Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury

Mechanical trauma to the spinal cord causes extensive neuronal death, contributing to the loss of sensory-motor and autonomic functions below the injury location. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise in caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesise that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mice with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using human SH-SY5Y cells overexpressing XIAP, we further showed that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome of spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI

The PHQ-PD as a screening tool for panicdisorder in theprimarcarsetting in Spain.

INTRODUCTION Panic disorder is a common anxiety disorder and is highly prevalent in Spanish primary care centres. The use of validated tools can improve the detection of panic disorder in primary care populations, thus enabling referral for specialized treatment. The aim of this study is to determine the accuracy of the Patient Health Questionnaire-Panic Disorder (PHQ-PD) as a screening and diagnostic tool for panic disorder in Spanish primary care centres. METHOD We compared the psychometric properties of the PHQ-PD to the reference standard, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interview. General practitioners referred 178 patients who completed the entire PHQ test, including the PHQ-PD, to undergo the SCID-I. The sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of the PHQ-PD were assessed. RESULTS The operating characteristics of the PHQ-PD are moderate. The best cut-off score was 5 (sensitivity .77, specificity .72). Modifications to the questionnaire's algorithms improved test characteristics (sensitivity .77, specificity .72) compared to the original algorithm. The screening question alone yielded the highest sensitivity score (.83). CONCLUSION Although the modified algorithm of the PHQ-PD only yielded moderate results as a diagnostic test for panic disorder, it was better than the original. Using only the first question of the PHQ-PD showed the best psychometric properties (sensitivity). Based on these findings, we suggest the use of the screening questions for screening purposes and the modified algorithm for diagnostic purposes

Nuevos invertebrados del Viseano (Mississippiano), Formación Santiago, Oaxaca, sudeste de México

En el estado de Oaxaca, al sur de México, aflora una secuencia de rocas carbonatadas-terrígenas que han sido agrupadas en la Formación Santiago. El Miembro Inferior de esta unidad está constituido por 67 metros de caliza, lutita y calcarenita con abundantes braquiópodos, briozoarios, bivalvos, rostroconquios, corales y esponjas, previamente descritos, que formaron parte de comunidades arrecifales o peri-arrecifales durante el Osageano (Tournasiano tardío- Viseano temprano). El Miembro Superior descansa en discordancia angular y está compuesto por 90 metros de lutita que subyacen a 120 metros de arenisca de grano fino. En la parte media de la lutita se presentan concreciones ferrosas y ligeramente calcáreas que contienen invertebrados fósiles entre los que se han determinado dos especies de braquiópodos chonétidos, una de espiriférinidos, tres de conuláridos, diez de gasterópodos, cinco de nautiloideos y tres de amonoideos, así como placas de crinoideos de tres morfotipos. La fragmentación y desarticulación que presentan los ejemplares, las características litológicas, así como la abundancia y diversidad de braquiópodos y la presencia de cefalópodos, indican que estos restos fósiles formaron parte de distintas comunidades que se depositaron en la parte externa de la plataforma. Esta fauna es diferente de la que se encuentra en el Miembro Inferior y de las formas ya determinadas. Algunas especies de cefalópodos sugieren una edad Merameciano-Chesteriano (Viseano medio-tardío), lapso que no ha sido mencionado previamente para México. En este trabajo se incluye el primer estudio sistemático de conuláridos y gasterópodos del Paleozoico superior de México y se reporta el registro más antiguo de amonoideos para la región. Todas las faunas que contiene la Formación Santiago presentan importantes afinidades a nivel de especie con faunas contemporáneas de la región del Mid-Continent.Sesiones libresFacultad de Ciencias Naturales y Muse

Molecular Pathways Leading to Induction of Cell Death and Anti-Proliferative Properties by Tacrolimus and mTOR Inhibitors in Liver Cancer Cells

