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Aim: Advanced glycation end-products (AGEs) have been involved in the atherogenic process in the high-risk population. The goal of this study was to demonstrate that AGEs are related to subclinical atheromatous disease in subjects with low to moderate vascular risk., Methods: A cross-sectional study in which 2,568 non-diabetic subjects of both sexes without cardiovascular disease were included. Subcutaneous content of AGEs was assessed by skin autofluorescence (SAF) and subclinical atheromatous disease was measured by assessing the atheromatous plaque burden in carotid and femoral regions using ultrasonography. In addition, serum pentosidine, carboxymethyl-lysine (CML) and AGE receptors (RAGE) were assessed in a nested case-control study with 41 subjects without plaque and 41 individuals subjects with generalized disease., Results: Patients with atheromatous plaque had a higher SAF than those with no plaque (1.9 [1.7 to 2.3] vs. 1.8 [1.6 to 2.1] arbitrary units (AU), p＜0.001). The SAF correlated with the total number of affected regions (r= 0.171, p＜0.001), increasing progressively from 1.8 [1.6 to 2.1] AU in those without atheromatous disease to 2.3 [1.9 to 2.7] AU in patients with ≥ 8 plaques (p＜0.001). A correlation was also observed between SAF and the total plaque area (r=0.113, p＜0.001). The area under the Receiver Operating Characteristic curve was 0.65 (0.61 to 0.68) for identifying male subjects with atheromatous disease. The multivariable logistic regression model showed a significant and independent association between SAF and the presence of atheromatous disease. However, no significant differences in serum pentosidine, CML, and RAGE were observed., Conclusions: Increased subcutaneous content of AGEs is associated with augmented atheromatous plaque burden. Our results suggest that SAF may provide clinically relevant information to the current strategies for the evaluation of cardiovascular risk, especially among the male population.

Background: Hospital wastewater is commonly polluted with high loads of pharmaceutically active compounds, which pass through wastewater treatment plants (WWTPs) and end up in water bodies, posing ecological and health risks. White-rot fungal treatments can cope with the elimination of a wide variety of micropollutants while remaining ecologically and economically attractive. Unfortunately, bacterial contamination has impeded so far a successful implementation of fungal treatment for real applications., Results: This work embodied a 91-day long-term robust continuous fungal operation treating real non-sterile hospital wastewater in an air pulsed fluidized bed bioreactor retaining the biomass. The hydraulic retention time was 3 days and the ageing of the biomass was avoided through partial periodic biomass renovation resulting in a cellular retention time of 21 days. Evolution of microbial community and Trametes abundance were evaluated., Conclusions: The operation was able to maintain an average pharmaceutical load removal of over 70% while keeping the white-rot fungus active and predominant through the operation., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Subsurface microorganisms must deal with quite extreme environmental conditions. The lack of light, oxygen, and potentially nutrients are the main environmental stresses faced by subsurface microbial communities. Likewise, environmental disruptions providing an unbalanced positive input of nutrients force microorganisms to adapt to varying conditions, visible in the changes in microbial community diversity. In order to test microbial community adaptation to environmental changes, we performed a study in a surface Managed Aquifer Recharge facility, consisting of a settlement basin (two-day residence time) and an infiltration pond. Data on groundwater hydrochemistry, soil texture, and microbial characterization was compiled from surface water, groundwater, and soil samples at two distinct recharge operation conditions. Multivariate statistics by means of Principal Component Analysis (PCA) was the technique used to map the relevant dimensionality reduced combinations of input variables that properly describe the system behavior. The methodology selected allows including variables of different nature and displaying very different range values. Strong differences in the microbial assemblage under recharge conditions were found, coupled to hydrochemistry and grain-size distribution variables. Also, some microbial groups displayed correlations with either carbon or nitrogen cycles, especially showing abundant populations of denitrifying bacteria in groundwater. A significant correlation was found between Methylotenera mobilis and the concentrations of NO 3 and SO 4 , and also between Vogesella indigofera and the presence of DOC in the infiltrating water. Also, microbial communities present at the bottom of the pond correlated with representative descriptors of soil grain size distribution., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: In Spain, women invited to breast screening are not usually informed about potential harms of screening. The objective of the InforMa study is to assess the effect of receiving information about the benefits and harms of breast screening on informed choice and other decision-making outcomes, in women approaching the age of invitation to mammography screening., Methods: Two-stage randomised controlled trial. In the first stage, 40 elementary territorial units of the public healthcare system were selected and randomised to intervention or control. In the second stage, women aged 49-50 years were randomly selected. The target sample size was 400 women. Women in the intervention arm received a decision aid (DA) with detailed information on the benefits and harms of screening. Women in the control arm received a standard leaflet that did not mention harms and recommended accepting the invitation to participate in the Breast Cancer Screening Program (BCSP). The primary outcome was informed choice, defined as adequate knowledge and intentions consistent with attitudes. Secondary outcomes included decisional conflict, worry about breast cancer, time perspective, opinions about the DA or the leaflet, and participation in the BCSP., Results: In the intervention group, 23.2% of 203 women made an informed choice compared to only 0.5% of 197 women in the control group (p < 0.001). Attitudes and intentions were similar in both study groups with a high frequency of women intending to be screened, 82.8% vs 82.2% (p = 0.893). Decisional conflict was significantly lower in the intervention group. No differences were observed in confidence in the decision, anxiety, and participation in BCSP., Conclusions: Women in Spain lack knowledge on the benefits and harms of breast screening. Providing quantitative information on benefits and harms has produced a considerable increase in knowledge and informed choice, with a high acceptance of the informative materials., Trial Registration: Trial identifier NCT03046004 at ClinicalTrials.gov registry. Registered on February 4 2017. Trial name: InforMa study., Competing Interests: The authors have declared that no competing interests exist.

Diabetic retinopathy (DR) may potentially cause vision loss and affect the patient's quality of life (QoL) and treatment satisfaction (TS). Using specific tools, we aimed to assess the impact of DR and clinical factors on the QoL and TS in patients with type 1 diabetes. This was a cross-sectional, two-centre study. A sample of 102 patients with DR and 140 non-DR patients were compared. The Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) and Diabetes Treatment Satisfaction Questionnaire (DTSQ-s) were administered. Data analysis included bivariate and multivariable analysis. Patients with DR showed a poorer perception of present QoL ( p = 0.039), work life ( p = 0.037), dependence ( p = 0.010), and had a lower average weighted impact (AWI) score ( p = 0.045). The multivariable analysis showed that DR was associated with a lower present QoL ( p = 0.040), work life ( p = 0.036) and dependence ( p = 0.016). With regards to TS, DR was associated with a higher perceived frequency of hypoglycaemia ( p = 0.019). In patients with type 1 diabetes, the presence of DR is associated with a poorer perception of their QoL. With regard to TS, these subjects also show a higher perceived frequency of hypoglycaemia.

