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Abstract Insufficient availability of molecular chaperones is observed as a major bottleneck for proper protein folding in recombinant protein production. Therefore, co-production of selected sets of cell chaperones along with foreign polypeptides is a common approach to increase the yield of properly folded, recombinant proteins in bacterial cell factories. However, unbalanced amounts of folding modulators handling folding-reluctant protein species might instead trigger undesired proteolytic activities, detrimental regarding recombinant protein stability, quality and yield. This minireview summarizes the most recent observations of chaperone-linked negative side effects, mostly focusing on DnaK and GroEL sets, when using these proteins as folding assistant agents. These events are discussed in the context of the complexity of the cell quality network and the consequent intricacy of the physiological responses triggered by protein misfolding.

Abstract Background At present, it is complicated to use screening trials to determine the optimal age intervals and periodicities of breast cancer early detection. Mathematical models are an alternative that has been widely used. The aim of this study was to estimate the effect of different breast cancer early detection strategies in Catalonia (Spain), in terms of breast cancer mortality reduction (MR) and years of life gained (YLG), using the stochastic models developed by Lee and Zelen (LZ). Methods We used the LZ model to estimate the cumulative probability of death for a cohort exposed to different screening strategies after T years of follow-up. We also obtained the cumulative probability of death for a cohort with no screening. These probabilities were used to estimate the possible breast cancer MR and YLG by age, period and cohort of birth. The inputs of the model were: incidence of, mortality from and survival after breast cancer, mortality from other causes, distribution of breast cancer stages at diagnosis and sensitivity of mammography. The outputs were relative breast cancer MR and YLG. Results Relative breast cancer MR varied from 20% for biennial exams in the 50 to 69 age interval to 30% for annual exams in the 40 to 74 age interval. When strategies differ in periodicity but not in the age interval of exams, biennial screening achieved almost 80% of the annual screening MR. In contrast to MR, the effect on YLG of extending screening from 69 to 74 years of age was smaller than the effect of extending the screening from 50 to 45 or 40 years. Conclusion In this study we have obtained a measure of the effect of breast cancer screening in terms of mortality and years of life gained. The Lee and Zelen mathematical models have been very useful for assessing the impact of different modalities of early detection on MR and YLG in Catalonia (Spain).

Abstract Background During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia.

Abstract The progressive solving of the conformation of aggregated proteins and the conceptual understanding of the biology of inclusion bodies in recombinant bacteria is providing exciting insights on protein folding and quality. Interestingly, newest data also show an unexpected functional and structural complexity of soluble recombinant protein species and picture the whole bacterial cell factory scenario as more intricate than formerly believed.

Abstract Background Breast cancer mortality has experienced important changes over the last century. Breast cancer occurs in the presence of other competing risks which can influence breast cancer incidence and mortality trends. The aim of the present work is: 1) to assess the impact of breast cancer deaths among mortality from all causes in Catalonia (Spain), by age and birth cohort and 2) to estimate the risk of death from other causes than breast cancer, one of the inputs needed to model breast cancer mortality reduction due to screening or therapeutic interventions. Methods The multi-decrement life table methodology was used. First, all-cause mortality probabilities were obtained by age and cohort. Then mortality probability for breast cancer was subtracted from the all-cause mortality probabilities to obtain cohort life tables for causes other than breast cancer. These life tables, on one hand, provide an estimate of the risk of dying from competing risks, and on the other hand, permit to assess the impact of breast cancer deaths on all-cause mortality using the ratio of the probability of death for causes other than breast cancer by the all-cause probability of death. Results There was an increasing impact of breast cancer on mortality in the first part of the 20th century, with a peak for cohorts born in 1945–54 in the 40–49 age groups (for which approximately 24% of mortality was due to breast cancer). Even though for cohorts born after 1955 there was only information for women under 50, it is also important to note that the impact of breast cancer on all-cause mortality decreased for those cohorts. Conclusion We have quantified the effect of removing breast cancer mortality in different age groups and birth cohorts. Our results are consistent with US findings. We also have obtained an estimate of the risk of dying from competing-causes mortality, which will be used in the assessment of the effect of mammography screening on breast cancer mortality in Catalonia.

