The initial soil microbiota impacts the potential for lignocellulose degradation during soil solarization.

AIMS: Soil biosolarization (SBS) is a pest control technology that includes the incorporation of organic matter into soil prior to solarization. The objective of this study was to measure the impact of the initial soil microbiome on the temporal evolution of genes encoding lignocellulose-degrading enzymes during SBS. METHODS AND RESULTS: Soil biosolarization field experiments were completed using green waste (GW) as a soil amendment and in the presence and absence of compost activating inoculum. Samples were collected over time and at two different soil depths for measurement of the microbial community and the predicted lignocellulosic-degrading microbiome. Compost inoculum had a significant positive effect on several predicted genes encoding enzymes involved in cellulose, hemicellulose and lignin degradation. These included beta-glucosidase, endo-1,3(4)-beta-glucanase, alpha-galactosidase and laccase. CONCLUSION: Amendment of micro-organisms found in compost to soil prior to SBS enhanced the degradation potential of cellulose, hemicellulose and lignin found in GW. SIGNIFICANCE AND IMPACT OF THE STUDY: The type of organic matter amended and its biotransformation by soil micro-organisms impact the efficacy of SBS. The results suggest that co-amending highly recalcitrant biomass with micro-organisms found in compost improves biomass conversion during SBS.

SPARC (secreted protein acidic and rich in cysteine) knockdown protects mice from acute liver injury by reducing vascular endothelial cell damage.

Secreted protein, acidic and rich in cysteine (SPARC) is involved in many biological process including liver fibrogenesis, but its role in acute liver damage is unknown. To examine the role of SPARC in acute liver injury, we used SPARC knock-out (SPARC(-/-)) mice. Two models of acute liver damage were used: concanavalin A (Con A) and the agonistic anti-CD95 antibody Jo2. SPARC expression levels were analyzed in liver samples from patients with acute-on-chronic alcoholic hepatitis (AH). SPARC expression is increased on acute-on-chronic AH patients. Knockdown of SPARC decreased hepatic damage in the two models of liver injury. SPARC(-/-) mice showed a marked reduction in Con A-induced necroinflammation. Infiltration by CD4+ T cells, expression of tumor necrosis factor-α and interleukin-6 and apoptosis were attenuated in SPARC(-/-) mice. Sinusoidal endothelial cell monolayer was preserved and was less activated in Con A-treated SPARC(-/-) mice. SPARC knockdown reduced Con A-induced autophagy of cultured human microvascular endothelial cells (HMEC-1). Hepatic transcriptome analysis revealed several gene networks that may have a role in the attenuated liver damaged found in Con A-treated SPARC(-/-) mice. SPARC has a significant role in the development of Con A-induced severe liver injury. These results suggest that SPARC could represent a therapeutic target in acute liver injury.

Discovering less toxic ionic liquids by using the Microtox® toxicity test.

New Microtox® toxicity data of 16 ionic liquids of different cationic and anionic composition were determined. The ionic liquids 1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate, [BMPyr(+)][TFO(-)], 1-butyl-1-methylpyrrolidinium chloride, [BMPyr(+)][Cl(-)], hydroxypropylmethylimidazolium fluoroacetate, [HOPMIM(+)][FCH2COO(-)], and hydroxypropylmethylimidazolium glycolate [HOPMIM(+)][glycolate(-)] were found to be less toxic than conventional organic solvent such as chloroform or toluene, accoding the Microtox® toxicity assays. The toxicity of pyrrolidinium cation was lower than the imidazolium and pyridinium ones. It was found that the inclusion of an hydroxyl group in the alkyl chain length of the cation also reduce the toxicity of the ionic liquid. To sum up, the Microtox® toxicity assays can be used as screening tool to easily determined the toxicity of a wide range of ionic liquids and the toxicity data obtained could allow the obtention of structure-toxicity relationships to design less toxic ionic liquids.

[Psychopathological disorders and quality of life in patients with brain infarction]. / Trastornos psicopatológicos y calidad de vida en el infarto cerebral.