Antidepressant drugs such as Venlafaxine (VFX) and O-desmethylvenlafaxine (ODMVFX) are emerging contaminants that are commonly detected in aquatic environments, since conventional wastewater treatment plants are unable to completely remove them. They can be precursors of hazardous by-products, such as the carcinogenic N-nitrosodimethylamine (NDMA), generated upon water chlorination, as they contain the dimethylamino moiety, necessary for the formation of NDMA. In this study, the capability of three white rot fungi (Trametes versicolor, Ganoderma lucidum and Pleurotus ostreatus) to remove both antidepressants from water and to decrease NDMA formation potential was investigated. Furthermore, transformation by-products (TPs) generated along the treatment process were elucidated and also correlated with their NDMA formation potential. Very promising results were obtained for T. versicolor and G. lucidum, both being able to remove up to 100% of ODMVFX. In the case of VFX, which is very recalcitrant to conventional wastewater treatment, a 70% of removal was achieved by T. versicolor, along with a reduction in NDMA formation potential, thus decreasing the associated problems for human health and the environment. However, the NDMA formation potential remained practically constant during treatment with G. lucidum despite of the equally high VFX removal (70%). This difference was attributed to the generation of different TPs during both fungal treatments. For example, G. lucidum generated more ODMVFX, which actually has a higher NDMA formation potential than the parent compound itself., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the usefulness of pleural fluid adenosine deaminase (ADA) for diagnosing tuberculous pleural effusions in the Spanish population, according to laboratory technique and cut-off point, and to compare the results with other populations., Methods: Meta-analysis of diagnostic studies on pleural fluid ADA in the Spanish population, extracted from the PubMed and Embase databases from inception until July 2017, with no language restrictions. The overall diagnostic accuracy of ADA and that of each of the measurement techniques (Giusti, manual and automated kinetic methods) and selected cut-offs were analyzed. The QUADAS-2 tool was used to evaluate the quality of studies. A bivariate random effects model was used. Results were compared with those obtained from previous meta-analyses in non-Spanish populations., Results: Sixteen studies in a total of 4,147 patients, 1,172 of whom had tuberculous pleural effusions, were included. ADA had 93% sensitivity, 92% specificity, positive likelihood ratio of 12, negative likelihood ratio of 0.08, and an area-under-the-curve of 0.968 for identifying tuberculosis. There were no differences in diagnostic accuracy between the techniques used for ADA measurement or the selected cut-offs. In 73 studies from non-Spanish populations a trend toward lower ADA sensitivity (88%, 95% CI:86%-90%) and specificity (88%, 95% CI: 86%-90%) was noted, but differences did not reach statistical significance., Conclusions: Pleural fluid ADA in the Spanish population shows good diagnostic accuracy (regardless of the measurement technique or cut-off), similar to that reported in non-Spanish populations., (Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Psoriasis is a very prevalent systemic chronic inflammatory disease. Major cardiovascular events are the main cause of mortality in these patients which suggests an association between psoriasis and traditional cardiovascular risk factors., Objective: To identify classic cardiovascular risk factors and metabolic syndrome (MS) in patients with psoriasis, their possible association with its severity and compare it with the non-psoriatic population., Methods: This is an observational and cross-sectional population study in Lleida (Spain) from a joint hospital/primary care database., Results: The database comprised 398 701 individuals. There were 6868 cases registered as psoriasis (1.7%), and 499 of them (7.3%) were classified as moderate-severe psoriasis. Patients with psoriasis had a higher prevalence of traditional cardiovascular risk factors than non-psoriatic population: diabetes mellitus 2 (13.9% vs 7.4%, OR 2.01), dyslipidaemia (28.8% vs 17.4%, OR 1.92), arterial hypertension (31.2% vs 19.0%, OR 1.93), obesity (33.7% vs 28.1%, OR 1.30), altered fasting basal glycaemia (21.4% vs 15.1%, OR 1.54), low cholesterol HDL (38.1% vs 32.3%, OR 1.29), hypertriglyceridaemia (45.7% vs 35.2%, OR 1.55) and high waist circumference (75.7% vs 72.3%, OR 1.19). MS was more prevalent in psoriatic patients (28.3% vs 15.1%, OR 2.21), and cardiovascular risk factors were similar between psoriasis severity groups. Psoriatic patients had a higher prevalence of ischaemic heart disease (3.3% vs 1.8%, OR 1.87) and vascular cerebral accidents (1.8% vs 1.2%, OR 1.55). A model for MS showed a significant nonlinear relationship with age and sex and significant differences between patients with and without psoriasis., Conclusion: We found statistically significant differences in relation to the prevalence of cardiovascular risk factors, MS and major cardiovascular events in psoriatic patients. However, differences were not seen between psoriasis severity groups. Our work reinforces the need for a multidisciplinary approach and close monitoring of cardiovascular risk factors in these patients to prevent a cardiovascular event., (© 2018 European Academy of Dermatology and Venereology.)

In this paper, the synthesis, comprehensive characterization and biological and photocatalytic properties of two series of neutral Ir III biscyclometalated complexes of general formula [Ir(C^N) 2 (N^O)], where the N^O ligands are 2-(benzimidazolyl)phenolate-N,O (L1, series a) and 2-(benzothiazolyl)phenolate-N,O (L2, series b), and the C^N ligands are 2-(phenyl)pyridinate or its derivatives, are described,. Complexes of types a and b exhibit dissimilar photophysical and biological properties. In vitro cytotoxicity tests conclusively prove that derivatives of series a are harmless in the dark against SW480 cancer cells (colon adenocarcinoma), but express enhanced cytotoxicity versus the same cells after stimulation with UV or blue light. In contrast, complexes of type b show a very high cytotoxic activity in the dark, but low photosensitizing ability. Thus, the ancillary N^O ligand is the main factor in terms of cytotoxic activity both in the dark and upon irradiation. However, the C^N ligands play a key role regarding cellular uptake. In particular, the complex of formula [Ir(dfppy) 2 (L1)] (dfppy=2-(4,6-difluorophenyl)pyridinate) [3 a] has been identified as both an efficient photosensitizer for 1 O 2 generation and a potential agent for photodynamic therapy. These capabilities are probably related to a combination of its notable cellular internalization, remarkable photostability, high photoluminescence quantum yield, and long triplet excited-state lifetime. Both types of complexes exhibit notable catalytic activity in the photooxidation of thioanisole and S-containing aminoacids with full selectivity., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new family of neutral ruthenium(II) arene complexes of the type [Ru(η 6 -arene)X(κ 2 - O, N-L)] (η 6 -arene = p-cym, bz; X = Cl - , SCN - ; HL1 = 2-(2'-hydroxyphenyl)benzimidazole, HL2 = 2-(2'-hydroxyphenyl)benzothiazole) has been synthesized and characterized. The cytotoxic activity of the Ru(II) complexes was evaluated in several tumor cell lines (A549, HepG2 and SW480) both in the dark and after soft irradiation with UV and blue light. None of the complexes bearing benzimidazole (HL1) as a ligand displayed phototoxicity, whereas the complexes with a benzothiazole ligand (HL2) exhibited photoactivation; the sensitivity observed for UV was higher than for blue light irradiation. The interesting results displayed by HL2 and [Ru(η 6 - p-cym)(NCS)(κ 2 - O, N-L2)], [3a], in terms of photo cytotoxicity prompted us to analyze their interaction with DNA, both in the dark and under irradiation conditions, in an effort to shed some light on their mechanism of action. The results of this study revealed that HL2 interacts with DNA by groove binding, whereas [3a] interacts by a dual mode of binding, an external groove binding, and covalent binding of the metal center to the guanine moiety. Interestingly, both HL2 and [3a] display a clear preference for AT base pairs, and this causes fluorescence enhancement. Additionally, cleavage of the pUC18 plasmid DNA by the complex is observed upon irradiation. The study of the irradiated form demonstrates that the arene ligand is released to yield species such as [Ru(κ 2 - O, N-L2)(κ 1 - S-DMSO) 2 (μ-SCN)] 2 [3c] and [Ru(κ 2 - O, N-L2)(κ 1 - S-DMSO) 3 (SCN)] [3d]. Such photo dissociation occurs even in the absence of oxygen and leads to cytotoxicity enhancement, an effect attributed to the presence of [3d], thus revealing the potential of [3a] as a pro-drug for photoactivated anticancer chemotherapy (PACT).

Introduction: Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored. The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH., Methods: This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA., Conclusions: This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH., (Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Two pairs of Rh(III) and Ir(III) biscyclometallated complexes with thiabendazole (L 1 ), named [Ir-a]Cl and [Rh-a]Cl, and N-benzyl-thiabendazole (L 2 ), named [Ir-b]Cl and [Rh-b]Cl, have been designed and synthesized to explore the photophysical and biological effects that arise from changing both the metal center and the ancillary ligand. In the dark, the four metal complexes exhibit greater cytotoxicity than cisplatin against human colon (SW480) and human lung (A549) adenocarcinoma cell lines. Moreover, the pair of complexes bearing the ligand L 2 is markedly more cytotoxic and present higher uptake values than complexes with L 1 , thereby their biological properties were studied further to determine their mechanism of action. Interestingly, in spite of the different metal center both the [Ir-b]Cl and [Rh-b]Cl complexes are responsible for the loss of mitochondrial functionality and the activation of apoptotic cell death pathways. Moreover, the photodynamic activity of the four complexes, [Ir-a,b]Cl and [Rh-a,b]Cl, was tested using visible blue light (460 nm) under soft irradiation conditions (20 min, 5.5 mW cm -2 ). While the Rh complexes are not photopotentiated, the phototoxicity index (IC 50 non-irradiated/IC 50 irradiated) of [Ir-a]Cl and [Ir-b]Cl complexes was 15.8 and 3.6, respectively. We also demonstrate that only the Ir derivatives are capable of photocatalyzing the oxidation of S-containing l-amino acids under blue light irradiation, [Ir-a]Cl being more active than [Ir-b]Cl, which provides a reasonable mechanism for their biological action (oxidative stress could be selectively promoted through a photocatalytic action) upon irradiation. This different PDT behaviour depending on the metal center and the ancillary substituent may be useful for future rational design of metal-based photosensitizers., (Copyright © 2018. Published by Elsevier Masson SAS.)