Abstract Background In Catalonia (Spain) breast cancer mortality has declined since the beginning of the 1990s. The dissemination of early detection by mammography and the introduction of adjuvant treatments are among the possible causes of this decrease, and both were almost coincident in time. Thus, understanding how these procedures were incorporated into use in the general population and in women diagnosed with breast cancer is very important for assessing their contribution to the reduction in breast cancer mortality. In this work we have modeled the dissemination of periodic mammography and described repeat mammography behavior in Catalonia from 1975 to 2006. Methods Cross-sectional data from three Catalan Health Surveys for the calendar years 1994, 2002 and 2006 was used. The dissemination of mammography by birth cohort was modeled using a mixed effects model and repeat mammography behavior was described by age and survey year. Results For women born from 1938 to 1952, mammography clearly had a period effect, meaning that they started to have periodic mammograms at the same calendar years but at different ages. The age at which approximately 50% of the women were receiving periodic mammograms went from 57.8 years of age for women born in 1938–1942 to 37.3 years of age for women born in 1963–1967. Women in all age groups experienced an increase in periodic mammography use over time, although women in the 50–69 age group have experienced the highest increase. Currently, the target population of the Catalan Breast Cancer Screening Program, 50–69 years of age, is the group that self-reports the highest utilization of periodic mammograms, followed by the 40–49 age group. A higher proportion of women of all age groups have annual mammograms rather than biennial or irregular ones. Conclusion Mammography in Catalonia became more widely implemented during the 1990s. We estimated when cohorts initiated periodic mammograms and how frequently women are receiving them. These two pieces of information will be entered into a cost-effectiveness model of early detection in Catalonia.

Background: At present, it is complicated to use screening trials to determine the optimal age intervals and periodicities of breast cancer early detection. Mathematical models are an alternative that has been widely used. The aim of this study was to estimate the effect of different breast cancer early detection strategies in Catalonia (Spain), in terms of breast cancer mortality reduction (MR) and years of life gained (YLG), using the stochastic models developed by Lee and Zelen (LZ).Methods: We used the LZ model to estimate the cumulative probability of death for a cohort exposed to different screening strategies after T years of follow-up. We also obtained the cumulative probability of death for a cohort with no screening. These probabilities were used to estimate the possible breast cancer MR and YLG by age, period and cohort of birth. The inputs of the model were: incidence of, mortality from and survival after breast cancer, mortality from other causes, distribution of breast cancer stages at diagnosis and sensitivity of mammography. The outputs were relative breast cancer MR and YLG.Results: Relative breast cancer MR varied from 20% for biennial exams in the 50 to 69 age interval to 30% for annual exams in the 40 to 74 age interval. When strategies differ in periodicity but not in the age interval of exams, biennial screening achieved almost 80% of the annual screening MR. In contrast to MR, the effect on YLG of extending screening from 69 to 74 years of age was smaller than the effect of extending the screening from 50 to 45 or 40 years.Conclusion: In this study we have obtained a measure of the effect of breast cancer screening in terms of mortality and years of life gained. The Lee and Zelen mathematical models have been very useful for assessing the impact of different modalities of early detection on MR and YLG in Catalonia (Spain). [ABSTRACT FROM AUTHOR]

Background: In Catalonia (Spain) breast cancer mortality has declined since the beginning of the 1990 s. The dissemination of early detection by mammography and the introduction of adjuvant treatments are among the possible causes of this decrease, and both were almost coincident in time. Thus, understanding how these procedures were incorporated into use in the general population and in women diagnosed with breast cancer is very important for assessing their contribution to the reduction in breast cancer mortality. In this work we have modeled the dissemination of periodic mammography and described repeat mammography behavior in Catalonia from 1975 to 2006.Methods: Cross-sectional data from three Catalan Health Surveys for the calendar years 1994, 2002 and 2006 was used. The dissemination of mammography by birth cohort was modeled using a mixed effects model and repeat mammography behavior was described by age and survey year.Results: For women born from 1938 to 1952, mammography clearly had a period effect, meaning that they started to have periodic mammograms at the same calendar years but at different ages. The age at which approximately 50% of the women were receiving periodic mammograms went from 57.8 years of age for women born in 1938-1942 to 37.3 years of age for women born in 1963-1967. Women in all age groups experienced an increase in periodic mammography use over time, although women in the 50-69 age group have experienced the highest increase. Currently, the target population of the Catalan Breast Cancer Screening Program, 50-69 years of age, is the group that self-reports the highest utilization of periodic mammograms, followed by the 40-49 age group. A higher proportion of women of all age groups have annual mammograms rather than biennial or irregular ones.Conclusion: Mammography in Catalonia became more widely implemented during the 1990 s. We estimated when cohorts initiated periodic mammograms and how frequently women are receiving them. These two pieces of information will be entered into a cost-effectiveness model of early detection in Catalonia. [ABSTRACT FROM AUTHOR]

