Inference of tobacco and alcohol consumption habits from DNA methylation analysis of blood.

DNA methylation has become a biomarker of great interest in the forensic and clinical fields. In criminal investigations, the study of this epigenetic marker has allowed the development of DNA intelligence tools providing information that can be useful for investigators, such as age prediction. Following a similar trend, when the origin of a sample in a criminal scenario is unknown, the inference of an individual's lifestyle such as tobacco use and alcohol consumption could provide relevant information to help in the identification of DNA donors at the crime scene. At the same time, in the clinical domain, prediction of these trends of consumption could allow the identification of people at risk or better identification of the causes of different pathologies. In the present study, DNA methylation data from the UK AIRWAVE study was used to build two binomial logistic models for the inference of smoking and drinking status. A total of 348 individuals (116 non-smokers, 116 former smokers and 116 smokers) plus a total of 237 individuals (79 non-drinkers, 79 moderate drinkers and 79 drinkers) were used for development of tobacco and alcohol consumption prediction models, respectively. The tobacco prediction model was composed of two CpGs (cg05575921 in AHRR and cg01940273) and the alcohol prediction model three CpGs (cg06690548 in SLC7A11, cg0886875 and cg21294714 in MIR4435-2HG), providing correct classifications of 86.49% and 74.26%, respectively. Validation of the models was performed using leave-one-out cross-validation. Additionally, two independent testing sets were also assessed for tobacco and alcohol consumption. Considering that the consumption of these substances could underlie accelerated epigenetic ageing patterns, the effect of these lifestyles on the prediction of age was evaluated. To do that, a quantile regression model based on previous studies was generated, and the potential effect of tobacco and alcohol consumption with the epigenetic age was assessed. The Wilcoxon test was used to evaluate the residuals generated by the model and no significant differences were observed between the categories analyzed.

Exploring the independent association of employment status to cancer survivors' health-related quality of life.

BACKGROUND: Having a job has been associated with better Health-Related Quality of Life (HRQOL) in cancer survivors. However, the sociodemographic and disease-related profiles characterizing the survivors being employed and those having better HRQOL largely overlap. The present study aims to discern the degree to which employment status is independently associated with cancer survivors' HRQOL or if it mainly reflects the impact of other sociodemographic and cancer-related variables. METHODS: Cross-sectional study on a heterogeneous sample of 772 working-age survivors of adult-onset cancer. An instrument specifically designed to assess HRQOL in cancer survivors and Multivariate Variance Analysis (MANOVA) were used. RESULTS: Survival phase, cancer type, and employment status showed the main effects on cancer survivors' HRQOL. In particular, being employed (vs unemployed) had the greatest positive association with HRQOL, affecting ten of the twelve HRQOL domains considered. Also, interaction effects highlighted the role of age (younger) and marital status (single) as risk factors for a greater negative impact of variables affecting the survivor's HRQOL. CONCLUSIONS: The application of a multivariate methodology sheds new light on two relevant issues for the cancer survivor's HRQOL: (i) the existence of differences between diagnostic groups that are not attributed to other variables such as sex, and (ii) the important and independent role that employment status plays. Comprehensive cancer survivorship care should focus more on high-risk groups and include having a job as an essential aspect to consider and prompt. The fact that the employment status is susceptible to change represents a valuable opportunity to care for the wellbeing of this population.

Epigenetic age estimation in saliva and in buccal cells.

Age estimation based on epigenetic markers is a DNA intelligence tool with the potential to provide relevant information for criminal investigations, as well as to improve the inference of age-dependent physical characteristics such as male pattern baldness or hair color. Age prediction models have been developed based on different tissues, including saliva and buccal cells, which show different methylation patterns as they are composed of different cell populations. On many occasions in a criminal investigation, the origin of a sample or the proportion of tissues is not known with certainty, for example the provenance of cigarette butts, so use of combined models can provide lower prediction errors. In the present study, two tissue-specific and seven age-correlated CpG sites were selected from publicly available data from the Illumina HumanMethylation 450 BeadChip and bibliographic searches, to help build a tissue-dependent, and an age-prediction model, respectively. For the development of both models, a total of 184 samples (N = 91 saliva and N = 93 buccal cells) ranging from 21 to 86 years old were used. Validation of the models was performed using either k-fold cross-validation and an additional set of 184 samples (N = 93 saliva and N = 91 buccal cells, 21-86 years old). The tissue prediction model was developed using two CpG sites (HUNK and RUNX1) based on logistic regression that produced a correct classification rate for saliva and buccal swab samples of 88.59 % for the training set, and 83.69 % for the testing set. Despite these high success rates, a combined age prediction model was developed covering both saliva and buccal cells, using seven CpG sites (cg10501210, LHFPL4, ELOVL2, PDE4C, HOXC4, OTUD7A and EDARADD) based on multivariate quantile regression giving a median absolute error (MAE): ± 3.54 years and a correct classification rate ( %CP±PI) of 76.08 % for the training set, and an MAE of ± 3.66 years and a %CP±PI of 71.19 % for the testing set. The addition of tissue-of origin as a co-variate to the model was assessed, but no improvement was detected in age predictions. Finally, considering the limitations usually faced by forensic DNA analyses, the robustness of the model and the minimum recommended amount of input DNA for bisulfite conversion were evaluated, considering up to 10 ng of genomic DNA for reproducible results. The final multivariate quantile regression age predictor based on the models we developed has been placed in the open-access Snipper forensic classification website.