[Background/Aims] Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with portal hypertension and/or increased bilirubinemia, but without vascular-associated diseases. Tumor recurrence, which is the main drawback for the survival of patients submitted to OLT for HCC, has been related to tumor-related variables and the immunosuppressive therapies. We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. This study identified the role of the immunosuppressant partners such as FK506-binding proteins (FKBPs) in the induction of cell death and arrest of cell proliferation by immunosuppressants in two representative liver cancer cells.[Methods] The regulation of endoplasmic reticulum (ER) stress, apoptosis/autophagy, cell proliferation, and FKBPs expression was determined in Tacrolimus-, Sirolimus- and Everolimus-treated primary human hepatocytes, and hepatoma HepG2 and Huh7 cell lines. The functional repercussion of FKBPs on cell death and proliferation was also addressed using the siRNA technology. The assessed antitumoral properties of the immunosuppressants were associated to microRNAs (miRNAs) pattern.[Results] The enhanced pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with increased protein kinase RNA-like endoplasmic reticulum kinase (PERK)-related ER stress, Ser15P-p53/p53 ratio and p21 protein expression that may counterbalance the risk of proliferative upregulation caused by enhanced Thr172P-Cdk4/Cdk4 activation in liver cancer cells. The inhibition of the mTOR pathway by Sirolimus and Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired translation likely at a very early step of the elongation phase. Tacrolimus and mTOR inhibitors increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role. Interestingly, the administration of immunosuppressants yields a specific pattern of miRNAs. Tacrolimus and mTOR inhibitors decreased miR-92a-1-5p, miR-197-3p, miR-483-3p and miR-720, and increased miR-22-3p, miR-376a-3p, miR-663b, miR-886-5p, miR-1300 and miR-1303 expressions in HepG2 cells.[Conclusion] The more potent pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with an increased activation of PERK and p53 signaling, and p21 protein expression. FKBP12 and FKBP51 appeared to be the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in HepG2 cells. The observed effects of immunosuppressants were related to a specific miRNA signature in liver cancer cells.We thank the Institute of Health Carlos III (ISCiii) cofinanced by the European Regional Development Fund “A way to achieve Europe” (ERDF) (PI13/00021, P16/00090 and PI19/01266), as well as the Andalusian Ministry of the Economy, Innovation, Science and Employment (CTS-6264) and Andalusian Ministry of Health (PI13/00025, PI16/0198, PIP-0215-2020 and PI-0216-2020) for their financial support to J.M. We also thank the Spanish Ministry of Economy and Competitiveness (MINECO) cofinanced by the ERDF (BFU2016-75352-P AEI/FEDER, EU) for their financial support to J.d.l.C. We thank Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCiii and cofinanced by the ERDF for their financial support. E.N-V. acknowledges IFI18/00014 fellowship from the ISCiii. P.d.l.C-O. acknowledges FPU17/00026 fellowship from the Spanish Ministry of Education (MEC). L.C. acknowledges FPU16/05127 fellowship from the MEC

Serum selenium levels do not differ in type 2 diabetic subjects with and without coronary artery disease

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to investigate whether selenium levels differ between type 2 diabetic subjects with and without coronary artery disease (CAD).</p> <p>Methods</p> <p>A total of 200 subjects with type 2 diabetes (100 with CAD and 100 without CAD), consecutively selected from the diabetes outpatient clinic of our hospital were enrolled into the study. A detailed medical history and a physical examination were obtained by all the participants.</p> <p>Results</p> <p>Serum selenium levels did not differ between diabetic subjects with and without CAD (102.40 ± 31.10 vs. 108.86 ± 33.88 microg/L, p = 0.16). In diabetic subjects with CAD multivariate linear regression analysis demonstrated significant independent associations between selenium and sex (beta = 0.21, p = 0.03) and glucose levels (beta = 0.25, p = 0.008). In diabetic subjects without CAD multivariate linear regression analysis demonstrated significant independent associations between selenium and peripheral artery disease (beta = 0.16, p = 0.05) and glucose levels (beta = -0.09, p = 0.05).</p> <p>Conclusion</p> <p>Serum selenium levels did not differ between diabetic subjects with and without CAD. In diabetic subjects with CAD, the only determinants of serum selenium levels were sex and glucose levels. In diabetic subjects without CAD the only determinants of serum selenium levels were peripheral artery disease and glucose levels.</p

The case of a southern European glacier disappearing under recent warming that survived Roman and Medieval warm periods

Mountain glaciers have generally experienced an accelerated retreat over the last three decades as a rapid response to current global warming. However, the response to previous warm periods in the Holocene is not well-described for glaciers of the of southern Europe mountain ranges, such as the Pyrenees. The situation during the Medieval Climate Anomaly (900-1300 CE) is particularly relevant since it is not certain whether the glaciers just experienced significant ice loss or whether they actually disappeared. We present here the first chronological study of a glacier located in the Central Pyrenees (N Spain), the Monte Perdido Glacier (MPG), carried out by different radiochronological techniques and their comparison with geochemical proxies with neighboring paleoclimate records. The result of the chronological model proves that the glacier endured during the Roman Period and the Medieval Climate Anomaly. The lack of ice from last 600 years indicates that the ice formed during the Little Ice Age has melted away. The analyses of the content of several metals of anthropogenic origin, such as Zn, Se, Cd, Hg, Pb, appear in low amounts in MPG ice, which further supports our age model in which the record from the industrial period is lost. This study confirms the exceptional warming of the last decades in the context of last two millennia. We demonstrate that we are facing an unprecedented retreat of the 55 Pyrenean glaciers which survival is compromised beyond a few decades