Objective: The aim of this study is to identify the risks factors for mortality and functional recovery in elderly patients admitted to hospital with a hip fracture., Materials and Methods: Longitudinal prospective study in patients 80 years old or more and patients between 75 and 79 in residential home care with a hip fracture and with a past medical history of dementia or followed-up by the Geriatric Unit. A total of 359 patients were included, and the demographic data, previous functional status, comorbidity, type of fracture, and dementia were recorded. The data collected during admission included time to surgery, delirium, functional recovery, length of stay, placement at discharge, and mortality. Patients were followed-up for one year and details were collected on placement at the end of follow-up, functional recovery, medical complications, and mortality., Results: The baseline characteristics of the patients with a strong association with mortality after a hip fracture were old age (> 92 years), medical complications delaying surgery (HR 2.17; 95% CI; 1.27-3.73), diagnosis of dementia (HR 1.78; 95% CI; 1.15-2.75), or heart failure (HR 1.75; 95% CI; 1.12-2.75). The fitted multivariable regression models showed that functional impairment before the hip fracture or lack of functional recovery are associated with higher mortality, and patients with increased age, delirium, dementia, and previous functional impairment showed worse functional recovery., Conclusion: In the elderly patients with a hip fracture, increased age, comorbidity and previous functional status is associated with mortality. Functional recovery prognosis will depend on age, previous functional status, past medical history of dementia, and the presence of delirium during admission., (Publicado por Elsevier España, S.L.U.)

A new family of heteroleptic bis-cyclometalated Ir III complexes with formula [Ir(CN^ ) 2 (NN^ )]Cl (CN^ =2-phenylpyridinate and NN^ =2,2'-dipyridylamine or N-benzylated 2,2'-dipyridylamines, were synthesized, characterized, and successfully used as photosensitizers in the catalytic photooxidation of an array of dialkyl, dibenzyl, alkyl aryl, and diaryl sulfides, as well as sulfur-containing amino acids. Furthermore, the reactions proceeded with optimal chemoselectivity, and atom economy under mild conditions. Experimental observations support a dual mechanism in which singlet oxygen and superoxide are the actual oxidants., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The use of microalgal consortia for urban wastewater treatment is an increasing trend, as it allows simultaneous nutrient removal and biomass production. Emerging contaminants proposed for the list of priority substances such as the hormone 17β-estradiol are commonly found in urban wastewater, and their removal using algal monocultures has been accomplished. Due to the inherent potential of algae-based systems, this study aimed to assess the capability of native photobioreactor biomass to remove 17β-estradiol under indoor and outdoor conditions. At the same time, the microbial community changes in regular and bioaugmented operations with Scenedesmus were assessed. The results show that almost complete removal (>93.75%) of the hormone 17β-estradiol can be attained in the system under favourable seasonal conditions, although these conditions greatly influence biomass concentrations and microbial diversity. Even under the harsh conditions of low temperatures and solar irradiation, the established consortium removed more than 50% of the pollutant in 24 h. While species from genus Chlorella were stable during the entire operation, the microbial diversity analysis revealed that assorted and evenly distributed populations stimulate the removal rates. Bioaugmentation assays proved that the input of additional biomass results in higher overall removal and decreases the yield per mg of biomass., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Influenza virus intimately associates with host RNA polymerase II (Pol II) and mRNA processing machinery. Here, we use mammalian native elongating transcript sequencing (mNET-seq) to examine Pol II behavior during viral infection. We show that influenza virus executes a two-pronged attack on host transcription. First, viral infection causes decreased Pol II gene occupancy downstream of transcription start sites. Second, virus-induced cellular stress leads to a catastrophic failure of Pol II termination at poly(A) sites, with transcription often continuing for tens of kilobases. Defective Pol II termination occurs independently of the ability of the viral NS1 protein to interfere with host mRNA processing. Instead, this termination defect is a common effect of diverse cellular stresses and underlies the production of previously reported downstream-of-gene transcripts (DoGs). Our work has implications for understanding not only host-virus interactions but also fundamental aspects of mammalian transcription., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

We evaluated the use of antimicrobials expressed as defined daily doses (DDDs) per 1,000 patient days and days of therapy (DOT) per 100 occupied bed-days in a intensive care unit (ICU) of a general hospital in Barcelona, Spain, before and after implementation of an antimicrobial stewardship (AMS) program (2007 to 2010 versus 2011 to 2015). The quarterly costs of antimicrobials used in the ICU and its weight in the overall hospital costs of antimicrobials were calculated. The effect of the applied AMS program on DDDs and DOT time series data was analyzed by means of intervention time series analysis. A total of 5,002 patients were included (1,971 for the first [before] period and 3,031 for the second [after] period). The percentage of patients treated with one or more antimicrobials decreased from 88.6 to 77.2% ( P < 0.001). DDDs decreased from 246.8 to 192.3 (mean difference, -54.5; P = 0.001) and DOT from 66.7 to 54.6 (mean difference, -12.1; P = 0.066). The mean cost per trimester decreased from €115,543 to €73,477 (mean difference, -42,065.4 euros; P < 0.001), and the percentage of ICU antimicrobials cost with respect to the total cost of hospital antimicrobials decreased from 28.5 to 22.8% (mean difference, -5.59; P = 0.023). Implementation of an AMS program in the ICU was associated with a marked reduction in the use of antimicrobials, with cost savings close to one million euros since its implementation. An AMS program can have a significant impact on optimizing antimicrobial use in critical care practice., (Copyright © 2018 American Society for Microbiology.)

Background: In this cross-sectional study, we assessed the possible association of vitamin D deficiency with self-reported treatment satisfaction and health-related quality of life in patients with type 2 diabetes., Methods: We performed a sub-analysis of a previous study and included a total of 292 type 2 diabetic patients. We evaluated treatment satisfaction and health-related quality of life through specific tools: the Diabetes Treatment Satisfaction Questionnaire and the Audit of Diabetes-Dependent Quality of Life. Vitamin D deficiency was defined as 25 (OH) D serum levels < 15 ng/mL., Results: Multivariable linear regression models were used to estimate the relationship of vitamin D deficiency with both outcomes once adjusted for self-reported patient characteristics. Vitamin D deficiency was significantly associated with the final score of the Diabetes Treatment Satisfaction Questionnaire and the single "diabetes-specific quality of life" dimension of the Audit of Diabetes-Dependent Quality of Life (p = 0.0198 and p = 0.0070, respectively). However, lower concentrations of 25-OH vitamin D were not associated with the overall quality of life score or the perceived frequency of hyperglycaemia and hypoglycaemia., Conclusions: Our study shows the association between vitamin D deficiency and both the self-reported diabetes treatment satisfaction and the diabetes-specific quality of life in patients with type 2 diabetes.

Objectives: The "Pneumonia Zero" project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ventilator-associated pneumonia in critically ill patients admitted to the ICU., Design: Prospective, interventional, and multicenter study., Setting: A total of 181 ICUs throughout Spain., Patients: All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012., Intervention: Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April-June 2010) as the baseline period. Ventilator-associated pneumonia rates were adjusted by characteristics of the hospital, including size, type (public or private), and teaching (postgraduate) or university-affiliated (undergraduate) status., Measurements and Main Results: The 181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of 171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0% of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42-11.48) per 1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22-5.84) after 19-21 months of participation., Conclusions: Implementation of the bundle measures included in the "Pneumonia Zero" project resulted in a significant reduction of more than 50% of the incidence of ventilator-associated pneumonia in Spanish ICUs. This reduction was sustained 21 months after implementation.

Objectives: Our main aim was to assess the quality of life (QoL) and treatment satisfaction (TS) of subjects with LADA (latent autoimmune diabetes of the adult) and compare these measures with those of patients with other diabetes types, i.e., type 1 (T1DM) and type 2 diabetes mellitus (T2DM)., Methods: This was a cross-sectional study with a total of 48 patients with LADA, 297 patients with T2DM and 124 with T1DM. The Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) questionnaire and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were administered. Relevant clinical variables were also assessed. The data analysis included comparisons between groups and multivariate linear models., Results: The LADA patients presented lower diabetes-specific QoL ( p  = 0.045) and average weighted impact scores ( p  = 0.007) than the T2DM patients. The subgroup of LADA patients with diabetic retinopathy (DR) who were treated with insulin had a lower ADDQoL average weighted impact score than the other diabetic groups. Although the overall measure of TS was not different between the LADA and T2DM ( p  = 0.389) and T1DM ( p  = 0.091) groups, the patients with LADA showed a poorer hyperglycemic frequency perception than the T2DM patients ( p  < 0.001) and an improved frequency of hypoglycemic perception compared with the T1DM patients ( p  = 0.021)., Conclusions: The current findings suggest a poorer quality of life, especially in terms of DR and insulin treatment, among patients with LADA compared with those with T1DM and T2DM. Hyperglycemia frequency perception was also poorer in the LADA patients than in the T1DM and T2DM patients. Further research with prospective studies and a large number of patients is necessary., Competing Interests: The authors declare there are no competing interests.