Age, Gleason Score, and PSA are important prognostic factors for survival in metastatic castration-resistant prostate cancer. Results of The Uroncor Group (Uro-Oncological Tumors) of the Spanish Society of Radiation Oncology (SEOR).

INTRODUCTION: The treatment of metastatic castration-resistant prostate cancer (mCRPC) has changed significantly in recent years. Inhibitors of androgen receptors have shown especially significant benefits in overall (OS) and progression-free survival (PFS), with a good toxicity profile. Treatment selection depends on the patient's individual clinical, radiological, and biological characteristics. OBJECTIVE: To describe treatment outcomes (efficacy, toxicity) in a cohort of patients with mCRPC in Spain. MATERIALS AND METHODS: Multicenter, retrospective study of patients with mCRPC included in a database of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR). Metastatic CRPC was defined according to the prostate cancer working group 3 (PCWG3) criteria. The Kaplan-Meier technique was used to evaluate OS and the Common Terminology Criteria for Adverse Events (CTCAE, v.4.0) were used to assess toxicity. Univariate and multivariate Cox regression analyses were performed to identify the factors significantly associated with OS. RESULTS: A total of 314 patients from 17 hospitals in Spain diagnosed with mCRPC between June 2010 and September 2017 were included in this study. Mean age at diagnosis was 68 years (range 45-89). At a median follow-up of 35 months, OS at 1, 3, and 5 years were 92%, 38%, and 28%, respectively. Grades 1-2 and grade 3 toxicity rates were, respectively, 68% and 19%. No grade 4 toxicities were observed. On the multivariate analysis, the following factors were significantly associated with OS: age (hazard ratio [HR] 0.42, p = 0.010), PSA value at diagnosis of mCRPC (HR 0.55, p = 0.008), and Gleason score (HR 0.61, p = 0.009). CONCLUSIONS: Age, Gleason score, and PSA at diagnosis of mCRPC are independently associated with overall survival in patients with mCRPC. The efficacy and toxicity outcomes in this patient cohort treated in radiation oncology departments in Spain are consistent with previous reports.

Positive prostate biopsy following radiotherapy can predict metastasis-free survival in localized prostate cancer.

BACKGROUND/AIMS: To determine the impact of post-treatment biopsy results on 10-year metastasis-free survival (MFS), overall survival (OS) and cause-specific survival (CSS) in localized prostate cancer (PCa) patients treated with high-dose radiotherapy (RT). MATERIALS/METHODS: Retrospective analysis of 232 patients with T1c-T3bN0M0 PCa who underwent a prostate biopsy 24-36 months after high-dose RT. Biopsies were categorized as positive biopsy (PB) if H&E staining showed evidence of residual malignancy and negative biopsy (NB) if no malignant cells were present. Kaplan-Meier estimates of 10-year MFS, OS and CSS rates were calculated for each group and Cox proportional-hazards models were used to estimate the hazard ratios. The median follow-up was 124 months (range 26-267). RESULTS: Sixty-two of 232 (26.7%) patients had post-treatment positive biopsies (PB). A positive post-treatment biopsy was significantly associated with a lower 10-year MFS (78.4% vs. 95.4%, p = 0.001, HR: 3.9, 95% CI: 1.8-8.3). Although patients with PB had worse outcomes that those with NB, we could not show a statistically significant difference in OS (81.0% vs. 87.9%, p = 0.282, HR: 1.3, 95% CI: 0.7-2.3) or CSS (96.2% vs. 99.4% (p = 0.201, HR. 2.4, 95% CI: 0.6-9.7). After multivariate analysis, the strongest predictor of MFS was the post-treatment biopsy status (p < 0.001, HR: 5.4, 95% CI 2.26-12.85) followed by Gleason score (p = 0.002, HR: 2.24, 95% CI 1.33-3.79). CONCLUSION: A positive biopsy following RT can predict MFS in localized prostate cancer. These data highlight the relevance of achieving a local control and support the use of aggressive local therapeutic interventions for PCa.

