Prostate Cancer.

Prostate Cancer (PC) is commonly known as one of the most frequent tumors among males. A significant problem of this tumor is that in early stages most of the cases course as indolent forms, so an active surveillance will anticipate the appearance of aggressive stages. One of the main strategies in medical and biomedical research is to find non-invasive biomarkers for improving monitoring and performing a more precise follow-up of diseases like PC. Here we report the relevant role of IGF2 and miR-93-5p as non-invasive biomarker for PC. This event could improve current medical strategies in PC.

Liquid biopsy and prostate cancer. Current evidence applied to clinical practice. / Biopsia líquida y cáncer de próstata. Evidencia actual aplicada a la clínica.

CONTEXT: Despite being a validated source of biomarkers, liquid biopsy has not yet succeeded in becoming part of the standard clinical practice in prostate cancer patients. Few biomarkers undergo adequate validation, prospective and independent, of their predictive and/or prognostic value, which results in a lack of the different available tests in the clinical practice. OBJECTIVE: To carry out a pragmatic synthesis of current scientific evidence on liquid biopsy for prostate cancer patients. EVIDENCE ACQUISITION: Non-systematic literature review, narrowing the search to papers on liquid biopsy from blood samples in prostate cancer patients. We mainly selected works evaluating clinical endpoints in prostate cancer. EVIDENCE SYNTHESIS: The most clinically advanced forms of liquid biopsy are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Both CTCs and ctDNA have demonstrated their prognostic value in metastatic disease. ARV7 determination is the first predictive biomarker of the disease. Its implementation into routine clinical practice requires methodological standardization and adequate clinical validation of the different available ways to detect it. The detection of CTCs in the early stages of the disease still depends on the optimization of the diagnostic methods and on the development of the biological characterization of these cells. The biological information provided by CTCs and ctDNA is different; therefore, the study of its adequate combination is the object of cutting-edge research. CONCLUSIONS: The absence of protocols and methodological standards is the limiting factor when aiming to reach conclusions that could have a potential impact on clinical practice. Therefore, the real short-term challenge for liquid biopsy is the establishment of consensus and common criteria.

Emerging non-13-valent pneumococcal conjugate vaccine (PCV13) serotypes causing adult invasive pneumococcal disease in the late-PCV13 period in Spain.

OBJECTIVE: An early reduction of adult invasive pneumococcal disease (IPD) was observed after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction for children in Spain. We analysed the epidemiology of adult IPD in the late-PCV13 period. METHODS: This was a prospective multicentre study of adult IPD involving six hospitals. Strains were serotyped, genotyped and studied for antimicrobial susceptibility. The late-PCV13 period was compared with the pre- and early-PCV13 periods. RESULTS: A total of 2197 episodes were collected-949 in 2008-2009, 609 in 2012-2013 and 639 in 2015-2016. The initial decrease of IPD observed (from 12.3/100 000 to 8.1/100 000; 2008-2009 versus 2012-2013) plateaued in 2015-2016 (8.3/100 000). IPD due to PCV13 serotypes decreased (from 7.7 to 3.5 to 2.3/100 000; p < 0.05), whereas IPD caused by non-PCV13 serotypes increased (from 4.5 to 4.6 to 6.0/100 000; p < 0.05). The most frequent serotypes in the late-PCV13 period were: 8 (15.1%), 3 (10.5%), 12F (7.9%) and 9N (5.4%). These serotypes were related to major genotypes: CC53 (59.8%) and CC404 (30.4%) for serotype 8, CC180 (64.1%) and CC260 (28.1%) for serotype 3, CC989 (91.7%) for serotype 12F and CC67 (84.8%) for serotype 9N. Penicillin-non-susceptibility (21.2%) was associated with serotypes 11A (CC156), 14 (CC156) and 19A (CC320), and macrolide-resistance was related to serotypes 24F and 19A. Rates of pneumococcal meningitis remained stable throughout the periods (ranges 0.9, 0.8 and 1.0/100 000). CONCLUSIONS: The initial decrease of adult IPD observed after PCV13 introduction for children has been balanced by the rise of non-PCV13 serotypes. The spread of antibiotic-resistant lineages related to non-PCV13 serotypes (11A and 24F) could be a threat for the treatment of serious pneumococcal diseases.

Genetic variants in xenobiotic detoxification enzymes, antioxidant defenses and hormonal pathways as biomarkers of susceptibility to prostate cancer.

Cancer is considered a complex disease that in many cases results from the interaction between chemical exposures, either from environmental or dietary sources, and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) or antioxidant enzymatic defenses. This study explored associations and interactions between genetic and environmental risk factors on the risk of prostate cancer (PCa) in 323 subjects that underwent prostate biopsy due to prostate specific antigen (PSA) levels above 4 ng/ml (161 PCa and 162 non-PCa). Eleven genes involved directly or indirectly in xenobiotic detoxification, oxidative stress and estrogen signaling were studied (GSTM1, GPX1 (rs1050450 and rs17650792), NAT2 (rs1801280), TXNRD1 (rs7310505), PRDX3 (rs3740562), CYP17A1 (rs743572), PON1 (rs662), SOD1 (rs10432782), SOD2 (rs4880), CAT (rs1001179), and ESR1 (rs746432)). A structured questionnaire was administered to all individuals to assess environmental and dietary chemical exposures. Medical data was collected by urologists. GPX1 rs17650792 polymorphism was the only one showing a significant inverse association with PCa risk. PRDX3 and GPX1 (rs17650792) genetic polymorphisms were significantly associated with Gleason score and PSA levels, respectively. The intake of nuts and soya products was associated with a reduced risk of PCa, as well as the performance of physical activity. Moreover, a number of gene-environmental interactions were found to increase the risk of PCa, particularly exposure to pesticides and rs1801280 (NAT2) and tobacco smoking and rs1050450 (GPX1). These findings suggest that the association of genetic and environmental risk factors with PCa risk should be assessed jointly for a better understanding of this complex disease.