Photodynamic therapy delivers more targeted cell killing than classical chemotherapy. It uses light-absorbing compounds, photosensitizers (PSs), to generate lethal reactive oxygen species (ROS) at sites of localized irradiation. Transition metal complexes are attractive PSs due to their photostability, visible-light absorption, and high ROS yields. Here, we introduce a low-molecular weight, photostable iridium complex, [Ir(thpy) 2 (benz)]Cl, 1 , that localizes to the Golgi apparatus, mitochondria, and endoplasmic reticulum, absorbs visible light, phosphoresces strongly, generates 1 O 2 with 43% yield, and undergoes cellular elimination after 24 h. 1 shows low dark toxicity and under remarkably low doses (3 min, 20-30 mJ s -1 cm -2 ) of 405 or 455 nm light, it causes killing of bladder (EJ), malignant melanoma (A375), and oropharyngeal (OPSCC72) cancer cells, with high phototoxic indices > 100-378. 1 is also an efficient PS in 3D melanoma spheroids, with repeated short-time irradiation causing cumulative killing.

We aimed to find out which are the most frequent complications for patients who suffer a traumatic brain injury (TBI) and its relation with brain biomarker levels. We conducted a hospital cohort study with patients who attended the Hospital Emergency Department between 1 June 2018 and 31 December 2020. Different variables were collected such as biomarkers levels after 6 h and 12 h of TBI (S100, NSE, UCHL1 and GFAP), clinical and sociodemographic variables, complementary tests, and complications 48 h and 7 days after TBI. Qualitative variables were analysed with Pearson's chi-square test, and quantitative variables with the Mann-Whitney U test. A multivariate logistic regression model for the existence of complications one week after discharge was performed to assess the discriminatory capacity of the clinical variables. A total of 51 controls and 540 patients were included in this study. In the TBI group, the mean age was 83 years, and 53.9% of the patients were male. Complications at seven days were associated with the severity of TBI (p < 0.05) and the number of platelets (p = 0.016). All biomarkers except GFAP showed significant differences in their distribution of values according to gender, with significantly higher values of the three biomarkers for women with respect to men. Patients with complications presented significantly higher S100 values (p < 0.05). The patient's baseline status, the severity of the TBI and the S100 levels can be very important elements in determining whether a patient may develop complications in the few hours after TBI., (© 2023. The Author(s).)

Introduction: Increased values in the fecal immunochemical test (FIT) are correlated with increasingly severe colorectal neoplasia, but little attention has been given to FIT values below the cut-off point (negative FIT, nFIT). We analysed the relationship between the concentrations of two consecutive nFIT and the risk of following screen-detected advanced neoplasia and interval cancer (IC) in a population-based colorectal cancer screening program., Methods: FIT results were categorised into non-detectable nFIT (0-3.8 μg haemoglobin/g feces), low nFIT (3.9-9.9) and high nFIT (10.0-19.9). Multivariable adjusted logistic regression was used to estimate the odds ratios (OR) of advanced neoplasia and IC with the nFIT results in the first two screens., Results: More than 90% of the 42,524 persons had non-detectable nFIT in the first and second screen; 4.5% and 5.8% had a low nFIT, respectively, and 2.2% and 2.9% had a high nFIT. The probability of testing positive and being diagnosed of advanced neoplasia or IC rose with increasing values of nFIT. Compared with those with two non-detectable nFIT results, the highest OR were found among those who had two high nFIT results (OR 21.75; 95% confidence interval: 12.44, 38.04) and those with one low nFIT and one high nFIT (ORs around 20)., Conclusions: Participants with nFIT results above the detection limit of the test had an increased risk of advanced neoplasia and IC in subsequent participations. This information could be used in the design of personalised screening strategies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

[This corrects the article DOI: 10.1371/journal.pone.0186921.].