Objective: The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) and observational studies is to assess the effect of decision aids (DAs) in women aged 50 and below facing the decision to be screened for breast cancer., Setting: Screening for breast cancer., Intervention: DAs aimed to help women make a deliberative choice regarding participation in mammography screening by providing information on the options and outcomes., Eligible Studies: We included published original, non-pilot, studies that assess the effect of DAs for breast cancer screening. We excluded the studies that evaluated only participation intention or actual uptake. The studies' risk of bias was assessed with the Cochrane Collaboration's tool for RCTs and the National Institutes of Health Quality Assessment Tool for non-RCTs., Primary and Secondary Outcomes: The main outcome measures were informed choice, decisional conflict and/or confidence, and knowledge. Secondary outcomes were values, attitudes, uncertainty and intention to be screened., Results: A total of 607 studies were identified, but only 3 RCTs and 1 before-after study were selected. The use of DAs increased the proportion of women making an informed decision by 14%, 95% CI (2% to 27%) and the proportion of women with adequate knowledge by 12%, 95% CI (7% to 16%). We observed heterogeneity among the studies in confidence in the decision. The meta-analysis of the RCTs showed a significant decrease in confidence in the decision and in intention to be screened., Conclusions: Tools to aid decision making in screening for breast cancer improve knowledge and promote informed decision; however, we found divergent results on decisional conflict and confidence in the decision. Under the current paradigm change, which favours informed choice rather than maximising uptake, more research is necessary for the improvement of DAs., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The reduction in blood pressure (BP) with continuous positive airway pressure (CPAP) is modest and highly variable. In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h -1 ) were included; 28.4% had hypertension. 62 patients finished the study, and 60 were analysed. The daytime diastolic BP (-2 mmHg) and norepinephrine (-109.5 nmol·day -1 ) were reduced after CPAP, but no changes in the 24-h BP, night-time BP, dopamine, epinephrine, CRP, leptin or adiponectin were detected. The nocturnal normotension was associated with an increased night-time-BP (+4 mmHg) after CPAP, whereas nocturnal hypertension was associated with a reduction of 24-h BP (-3 mmHg). A multivariate linear regression model showed differential night-time BP changes after CPAP. Specifically, low night-time heart rate (<68 bpm) and BP dipper profile were associated with increased night-time BP and new diagnosis of nocturnal hypertension.Our results suggest that nocturnal hypertension, circadian BP pattern and night-time heart rate could be clinical predictors of BP response to CPAP and support the usefulness of 24-h ABPM for OSA patients before treatment initiation. These results need to be confirmed in further studies., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

Background: Evidence from longitudinal studies has reported contradictory results regarding the association between OSA and hypertension. In a previous analysis of the Vitoria Sleep Cohort, the relationship between OSA and the risk of developing hypertension was evaluated and no independent association after adjustment for confounding factors was found. In the present study, a post hoc analysis to assess the association between OSA and incident stage 2 hypertension (systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 100 mm Hg) was made on the basis of sex differences., Methods: A prospective study was performed over 7.5 ± 0.8 years on a middle-aged general population, which included 1,155 normotensive subjects (43.7% men) who completed the follow-up. BP measurements (at baseline and follow-up) and polygraphy at baseline were performed. Logistic regression models were used to determine the association between the respiratory disturbance index (RDI) and stage 2 hypertension and a recursive partitioning method was used to determine the variables related to the incidence of stage 2 hypertension. The RDI was divided into subgroups (0-2.9, 3-6.9, 7-13.9, and ≥ 14), using the first subgroup as reference., Results: For men, an RDI ≥ 14 was associated with a significantly increased OR for stage 2 hypertension (OR, 2.54 [95% CI, 1.09-5.95], P = .032). This association was not statistically significant among women (P = .371)., Conclusions: The results suggest an association between moderate and severe OSA, and the incidence of more severe forms of hypertension occurring in men but not in women. However, because this is a community-based study, the women's population characteristics may differ from women usually seen in sleep-disorders clinics., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The decision to participate or not in breast cancer screening is complex due to the trade-off between the expected benefit of breast cancer mortality reduction and the major harm of overdiagnosis. It seems ethically necessary to inform women so that they can actively participate in decision-making and make an informed choice based on their values and preferences. The objective of this study is to assess the effects of receiving information about the benefits and harms of screening on decision-making, in women approaching the age of invitation to mammography screening., Methods: A two-stage, randomized controlled trial (RCT). In the first stage, 40 Basic Health Areas (BHAs) will be selected and randomized to intervention or control. In the second stage, women within each BHA will be randomly selected (n = 400). Four breast cancer screening programs (BCSPs) of the Spanish public health system, three in Catalonia and one in the Canary Islands will participate in the study. Women in the intervention arm will receive a leaflet with detailed information on the benefits and harms of screening using mammography. Women in the control arm will receive a standard leaflet that does not mention harms and recommends accepting the invitation to participate in the biennial examinations of the BCSP. The primary outcome is informed choice, a dichotomous variable that combines knowledge, attitudes, and intentions. Secondary outcomes include decisional conflict; confidence in the decision made; anxiety about screening participation; worry about breast cancer; anticipated regret; time perspective; perceived importance of benefits/harms of screening; perceived risk of breast cancer; and leaflet acceptability. Primary and secondary outcomes are assessed 2-3 weeks after the intervention., Discussion: This is the first RCT that assesses the effect of informing about the benefits and harms of breast cancer screening in Spain in women facing the decision to be screened using mammography. It aims to assess the impact of information on several decisional outcomes and to contribute to paving the road towards shared decision-making in breast cancer screening in our country., Trial Registration: ClinicalTrials.gov registry, ID: NCT03046004 . Retrospectively registered on 4 February 2017. Trial name: InforMa study.

A series of bis-cyclometalated iridium(III) complexes of general formula [Ir(ppy) 2 (N ∧ N)][PF 6 ] (ppy - = 2-phenylpyridinate; N ∧ N = 2-(1H-imidazol-2-yl)pyridine (1), 2-(2-pyridyl)benzimidazole (2), 1-methyl-2-pyridin-2-yl-1H-benzimidazole (3), 2-(4'-thiazolyl)benzimidazole (4), 1-methyl-2-(4'-thiazolyl)benzimidazole (5)) is reported, and their use as electroluminescent materials in light-emitting electrochemical cell (LEC) devices is investigated. [2][PF 6 ] and [3][PF 6 ] are orange emitters with intense unstructured emission around 590 nm in acetonitrile solution. [1][PF 6 ], [4][PF 6 ], and [5][PF 6 ] are green weak emitters with structured emission bands peaking around 500 nm. The different photophysical properties are due to the effect that the chemical structure of the ancillary ligand has on the nature of the emitting triplet state. Whereas the benzimidazole unit stabilizes the LUMO and gives rise to a 3 MLCT/ 3 LLCT emitting triplet in [2][PF 6 ] and [3][PF 6 ], the presence of the thiazolyl ring produces the opposite effect in [4][PF 6 ] and [5][PF 6 ] and the emitting state has a predominant 3 LC character. Complexes with 3 MLCT/ 3 LLCT emitting triplets give rise to LEC devices with luminance values 1 order higher than those of complexes with 3 LC emitting states. Protecting the imidazole N-H bond with a methyl group, as in complexes [3][PF 6 ] and [5][PF 6 ], shows that the emissive properties become more stable. [3][PF 6 ] leads to outstanding LECs with simultaneously high luminance (904 cd m -2 ), efficiency (9.15 cd A -1 ), and stability (lifetime over 2500 h).