OBJECTIVES: To study the influence of various factors on the health related quality of life (HRQOL) of patients who have suffered a brain infarction (BI), with special attention to psychopathological disorders (PD). PATIENTS AND METHODS: Prospective observational study on 45 patients admitted due to a BI, evaluated at 4, 12 and 26 weeks of the acute event. Social and demographic data, and medical history were collected; the SF-36 scale was used for the assessment of HRQOL, and the Neuropsychiatric Inventory (NPI), MMSE, Canadian Neurological Scale, Modified Rankin Scale and other instruments for assessing psychopathological, cognitive, neurological and functional status. A linear regression analysis was performed to identify potential predictors of the SF-36 scores at 26 weeks, introducing, as independent variables, medical and psychiatric history, demographic characteristics and the functional, neuropsychological and psychopathological assessments at 4 weeks. RESULTS: Valid predictive models for all the SF-36 domains were obtained, in which a history of pre-morbid depression, higher scores in the NPI and Rankin Scale, and lowest in the Canadian Neurological Scale were the main predictors of a worse HRQOL in the long term. Psychopathology related caregiver's distress (assessed with the NPI) was associated with a lower score in the social function index. CONCLUSIONS: PDs and functional status were the main determinants of HRQOL in patients with BI.

Intrathecal Administration of an Anti-nociceptive Non-CpG Oligodeoxynucleotide Reduces Glial Activation and Central Sensitization.

Inflammatory pain associates with spinal glial activation and central sensitization. Systemic administration of IMT504, a non-CpG oligodeoxynucleotide originally designed as an immunomodulator, exerts remarkable anti-allodynic effects in rats with complete Freund´s adjuvant (CFA)-induced hindpaw inflammation. However, the anti-nociceptive mechanisms of IMT504 remain unknown. Here we evaluated whether IMT504 blocks inflammatory pain-like behavior by modulation of spinal glia and central sensitization. The study was performed in Sprague Dawley rats with intraplantar CFA, and a single lumbosacral intrathecal (i.t.) administration of IMT504 or vehicle was chosen to address if changes in glial activation and spinal sensitization relate to the pain-like behavior reducing effects of the ODN. Naïve rats were also included. Von Frey and Randall-Selitto tests, respectively, exposed significant reductions in allodynia and mechanical hypersensitivity, lasting at least 24 h after i.t. IMT504. Analysis of electromyographic responses to electrical stimulation of C fibers showed progressive reductions in wind-up responses. Accordingly, IMT504 significantly downregulated spinal glial activation, as shown by reductions in the protein expression of glial fibrillary acidic protein, CD11b/c, Toll-like receptor 4 (TLR4) and the phosphorylated p65 subunit of NFκB, evaluated by immunohistochemistry and western blot. In vitro experiments using early post-natal cortical glial cultures provided further support to in vivo data and demonstrated IMT504 internalization into microglia and astrocytes. Altogether, our study provides new evidence on the central mechanisms of anti-nociception by IMT504 upon intrathecal application, and further supports its value as a novel anti-inflammatory ODN with actions upon glial cells and the TLR4/NFκB pathway. Intrathecal administration of the non-CpG ODN IMT504 fully blocks CFA-induced mechanical allodynia and hypersensitivity, in association with reduced spinal sensitization. Administration of the ODN also results in downregulated gliosis and reduced TLR4-NF-κB pathway activation. IMT504 uptake into astrocytes and microglia support the concept of direct modulation of CFA-induced glial activation.

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer.

Goals of endocrine therapy for advanced breast cancer (ABC) include prolonging survival rates, maintaining the quality of life, and delaying the initiation of chemotherapy. We evaluated the effectiveness of fulvestrant as first-line in patients with estrogen receptor (ER)-positive ABC with relapse during or after adjuvant anti-estrogenic therapy in real-world settings. Retrospective, observational study involving 171 postmenopausal women with ER-positive ABC who received fulvestrant as first-line between January 2011 and May 2018 in Spanish hospitals. With a median follow-up of 31.4 months, the progression-free survival (PFS) with fulvestrant was 14.6 months. No differences were seen in the visceral metastatic (14.3 months) versus non-visceral (14.6 months) metastatic subgroup for PFS. Overall response rate and clinical benefit rate were 35.2% and 82.8%. Overall survival was 43.1 months. The duration of the clinical benefit was 19.2 months. Patients with ECOG performance status 0 at the start of treatment showed a significant greater clinical benefit rate and overall survival than with ECOG 1-2. Results in real-world settings are in concordance with randomized clinical trials. Fulvestrant continues to demonstrate clinical benefits in real-world settings and appears be well tolerated as first-line for the treatment of postmenopausal women with ER-positive ABC.

SEOM clinical guideline for secondary prevention (2019).

Cancer is one of the major public health problems in our society. It is estimated that more than 18 million new cases are diagnosed worldwide every year; 280,000 in Spain. Incidence in following a growing trend. This epidemic could be controlled with research into new treatments and, above all, with adequate prevention. Primary prevention could prevent avoid up to half of all cases. For many others, secondary prevention is essential, as it make diagnosis possible in the stages of the disease when it is easily curable. These guidelines present the scientific evidence regarding secondary prevention in tumors in which its use is well-accepted: breast, cervical, colorectal, prostate, lung, ovarian, melanoma, and gastric cancer.