Background: Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnoea (OSA), but an evaluation of CPAP adherence is rarely carried out among patients with acute coronary syndrome (ACS). The goals of the study are to analyse long-term adherence and identify the predictors of non-compliance with CPAP treatment for patients with non-sleepy OSA and ACS., Methods: This is an ancillary study of the ISAACC study, which is a multicentre, prospective, open-label, parallel, randomized, and controlled trial (NCT01335087) in patients with hospital admission for ACS. For the purpose of this study, only non-sleepy patients with moderate or severe OSA and randomized to receive CPAP treatment were analysed (n=357). Non-compliance was defined as CPAP dropout or average cumulative CPAP use of <4 hours/night. Multivariable logistic regression analysis was performed to identify predictors of CPAP adherence., Results: Adherence to treatment was 35.3% at 12 months. According to the unadjusted analysis, higher apnoea-hypopnea index (AHI) (P<0.001) and oxygen desaturation index (ODI) (P=0.001) were associated with a lower risk of non-compliance. Multivariable logistic regression analysis showed that high AHI (P=0.0051), high amounts of smoking pack-year (P=0.0170), and long intensive care unit (ICU) stays (P=0.0263) were associated with lower odds of non-compliance. It also showed a significant interaction between ACS history and age (P=0.0131), such that young patients with their first ACS showed significantly lower odds of CPAP non-compliance than patients with recurrent ACS and significantly lower odds of CPAP non-compliance were associated with ageing only in patients with recurrent ACS., Conclusions: Protective factors against non-compliance with CPAP treatment in non-sleepy patients with ACS were illness severity (high values of AHI or ICU stay length) or smoking amount. Patients with no previous history of ACS showed lower odds of CPAP non-compliance than patients with a recurrent ACS with younger age., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: There is limited and inconclusive information regarding the influence of the modality of renal replacement therapy on the atherosclerotic burden of patients on dialysis. The aim of this study was to compare the prevalence of asymptomatic atheromatous carotid disease, as also its rate of progression and cardiovascular outcomes, in two matched populations of patients treated with hemodialysis (HD) and peritoneal dialysis (PD)., Methods: Following a prospective, observational and multicenter design, we compared 237 PD and 237 HD patients without previous cardiovascular disease, included in the NEFRONA study, and matched for age, sex, diabetes and time on dialysis. Carotid ultrasound study was performed at baseline and after two years of follow-up in 6 carotid territories. Atheromatous vascular disease (AVD) progression was defined as any increase in the number of territories with plaques after 2 years. Fatal and non fatal cardiovascular events were also recorded during 36-month of follow-up., Main Results: At baseline, PD patients presented a worse general cardiovascular risk profile than HD patients. On the contrary, some markers of prevalent atherosclerotic disease (common carotid intima-media thickness and ankle-brachial index) were more favorable in PD patients. During follow-up, we observed no differences either in the rate of progression of atheromatous vascular disease (OR 1.78, 95% CI 0.80-4.06, p = 0.161) or in the incidence of cardiovascular events (OR 1.51, 95% CI 0.85-2.66, p = 0.159), according to the modality of dialysis., Conclusion: Dialysis modality did not impact on atherosclerotic carotid disease progression or cardiovascular outcomes, in two groups of patients treated with PD or HD.

