S194-P-FADD as a marker of aggressiveness and poor prognosis in human T-cell lymphoblastic lymphoma

T-cell lymphoblastic lymphoma is a haematological disease with an urgent need for reliable prognostic biomarkers that allow therapeutic stratification and dose adjustment. The scarcity of human samples is responsible for the delayed progress in the study and the clinical management of this disease, especially compared with T-cell acute lymphoblastic leukaemia, its leukemic counterpart. In the present work, we have determined by immunohistochemistry that S194-P-FADD protein is significantly reduced in a cohort of 22 samples from human T-cell lymphoblastic lymphoma. Notably, the extent of such reduction varies significantly among samples and has revealed determinant for the outcome of the tumour. We demonstrate that Fas-associated protein with death domain (FADD) phosphorylation status affects protein stability, subcellular localization and non-apoptotic functions, specifically cell proliferation. Phosphorylated FADD would be more stable and preferentially localized to the cell nucleus; there, it would favour cell proliferation. We show that patients with higher levels of S194-P-FADD exhibit more proliferative tumours and that they present worse clinical characteristics and a significant enrichment to an oncogenic signature. This supports that FADD phosphorylation may serve as a predictor for T-cell lymphoblastic lymphoma aggressiveness and clinical status. In summary, we propose FADD phosphorylation as a new biomarker with prognostic value in T-cell lymphoblastic lymphoma

A hospital incident reporting system (2016-2019) : Learning from notifier's perception on incidents'risk, severity and frecuency of adverse events

Incident reporting systems (IRSs) are considered safety culture promoters. Nevertheless, they have not been contemplated to monitor professionals' perception about patient safety related risks. This study aims to describe the characteristics and evolution of incident notifications reported between 2016 and 2019 in a high complexity reference hospital in Barcelona and explores the association between notifications' characteristics and notifier's perception about incidents severity, probability of occurrence and risk. The main analysis unit was notifications reported. A descriptive analysis was performed and taxes by hospital activity were calculated. Odds ratios were obtained to study the association between the type of incident, the moment of incident, notifiers' professional category, reported incident's severity, probability and incidents' calculated risk. Through the study period, a total of 6379 notifications were reported, observing an annual increase of notifications until 2018. Falls (21.22%), Medical and procedures management (18.91%) and Medication incidents (15.49%) were the most frequently notified. Departments reporting the highest number of notifications were Emergency room and Obstetrics & Gynaecology. Incident type and notifiers' characteristics were consistently included in the models constructed to assess risk perception. Pharmaceutics were the most frequent notifiers when considering the proportion of staff members. Notification patterns can inform professionals' patient risk perception and increase awareness of professionals' misconceptions regarding patient safety

Onset of microglial entry into developing quail retina coincides with increased expression of active caspase-3 and is mediated by extracellular ATP and UDP

Microglial cell precursors located in the area of the base of the pecten and the optic nerve head (BP/ONH) start to enter the retina of quail embryos at the 7 th day of incubation (E7), subsequently colonizing the entire retina by central-to-peripheral tangential migration, as previously shown by our group. The present study demonstrates a precise chronological coincidence of the onset of microglial cell entry into the retina with a striking increase in death of retinal cells, as revealed by their active caspase-3 expression and TUNEL staining, in regions dorsal to the BP/ONH area, suggesting that dying retinal cells would contribute to the microglial cell inflow into the retina. However, the molecular mechanisms involved in this inflow are currently unclear. Extracellular nucleotides, such as ATP and UDP, have previously been shown to favor migration of microglia towards brain injuries because they are released by apoptotic cells and stimulate both chemotaxis and chemokinesis in microglial cells via signaling through purinergic receptors. Hence, we tested here the hypothesis that ATP and UDP play a role in the entry and migration of microglial precursors into the developing retina. For this purpose, we used an experimental model system based on organotypic cultures of E6.5 quail embryo retina explants, which mimics the entry and migration of microglial precursors in the in situ developing retina. Inhibition of purinergic signaling by treating retina explants with either apyrase, a nucleotide-hydrolyzing enzyme, or suramin, a broad spectrum antagonist of purinergic receptors, significantly prevents the entry of microglial cells into the retina. In addition, treatment of retina explants with either exogenous ATP or UDP results in significantly increased numbers of microglial cells entering the retina. In light of these findings, we conclude that purinergic signaling by extracellular ATP and UDP is necessary for the entry and migration of microglial cells into the embryonic retina by inducing chemokinesis in these cells

Quantitative determination of active Bowman-Birk isoinhibitors, IBB1 and IBBD2, in commercial soymilks

