Effects of fresh and field-aged holm-oak biochar on As, Cd and Pb bioaccumulation in different rice growing environments

Arsenic, Cd, and Pb environmental fate is influenced when the traditional permanent flooding rice production systems are replaced by water-saving and soil conservation practices, urging for additional strategies that avoid their bioaccumulation in rice grain. The aim of this two-years field study was to evaluate the effects of fresh and field-aged biochar on As, Cd, and Pb bioaccumulation, and on As speciation, in rice grain produced in different growing environments (flooding versus sprinkler and conventional tillage versus direct seeding). Biochar produced from holm-oak pruning residues (pyrolysis at 550 °C, 48 h), in a single application (28Mg ha−1), reduced As bioaccumulation in rice grain in the permanent flooding system to non-quantifiable concentrations (e.g., from 0.178 mg kg−1 to <0.04 mg kg−1, for inorganic-As, respectively), an effect which remained under field-aging conditions, increasing rice commercial value. When adopting sprinkler irrigation, the undesirable increase in Cd bioaccumulation in rice, relatively to the anaerobic system, was counteracted by biochar application, reducing its bioaccumulation in kernels between 32 and 80%, allowing a simultaneous control ofmetals and metalloids bioaccumulation in rice. The bioaccumulation of Pb was also prevented with biochar application, with a reduction in its concentration four- to 13-times, in all the management systems, relatively to the non-amended plots, under fresh biochar effects. However, Pb immobilization decreased with biochar field-aging, indicating that the biochar application may have to be repeated to maintain the same beneficial effect. Therefore, the present study shows that the implementation of sprinkler irrigation with holm-oak biochar could reduce the risk of heavy metals(loids) bioaccumulation in rice grains and, thereby, ensuring food safety aspects, particularly under fresh biochar effectsinfo:eu-repo/semantics/publishedVersio

Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment

Inflammatory bowel disease; Pediatrics; PharmacogenomicsEnfermedad inflamatoria intestinal; Pediatría; FarmacogenómicaMalaltia inflamatòria intestinal; Pediatria; FarmacogenòmicaBackground/aims Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment. Methods We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. Results Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10–7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). Conclusions We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.Instituto de Salud Carlos III (ISCIII), "PI19/00792 and PI22/00584", co-funded by the European Union (L.L-F); Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), grant number 2021-II-postdoc-01 (S.S-M.), and by Consejería de Educación, Ciencia y Universidades Comunidad de Madrid, grant number PEJ-2021-AI/BMD-21866 and PIPF2022/SAL-GL-24790 (P.Z-C.)

Impact of Pain Neuroscience Education Program in Community Physiotherapy Context on Pain Perception and Psychosocial Variables Associated with It in Elderly Persons: A Ranzomized Controlled Trial

This study investigated the long-term effect (six-months) of a Pain Neuroscience Education (PNE) program on pain perception, quality of life, kinesiophobia and catastrophism in older adults with multimorbidity and chronic pain. Fifty participants (n = 50) were randomly assigned to the pain education therapy group (PET; n = 24) and control group (CG; n = 26). The PET group received six sessions (i.e., once a week, 50 min) about neurophysiology of pain while the CG carried on with their usual life. Perception of pain through the visual analogue scale (VAS), quality of life (EQ-5D questionnaire), kinesiophobia (TSK-11) and catastrophism (PCS) were assessed after six months since the last PNE session. Statistically significant differences on VAS (t(48) = 44, p = 0.01, ES = 0.42 [0.13, 0.65]) was found in favor to PET group. No other statistically significant differences were found. This study found that the application of a PNE intervention in an isolated form was able to significantly reduce pain perception with low effect size in the long-term (six months after intervention) in elderly people with chronic pain.Medicin

Association of body mass index with clinical outcomes in patients with atrial fibrillation: a report from the FANTASIIA Registry