Patients with chronic kidney disease (CKD) have an increased incidence of cardiovascular events (CVE). The contribution of subclinical atheromatosis extent, including femoral arteries, to CVE in CKD patients has not been investigated. In this paper, we examine the prognostic value of subclinical atheromatosis extent, assessed as the number of arterial territories with plaque, in predicting the incidence of major and minor CVE. The NEFRONA is a multicenter, prospective cohorts study that recruited 2445 CKD subjects and 559 controls, free from previous cardiovascular disease, in 81 medical centers across Spain. The presence of atheroma plaque was assessed by arterial ultrasound in ten arterial territories (carotid and femoral). The predictive power of the presence or absence of atheroma plaque in any territory was compared with the quantification of atheroma extent as the number of territories with plaque. During the median follow up of 48 months, 216 CVE were reported. Factors predicting the incidence of CVE in the whole cohort were being male, CKD patient, lower levels of 25(OH) vitamin D, higher levels of cholesterol and the extent of subclinical atheromatosis, yielding a higher concordance (C) index than the presence or absence of plaque. In stratified analysis including specific factors of CKD patients not on dialysis, the variables predicting CVE were the same as in the whole cohort, plus higher levels of potassium. Again, the inclusion of the information about atheromatosis as number of territories with plaque, presented a higher C index than the presence or absence of plaque. In the dialysis population, significant variables were older age, diabetes, dialysis vintage and higher levels of cholesterol and phosphate. In this case the higher C index was obtained with the information about plaque presence. Subclinical atheromatosis extent, including femoral arteries, influences CVE in CKD and its detection could improve the prediction of cardiovascular events.

Objective: To determine the influence of body mass index (BMI) on cognition in euthymic bipolar patients and healthy matched controls in a post hoc study of 2 cross-sectional and longitudinal exploratory studies., Method: A total sample of 121 individuals was examined, which included 52 euthymic bipolar disorder I or II patients (DSM-IV-TR criteria) and 69 healthy controls matched by age and gender, categorized in 2 subgroups in terms of body mass index (BMI-factor): normal weight (BMI: 18.5-24.9 kg/m²) versus overweight-obesity (overweight, BMI: 25.0-29.9 kg/m²; and obese, BMI ≥ 30 kg/m²). Demographic, clinical, cognitive, and psychosocial functioning data were collected from 2003 until 2011. Cognitive domains studied were executive function, attention, processing speed, verbal memory, and visual memory. Fifty-four subjects (28 bipolar and 26 healthy controls) were reevaluated after 6 years of follow-up., Results: Obesity and bipolar disorder showed a significant effect on cognition in cross-sectional and long-term MANOVA analyses (F₇,₁₁₁ = 2.54, P = .018 and F₁₉,₂₃ = 2.25, P = .033, respectively). In the cross-sectional linear regression model, global cognitive functioning was predicted by the interaction of BMI-factor by group (β = -0.44, SE = 0.14, P = .002), current age (β = -0.44, P < .0001), and premorbid IQ (β = 0.28, P = .0002), which explained 56% of variance (F₅,₁₁₅ = 29.6, P < .0001). Change in cognitive functioning over time was predicted by the interaction of BMI-factor by group (β = -0.8, SE = 0.33, P = .022) and cognition at baseline (β = -0.46, SE = 0.15, P = .004), which explained 27.65% of variance (F₆,₄₀ = 2.548, P = .0349). Generalized estimating equations analysis showed that interaction of group by BMI (Wald χ²₁ = 5.37, P = .02), age (Wald χ²₁ = 22.08, P < .0001), and premorbid IQ (Wald χ²₁ = 25.65, P < .0001) were the significant predictors., Conclusions: Obesity was significantly associated with cognitive impairment in euthymic bipolar patients, and it also appeared to affect cognition in the long term., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Aims: To assess whether circulating 25-hydroxyvitamin D 3 (25OHD) and mineral metabolism-related factors (serum phosphate, calcium, and parathormone) are associated with subclinical carotid atherosclerosis (SCA), defined as the presence of carotid atherosclerotic plaques (main study outcome), in patients with type 2 diabetes mellitus (T2DM) without kidney disease or previous cardiovascular disease., Methods: We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained., Results: We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg 2 /dL 2 ) product was positively associated with the presence of carotid plaques (OR adj  = 1.078; 95% CI: 1.017-1.142). An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus <20 ng/mL concentrations) and common carotid intima-media thickness (cIMT; mm) ( β adj  ± SE = -0.055 ± 0.024). We conclude that the CaP product is independently associated with the presence of established subclinical carotid atherosclerosis in patients with T2DM.