Genomic mutation profile in progressive chronic lymphocytic leukemia patients prior to first-line chemoimmunotherapy with FCR and rituximab maintenance (REM)

Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. This variability is partly reflected by the mutational status of IGHV genes. Many CLL samples have been studied in recent years by next-generation sequencing. These studies have identified recurrent somatic mutations in NOTCH1, SF3B1, ATM, TP53, BIRC3 and others genes that play roles in cell cycle, DNA repair, RNA metabolism and splicing. In this study, we have taken a deep-targeted massive sequencing approach to analyze the impact of mutations in the most frequently mutated genes in patients with CLL enrolled in the REM (rituximab en mantenimiento) clinical trial. The mutational status of our patients with CLL, except for the TP53 gene, does not seem to affect the good results obtained with maintenance therapy with rituximab after front-line FCR treatment

Factor structure and measurement invariance across various demographic groups and over time for the phq-9 in primary care patients in spain

The Patient Health Questionnaire (PHQ-9) is a widely-used screening tool for depression in primary care settings. The purpose of the present study is to identify the factor structure of the PHQ-9 and to examine the measurement invariance of this instrument across different sociodemographic groups and over time in a sample of primary care patients in Spain. Data came from 836 primary care patients enrolled in a randomized controlled trial (PsicAP study) and a subsample of 218 patients who participated in a follow-up assessment at 3 months. Confirmatory factor analysis (CFA) was used to test one- and two-factor structures identified in previous studies. Analyses of multiple-group invariance were conducted to determine the extent to which the factor structure is comparable across various demo- graphic groups (i.e., gender, age, marital status, level of education, and employment situa- tion) and over time. Both one-factor and two-factor re-specified models met all the pre- established fit criteria. However, because the factors identified in the two-factor model were highly correlated (r = .86), the one-factor model was preferred for its parsimony. Multi-group CFA indicated measurement invariance across different demographic groups and across time. The present findings suggest that physicians in Spain can use the PHQ-9 to obtain a global score for depression severity in different demographic groups and to reliably monitor changes over time in the primary care setting

Documento de posición sobre las necesidades y niveles óptimos de vitamina D

IntroducciónEn los últimos años se ha producido un notable interés por la vitamina D, no sólo por su importancia crucial en el metabolismo mineral óseo, sino también por los efectos extraóseos, cada vez mejor conocidos. Asi mismo, se ha constatado la existencia de valores séricos bajos de vitamina D, por debajo de lo deseable, en diferentes poblaciones, tanto sanas como enfermas, y se discute cuáles serían los niveles óptimos de vitamina D en sangre. Por todo ello, la Sociedad Española de Investigación Ósea y Metabolismo Mineral (SEIOMM), conjuntamente con todas las Sociedades Científicas implicadas en el estudio del metabolismo óseo, han elaborado el presente documento de posición sobre las necesidades y niveles óptimos de vitamina D

Differentiation of haploid and diploid fertilities in Gracilaria chilensis affect ploidy ratio

Background Algal isomorphic biphasic life cycles alternate between free-living diploid (tetrasporophytes) and haploid (dioicious gametophytes) phases and the hypotheses explaining their maintenance are still debated. Classic models state that conditional differentiation between phases is required for the evolutionary stability of biphasic life cycles while other authors proposed that the uneven ploidy abundances observed in the field are explained by their cytological differences in spore production. Results We monitored the state and fate of individuals of the red seaweed Gracilaria chilensis periodically for 3 years in five intertidal pools from two sites with distinct conditions. We tested for differentiation in fecundity and spore survival among the gametophyte males and females (haploids) and the tetrasporophytes (diploids). We tested for the influence of fecundity and spore survival on the observed uneven ploidy abundances in recruits. The probability of a frond becoming fecund was size-dependent, highest for the haploid males and lowest for the haploid females, with the diploids displaying intermediate probabilities. Fecund diploids released more tetraspores than carpospores released by the haploid females. Spore survival depended on ploidy and on the local density of co-habiting adult fronds. An advantage of diploid over haploid germlings was observed at very low and very high adult fronds densities. Conclusions Neither spore production nor spore survival determined the highly variable ploidy ratio within G. chilensis recruits. This result invalidates the hypothesis of natural cytological differences in spore production as the only driver of uneven field ploidy abundances in this species. Diploid spores (carpospores) survived better than haploid spores (tetraspores), especially in locations and time periods that were associated with the occurrence of strong biotic and abiotic stressors. We hypothesise that carpospore survival is higher due to support by their haploid female progenitors passing-on nutrients and chemical compounds improving survival under stressful conditions.AHE was supported by fellowships SFRH/BPD/63703/2009, SFRH/BPD/ 107878/2015 and UID/Multi/04326/2016 of the National Science Foundation FCT of Portugal.info:eu-repo/semantics/publishedVersio