Are there enough radiation oncologists to lead the new Spanish radiotherapy?

AIM: Radiation oncology services in Spain are undergoing a process of technical modernization, but-in a context of increasing demand by an ageing population-it is unclear whether there are enough radiation oncologists to staff the newly equipped units. This study aims to assess the number of specialists working in radiation oncology services in Spain relative to current and future needs. MATERIALS AND METHODS: In the second half of 2017, the Commission on Infrastructures of the Spanish Society for Radiation Oncology (SEOR) sent a questionnaire on radiation oncology staff to the heads of all 122 public (n = 76, 62%) and private (n = 46, 38%) radiation oncology services in Spain. Data collected were the number of professionals, their position, and their year of birth for specialists and residents in each service. In the descriptive analysis, for continuous variables we calculated means, standard deviations and ranges for each Spanish region and work post. For qualitative variables, we constructed frequency tables. All analyses were performed with R statistical software, version 3.5.1. RESULTS: The survey response rate was 100% among service heads across all 122 centers. The total number of radiation oncologists working in these centers is 721, or 15.4 per million population, with considerable variations between regions. Given the national recommendations to have 20 radiation oncologists per million population, there is currently a deficit of 204 specialists. If the 163 upcoming retirements are also taken into account, there will be 367 fewer radiation oncologists than required to meet the 25% increase in indications for radiotherapy projected for 2025. CONCLUSIONS: The classic model for calculating staff needs based on the number of treatments is outdated, and recommendations should be revised to reflect the current reality. A new model should integrate the most complex technological advances and emerging plans in radiotherapy, without neglecting the other activities carried out in radiation oncology services that are not directly linked to patient care.

Time for radioimmunotherapy: an overview to bring improvements in clinical practice.

Harnessing the patient's own immune system against an established cancer has proven to be a successful strategy. Within the last years, several antibodies blocking critical "checkpoints" that control the activation of T cells, the immune cells able to kill cancer cells, have been approved for the use in patients with different tumours. Unfortunately, these cases remain a minority. Over the last years, radiotherapy has been reported as a means to turn a patient's own tumour into an in situ vaccine and generate anti-tumour T cells in patients who lack sufficient anti-tumour immunity. Indeed, review data show that the strategy of blocking multiple selected immune inhibitory targets in combination with radiotherapy has the potential to unleash powerful anti-tumour responses and improve the outcome of metastatic solid tumours. Here, we review the principal tumours where research in this field has led to new knowledge and where radioimmunotherapy becomes a reality.

Evaluation of bacterial adherence of clinical isolates of Staphylococcus sp. using a competitive model: An in vitro approach to the "race for the surface" theory.

OBJECTIVES: Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the in vitro studies did not evaluate bacterial adhesion in the presence of eukaryotic cells, as stated by the 'race for the surface' theory. Moreover, the adherence of numerous clinical strains with different initial concentrations has not been studied. METHODS: We describe a method for the study of bacterial adherence in the presence of preosteoblastic cells. For this purpose we mixed different concentrations of bacterial cells from collection and clinical strains of staphylococci isolated from implant-related infections with preosteoblastic cells, and analysed the minimal concentration of bacteria able to colonise the surface of the material with image analysis. RESULTS: Our results show that clinical strains adhere to the material surface at lower concentrations than collection strains. A destructive effect of bacteria on preosteoblastic cells was also detected, especially with higher concentrations of bacteria. CONCLUSIONS: The method described herein can be used to evaluate the effect of surface modifications on bacterial adherence more accurately than conventional monoculture studies. Clinical strains behave differently than collection strains with respect to bacterial adherence.Cite this article: M. Martinez-Perez, C. Perez-Jorge, D. Lozano, S. Portal-Nuñez, R. Perez-Tanoira, A. Conde, M. A. Arenas, J. M. Hernandez-Lopez, J. J. de Damborenea, E. Gomez-Barrena, P. Esbrit, J. Esteban. Evaluation of bacterial adherence of clinical isolates of Staphylococcus sp. using a competitive model: An in vitro approach to the "race for the surface" theory. Bone Joint Res 2017;6:315-322. DOI: 10.1302/2046-3758.65.BJR-2016-0226.R2.

Reduced late urinary toxicity with high-dose intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer.