Chronic kidney disease (CKD) patients, characterized by traditional and nontraditional risk factors, are prone to develop atheromatosis and thus cardiovascular events and mortality. The angiogenesis of the adventitial vasa vasorum (aVV) surrounding the carotid has been described as the atheromatosis initiator. Therefore, the aim of the study was to (1) evaluate if the carotid aVV in CKD patients increases in comparison to its physiological value of healthy patients; (2) explore which traditional or nontraditional risk factor including inflammation, bone and mineral metabolism, and anemia could be related to the aVV angiogenesis. CKD patients without previous cardiovascular events (44, stages 3-4; 37, stage 5D) and 65 healthy subjects were compared. The carotid aVV and the intima-media thickness (cIMT) were evaluated by ultrasound. CKD patients at stages 3-4 showed higher aVV of the right carotid artery even after adjusting for age. Importantly, a multiple linear regression model showed hemoglobin levels > 12.5 g/dL as the factor for an estimated higher aVV of the right carotid artery. In conclusion, the association of hemoglobin with higher aVV could suggest the role of high hemoglobin in the higher incidence of adverse cardiovascular outcomes in CKD patients., Competing Interests: The authors declare that they have no competing interests.

Purpose: In this study, we first aimed to evaluate the effects in vitro and in vivo, of the Hsp90 inhibitor NVP-AUY922, in endometrial cancer (EC). We also aimed to track nuclear factor kappa B (NF-κB) signalling, a key pathway involved in endometrial carcinogenesis and to check whether NVP-AUY922 treatment modulates it both in vitro and in vivo., Procedures: I n vitro effects of NVP-AUY922 on EC cell growth and the signalling pathways were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic assays, Western Blot and luciferase assay. NVP-AUY922 effect on Ishikawa (IK) xenograft growth was evaluated in vivo, and NF-κB activity was monitored using bioluminescence imaging., Results: NVP-AUY922 inhibited the growth of three endometrial cell lines tested in vitro. In vivo, NVP-AUY922 reduced tumour growth of 47 % (p = 0.042) compared to control condition. Moreover, the bioluminescence signal of the tumours harbouring IK NF-κB-LUC cells was significantly reduced in NVP-AUY922-treated animals compared to untreated ones., Conclusions: NVP-AUY922 reduced EC tumour growth and NF-κB signalling both in vitro and in vivo. As therapeutic resistance of EC remains a challenge for oncologists nowadays, we think that NVP-AUY922 represents a valid alternative to conventional chemotherapy, and we believe that this approach for assessing and tracking the activation of NF-κB pathway may be of therapeutic benefit.

Background and Objectives: Chronic kidney disease (CKD) and atherosclerosis are 2 interrelated diseases that increase the risk of cardiovascular morbidity and mortality. The objectives of the ILERVAS project are: 1) to determine the prevalence of subclinical arterial disease and hidden kidney disease; 2) to assess the impact of early diagnosis of both diseases on cardiovascular morbidity and mortality and also on the progression of CKD; 3) to have a platform of data and biological samples., Methods: Randomized intervention study. From 2015 to 2017, 19,800 people (9,900 in the intervention group and 9,900 in the control group) aged between 45 and 70 years without previous history of cardiovascular disease and with at least one cardiovascular risk factor will be randomly selected from the primary health care centres across the province of Lérida. A team of experts will travel around in a mobile unit to carry out the following baseline tests on the intervention group: Artery ultrasound; (carotid, femoral, transcranial and abdominal aorta); ankle-brachial index; spirometry; determination of advanced glycation end products; dried blood spot and urine spot tests. Additionally, blood and urine samples will be collected and stored in the biobank to identify new biomarkers using omics studies. Participants will be followed up until 2025 for identification of cardiovascular events, treatment changes and changes in lifestyle., Conclusions: The ILERVAS project will reveal the prevalence of subclinical vascular disease and hidden kidney disease, determine whether or not their early diagnosis brings health benefits and will also allow investigation of new risk factors., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)