[Abstract] Background. Obesity and atrial fibrillation (AF) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF. Methods and Results. Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: <25 kg/m2, overweight: 25–30 kg/m2, and obese: ≥30 kg/m2), assessing all‐cause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years’ follow‐up. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8±9.4 years): 358 (18.3%) had normal body mass index, 871 (44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger (P<0.01) and had more comorbidities. Mean time in the therapeutic range was similar across body mass index categories (P=0.42). After a median follow‐up of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse cardiovascular event (8.6%). Event rates were similar between groups for total mortality (P=0.29), stroke (P=0.90), major bleeding (P=0.31), and major adverse cardiovascular events (P=0.24). On multivariate Cox analysis, body mass index was not independently associated with all‐cause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions. In this prospective cohort of patients anticoagulated for AF, obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis

Lapse of coactivation as reference for prevention of nonspecific low back pain. A Pilot study

[Resumen] El dolor lumbar inespecífico, que afecta al 70% de la población, está vinculado a conductas sedentarias y presenta una desconexión entre anomalías estructurales y la experiencia dolorosa. Actualmente el ejercicio es considerado la primera línea de tratamiento, mejorando la biomecánica y la autogestión del dolor. El objetivo principal de este estudio piloto fue medir antes, y tras un programa de ejercicios, la activación de la musculatura central encargada de la estabilización global y local del tronco, empleando electromiografía de superficie en una hiperflexión de tronco. Se realizó un diseño de estudio prospectivo, cuasi-experimental, incluyendo un grupo de intervención con dos momentos de evaluación (pre-intervención y tras 4 semanas post-intervención). Se observó un descenso significativo del lapso de activación en todos los músculos estudiados tras la finalización del programa: CL derecho e izquierdo con carga (p= .015 y p= .0003 respectivamente) y MT derecho e izquierdo sin carga (p= .028 y p= .036 respectivamente), y una alta correlación de este valor con el descenso del dolor lumbar (rho= .07). El descenso del lapso de coactivación, como indicador de mayor y mejor respuesta muscular ante perturbaciones, podría ser una alternativa en la prevención del dolor lumbar inespecífico.[Abstract] Nonspecific low back pain, affecting 70% of the population, is linked to sedentary behaviors and presents a disconnect between structural abnormalities and the pain experience. Currently, exercise is considered the first line of treatment, improving biomechanics and pain self-management. The primary objective of this pilot study was to measure, before and after an exercise program, the activation of the core muscles responsible for global and local trunk stabilization, using surface electromyography during trunk hyperflexion. A prospective, quasi-experimental study design was implemented, including an intervention group with two evaluation points (preintervention and 4 weeks post-intervention). A significant reduction in activation time was observed in all muscles studied after completing the program: right and left CL under load (p = .015 and p = .0003, respectively) and right and left MT without load (p = .028 and p = .036, respectively), with a strong correlation between this value and the reduction in low back pain (rho = .07). The reduction in coactivation time, as an indicator of improved and more efficient muscle response to disturbances, could be an alternative in the prevention of nonspecific low back pain

Intake of Proton-Pump Inhibitors and Gastric Cancer within the Stomach Cancer Pooling (StoP) Project

Background: A potential association between proton-pump inhibitors (PPI) and gastric cancer remains undefined. Thus, we aimed to evaluate such association within the Stomach cancer Methods: Data from five case-control studies of the StoP Project were included (1,889 cases and 6,517 controls). We assessed the impact of different exposure definitions, specifically any reported use of PPIs and exposure definitions based on the duration of PPI intake. Additionally, we modeled the dose-response relationship between the cumulative duration of PPI intake and gastric cancer. Results: Significant associations between PPI intake and gastric cancer, both overall and in the stratified analyses, were limited to exposure definitions based on short durations of intake. The overall odds ratio (OR) for any reported PPI intake was 1.78 [95% confidence interval (CI): 0.76-4.14]. In the dose-response analysis, the ORs of gastric cancer were found to be higher for short durations of PPI intake (6 months: OR 3.26; 95% CI: 2.40-4.42; one year: OR 2.14; 95% CI: 1.69-2.70; 2 years: OR 1.50; 95% CI: 1.22-1.85; 3 years: OR 1.27; 95% CI: 1.03-1.56), with the association becoming not significant for durations longer than 3 years. Conclusions: Our findings suggest that the observed association between PPIs and gastric cancer might be mainly due to reverse causality. Impact: The results of this study suggest that PPIs area safe thera-peutic choice regarding their effect on the occurrence of gastric cancer. See related commentary by Richman and Leiman, p. 112