Naturally-occurring serine protease inhibitors of the Bowman-Birk family exert their potential chemopreventive and/or therapeutic properties via protease inhibition. In this study, we have quantified the amounts of active BBI isoinhibitors, IBB1 and IBBD2, in six commercial soymilks. By using cation exchange chromatography, the BBI isoinhibitors were isolated and their specific trypsin inhibitory activity was used to estimate their amounts in soymilk samples. IBB1 and IBBD2 concentrations ranged from 0.44 to 5.20 and 0.27 to 4.60 mg/100 ml of soymilk, respectively; total BBI, considered as the sum of both isoinhibitors, ranged from 0.60 to 9.07 mg/100 ml of soymilk. These data show that physiologically relevant amounts of active BBI are present in commercial soymilk and may exert potential health-promoting effects.A.C. acknowledges support by ERDF-co-financed Grant from the Spanish CICYT (AGL2011-26353). A.C. is involved in COST Action FA1005 INFOGEST on Food Digestion. L.C.B.R. acknowledges support from CAPES (Programa Institucional de Doutorado Sanduíche no Exterior–PDSE process number 9004-11-4), Brazil. We are grateful to the proteomics Facility of University of Cordoba (Spain) for carrying out peptide mass fingerprinting. B.H.-L. thanks Ministry of Economy and Competitiveness for her “Ramón y Cajal” contract.Peer Reviewe

Effects of A Concentrate Rich in Agro-Industrial By-Products on Productivity Results, Carcass Characteristics and Meat Quality Traits of Finishing Heifers

Finishing diets in intensive beef production systems are mainly based on cereals, which does not take advantage of the capacity of the ruminant digestive system to digest fibrous feeds, cannot be considered sustainable and does not contribute to the circular bioeconomy. Our aim was to investigate the effects of an alternative concentrate rich in agro-industrial by-products for finishing crossbred Limousine heifers. Four pens with 12 heifers and four pens with 13 heifers were randomly allocated to one of two treatments: control (CON), a commercial concentrate with a 43.3% cereal composition, and alternative (ALT), a concentrate with a composition of 26% cereals and up to 73.5% agro-industrial by-products. Growth performance data were collected along the 91 days of the experimental period. Carcass characteristics were collected after slaughter and 24 h later. Vacuum-packaged samples from longissimus muscle were aged for 7, 21 or 28 days to study meat quality traits. Feed intake was higher and feed conversion rate was lower in the ALT treatment, but no differences were found in average daily gain and feeding costs. Treatment had no effects on any of the measured carcass traits (grading, hot and cold carcass weight, dressing out, chilling losses, subcutaneous fat depth, pH, temperature and lean and fat colour) nor on the meat quality traits (drip loss, cooking loss, shear force, oxidative stability, chromatic indices and pigment contents). Ageing time decreased drip loss and shear force, increased lightness and did not affect redness or surface colour stability. In conclusion, feeding crossbred Limousine heifers a finishing diet rich in agro-industrial by-products did not have any negative effects on performance, carcass and meat quality traits, which might be considered positive from the point of view of sustainability of beef production. Under the conditions assayed, ageing for 21 and 28 days improved tenderness of meat, without detrimental effects on oxidative stability or traits related to visual acceptability

A transfer matrix method for the analysis of fractal quantum potentials

The scattering properties of quantum particles on fractal potentials at different stages of fractal growth are obtained by means of the transfer matrix method. This approach can be easily adopted for project assignments in introductory quantum mechanics for undergraduates. The reflection coefficients for both the fractal potential and the finite periodic potential are calculated and compared. It is shown that the reflection coefficient for the fractal has a self-similar structure associated with the fractal distribution of the potential

Maternal obesity in twin pregnancy: the role of nutrition to reduce maternal and fetal complications

There are more and more obese mothers with twin gestations. For a long time before, the responses of lymphocytes and platelets in obese women can cause a low-grade inflammation. In addition, a proper control of gestational weight gain would improve the outcomes in mothers with high pre-gestational body mass index (BMI). In women with high pre-gestational BMI and twin pregnancy, our aims were to explore the biochemical and hematological parameters and to study the rate of obstetric adverse outcomes. This was an observational and retrospective study conducted in the Hospital Universitario La Paz (Madrid, Spain). We included 20 twin pregnancies as the lean group (BMI = 18.5–24.9 kg/m2 ), homogeneous in the maternal age and ethnicity, and having parity with other 20 twin pregnancies as the obese group (BMI ≥ 30 kg/m2 ). The maternal data and maternal, fetal, obstetric, and neonatal complications were collected from the medical records. In the first and third trimester of pregnancy, the biochemical and hematological parameters of the blood were assayed. In this cohort, gestational weight gain was significantly lower in the obese than lean group. In the first trimester, the hemoglobin levels in obese women (12.1 ± 0.8 g/dL) were lower than lean women (12.6 ± 0.7 g/dL; p-Value = 0.048). In addition, the tendency of glucose levels, TSH levels and platelets was to increase in obese compared to lean women. In the third trimester, the TSH levels were higher in obese (3.30 ± 1.60 mUI/L) than lean women (1.70 ± 1.00 mUI/L; p-Value = 0.009). Furthermore, there was a tendency for levels of platelets and lymphocytes to increase in obese compared to lean women. No significant differences were detected in the rate of maternal, fetal, obstetrical, and neonatal complications between the groups. The hemoglobin, platelets, lymphocytes and TSH levels need further investigation to understand potential subclinical inflammation in obese women. Furthermore, obese women with twin pregnancies should follow-up with a specialist nutritionist, to help them control their gestational weight gain with appropriate dietary measure

Maintenance of immune tolerance by Foxp3+ regulatory T cells requires CD69 expression

Although FoxP3+ regulatory T cells are key players in the maintenance of immune tolerance and autoimmunity, the lack of specific markers constitute an obstacle to their use for immunotherapy protocols. In this study, we have investigated the role of the C-type lectin receptor CD69 in the suppressor function of Tregs and maintenance of immune tolerance towards harmless inhaled antigens. We identified a novel FoxP3+CD69+ Treg subset capable to maintain immune tolerance and protect to developing inflammation. Although CD69+ and CD69−FoxP3+ Tregs exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4, ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of TGFβ and have potent suppressor activity. This activity is regulated by STAT5 and ERK signaling pathways and is impaired by antibody-mediated down-regulation of CD69 expression. Moreover, immunotherapy with FoxP3+CD69+ Tregs restores the homeostasis in Cd69−/− mice, that fail to induce tolerance, and is also highly proficient in the prevention of inflammation. The identification of the FoxP3+CD69+ Treg subset paves the way toward the development of new therapeutic strategies to control immune homeostasis and autoimmunityThis work was supported by funding from the Spanish Ministry of Economy and Competitiveness: SAF2011-27330 to P.M., SAF2010-15106 to M.L.T and SAF2011-25834 to F.S-M.; grant INDISNET (S2010/BMD-2332) from Comunidad de Madrid and RETICS Enfermedades Cardiovasculares (RD12/0042/0056) from Instituto de Salud Carlos III to P.M and F. S-M; and ERC-2011-AdG294340-GENTRIS to F.S-M. J.R.C. was supported by a CNIC post-doctoral fellowship, R. S-D is funded with a pre-doctoral fellowship from Comunidad de Madrid and E.R.B. and A.M-M. were supported by a FPI pre-doctoral fellowship from the Spanish Ministry of Economy and Competitiveness. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro CNIC Foundatio

Healthcare experience and their relationship with demographic, disease and healthcare-related variables: a cross-sectional survey of patients with chronic diseases using the IEXPAC scale.

[Abstract] BACKGROUND: Patient experience is acknowledged as a principal aspect of quality healthcare delivery, and it has implications with regard to outcomes. OBJECTIVES: Our objective was to evaluate the healthcare experience of patients with chronic diseases to identify patient-perceived healthcare gaps and to assess the influence of demographic and healthcare-related variables on patient experiences. METHODS: A cross-sectional survey was delivered to adult patients with chronic diseases: diabetes mellitus (DM), human immunodeficiency virus (HIV) infection, inflammatory bowel disease (IBD) or rheumatic diseases. Patient experiences were assessed with the Instrument for Evaluation of the Experience of Chronic Patients (IEXPAC) questionnaire, with possible scores ranging from 0 (worst) to 10 (best experience). RESULTS: Of the 2474 patients handed the survey, 1618 returned it (response rate 65.4%). Patients identified gaps in healthcare related mainly to access to reliable information and services, interaction with other patients and continuity of healthcare after hospital discharge. The mean ± standard deviation (SD) IEXPAC score was 6.0 ± 1.9 and was higher for patients with HIV (6.6 ± 1.7) than for those with rheumatic disease (5.5 ± 2.0), IBD (5.9 ± 2.0) or DM (5.9 ± 1.9) (p < 0.001). In multivariate models, better overall IEXPAC experience was associated with follow-up by the same physician, follow-up by a nurse, receiving healthcare support from others and treatment with subcutaneous or intravenous drugs. The multivariate model that confirmed patients with HIV or DM had better experience than did those with rheumatic diseases. CONCLUSIONS: Through IEXPAC, patients identified aspects for healthcare quality improvements and circumstances associated with better experience, which may permit greater redirection of healthcare toward patient-centered goals while facilitating improvements in social care and long-term healthcare quality