BACKGROUND/PURPOSE: To evaluate the impact of intensity-modulated radiotherapy (IMRT) with intra-prostate fiducial markers image-guided radiotherapy (IGRT) on the incidence of late urinary toxicity compared to 3D conformal radiotherapy (3DCRT) for patients with prostate cancer (PC). METHODS AND MATERIALS: We selected 733 consecutive patients with localized PC treated with dose-escalation radiotherapy between 2001 and 2014. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up 24 months. 438 patients were treated with 3DCRT and 295 with IMRT. Acute and late urinary complications were assessed using the EORTC/RTOG and CTCAEs v3.0 definition. The Cox regression model was used to compare grade ≥2 urinary toxicity between both techniques. The median follow-up was 75 months (range 24-204). RESULTS: The median isocenter radiation dose was 78.7 Gy for 3DCRT and 80.7 Gy for IMRT/IGRT (p < 0.001). The 5-year incidence of late grade ≥2 urinary toxicity was 6.4% for IMRT and 10.8% for 3DCRT [hazard ratio (HR) 0.575, p = 0.056]. The corresponding 5-year estimates of late grade ≥2 hematuria were 2% for IMRT and 5.3% for 3DCRT (HR 0.296, p = 0.024). On multivariate analysis, the antecedent of prior transurethral resection of the prostate was also a strong predictor of a higher risk of urinary complications (HR 2.464, p = 0.002) and of hematuria (HR 5.196, p < 0.001). CONCLUSION: Compared with 3DCRT, high-dose IMRT/IGRT is associated with a lower rate of late urinary complications in spite of higher radiation dose.

Prognostic value of glomerular filtration rate estimation equations in acute heart failure with preserved versus reduced ejection fraction.

AIMS: Renal function is an important prognostic factor in heart failure. The aim of this study was to compare the predictive value of estimated renal function calculated by the Chronic Kidney Disease-Epidemiology Collaboration equation (CKD-EPI) and the abbreviated Modification of Diet in Renal Disease (MDRD-4) equation for long-term all-cause mortality in patients admitted for acute decompensated heart failure (ADHF) with both preserved ejection fraction (HF-PEF) and reduced ejection fraction (HF-REF). METHODS AND RESULTS: We evaluated patients included in the Spanish National Registry of Heart Failure (RICA). RICA is a multicentre, prospective, cohort study that included patients admitted to the Internal Medicine units with ADHF. Estimated glomerular filtration rate (eGFR) was calculated with CKD-EPI and MDRD-4 equations. A total of 1805 patients admitted for ADHF were studied (52% women; median age 80 years, interquartile range 73.9-84.6 years); of these, 1044 (58%) had HF-PEF. eGFR values were lower with the CKD-EPI formula than with the MDRD-4 formula (51 ml/min/1.73 m(2) vs. 55.7 ml/min/1.73 m(2) ; p < 0.001). The two formulas provided independent prognostic information over long-term follow-up, in both HF-PEF and HF-REF patients. However, in HF-PEF patients, CKD-EPI equation was associated with a significant improvement in reclassification analyses (net reclassification improvement 6.78%; p = 0.009). CONCLUSIONS: In this clinical cohort of ADHF patients, eGFR as calculated by both the CKD-EPI and the MDRD-4 formulas offered similar prognostic information, irrespective of ejection fraction status, but in HF-PEF patients specifically, the CKD-EPI formula seems to improve clinical risk stratification as compared with MDRD-4.

Evaluación de la adherencia a las recomendaciones para disminuir el riesgo de Síndrome de Muerte Súbita del lactante / Adherence to recommendations to reduce the risk of Sudden infant Death Syndrome

Introduction: Recommendations for Sudden Infant Death Syndrome (SIDS) are available, although it is uncertain the degree of adherence to these measures. The aim of the study is to assess the adherence to recommendations to reduce the risk of SIDS, seeking factors associated to the noncompliance with these recommendations. Patients and Method: 468 infants were enrolled in two maternity hospitals, one public and one private. Postpartum and 4-month assessments were performed. A questionnaire was used adapting a model validated by the International Child Care Practices Study. Results: Adherence to obstetric recommendations was higher (75.4%) than to pediatric recommendations (53.3%). Regarding pediatric recommendations, a compliance decrease was detected after 4 months. Follow-ups showed decrease in breastfeeding (p < 0.001 84.9% vs 48.6%) and supine position (61.2% vs 21.2%, p < 0.001). Conclusions: The decreased adherence to recommendations for SIDS prevention was mainly observed in younger and less educated women, who were not in a relationship and living in poor housing quality and crowded environments.