Association of Body Mass Index With Clinical Outcomes in Patients With Atrial Fibrillation: A Report From the FANTASIIA Registry

Background Obesity and atrial fibrillation (AF) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF. Methods and Results Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: <25 kg/m2, overweight: 25-30 kg/m2, and obese: ≥30 kg/m2), assessing all‐cause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years' follow‐up. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8±9.4 years): 358 (18.3%) had normal body mass index, 871 (44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger (P<0.01) and had more comorbidities. Mean time in the therapeutic range was similar across body mass index categories (P=0.42). After a median follow‐up of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse cardiovascular event (8.6%). Event rates were similar between groups for total mortality (P=0.29), stroke (P=0.90), major bleeding (P=0.31), and major adverse cardiovascular events (P=0.24). On multivariate Cox analysis, body mass index was not independently associated with all‐cause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions In this prospective cohort of patients anticoagulated for AF, obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir/ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an anti-apoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence

CHL1 hypermethylation as a potential biomarker of poor prognosis in breast cancer

The CHL1 gene encodes a cell-adhesion molecule proposed as being a putative tumour-suppressor gene in breast cancer (BC). However, neither the underlying molecular mechanisms nor the clinical value of CHL1 downregulation in BC has been explored. The methylation status of three CpG sites in the CHL1 promoter was analysed by pyrosequencing in neoplastic biopsies from 142 patients with invasive BC and compared with that of non-neoplastic tissues. We found higher CHL1 methylation levels in breast tumours than in non-neoplastic tissues, either from mammoplasties or adjacent-to-tumour, which correlated with lower levels of protein expression in tumours measured by immunohistochemistry. A panel of five BC cell lines was treated with two epigenetic drugs, and restoration of CHL1 expression was observed, indicating in vitro dynamic epigenetic regulation. CHL1 was silenced by shRNA in immortalized but non-neoplastic mammary cells, and enhanced cell proliferation and migration, but not invasion, were found by real-time cell analysis. The prognostic value of CHL1 hypermethylation was assessed by the log-rank test and fitted in a Cox regression model. Importantly, CHL1 hypermethylation was very significantly associated with shorter progression-free survival in our BC patient series, independent of age and stage (p = 0.001). In conclusion, our results indicate that CHL1 is downregulated by hypermethylation and that this epigenetic alteration is an independent prognostic factor in BC

Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products

Due to the low structural diversity within the set of antimalarial drugs currently available in the clinic and the increasing number of cases of resistance, there is an urgent need to find new compounds with novel modes of action to treat the disease. Microbial natural products are characterized by their large diversity provided in terms of the chemical complexity of the compounds and the novelty of structures. Microbial natural products extracts have been underexplored in the search for new antiparasitic drugs and even more so in the discovery of new antimalarials. Our objective was to find new druggable natural products with antimalarial properties from the MEDINA natural products collection, one of the largest natural product libraries harboring more than 130,000 microbial extracts. In this work, we describe the optimization process and the results of a phenotypic high throughput screen (HTS) based on measurements of Plasmodium lactate dehydrogenase. A subset of more than 20,000 extracts from the MEDINA microbial products collection has been explored, leading to the discovery of 3 new compounds with antimalarial activity. In addition, we report on the novel antiplasmodial activity of 4 previously described natural productsThis work was supported by the Junta de Andalucía [BIO-199, P09-CVI- 5367], the VI Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008-2011, Instituto de Salud Carlos III-Subdirección General de Redes y Centros de Investigación Cooperativa-Red de Investigación Cooperativa en Enfermedades Tropicales (RICET FIS Network: RD12/0018/0017),the Plan Nacional (SAF2013-48999-R), the FEDER funds from the EU and the PARAMET network (FP7-PEOPLE-2011-ITN. GA290080) to DG-P. Research of FV and OG was supported by the Instituto de Salud Carlos III-Subdirección General de Redes y Centros de Investigación Cooperativa-Red de Investigación Cooperativa en Enfermedades Tropicales (RICET FIS Network: RD12/0018/0005) and the FEDER funds from the EU and the PARAMET network (FP7-PEOPLE-2011-ITN. GA290080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe