Kinetic study of the gas-phase reaction of atomic chlorine with a series of aldehydes

The reactions of Cl atoms with a series of unsaturated aldehydes have been investigated for the first time using a relative method. In order to obtain additional information for a qualitative structure versus reactivity discussion, we have also determined the rate coefficients for the reactions of atomic chlorine with their respective saturated aldehydes. These relative measurements were performed at room temperature and atmospheric pressure of air and N₂, by using ethane, propene and 1-butene as reference compounds. The weighted average relative rate constants obtained, k_Cl&plusmn;2&sigma; (in units of cm³ molecule^&minus;1 s^&minus;1) were: trans-2-pentenal (1.31&plusmn;0.19)&times;10^&minus;10; trans-2-hexenal (1.92&plusmn;0.22)&times;10^&minus;10; trans-2-heptenal (2.40&plusmn;0.29)&times;10^&minus;10; n-pentanal (2.56&plusmn;0.27)&times;10^&minus;10; n-hexanal (2.88&plusmn;0.37)&times;10^&minus;10; n-heptanal (3.00&plusmn;0.34)&times;10^&minus;10. <P style='line-height: 20px;'> Finally, results and atmospheric implications are discussed and compared with the reactivity with OH and NO₃ radicals

The influence of crossbite in early development of mandibular bone asymmetries in paediatric patients

All authors agree that posterior crossbite is a malocclusion that affects mandibular growth and may lead to skeletal asymmetry but there are few data on which age these modifications are easily quantifiable. For this study, the researchers used x-ray records of 217 children between 6 and 9 years of age, in the mixed dentition stage and with unilateral posterior crossbite. All the horizontal variables were traced and evaluated by the principal researcher, using the tpsDig version 2 computer program. Subsequently, a descriptive and statistical analysis was carried out, using the SPSS 17.0 for Windows program. After analysing the vertical mandibular traces on the x-rays, the researchers found, in all cases, quantifiable differences between the crossbite side and the non-crossbite side. The differences between horizontal variables were statistically significant (p<0.005) for the entire sample (H3-H4), in the group of boys (H3-H4) and in the 7-year old age group (H1-H2 and H3-H4). Differences were observed in the size of the horizontal measures between the crossbite side and the non-crossbite side. Some of these differences were significant as a function of the sex and age of the study sample

Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this entity has increased in recent years, new molecular alterations have emerged that could be helpful to refine current risk models. Here, we evaluated NAB2-STAT6 fusion variants and other molecular alterations in a series of 83 SFTs that are enriched in progressing cases. Gene fusion variants were identified by targeted RNA-seq in the whole series, whereas TERT promoter (pTERT) mutations were inspected by Sanger sequencing in a subset of 18 cases. Immunohistochemical assays were performed to assess BCOR and NTRK expression as well as P53 mutation status in 45, 44, and 44 cases, respectively. While confirming the associations of gene fusion variants with clinicopathological parameters, our results do not prove their prognostic value. Pan-TRK immunoexpresion correlated with recurrence/progression, P53 staining associated with higher mitotic counts, and pTERT mutations were enriched in cases with fatal outcome. An intriguing correlation was found for BCOR protein expression with gene fusion variants, size, and tumor location

Continuous vocational training in response to the challenge of industry 4.0: Required skills and business results

Purpose: To identify the technical skills which, linked to digitalization processes, are required to achieve different types of business results. Design/methodology/approach: The Delphi method was applied, through the opinions of a group of Spanish experts, to identify the importance of certain skills for the advancement of digitalization and the implementation of Industry 4.0. Findings: The results show that: 1) skills in Robotics, the Internet of Things, Networks and Artificial Intelligence are necessary to achieve results in the management of company technical areas; 2) commercial management needs skills in Intelligent Systems, Big Data, Cybersecurity, Distributed Technology and Contents; and 3) for the business challenges of sustainable development, the environment and energy efficiency, the most needed skills are in Big Data, Intelligent Systems and Artificial Intelligence. Originality/value: The results are useful, firstly, in providing firms with a training and selection tool for the development of I4.0 and, secondly, in offering training centers criteria for drawing up their training programsPeer Reviewe

Mice carrying an epithelial deletion of the glucocorticoid receptor NR3C1 develop a higher tumor load in experimental colitis associated cancer

The glucocorticoid receptor NR3C1 is expressed in multiple cell types in the gut and elsewhere. Intestinal epithelial cells both produce and respond to glucocorticoids in different physiological and pathological contexts. In experimental colitis glucocorticoids have been shown to exert a dual role, dampening inflammation while producing a deterioration in animal status, including death. Mice with tamoxifen inducible, intestinal epithelial specific deletion of NR3C1 (NR3C1IEC mice) are protected against experimental colitis, suggesting glucocorticoid epithelial actions are deleterious. Since glucocorticoids modulate epithelial proliferation it follows that they may affect the development of colon cancer. In this study we set out to test this hypothesis using the dextran sulfate sodium - azoxymethane model of colitis-associated cancer. KO mice were found to exhibit a 2-fold higher tumor load but similar incidence and tumor size. Tumors had a higher trend to extend to the submucosal layer (36% vs. 0%) in NR3C1IEC mice, and overexpressed Lgr5, Egfr and Myc, consistent with increased proliferation and neoplastic transformation. Snai1 and Snai2 were upregulated specifically in tumors of NR3C1ΔIEC mice, suggesting enhanced epithelial to mesenchymal transition in the absence of the intestinal epithelial GC receptor. We conclude that endogenous GC epithelial signaling is involved in colitis associated cancer.This work was supported by funds from the Ministry of Economy and Competitivity, partly with Fondo Europeo de Desarrollo Regional (FEDER) funds [SAF2017-88457-R, AGL2017-85270-R, BFU2014-57736-P, AGL2014-58883-R] and by Junta de Andalucía [CTS235, CTS164]. MA and CJA were supported by the University of Granada (Contrato Puente Program - Plan Propio) and the Ministry of Education [Spain], respectively. CIBERehd is funded by Instituto de Salud Carlos III

The Cytotoxicity of Epsilon toxin from Clostridium perfringens on lymphocytes is mediated by MAL protein expression

Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein that crosses the blood-brain barrier, binds to myelin, and, hence, has been suggested to be a putative agent for the onset of multiple sclerosis, a demyelinating neuroinflammatory disease. Recently, myelin and lymphocyte (MAL) protein has been identified to be a key protein in the cytotoxic effect of Etx; however, the association of Etx with the immune system remains a central question. Here, we show that Etx selectively recognizes and kills only human cell lines expressing MAL protein through a direct Etx-MAL protein interaction. Experiments on lymphocytic cell lines revealed that MAL protein-expressing T cells, but not B cells, are sensitive to Etx and reveal that the toxin may be used as a molecular tool to distinguish subpopulations of lymphocytes. The overall results open the door to investigation of the role of Etx and Clostridium perfringens on inflammatory and autoimmune diseases like multiple sclerosis

Immunoregulatory Effects of Porcine Plasma Protein Concentrates on Rat Intestinal Epithelial Cells and Splenocytes

This study was funded by APC Europe and the Ministry of Economy and Competitivity, partly with Fondo Europeo de Desarrollo Regional FEDER funds [SAF2017-88457-R, AGL2017-85270- R, BFU2014-57736-P, AGL2014-58883-R], and by Junta de Andalucía [CTS235, CTS164]. CHC, CJA and BO were supported by the University of Granada (Contrato Puente Program-Plan Propio) and the Ministry of Education [Spain], respectively. CIBERehd is funded by Instituto de Salud Carlos III.Blood contains proteins which have interest as products that may regulate immune function. For this reason some protein-based products are currently used as nutritional supplements for animals, for instance two porcine concentrates, spray dried serum (SDS), and an immunoglobulin concentrate (IC). These products have shown to protect against colonic inflammation in rodents. In the present study we characterize the ability of these products to modulate immune function in isolated cells, namely intestinal epithelial cells (IEC18 cells) and rat spleen cells. Our data indicate that both porcine protein concentrates indeed alter immune cell function, based on the secretion of the modulators known as cytokines. In intestinal epithelial IEC18 cells they promoted the secretion of GRO alpha and MCP-1 cytokines. In spleen cells they mainly inhibited the production of TNF, a key proinflammatory cytokine. In addition, the IC product augmented the release of IL-10, an anti-inflammatory cytokine. Taken together, our data indicate that the immunomodulatory effects observed in vivo are consistent with the direct actions of the protein concentrates on epithelial cells, T lymphocytes, and monocytes. Serum protein concentrates have been shown to exert in vivo anti-inflammatory effects. Specific effects on different cell types and their mechanism of action remain unraveled. We aimed to characterize the immunomodulatory effect of two porcine plasma protein concentrates, spray dried serum (SDS) and an immunoglobulin concentrate (IC), currently used as animal nutritional supplements with established in vivo immunomodulatory properties. Cytokine production by the intestinal epithelial cell line IEC18 and by primary cultures of rat splenocytes was studied. The molecular pathways involved were explored with specific inhibitors and gene knockdown. Our results indicate that both products induced GRO alpha and MCP-1 production in IEC18 cells by a MyD88/NF-kappa B-dependent mechanism. Inhibition of TNF production was observed in rat primary splenocyte cultures. The immunoglobulin concentrate induced IL-10 expression in primary splenocytes and lymphocytes. The effect on TNF was independent of IL-10 production or the stimulation of NF-kB, MAPKs, AKT, or RAGE. In conclusion, SDS and IC directly regulate intestinal and systemic immune response in murine intestinal epithelial cells and in T lymphocytes and monocytes.APC EuropeMinistry of Economy and CompetitivityEuropean Commission SAF2017-88457-R AGL2017-85270R BFU2014-57736-P AGL2014-58883-RJunta de Andalucia CTS235 CTS164University of Granada (Contrato Puente Program-Plan Propio)Ministry of Education [Spain]Instituto de Salud Carlos IIIEuropean Commissio