Introducción: Existen recomendaciones preventivas en el Sindrome de Muerte Súbita del lactante (SMSL), aunque es incierto el grado de adherencia a dichas medidas. El objetivo del estudio fue evaluar la adherencia a las recomendaciones para disminuir el riesgo de SMSL, buscando factores asociados al no cumplimiento de dichas recomendaciones. Pacientes y Método: Se incluyeron 468 recién nacidos de dos maternidades, pública y privada. Se efectuó una evaluación posparto y a los 4 meses de la adherencia a las recomendaciones. Se utilizó un cuestionario adaptando un modelo de encuesta validado por el International Child Care Practices Study Resultados: La adherencia a las recomendaciones obstétricas fue mayor (75,4%) que a las recomendaciones pediátricas (53,3%). A su vez en las recomendaciones pediátricas se evidenció una caída del cumplimiento de las recomendaciones a los 4 meses. Al seguimiento se observó reducción de lactancia (84,9% vs 48,6%; p < 0,001) y de posición supina (61,2% vs 21,2%; p < 0,001). Conclusiones: La disminución de la adherencia a las recomendaciones para la prevención del SMSL se observó principalmente en las mujeres de menor edad y menor nivel educativo, no estar en pareja, mala calidad habitacional y presencia de numerosos convivientes.

A case-control study suggests that the CCR6 locus is not involved in the susceptibility to giant cell arteritis.

OBJECTIVES: Polymorphisms of the CC chemokine receptor 6 (CCR6) gene have been recently reported to be associated with a number of autoimmune diseases. We aimed to investigate the possible influence of CCR6 rs3093024 gene variant in the susceptibility to and clinical expression of GCA. METHODS: The CCR6 polymorphism rs3093024 was genotyped in a total of 463 Spanish patients diagnosed with biopsy-proven GCA and 920 healthy controls using a TaqMan® allelic discrimination assay. PLINK software was used for the statistical analyses. RESULTS: No significant association between this CCR6 variant and GCA was observed (p=0.42, OR=0.94, CI95% 0.79-1.10). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischaemic manifestations or irreversible occlusive disease, no statistical significant difference was detected either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. CONCLUSIONS: Our results suggest that the CCR6 rs3093024 polymorphism may not play a relevant role in the GCA pathophysiology.

Corrosion behaviour and biocompatibility of a novel Ni-free intermetallic coating growth on austenitic steel by hot dipping in an Al-12.6%Si alloy.

Commercial 316 LVM austenitic stainless steel samples have been coated by immersion in a bath of molten Al-12.6%Si alloy for 120 s. The coating consists of the Al(12)(Fe,Cr)(3)Si(2) intermetallic. In vitro corrosion behaviour has been evaluated in the Ringer's solution by means of potentiodynamic curves and electrochemical impedance spectroscopy. The results reveal that the coated specimens exhibit lower susceptibility to localised corrosion with respect to the substrate. XPS analysis suggests that the ennoblement of the pitting potential is due to the formation of a chromium oxyhydroxide containing passive layer. The intermetallic coating shows a good biocompatibility, as demonstrated by culturing human mesenchymal stem cells isolated from bone marrow which attached, grew and differentiated to the osteoblastic lineage to a similar extent on coated and bare steels. In summary, this study proposes a method that generates Ni-free coatings of the stainless steel with useful properties for biomedical applications.

Precise measurement of the e+e- --> pi+pi-(gamma) cross section with the initial state radiation method at BABAR.

A precise measurement of the cross section of the process e(+)e(-) --> pi(+)pi(-)(gamma) from threshold to an energy of 3 GeV is obtained with the initial state radiation (ISR) method using 232 fb(-1) of data collected with the BABAR detector at e(+)e(-) center-of-mass energies near 10.6 GeV. The ISR luminosity is determined from a study of the leptonic process e(+)e(-) --> mu(+)mu(-)gamma(gamma). The leading-order hadronic contribution to the muon magnetic anomaly calculated using the pipi cross section measured from threshold to 1.8 GeV is (514.1 +/- 2.2(stat) +/- 3.1(syst)) x 10(-10).

Frecuencia de gérmenes causantes de Micosis superficiales / Frequency of germs causes of superficial Mycoses

Las micosis superficiales representan un grupo heterogéneo de infecciones muy frecuentes a nivel mundial. Con objeto de conocer la frecuencia de hongos productores de micosis superficiales y conformar indicadores epidemiológicos que no aproximen a la realidad local es que, en el laboratorio de bacteriología del Hospital Obrero, se realizó un estudio retrospectivo de muestras de pacientes ambulatorios e internos de ambos sexos con diagnóstico presuntivo de dermatomicosis.