SEOM clinical guidelines to primary prevention of cancer (2018).

Cancer is the leading social and healthcare problem of the twenty-first century. The aim of primary prevention is to decrease the incidence of cancer by avoiding the known causes and risk factors. Nevertheless, it has been estimated that cancer diagnoses could be halved through primary prevention measures. A comprehensive review of the scientific evidence regarding the main carcinogens and risk factors and primary prevention recommendations have been put forth based on this evidence. The GRADE scale has been used to classify the grade of evidence. We present the scientific evidence and recommendations for primary prevention of the major modifiable risk factors: smoking, alcohol, diet, obesity, physical activity, occupational and environmental factors, ultraviolet radiation, infections, and socioeconomic factors. Primary prevention is a simple, effective means to lower the incidence of cancer. Preventive measures must be circulated in the fight against cancer.

Assessment of pesticide availability in soil fractions after the incorporation of winery-distillery vermicomposts.

The influence of two vermicomposts from winery and distillery wastes on the distribution of diuron in agricultural soil was studied. Physical soil fractionations at 0, 9, 27, 49 and 77 days, allowed the quantification of pesticide residues in different particle-size fractions, coarse waste (WF), sand-sized (SF), silt-sized (SiF), clay-sized (CF) and dissolved organic matter-sized fraction (DOM). The SiF made a greater contribution to the formation of non-extractable residues in unamended soil, but when vermicomposts were added, new sorption sites in WF appeared, being higher for the more humified vermicompost V2. The dissolved organic carbon (DOC) increased with the addition of vermicompost, but the concentration of the desorbed 14C-radiochemical did not increase. Non-significant increment was observed with time for the non-extractable fraction with amendments. Diuron was transformed in all samples, although less than 0.5% was mineralized. The main effect caused by vermicomposts was a reduction in the availability of diuron in soil.

Analysis of blood markers for early breast cancer diagnosis.

PURPOSE: Breast cancer is the most common neoplasm in women and has the highest associated mortality rate. Rapid detection programmes can provide early diagnosis and increase the chances of survival. There are no specific tumor biomarkers for the early phase of the disease. The primary aim of this study was to search a blood biomarker with levels that exceeded the normal range established in the general population that could be used to screen breast cancer. METHODS/PATIENTS: Case-control study. Conventional as well as research (NGAL, EGFR and 8-OHdG) tumor biomarkers were analyzed. RESULTS: A total of 126 women were enrolled (cases: 63 patients with local breast cancer; Controls: 63 healthy women). Significant differences were found in patients with higher levels of the conventional markers, Ca15.3, CEA, Cyfra 21.1 and NSE. However, when commercial cut-off values were used, only Ca 15.13 was significant. In the group of research biomarkers, significantly higher levels of EGFR were found in the control group, and of 8-OHdG in the case group. Using logistic regression analysis and a ROC curve, an equation composed of five markers, Ca 15.3, NSE, NGAL, EGFR and 8-OHdG, which yielded a correct diagnostic probability of breast cancer of 91.8% was obtained. CONCLUSIONS: 8-OHdG has been identified as a new potential marker for screening early stage breast cancer. In addition, a model that combines five blood markers that can be used as a diagnostic test in certain groups of patients has been developed. New studies with a larger sample size are needed to verify the results obtained.

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

INTRODUCTION: This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. MATERIALS AND METHODS: Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. RESULTS: A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). CONCLUSIONS: Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

Correction to: Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

A sentence under 'Results' heading in the Abstract section was published incorrectly. The correct sentence should read as follows.

[Metformin in the treatment of type 2 diabetes in overweighted or obese patients]. / Metformina en el tratamiento de la diabetes tipo 2 con sobrepeso u obesidad.