Introduction: The influence of age and gender in the electrical charge delivered in a given population was analysed using an electroconvulsive therapy (ECT) clinical database., Material and Method: An observational, prospective, longitudinal study with descriptive analysis was performed using data from a database that included total bilateral frontotemporal ECT carried out with a Mecta spECTrum 5000Q ® in our hospital over 6 years. From 2006 to 2012, a total of 4,337 ECT were performed on 187 patients. Linear regression using mixed effects analysis was weighted by the inverse of the number of ECT performed on each patient per year of treatment., Results: The results indicate that age is related with changes in the required charge (P=.031), as such that the older the age a higher charge is needed. Gender is also associated with changes in charge (P=.014), with women requiring less charge than men, a mean of 87.3mC less. When the effects of age and gender are included in the same model, both are significant (P=.0080 and P=.0041). Thus, for the same age, women require 99.0mC less charge than men, and in both genders the charge increases by 2.3mC per year., Conclusions: From our study, it is concluded that the effect of age on the dosage of the electrical charge is even more significant when related to gender. It would be of interest to promote the systematic collection of data for a better understanding and application of the technique., (Copyright © 2015 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.)

Biodegradation of dichloromethane (DCM) under reducing conditions is of major concern due to its widespread detection in contaminated groundwaters. Here, we report an anaerobic enrichment culture derived from a membrane bioreactor operating in an industrial wastewater treatment plant, capable of fermenting DCM and the brominated analogue dibromomethane (DBM). Comparative analysis of bacterial 16S rDNA-DGGE profiles from fresh liquid medium inoculated with single colonies picked from serial dilution-to-extinction agar vials showed that cultures degrading DCM contained a predominant band belonging to Dehalobacterium, however this band was absent in cultures unable to degrade DCM. Analysis of the microbial composition of the enrichment by bacterial 16S rRNA gene amplicon paired-end sequencing confirmed the presence of Dehalobacterium together with three additional phylotypes belonging to Acetobacterium, Desulfovibrio, and Wolinella, representing all four operational taxonomic units >99.9% of the retrieved sequences. The carbon isotopic fractionation (ε) determined for DCM degradation in this culture was -27±2‰. This value differs from the ε previously reported for the DCM-fermentative bacteria Dehalobacter (-15.5±1.5‰) but they are both significantly different from those reported for facultative methylotrophic organisms (ranging from -45 to -61‰). This significant difference in the ε allows differentiating between hydrolytic transformation of DCM via glutathione-dependent dehalogenases and fermentation pathway., Capsule: The carbon isotopic fractionation of dichloromethane by an enriched Dehalobacterium-containing culture has significant potential to monitor biodegradation of DCM in groundwaters., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Unlabelled: Influenza viruses subvert the transcriptional machinery of their hosts to synthesize their own viral mRNA. Ongoing transcription by cellular RNA polymerase II (Pol II) is required for viral mRNA synthesis. By a process known as cap snatching, the virus steals short 5' capped RNA fragments from host capped RNAs and uses them to prime viral transcription. An interaction between the influenza A virus RNA polymerase and the C-terminal domain (CTD) of the large subunit of Pol II has been established, but the molecular details of this interaction remain unknown. We show here that the influenza virus ribonucleoprotein (vRNP) complex binds to the CTD of transcriptionally engaged Pol II. Furthermore, we provide evidence that the viral polymerase binds directly to the serine-5-phosphorylated form of the Pol II CTD, both in the presence and in the absence of viral RNA, and show that this interaction is conserved in evolutionarily distant influenza viruses. We propose a model in which direct binding of the viral RNA polymerase in the context of vRNPs to Pol II early in infection facilitates cap snatching, while we suggest that binding of free viral polymerase to Pol II late in infection may trigger Pol II degradation., Importance: Influenza viruses cause yearly epidemics and occasional pandemics that pose a threat to human health, as well as represent a large economic burden to health care systems globally. Existing vaccines are not always effective, as they may not exactly match the circulating viruses. Furthermore, there are a limited number of antivirals available, and development of resistance to these is a concern. New measures to combat influenza are needed, but before they can be developed, it is necessary to better understand the molecular interactions between influenza viruses and their host cells. By providing further insights into the molecular details of how influenza viruses hijack the host transcriptional machinery, we aim to uncover novel targets for the development of antivirals., (Copyright © 2016 Martínez-Alonso et al.)

The diagnosis of malignant pleural effusions may be challenging when cytological examination of aspirated pleural fluid is equivocal or noncontributory. The purpose of this study was to identify protein candidate biomarkers differentially expressed in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis (TB).A multiplex protein biochip comprising 120 biomarkers was used to determine the pleural fluid protein profile of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The relative abundance of these predetermined biomarkers among groups served to establish the differential diagnosis of: malignant versus benign (TB) effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus TB. The selected putative markers were validated using widely available commercial techniques in an independent sample of 102 patients.Significant differences were found in the protein expressions of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate between malignant and TB effusions. When integrated into a scoring model, these proteins yielded 85% sensitivity, 100% specificity, and an area under the curve (AUC) of 0.98 for labeling malignancy in the verification sample. For lung adenocarcinoma-mesothelioma discrimination, combining CA19-9, CA15-3, and kallikrein-12 had maximal discriminatory capacity (65% sensitivity, 100% specificity, AUC 0.94); figures which also refer to the validation set. Last, cathepsin-B in isolation was only moderately useful (sensitivity 89%, specificity 62%, AUC 0.75) in separating lymphomatous and TB effusions. However, this last differentiation improved significantly when cathepsin-B was used with respect to the patient's age (sensitivity 72%, specificity 100%, AUC 0.94).In conclusion, panels of 4 (i.e., MMP-9, cathepsin-B, C-reactive protein, chondroitin sulfate), or 3 (i.e., CA19-9, CA15-3, kallikrein-12) different protein biomarkers on pleural fluid samples are highly discriminative for signaling a malignant versus tuberculous effusion, or lung adenocarcinoma versus mesothelioma, respectively. Cathepsin-B could also be helpful in establishing the presence of a lymphomatous effusion versus that of TB, if the patient's age is simultaneously taken into consideration., Competing Interests: The authors have no conflicts of interest to disclose.

The fluctuation of Meloidogyne population density and the percentage of fungal egg parasitism were determined from July 2011 to July 2013 in two commercial organic vegetable production sites (M10.23 and M10.55) in plastic greenhouses, located in northeastern Spain, in order to know the level of soil suppressiveness. Fungal parasites were identified by molecular methods. In parallel, pot tests characterized the level of soil suppressiveness and the fungal species growing from the eggs. In addition, the egg parasitic ability of 10 fungal isolates per site was also assessed. The genetic profiles of fungal and bacterial populations from M10.23 and M10.55 soils were obtained by Denaturing Gradient Gel Electrophoresis (DGGE), and compared with a non-suppressive soil (M10.33). In M10.23, Meloidogyne population in soil decreased progressively throughout the rotation zucchini, tomato, and radish or spinach. The percentage of egg parasitism was 54.7% in zucchini crop, the only one in which eggs were detected. Pochonia chlamydosporia was the only fungal species isolated. In M10.55, nematode densities peaked at the end of the spring-summer crops (tomato, zucchini, and cucumber), but disease severity was lower than expected (0.2-6.3). The percentage of fungal egg parasitism ranged from 3 to 84.5% in these crops. The results in pot tests confirmed the suppressiveness of the M10.23 and M10.55 soils against Meloidogyne. The number of eggs per plant and the reproduction factor of the population were reduced (P < 0.05) in both non-sterilized soils compared to the sterilized ones after one nematode generation. P. chlamydosporia was the only fungus isolated from Meloidogyne eggs. In in vitro tests, P. chlamydosporia isolates were able to parasitize Meloidogyne eggs from 50 to 97% irrespective of the site. DGGE fingerprints revealed a high diversity in the microbial populations analyzed. Furthermore, both bacterial and fungal genetic patterns differentiated suppressive from non-suppressive soils, but the former showed a higher degree of similarity between both suppressive soils than the later.

