GTPBP3 is an evolutionary conserved protein presumably involved in mitochondrial tRNA (mt-tRNA) modification. In humans, GTPBP3 mutations cause hypertrophic cardiomyopathy with lactic acidosis, and ...have been associated with a defect in mitochondrial translation, yet the pathomechanism remains unclear. Here we use a GTPBP3 stable-silencing model (shGTPBP3 cells) for a further characterization of the phenotype conferred by the GTPBP3 defect. We experimentally show for the first time that GTPBP3 depletion is associated with an mt-tRNA hypomodification status, as mt-tRNAs from shGTPBP3 cells were more sensitive to digestion by angiogenin than tRNAs from control cells. Despite the effect of stable silencing of GTPBP3 on global mitochondrial translation being rather mild, the steady-state levels and activity of Complex I, and cellular ATP levels were 50% of those found in the controls. Notably, the ATPase activity of Complex V increased by about 40% in GTPBP3 depleted cells suggesting that mitochondria consume ATP to maintain the membrane potential. Moreover, shGTPBP3 cells exhibited enhanced antioxidant capacity and a nearly 2-fold increase in the uncoupling protein UCP2 levels. Our data indicate that stable silencing of GTPBP3 triggers an AMPK-dependent retrograde signaling pathway that down-regulates the expression of the NDUFAF3 and NDUFAF4 Complex I assembly factors and the mitochondrial pyruvate carrier (MPC), while up-regulating the expression of UCP2. We also found that genes involved in glycolysis and oxidation of fatty acids are up-regulated. These data are compatible with a model in which high UCP2 levels, together with a reduction in pyruvate transport due to the down-regulation of MPC, promote a shift from pyruvate to fatty acid oxidation, and to an uncoupling of glycolysis and oxidative phosphorylation. These metabolic alterations, and the low ATP levels, may negatively affect heart function.
Aliment Pharmacol Ther 2011; 33: 619–633
Summary
Background Viral hepatitis is a very common infection.
Aim To review the prevention and management of hepatitis B virus (HBV) and hepatitis C virus ...(HCV) infection in inflammatory bowel disease (IBD).
Methods Bibliographical searches were performed in MEDLINE up to September 2010.
Results The prevalence of both HBV and HCV infection in IBD patients is now similar to that of the general population. All IBD patients should be screened for HBV markers at diagnosis. Liver dysfunction in IBD patients treated with immunosuppressants is more frequent and severe in HBV than in HCV carriers and is associated with combined immunosuppression. In patients receiving anti‐TNF drugs, HBV reactivation is common unless anti‐viral prophylaxis is administered. HBsAg‐positive patients should receive anti‐viral prophylaxis before starting immunosuppressants. As interferon might worsen underlying IBD, nucleoside/nucleotide analogues are preferred for anti‐viral prophylaxis in patients with HBV (tenofovir/entecavir are preferred to lamivudine). IBD patients should be vaccinated against HBV at diagnosis. The response rate to HBV vaccination is low, mainly in those receiving anti‐TNF therapy. The serological response to HBV vaccine should be confirmed, and patients with an inadequate response should receive a second full series of vaccine. Peginterferon (±ribavirin) for HCV infection is as effective and safe as in non‐IBD patients.
Conclusions The present manuscript poses a series of questions on the prevention and management of HBV/HCV infection in IBD, and attempts to answer them using scientific evidence in order to provide practical conclusions for the clinician.
Implementation of digital tools and processes in Higher Education Institutions (HEIs) as an emergent activity depends on the sociomaterial relationships between institutional factors that dynamically ...interact with each other. This article systematically explores through a literature review some of the most relevant and up‐to‐date published studies to identify the ‘important factors’ to consider for the implementation of digital tools and processes in HEI. The goal of the paper is to turn these factors, conceived initially as previous conditions or characteristics of the institutions or people, into a list of strategic elements to be fostered by HEI leadership teams to promote better implementation of digital tools and processes in their institutions. In the final part of this work, we propose a framework that reflects these elements in a visual approach that highlights the activity‐centred character of the framework as well as the emergent character of the implementation process itself.
La implementación de herramientas y procesos digitales en las Instituciones de Educación Superior (IES) como actividad emergente depende de las relaciones sociomateriales entre los factores institucionales que interactúan dinámicamente entre sí. Este artículo explora de manera sistemática a través de una revisión de la literatura algunos de los estudios publicados más relevantes y actualizados para identificar los ‘factores importantes’ a considerar para la implementación de herramientas y procesos digitales en las IES. El objetivo del artículo es convertir estos factores, concebidos inicialmente como condiciones o características previas de las instituciones o de las personas, en una lista de elementos estratégicos que deben ser impulsados por los equipos de dirección de las IES para promover una mejor implementación de herramientas y procesos digitales en sus instituciones. En la parte final de este trabajo, proponemos un marco que refleja estos elementos en un enfoque visual destacando el carácter centrado en la actividad del marco, así como el carácter emergente del propio proceso de implementación.
Introduction
About the term cognitive-behavioral minority disease or rare disease are a group of diseases that affect between 6-8% of the populatio. It is estimated that there are more than 7000 in ...the world, the majority with a genetic basis and affect various organs and systems, they also present psychiactric comorbidities and cause a physical or mental disability. Given its definition, it is difficult to see a large number of these patients in our usual clinical activity, so their management can be complicated.
Objectives
To evaluate the prevalence of psychiatric comorbidity and the prevalence of psyhcopharmacological treatment in children and adolescents whe present a minority disease.