UNLABELLED: FUNDAMENTALS AND OBJECTIVES: [corrected] Diabetes is the disease that has suffered a greater increase in his incidence in the last years. Obesity is the most important risk factor to develop this disease and metformin is considered as a first line drug in overweighted diabetic patients. The aim of this study is to evaluate the use of metformin and the degree of control of the associated cardiovascular risk factors (CVRF) in patients suffering of type 2 diabetes and overweight or obesity. PATIENTS AND METHODS: This is a transversal descriptive study over a random chosen group of 308 patients followed at primary care level. They were classified in four different groups depending on the treatment used to control them (diet, insulin, metformin and other oral antidiabetic drugs). They were evaluated upon the degree of control of the modifiable CVRF, the presence of complications and the metabolic control. RESULTS: The average age was 69.6 years, 54% of the patients female. 36.6% followed treatment with metformin and 40.5% with sulfonylureas. The macrovascular percentage of affection was 19.4%. The most frequent CVRF was arterial hypertension (76%). The goal levels of control that were less in range were the levels of cLDL < 100 mg/dl and systolic blood pressure < 130 mmHg. Diabetic patients only treated with diet had a better control of fasten glycemia and HbA1c% than those ones treated with metformin (p < 0.001). The group treated with metformin showed levels of triglycerides (TG) significantly higher than those of the diet controlled group (p = 0.009) and insulin group (p < 0.001). CONCLUSIONS: Metformin and sulfonylureas are used in a similar proportion in type 2 diabetics with overweight or obesity. There is a poor control of the majority of the CVRF in the diabetic population studied.

Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer.

BACKGROUND: Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited. PATIENTS AND METHODS: AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg, gemcitabine 2,000 mg/m(2) plus paclitaxel 150 mg/m(2), on days 1 and 15 of each 28-day course in previously untreated HER-2 negative patients. RESULTS: Median progression-free survival (PES): 12.3 months. The overall response and clinical benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9-82.0 %) and 89 % (95 % CI 80.3-95.3 %), respectively. Median overall survival: 27.4 mo. Baseline circulating tumor cell (CTCs) ≥2 versus CTCs <2 was associated with lower PFS, p = 0.046. Overall response was significantly greater in patients with intense angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse events of interest with bevacizumab included bleeding (1 %) and hypertension (4 %). One patient developed cardiac ischemia (1 %). CONCLUSIONS: Adding bevacizumab to chemotherapy appeared feasible and well tolerated, producing toxicity comparable to other effective combined first-line regimens. Baseline circulating endothelial cells and AGTR1 expression are predictive of PFS and response.

Chloramphenicol extraction from milk by using the diphasic dialysis method followed by liquid chromatographic determination.

An economical, fast, and simple method for the extraction and liquid chromatographic determination of chloramphenicol (CAP) in milk is described. CAP is extracted by using a recently developed membrane-based method named "diphasic dialysis." CAP is detected and quantitated in the organic solvent used in dialysis without additional cleanup steps by reversed-phase liquid chromatography and UV detection (270 nm). The determination limit of CAP in milk was about 5 micrograms/L, although as little as 1 microgram/L could be detected under optimal working conditions.

Electroanalytical determination of cadmium and lead in deciduous teeth after microwave oven digestion.

A method using differential pulse anodic stripping voltammetry after microwave oven digestion was developed for the simultaneous determination of Cd(II) and Pb(II) in the deciduous teeth of children. Each tooth was weighed; deposited in a 120 mL capped Teflon vessel with 5 mL 65% nitric acid, Suprapur analytical grade; and digested in a 2-step microwave oven for 15 min. The detection limits for Cd(II) and Pb(II) in the final solution were 0.078 and 0.323 microg/L, and the quantitation limits 0.394 and 1.613 microg/L, respectively, with a linearity range of 2 microg/L for Cd(II) and 23.3 microg/L for Pb(II). The sensitivity was 2.51 nA/microg-L and 1.37 nA/microg-L, for Cd(II) and Pb(II). The main advantages of this technique are a complete and satisfactory dissolution of the tooth material with the proposed microwave oven digestion procedure, without sample pretreatments, such as drying, ashing, or powdering. The voltammetric procedure proved to be well designed because of significant goodness of fit to a linear model, and the accuracy of the method was established as compared with standard reference material. The methodology has enabled us to study Cd(II) and Pb(II) in 371 deciduous teeth from school children in Cartagena, Spain.

[Risk factors associated with prevalence of non-insulin dependent diabetes mellitus in Lejona (Vizcaya)]. / Factores de riesgo asociados a la prevalencia de diabetes mellitus no insulinodependiente en Lejona (Vizcaya).

BACKGROUND: The aim of study was to define risk factors (age, body mass index, height, weight, systolic and diastolic blood pressure) associated to non insulin dependent diabetes mellitus (NIDDM) and abnormal glucose tolerance (AGT). PATIENTS, MATERIAL AND METHODS: This study was carried out in people > or = 30 years old in Lejona (Vizcaya) by randomized sampling of population, stratified by pyramids of age and sex (N = 862), with a low rate of non-responders (12.6%). An oral glucose tolerance test was done following the criteria recommended by the Committee of Experts of the World Health Organization (WHO). A multivariate analysis was performed, with presence/absence of NIDDM and/or AGT, as dependent variable in several models of logistic regression. RESULTS: The prevalence of NIDDM was 6.4% (56% previously unknown). Strong association of NIDDM with age, BMI, and systolic blood pressure (SBP) was observed both in univariate, as well as multivariate analysis. However, SBP lost its value in the multivariate study. Multivariate analysis showed that NIDDM was 8.2 fold more frequent in the population > or = 60 years than in the < or = 45 years old group. NIDDM was 8.3 fold more frequent when BMI > or = 30 kg/m2 compared to < or = 25. NIDDM was 3.8 fold more frequent in the population with SBP > or = 140 mmHg than in the group with SBP < or = 120 mmHg. The prevalence of AGT in women is almost double than in men (13.4% vs 7.3%). Risk factors were also associated with AGT. CONCLUSIONS: Weight and SBP are important risk factors for NIDDM and AGT prediction. The possibility of modifying these factors could possibly allow interventions in order to decrease the prevalence of NIDDM and AGT.

[Prevalence of non-insulin dependent diabetes mellitus in Lejona (Vizcaya, Spain)]. / Prevalencia de la diabetes mellitus no dependiente de la insulina en Lejona (Vizcaya).

BACKGROUND: Diabetes mellitus presents a high prevalence and morbimortality. The aim of the present study was to know the number of newly diagnosed diabetic patients in addition to those who present abnormal glucose tolerance and possible presence of associated risk factors. METHODS: This study was carried out in Lejona (Vizcaya) from 1984-1985. The prevalence of non insulin-dependent diabetes mellitus (NIDDM) and abnormal glucose tolerance (AGT) in people older than or equal to 30 years of age by a randomized sample stratified by pyramids of age and sex (n = 862). The following data were collected: age, sex, height, weight, medications taken, family and personal history of diabetes mellitus (DM) and blood pressure. A glycemia curve was made following the criteria recommended by the Committee of Experts of the World Health Organization (WHO). RESULTS: The prevalence of DM observed in the sample was of 6.4% (confidence interval of 95%: 4.75-8.01%) of which 3.6% corresponded to unknown DM and 2.8% to known DM. The prevalence of AGT was 10.4% (confidence interval 95%: 8.40-12.48%). Greater association was observed between DM and obesity, lower height, high blood pressure and age over 50. CONCLUSIONS: More than half of the diabetics were unaware of the disease. Given the association of non insulin-dependent diabetes mellitus with modifiable factors (obesity, high blood pressure) control of risk factors would be useful with the aim of decreasing the prevalence of diabetes mellitus and avoid the associated chronic complications of the disease.

[Left ventricular hypertrophy in a general hypertensive population in Barcelona]. / Hipertrofia ventricular izquierda en una población hipertensa general de Barcelona.

BACKGROUND: Left ventricular hypertrophy (LVH) is a well known cardiac risk factor. There are no data available as to the epidemiology of this disease in the general hypertensive population in Spain. METHODS: A randomized sample (n = 267) of a general hypertensive population under the age of 80 years was followed in a Basic Health Care Area located in the center of Barcelona, Spain. A Doppler-echocardiographic study of the patients was carried out. The patients were considered to have LVH when they demonstrated an index > 134 g/m2 of left ventricular mass in males and > 110 g/m2 in females. The odds ratio (OR) was estimated on presentation of LVH associated with exposure to different factors. RESULTS: A prevalence of LVH diagnosed by echocardiogram was observed in 64% (confidence interval 95% from 58.3 to 69.8%). The independent risk factors associated with the presence of LVH were female sex, age and systolic blood pressure. CONCLUSIONS: Left ventricular hypertrophy is a frequent cardiovascular risk factor in the general hypertensive population in Spain. A systematic search by echocardiography cannot be recommended in primary health care until cost-effectiveness studies have been performed.

[Study of the accumulation of lead in the primary teeth]. / Estudio de la acumulación de plomo en dientes primarios.

The purpose of the study was to determine the accumulation of lead in deciduous teeth in children living in the area of Pamplona (Spain). In this manner, we tried to make a relationship between the quantity of lead accumulated in the tooth against certain factors of exposure that were documented on a questionnaire carried out at the time that the tooth was presented. We analysed 457 deciduous teeth using a technique of microwave digestion follow by Atomic Absorption Spectrometry (AAS), to determine the concentration of lead in the sample. The mean lead concentration was 2.60+/-1.36 microg/g (range 0.25-10.71 microg/g). The lead concentration in our study is inferior to those observed in other European studies.