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease

Background: Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). Methods: This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. Results: During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m(2)/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. Conclusions: Renal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patients

Epithelial deletion of the glucocorticoid receptor protects the mouse intestine against experimental inflammation

Intestinal epithelium glucocorticoid receptor knockout mice (NR3C1 IEC) were treated with dextran sulfate sodium (DSS, 2.5%) to induce colitis. Inflammatory status was assessed by morphological and biochemical methods and corticoid production was measured in colonic explants. Key Results. After 7 days of DSS NR3C1 mice exhibited lower weight loss and tissue damage, reduced colonic expression of S100A9, attenuated phosphorylation of STAT3 and a better overall state compared with WT. Ki67 immunoreactivity was also shifted, indicating an effect on epithelial proliferation. A subgroup of mice were treated with budesonide and showed completely prevented budesonide induced weight loss. Epithelial deletion of the glucocorticoid receptor also protected mice in a protracted colitis protocol. Conversely knockout mice presented a worse status compared to the control group at 1 day post DSS, as shown by blood in feces and increased inflammatory parameters. In a separate experiment colonic corticosterone production was shown to be significantly increased in knockout mice at 7 days of colitis but not at earlier stages. Conclusions and Implications. The intestinal epithelial glucocorticoid receptor has deleterious effects in experimental colitis induced by dextran sodium sulfate, probably related to inhibition of epithelial proliferative responses leading to impaired wound healing and reduced endogenous corticosterone production.Ministry of Economy and Competitivity, partly with Fondo Europeo de Desarrollo Regional FEDER funds [BFU2014-57736-P, AGL2014-58883-R, SAF2017-88457-R, AGL2017-85270-R]Junta de Andalucía [CTS235, CTS164]Ministry of EducationCIBERehd is funded by Instituto de Salud Carlos II

Relationship between physical fitness and cyberbullying patterns (cybervictimization and cyberperpetration) in Spanish adolescents

Background: Cyberbullying is a growing problem among adolescents, and deeper knowledge of this phenomenon could facilitate the implementation of adequate prevention and intervention strategies. Therefore, the aim of this study was to analyze the relationships between victimization and aggression patterns in cyberbullying and physical fitness levels in Spanish adolescents. (2) Methods: A total of 741 adolescents aged 12 to 19 years from two high schools in Andalusia, Spain (mean = 14.52 ± 1.96 years; 50.9% girls, 49.1% boys) participated in the study. The participants underwent the EUROFIT battery test and completed the Spanish version of the European Cyberbullying Intervention Project Questionnaire (ECIPQ) scale. T-test, bivariate correlations and a linear regression analysis were used for statistical analysis. (3) Results: The study results indicated positive relationships between cyberbullying patterns, especially cybervictimization, and age, as well as several physical fitness measures, including BMI, sit-ups, sit-and-reach, and handgrip tests. On the other hand, cyberperpetration was positively related only to age and the specific grip strength test. Further statistical analysis revealed that cybervictimization was primarily influenced by age, while cyberperpetration was mainly influenced by age and performance in a functional test (sit-and-reach). (4) Conclusions: Cyberbullying roles, both as victims and aggressors, may not be strongly influenced by isolated physical fitness factors. Thus, in order to reach a more comprehensive understanding and better explanations of individual involvement in cyberbullying behavior, future studies should analyze psychological and social factors along with the variables considered in this study