Background and Objectives: Ultrasonographic detection of subclinical atheromatosis is a noninvasive method predicting cardiovascular events. Risk factors predicting atheromatosis progression in CKD are unknown. Predictors of atheromatosis progression were evaluated in patients with CKD., Design, Setting, Participants, & Measurements: Our multicenter, prospective, observational study included 1553 patients with CKD (2009-2011). Carotid and femoral ultrasounds were performed at baseline and after 24 months. A subgroup of 476 patients with CKD was also randomized to undergo ultrasound examination at 12 months. Progression of atheromatosis was defined as an increase in the number of plaque territories analyzed by multivariate logistic regression., Results: Prevalence of atheromatosis was 68.7% and progressed in 59.8% of patients after 24 months. CKD progression was associated with atheromatosis progression, suggesting a close association between pathologies. Variables significantly predicting atheromatosis progression, independent from CKD stages, were diabetes and two interactions of age with ferritin and plaque at baseline. Given that multiple interactions were found between CKD stage and age, phosphate, smoking, dyslipidemia, body mass index, systolic BP (SBP), carotid intima-media thickness, plaque at baseline, uric acid, cholesterol, 25-hydroxy vitamin D (25OH vitamin D), and antiplatelet and phosphate binders use, the analysis was stratified by CKD stages. In stage 3, two interactions (age with phosphate and plaque at baseline) were found, and smoking, diabetes, SBP, low levels of 25OH vitamin D, and no treatment with phosphate binders were positively associated with atheromatosis progression. In stages 4 and 5, three interactions (age with ferritin and plaque and plaque with smoking) were found, and SBP was positively associated with atheromatosis progression. In dialysis, an interaction between body mass index and 25OH vitamin D was found, and age, dyslipidemia, carotid intima-media thickness, low cholesterol, ferritin, and uric acid were positively associated with atheromatosis progression., Conclusions: Atheromatosis progression affects more than one half of patients with CKD, and predictive factors differ depending on CKD stage., (Copyright © 2016 by the American Society of Nephrology.)

Background: A normal vitamin D status is required for bones and muscles to maintain their function and structure, but it also contributes to the functional integrity of other multiple physiologic systems in the body., Aim: To assess the relationship of Vitamin D deficiency with health-related quality-of-life issues, fatigue, and physical functioning in advanced cancer patients., Design: This is a cross-sectional study., Patients/settings: Adults under palliative care, having a locally advanced or metastatic or inoperable solid cancer., Results: Among 30 patients in palliative care with advanced solid cancer, 90% were vitamin D deficient. Serum Vitamin D concentration was positively correlated with patient-reported absence of fatigue (s = 0.49), and physical and functional well-being (s = 0.44 and s = 0.41, respectively, p < 0.01). Fatigue was the symptom with the highest median impact on their lives and was the only one associated with serum vitamin D (p = 0.031), with lower fatigue in patients with vitamin D concentrations in the third tertile. There was no evidence of a direct association between health-related quality of life and vitamin D status., Conclusion: The 90% frequency of advanced cancer patients with vitamin D deficiency, together with the positive correlation of vitamin D status with the absence of fatigue and improved physical and functional well-being, points to vitamin D supplementation as a potential therapy to enhance the patient's quality of life., (© The Author(s) 2015.)

Obstructive sleep apnea (OSA) is a frequent and underdiagnosed disease in hypertensive individuals who experience cardiovascular events. The aim of this study was to define the best model that combined the ambulatory blood pressure (BP) monitoring (ABPM), anthropometric, sociodemographic, and biological variables to identify moderate to severe OSA. A total of 105 ABPM-confirmed hypertensive patients were evaluated using their clinical histories, blood analyses, ABPM, and home respiratory polygraphic results. A multivariate logistic regression analysis was performed to identify the significant variables. The best model included sex, presence of obesity (body mass index ≥30 kg/m(2) and abdominal obesity), mean daytime BP, mean nocturnal heart rate, and minimal diastolic nighttime BP to achieve an area under the curve of 0.804. Based on this model, a validated scoring system was developed to identify the patients with an apnea-hypopnea index ≥15. Therefore, in untreated hypertensive patients who snored, ABPM variables might be used to identify patients at risk for OSA., (© 2015 Wiley Periodicals, Inc.)

One of the main avocado diseases in southern Spain is white root rot caused by the fungus Rosellinia necatrix Prill. The use of organic soil amendments to enhance the suppressiveness of natural soil is an inviting approach that has successfully controlled other soilborne pathogens. This study tested the suppressive capacity of different organic amendments against R. necatrix and analyzed their effects on soil microbial communities and enzymatic activities. Two-year-old avocado trees were grown in soil treated with composted organic amendments and then used for inoculation assays. All of the organic treatments reduced disease development in comparison to unamended control soil, especially yard waste (YW) and almond shells (AS). The YW had a strong effect on microbial communities in bulk soil and produced larger population levels and diversity, higher hydrolytic activity and strong changes in the bacterial community composition of bulk soil, suggesting a mechanism of general suppression. Amendment with AS induced more subtle changes in bacterial community composition and specific enzymatic activities, with the strongest effects observed in the rhizosphere. Even if the effect was not strong, the changes caused by AS in bulk soil microbiota were related to the direct inhibition of R. necatrix by this amendment, most likely being connected to specific populations able to recolonize conducive soil after pasteurization. All of the organic amendments assayed in this study were able to suppress white root rot, although their suppressiveness appears to be mediated differentially., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: The role of fluorodeoxyglucose (FDG)-PET imaging for diagnosing malignant pleural effusions is not well defined. The aim of this study was to summarize the evidence for its use in ruling in or out the malignant origin of a pleural effusion or thickening., Methods: A meta-analysis was conducted of diagnostic accuracy studies published in the Cochrane Library, PubMed, and Embase (inception to June 2013) without language restrictions. Two investigators selected studies that had evaluated the performance of FDG-PET imaging in patients with pleural effusions or thickening, using pleural cytopathology or histopathology as the reference standard for malignancy. Subgroup analyses were conducted according to FDG-PET imaging interpretation (qualitative or semiquantitative), PET imaging equipment (PET vs integrated PET-CT imaging), and/or target population (known lung cancer or malignant pleural mesothelioma). Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. We used a bivariate random-effects model for the analysis and pooling of diagnostic performance measures across studies., Results: Fourteen non-high risk of bias studies, comprising 407 patients with malignant and 232 with benign pleural conditions, met the inclusion criteria. Semiquantitative PET imaging readings had a significantly lower sensitivity for diagnosing malignant effusions than visual assessments (82% vs 91%; P = .026). The pooled test characteristics of integrated PET-CT imaging systems using semiquantitative interpretations for identifying malignant effusions were: sensitivity, 81%; specificity, 74%; positive likelihood ratio (LR), 3.22; negative LR, 0.26; and area under the curve, 0.838. Resultant data were heterogeneous, and spectrum bias should be considered when appraising FDG-PET imaging operating characteristics., Conclusions: The moderate accuracy of PET-CT imaging using semiquantitative readings precludes its routine recommendation for discriminating malignant from benign pleural effusions.

The ligands 2-pyridin-2-yl-1H-benzimidazole (HL(1)), 1-methyl-2-pyridin-2-ylbenzimidazole (HL(2)), and 2-(1H-imidazol-2-yl)pyridine (HL(3)) and the proligand 2-phenyl-1H-benzimidazole (HL(4)) have been used to prepare five different types of new ruthenium(II) arene compounds: (i) monocationic complexes with the general formula [(η(6)-arene)RuCl(κ(2)-N,N-HL)]Y [HL = HL(1), HL(2), or HL(3); Y = Cl or BF4; arene = 2-phenoxyethanol (phoxet), benzene (bz), or p-cymene (p-cym)]; (ii) dicationic aqua complexes of the formula [(η(6)-arene)Ru(OH2)(κ(2)-N,N-HL(1))](Y)2 (Y = Cl or TfO; arene = phoxet, bz, or p-cym); (iii) the nucleobase derivative [(η(6)-arene)Ru(9-MeG)(κ(2)-N,N-HL(1))](PF6)2 (9-MeG = 9-methylguanine); (iv) neutral complexes consistent with the formulation [(η(6)-arene)RuCl(κ(2)-N,N-L(1))] (arene = bz or p-cym); (v) the neutral cyclometalated complex [(η(6)-p-cym)RuCl(κ(2)-N,C-L(4))]. The cytototoxic activity of the new ruthenium(II) arene compounds has been evaluated in several cell lines (MCR-5, MCF-7, A2780, and A2780cis) in order to establish structure-activity relationships. Three of the compounds with the general formula [(η(6)-arene)RuCl(κ(2)-N,N-HL(1))]Cl differing in the arene moiety have been studied in depth in terms of thermodynamic dissociation constants, aquation kinetic constants, and DNA binding measurements. The biologically most active compound is the p-cym derivative, which strongly destabilizes the DNA double helix, whereas those with bz and phoxet have only a small effect on the stability of the DNA double helix. Moreover, the inhibitory activity of several compounds toward CDK1 has also been evaluated. The DNA binding ability of some of the studied compounds and their CDK1 inhibitory effect suggest a multitarget mechanism for their biological activity.

Viruses use virions to spread between hosts, and virion composition is therefore the primary determinant of viral transmissibility and immunogenicity. However, the virions of many viruses are complex and pleomorphic, making them difficult to analyse in detail. Here we address this by identifying and quantifying virion proteins with mass spectrometry, producing a complete and quantified model of the hundreds of host-encoded and viral proteins that make up the pleomorphic virions of influenza viruses. We show that a conserved influenza virion architecture is maintained across diverse combinations of virus and host. This 'core' architecture, which includes substantial quantities of host proteins as well as the viral protein NS1, is elaborated with abundant host-dependent features. As a result, influenza virions produced by mammalian and avian hosts have distinct protein compositions. Finally, we note that influenza virions share an underlying protein composition with exosomes, suggesting that influenza virions form by subverting microvesicle production.

Locally advanced rectal cancer (LARC) is associated with a 25 % rate of metastases. The prognostic and predictive relevances of the expression of five proteins (c-FLIPL/s, HIF-1α, β-catenin, p65, and p105/p50 NF-κβ) were assessed. This is a retrospective study. From 1998 to 2009, 152 patients with stage II/III rectal cancer were treated with radio-chemotherapy. TMAs constructed with tumor and normal tissue from the diagnostic endoscopic biopsy and the surgical specimen after chemoradiotherapy were subjected to immunohistochemical (IHC) analysis. Results were correlated with clinical and pathological data, including progression-free survival (PFS). Four different IHC conditions were independent prognostic parameters for PFS: (1) cytoplasmic c-FLIPL/s (p = 0.007), (2) nuclear HIF-1α (p = 0.020), (3) a change in the cytoplasmic p65 between the diagnostic biopsy and the post-treatment specimen (p = 0.004), and (4) a change in the cytoplasmic c-FLIPL/s between the diagnostic biopsy and the post-treatment specimen (p = 0.021). Three different protein expression profiles, combining biomarkers, showed prognostic significance. IHC evaluation of these biomarkers in our three protein expression profiles may help to identify patients with worse prognosis and design more effective therapeutic strategies to personalize the treatment of rectal cancer.

The synthesis and full characterization of the new aqua-complex [(η(6)-p-cymene)Ru(OH2)(κ(2)-N,N-2-pydaT)](BF4)2, [2](BF4)2, and the nucleobase derivative [(η(6)-p-cymene)Ru(9-MeG)(κ(2)-N,N-2-pydaT)](BF4)2, [4](PF6)2, where 2-pydaT = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine and 9-MeG = 9-methylguanine, are reported here. The crystal structures of both [4](PF6)2 and the chloro complex [(η(6)-p-cymene)RuCl(κ(2)-N,N-2-pydaT)](PF6), [1](PF6), have been elucidated by X-ray diffraction. The former provided relevant information regarding the interaction of the metallic fragment [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) and a simple model of DNA. NMR and kinetic absorbance studies have proven that the aqua-complex [2](BF4)2 binds to the N7 site of guanine in nucleobases, nucleotides, or DNA. A stable bifunctional interaction (covalent and partially intercalated) between the [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) fragment and CT-DNA has been corroborated by kinetic, circular dichroism, viscometry, and thermal denaturation experiments. The reaction mechanism entails the very fast formation of the Ru-O-(PO3) linkage prior to the fast intercalation of the 2-pydaT fragment. Then, a Ru-N7-(G) covalent bond is formed at the expense of the Ru-O-(PO3) bond, yielding a bifunctional complex. The dissociation rate of the intercalated fragment is slow, and this confers additional interest to [2](BF4)2 in view of the likely correlation between slow dissociation and biological activity, on the assumption that DNA is the only biotarget. Furthermore, [2](BF4)2 displays notable pH-dependent cytotoxic activity in human ovarian carcinoma cells (A2780, IC50 = 11.0 μM at pH = 7.4; IC50 = 6.58 μM at pH = 6.5). What is more, complex [2](BF4)2 is not cross-resistant with cisplatin, exhibiting a resistance factor, RF(A2780cis), of 0.28, and it shows moderate selectivity toward the cancer cell lines, in particular, A2780cis (IC50 = 3.0 5 ± 0.08 μM), relative to human lung fibroblast cells (MRC-5; IC50 = 24 μM), the model for healthy cells.

Background: Patients with diabetes mellitus are at increased risk of postoperative complications. Data from randomised clinical trials and meta-analyses point to a potential benefit of intensive glycaemic control, targeting near-normal blood glucose, in patients with hyperglycaemia (with and without diabetes mellitus) being submitted to surgical procedures. However, there is limited evidence concerning this question in patients with diabetes mellitus undergoing surgery., Objectives: To assess the effects of perioperative glycaemic control for diabetic patients undergoing surgery., Search Methods: Trials were obtained from searches of The Cochrane Library, MEDLINE, EMBASE, LILACS, CINAHL and ISIS (all up to February 2012)., Selection Criteria: We included randomised controlled clinical trials that prespecified different targets of perioperative glycaemic control (intensive versus conventional or standard care), Data Collection and Analysis: Two authors independently extracted data and assessed risk of bias. We summarised studies using meta-analysis or descriptive methods., Main Results: Twelve trials randomised 694 diabetic participants to intensive control and 709 diabetic participants to conventional glycaemic control. The duration of the intervention ranged from just the duration of the surgical procedure up to 90 days. The number of participants ranged from 13 to 421, and the mean age was 64 years. Comparison of intensive with conventional glycaemic control demonstrated the following results for our predefined primary outcomes: analysis restricted to studies with low or unclear detection or attrition bias for infectious complications showed a risk ratio (RR) of 0.46 (95% confidence interval (CI) 0.18 to 1.18), P = 0.11, 627 participants, eight trials, moderate quality of the evidence (grading of recommendations assessment, development and evaluation - (GRADE)). Evaluation of death from any cause revealed a RR of 1.19 (95% CI 0.89 to 1.59), P = 0.24, 1365 participants, 11 trials, high quality of the evidence (GRADE).On the basis of a posthoc analysis, there is the hypothesis that intensive glycaemic control may increase the risk of hypoglycaemic episodes if longer-term outcome measures are analysed (RR 6.92, 95% CI 2.04 to 23.41), P = 0.002, 724 patients, three trials, low quality of the evidence (GRADE). Analysis of our predefined secondary outcomes revealed the following findings: cardiovascular events had a RR of 1.03 (95% CI 0.21 to 5.13), P = 0.97, 682 participants, six trials, moderate quality of the evidence (GRADE) when comparing the two treatment modalities; and renal failure also did not show significant differences between intensive and regular glucose control (RR 0.61, 95% CI 0.34 to 1.08), P = 0.09, 434 participants, two trials, moderate quality of the evidence (GRADE). We did not meta-analyse length of hospital stay and intensive care unit (ICU) stay due to substantial unexplained heterogeneity. Mean differences between intensive and regular glucose control groups ranged from -1.7 days to 2.1 days for ICU stay and between -8 days to 3.7 days for hospital stay (moderate quality of the evidence (GRADE)). One trial assessed health-related quality of life in 12/37 (32.4%) of participants in the intervention group and 13/44 (29.5%) of participants in the control group, and did not show an important difference (low quality of the evidence (GRADE)) in the measured physical health composite score of the short-form 12-item health survey (SF-12). None of the trials examined the effects of the interventions in terms of costs., Authors' Conclusions: The included trials did not demonstrate significant differences for most of the outcomes when targeting intensive perioperative glycaemic control compared with conventional glycaemic control in patients with diabetes mellitus. However, posthoc analysis indicated that intensive glycaemic control was associated with an increased number of patients experiencing hypoglycaemic episodes. Intensive glycaemic control protocols with near-normal blood glucose targets for patients with diabetes mellitus undergoing surgical procedures are currently not supported by an adequate scientific basis. We suggest that insulin treatment regimens, patient- and health-system relevant outcomes, and time points for outcome measures should be defined in a thorough and uniform way in future studies.

Background and Objectives: Vascular calcification (VC) has a significant effect in cardiovascular diseases on dialysis patients. However, VC is assessed with x-ray-based techniques, which do not inform about calcium localization (intima, media, atherosclerosis-related). The aim of this work is to study VC and its related factors using arterial ultrasound to report the exact location of calcium., Design, Setting, Participants, & Measurements: This was an observational, cross-sectional, case-control study that included 232 patients in dialysis and 208 age- and sex-matched controls with normal kidney function. Demographic data and laboratory values were collated. Carotid, femoral, and brachial ultrasounds were performed to assess VC and atherosclerosis burden using a standardized protocol., Results: Cardiovascular risk factors were predominantly found in controls, although the burden of atherosclerosis was higher in the dialysis group. VC was significantly more prevalent in the group of patients on dialysis than control subjects, and in both groups the most prevalent pattern of VC was linear calcification located in the intima of the artery wall. Age and undergoing dialysis (with or without previous cardiovascular diseases) were positively and significantly associated with linear calcification. Conversely, the absence of atherosclerosis and low levels of C-reactive protein and phosphorus significantly impeded the development of linear calcification., Conclusions: VC in large, conduit arteries is more prevalent in patients on dialysis than controls and is predominantly located in a linear fashion in the intima of the arteries.

Background: The management of patients with community-acquired pneumonia (CAP) who fail to improve constitutes a challenge for clinicians. This study investigated the usefulness of C-reactive protein (CRP) changes in discriminating true treatment failure from slow response to treatment., Methods: This prospective multicenter observational study investigated the behavior of plasma CRP levels on days 1 and 4 in hospitalized patients with CAP. We identified non-responding patients as those who had not reached clinical stability by day 4. Among them, true treatment failure and slow response situations were defined when initial therapy had to be changed or not after day 4 by attending clinicians, respectively., Results: By day 4, 78 (27.4%) out of 285 patients had not reached clinical stability. Among them, 56 (71.8%) patients were cured without changes in initial therapy (mortality 0.0%), and in 22 (28.2%) patients, the initial empirical therapy needed to be changed (mortality 40.9%). By day 4, CRP levels fell in 52 (92.9%) slow responding and only in 7 (31.8%) late treatment failure patients (p<0.001). A model developed including CRP behavior and respiratory rate at day 4 identified treatment failure patients with an area under the Receiver Operating Characteristic curve of 0.87 (CI 95%, 0.78-0.96)., Conclusion: Changes in CRP levels are useful to discriminate between true treatment failure and slow response to treatment and can help clinicians in management decisions when CAP patients fail to improve., (Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). As matrix metalloproteinases have a major role in atherosclerosis, we hypothesized that alterations in metalloproteinases-8, -10 and their tissue inhibitor-1 can be associated with the severity of atherosclerosis in patients with kidney disease. This was evaluated in a cross-sectional, observational study of 111 patients with stages I-V kidney disease, 217 patients on dialysis and 50 healthy controls. The severity of atherosclerosis was estimated with the atherosclerosis score (AS), combining the results of ankle-brachial index and carotid ultrasound. Serum levels of the two metalloproteinases and tissue inhibitor-1 were measured by enzyme-linked immunosorbent assay and were significantly increased in patients with kidney disease compared with the healthy controls, and higher in patients on dialysis than in earlier stages of CKD. The severity of the AS was also more prevalent in the dialysis group, in which serum levels of both metalloproteinases and tissue inhibitor-1 were significantly higher. After multivariate analysis, metalloproteinase-10, dialysis, C-reactive protein, age, and male gender were associated with increased risk of atherosclerosis. Thus, patients with CKD exhibit elevated levels of circulating metalloproteinase-10, and this was independently associated with the severity of atherosclerosis and may represent a new biomarker of atherosclerotic diseases.

Background: The decrease of breast cancer (BC) mortality rates has been attributed to early detection programs and therapeutic advances. The objective is to compare BC mortality trend in health regions of Catalonia during the period 1993-2007. In parallel, dissemination of periodic mammography in the health regions has been analyzed., Methods: Mortality and health surveys data were used. Poisson and «joinpoint» regression analyses were used to compare regional BC mortality rates and quantify their temporal evolution. Mixed effects models were used to compare the rates and their evolution by region., Results: The BC mortality rate decreased 3% annually in Cataluña. Between 1993 and 2007, the standard mortality rate changed from 34.8 to 23.3 per 100,000 women. Barcelona ciutat showed higher mortality rates than the Centre (rate ratio (RR)=0.873), Costa de Ponent (RR=0.885), Tarragona (RR=0.9) and Lleida regions (RR=0.915), but these differences tend to disappear over time. There were no observed trend changes in the evolution of the regional mortality rates, except in the Centre region. The use of periodic mammography was similar across health regions. During the 90s, Barcelona ciutat had a 36.1% utilization of periodic mammography in women aged 40-74, in the 1994 survey, the Centre 23.7 and Costa de Ponent 25.2%., Conclusions: The progressive increase in the use of periodic mammography and the decrease of BC mortality were similar in the eight health regions of Catalonia.

Some series have shown a decrease in the incidence of intestinal invaginations in last years. Moreover, the recent introduction of new types of rotavirus vaccines increases the interest of invagination' s incidence. To this purpose, reliable local epidemiological data are needed. In order to ascertain the trend in the incidence of invaginations and their current value in our area we have performed a retrospective review of patients under 3 years of age with the diagnosis of intussusception and confiemes with barium enema or ultrasound examination during the past 21 years. Our results show a statistically significant decrease in the incidence rate, with an incidence rate of one year from the previous 0.82 (95% 0,78-0, 86) from an estimated incidence for 1987 of 17.74 cases per 10,000 girls and 30.04 cases per 10,000 boys, in 2008 an estimated incidence of 0.27 cases per 10,000 girls and 0.49 cases per 10,000 boys. We conclude that in our population during the dtudy period a significant decrease of invagination' sincidence has been seen, especially in patients younger than one year. The current incidence is 0.27 cases per 10,000 girls and 0.49 cases per 10,000 boys less than 3 years old.

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.

Background: Cardiovascular risk scoring (Score) does not specifically address chronic kidney disease (CKD) patients. The aim of our study is to quantify atherosclerosis using carotid ultrasound and ankle-brachial index (ABI) and to assess its additional value in risk scoring., Methods: In this cross-sectional, observational study, patients were studied according to a standardized protocol including carotid ultrasound and ABI to determine the atherosclerosis score (AS), ranging from absence of to severe atherosclerosis (AS 0 to AS 3)., Results: We included 409 CKD-affected patients (231 on dialysis, 99 in CKD Stages IV-V and 79 in CKD Stages I-III) and 851 subjects with normal renal function. The presence and severity of atherosclerosis was significantly higher in the CKD group than in the controls at every decade of age studied. Among the CKD-affected subjects, the prevalence of carotid plaques was significantly higher in the dialysis group (78.3%) than in the group in CKD Stages I-III (55.6%, P < 0.001). We identified 174 patients at low-intermediate risk. Among them, 110 (63.2%) presented either moderate (AS 2) or severe (AS 3) atherosclerosis. Variables significantly (P < 0.05) and positively related to atherosclerosis were being on dialysis [OR = 3.40, 95% CI (1.73, 6.78) vs CKD Stages I-III], age [OR = 1.08, 95% CI (1.06-1.11)] and C-reactive protein [OR = 1.04, 95% CI (1.01-1.08)]. Conversely, female sex was negatively related to atherosclerosis [OR = 0.40, 95% CI (0.23-0.71), P = 0.002]., Conclusion: The use of carotid ultrasound and ABI identifies atherosclerosis in a population of CKD patients in which risk scoring underestimates atherosclerosis burden.

A cultivation-independent approach based on polymerase chain reaction (PCR)-amplified partial small subunit rRNA genes was used to characterize bacterial populations in the surface soil of a commercial pear orchard consisting of different pear cultivars during two consecutive growing seasons. Pyrus communis L. cvs Blanquilla, Conference, and Williams are among the most widely cultivated cultivars in Europe and account for the majority of pear production in Northeastern Spain. To assess the heterogeneity of the community structure in response to environmental variables and tree phenology, bacterial populations were examined using PCR-denaturing gradient gel electrophoresis (DGGE) followed by cluster analysis of the 16S ribosomal DNA profiles by means of the unweighted pair group method with arithmetic means. Similarity analysis of the band patterns failed to identify characteristic fingerprints associated with the pear cultivars. Both environmentally and biologically based principal-component analyses showed that the microbial communities changed significantly throughout the year depending on temperature and, to a lesser extent, on tree phenology and rainfall. Prominent DGGE bands were excised and sequenced to gain insight into the identities of the predominant bacterial populations. Most DGGE band sequences were related to bacterial phyla, such as Bacteroidetes, Cyanobacteria, Acidobacteria, Proteobacteria, Nitrospirae, and Gemmatimonadetes, previously associated with typical agronomic crop environments.