Long-term fertilization with dairy cattle slurry in intensive production systems: effects on soil porosity and pore morphology

In Mediterranean environments, livestock effluents might improve soil physical properties. The study was located in an intensive crop production system of northwest Spain. After nine consecutive years of dairy cattle slurry (DCS) use as fertilizer, the aim of the experiment was to evaluate the impacts of DCS on soil porosity and pore shape. Soil texture was loam. The applied DCS rates were equivalent to 170 and 250 kg N ha−1 (170DCS and 250DCS, respectively) and they were complemented with mineral N up to 450 kg N ha-1 (two crops). A nonfertilized control was included. Digital binary images were obtained from soil thin sections. Pores with an apparent diameter (AD) >30 µm were analysed. The 250DCS treatment improved soil porosity (>30 µm): it doubled in comparison with the 170DCS and the control. The application of DCS favored the presence of pores with an AD >400 µm, the roughness for AD >100 µm and the elongation in the AD interval of 100-200 µm. From the study, the 250DCS treatment is recommended as it increases macroporosity (compaction reduction) and produces more elongated and tortuous pores, which will be a constraint for fast drainage but it will be advantageous in coarse textured soils.In Mediterranean environments, livestock effluents might improve soil physical properties. The study was located in an intensive crop production system of northwest Spain. After nine consecutive years of dairy cattle slurry (DCS) use as fertilizer, the aim of the experiment was to evaluate the impacts of DCS on soil porosity and pore shape. Soil texture was loam. The applied DCS rates were equivalent to 170 and 250 kg N ha−1 (170DCS and 250DCS, respectively) and they were complemented with mineral N up to 450 kg N ha-1 (two crops). A nonfertilized control was included. Digital binary images were obtained from soil thin sections. Pores with an apparent diameter (AD) >30 µm were analysed. The 250DCS treatment improved soil porosity (>30 µm): it doubled in comparison with the 170DCS and the control. The application of DCS favored the presence of pores with an AD >400 µm, the roughness for AD >100 µm and the elongation in the AD interval of 100-200 µm. From the study, the 250DCS treatment is recommended as it increases macroporosity (compaction reduction) and produces more elongated and tortuous pores, which will be a constraint for fast drainage but it will be advantageous in coarse textured soils

Lack of Functional Trehalase Activity in Candida parapsilosis Increases Susceptibility to Itraconazole

Central metabolic pathways may play a major role in the virulence of pathogenic fungi. Here, we have investigated the susceptibility of a Candida parapsilosis mutant deficient in trehalase activity (atc1Δ/ntc1Δ strain) to the azolic compounds fluconazole and itraconazole. A time-course exposure to itraconazole but not fluconazole induced a significant degree of cell killing in mutant cells compared to the parental strain. Flow cytometry determinations indicated that itraconazole was able to induce a marked production of endogenous ROS together with a simultaneous increase in membrane potential, these effects being irrelevant after fluconazole addition. Furthermore, only itraconazole induced a significant synthesis of endogenous trehalose. The recorded impaired capacity of mutant cells to produce structured biofilms was further increased in the presence of both azoles, with itraconazole being more effective than fluconazole. Our results in the opportunistic pathogen yeast C. parapsilosis reinforce the study of trehalose metabolism as an attractive therapeutic target and allow extending the hypothesis that the generation of internal oxidative stress may be a component of the antifungal action exerted by the compounds currently available in medical practice

Efecto del trabajo cooperativo en el aprendizaje de la escritura mediante la implicación familiar

Certain skills such as lexical wealth, phonological processing, alphabet knowledge and speed of naming are important precursors of writing learning at an early age as they show a high correlation with the initial learning of written language. However, there are no studies aiming at analyzing the impact that the development of these skills has on the process of acquiring writing through family participation. The objective of this study was to analyze the effect that the intervention of a program focused on the development of the skills that favor the learning of writing through family involvement by means of the organization of cooperative groups has on the learning of writing at a young age. A quasi-experimental study was used to compare compliance of groups pre-test and post-test. The study involved 386 students between the ages of fi ve and six years old. The results support the effectiveness of family collaboration in accessing the writing system. It is suggested the implementation of teaching models that integrate the development of skills that facilitate the learning of writing through cooperative dynamics with family participation encouraged.Se sabe que determinadas habilidades como la riqueza léxica, el procesamiento fonológico, el conocimiento alfabético y la velocidad de denominación son precursores importantes del aprendizaje de la escritura en las primeras edades, ya que muestran una alta correlación con el aprendizaje inicial del lenguaje escrito. Sin embargo, no se encuentran trabajos orientados a analizar el impacto que el desarrollo de estas habilidades presenta en el proceso de adquisición de la escritura mediante la participación familiar. El objetivo de este estudio fue analizar el efecto que la intervención de un programa centrado en el desarrollo de las habilidades favorecedoras del aprendizaje de la escritura mediante la implicación familiar a través de la organización de grupos cooperativos presenta en el aprendizaje de la escritura en las primeras edades. Se empleó un diseño cuasi-experimental de comparación entre grupos con medidas pretest y postest. En el estudio han participado 386 alumnos con edades comprendidas entre los 5 y los 6 años. Los resultados apoyan la efi cacia de la colaboración de las familias en el acceso al sistema de la escritura. Se sugiere la implementación de modelos de enseñanza que integren el desarrollo de las habilidades facilitadoras del aprendizaje de la escritura a través de dinámicas cooperativas en las que se fomente la participación familiar.  

Planning and community development: case studies

Planning and Comunity Development: Case Studies, presents the findings of the inter-university Seminar held on 28?29 July 2011 and organized by researchers from the Technical University of Madrid and the University of California, Berkeley, who were fortunate to have the presence of the renowned Professor John Friedmann. Professors, researchers and PhD students from our research groups presented their works as scientific communications that were enriched by the debate among the different researches who attended the Seminar. All of them appear in the picture below in front of the gate of Haviland Hall at UC Berkeley. This book analyses the concept of planning and its evolution so far, leading to the conceptualization of governance as an expression of the planning practice. It also studies the role of social capital and cooperation as tools for the community development. The conceptual analysis is complemented by the development of six case studies that put forward experiences of planning and community development carried out in diverse social and cultural contexts of Latin-America, Europe and North America. This publication comes after more than 20 years of work of the researchers that met at the seminar. Through their work in managing development initiatives, they have learned lessons and have contribute to shape their own body of teaching that develops and analyses the role of planning in public domain to promote community development. This knowledge is synthesized in the model Planning as Working With People, that shows that development is not effective unless is promoted in continuous collaboration with all the actors involved in the process

Risk of cancer in family members of patients with lynch-like syndrome

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56-2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67-4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44-2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26-5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: Study protocol for the SAFO trial

Introduction Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (=18 years) with isolation of MSSA from at least one blood culture =72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3