Methods
This is a descriptive, controlled, retrospective cross-sectional study of a sample obtained by non-probabilistic sampling, which is representative of the study population.
The statistical analysis was made using the statistical program SPSS V22 (2013).
Results
With a sample of 114 patients, of which 26,6% presented fragile X syndrome, secondly 25,3% presented Prader-Willi Syndrome and 48,1% other chromosomal abnormalities.
By subgroups (male:female): in Prader-Willi syndrome 6:14 (30%:70%), in Fragile X syndrome 12:9 (57,14%: 42,86%) and in other diseases 25:13 (75,69%: 34,21%).
Conclusions
The creation of clinical expert units makes the possibility to increase knowledge of diseases whose prevalence in the population, thanks to technological advances, is increasing and where scientific knowledge is still limited.
These units are also important, in order to be able to offer personalized intensive treatments in order to reduce polypharmacy. There is not a great difference between the minority diagnosis and polypharmacy, although there is less polypharmacy than expected, which may be the result of the success of the most intensive and personal psychotherapeutic intervention in the unit.
Disclosure of Interest
None Declared
The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess ...the safety of thiopurines and anti-TNF-α drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy.
Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-α drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn.
A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio = 0.6; 95% confidence interval = 0.4-0.9, P = 0.02) was the only predictor of favorable GPO, whereas maternal age >35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-α drugs was not associated with an unfavorable GPO.
The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.
Borrelia burgdorferi, the aetiological agent of Lyme disease, utilizes multiple adhesins to interact with both the arthropod vector and mammalian hosts it colonizes. One such adhesive molecule is a ...surface‐exposed fibronectin‐binding lipoprotein, designated BBK32. Previous characterization of BBK32‐mediated fibronectin binding has been limited to biochemical analyses due to the difficulty in mutagenizing infectious isolates of B. burgdorferi. Here we report an alternative method to inactivate bbk32 via allelic exchange through use of a low‐passage variant of B. burgdorferi strain B31 that is more readily transformed. The resulting mutant does not synthesize BBK32, exhibits reduced fibronectin binding in solid phase assays and manifests decreased interactions with mouse fibroblast cells relative to both the infectious parent and genetic complement. Furthermore, the bbk32 knockout was significantly attenuated in the murine model of Lyme disease, whereas a genetically complemented control was not, indicating that BBK32 is necessary for maximal B. burgdorferi infection in the mouse. To our knowledge this is the first mutational analysis of a surface exposed, functional borrelial lipoprotein adhesin whose activity is associated with the mammalian host environment. By analogy with other pathogens that utilize fibronectin binding as an important virulence determinant, the borrelial fibronectin-BBK32 interaction is likely to be important in B. burgdorferi‐specific pathogenic mechanisms, particularly in the context of dissemination, secondary colonization and/or persistence.
A reduction in adult survival in long-living species may compromise population growth rates. The spur-thighed tortoise (Testudo graeca) is a long-lived reptile that is threatened by habitat loss and ...fragmentation. Golden eagles (Aquila chrysaetos), whose breeding habitats overlap that of tortoises, may predate them by dropping them onto rocks and breaking their carapaces. In SE Spain, the number of golden eagles has increased in the last decades and the abundance of their main prey (i.e., rabbits Oryctolagus cuniculus) has decreased. Our aims were to 1) describe the role of tortoises in golden eagles' diet, and 2) estimate the predation impact of golden eagles on tortoises in eagles' territories and in the regional tortoise population. We collected regurgitated pellets and prey remains under eagle nests and roosts, and obtained information on tortoise abundance and population structure and rabbit abundance. We found that tortoises were an alternative prey to rabbits, so that eagles shifted to the former where the latter were scarce. The average predation rate on tortoises was very low at the two studied scales. However, eagles showed a marked selection for adult female tortoises, which led the tortoise sex ratio to be biased towards males in those eagle territories with higher tortoise predation. Whether this may compromise the spur-thighed tortoise long-term population viability locally deserves further attention.
The degradation kinetics of ascorbic acid was determined in orange–carrot juice treated by PEF in order to establish its shelf life. Different electric field intensities (25, 30, 35, and 40
kV/cm) ...and different treatment times (from 30 to 340
μs) were studied. The ascorbic acid degradation rate (
k) obtained was −0.009
±
0.0008
μs
−1, −0.0140
±
0.0009
μs
−1, −0.0220
±
0.0023
μs
−1 and −0.0187
±
0.0049
μs
−1 for fields of 25, 30, 35, and 40
kV/cm, respectively. The treatment selected was 25
kV/cm. The shelf life of the orange–carrot juice treated by pulses at 25
kV/cm for two times (280
μs and 330
μs) was compared with a heat-treated juice (98
°C, 21
s) kept in refrigerated storage at 2 and 10
°C. The remaining concentration of ascorbic acid in the pasteurized orange–carrot juice was 83%, whereas in the PEF-treated juice it was 90%. The ascorbic acid degradation rate in the juice stored at 2
°C was less than in the juice stored at 10
°C, and in the pasteurized juice it was greater. PEF treatment at 25
kV/cm for 280–330
μs extended the half-life of the juice stored at 2
°C to 50 days.
There is no information about the frequency of liver dysfunction in patients with inflammatory bowel disease (IBD) treated with immunosuppressants and infected with hepatitis B (HBV) and/or C virus ...(HCV).
To assess the influence of immunosuppressants on the course of HBV and HCV infection in IBD.
Patients with IBD with HBV and/or HCV infection from 19 Spanish hospitals were included. Clinical records were reviewed for the type of immunosuppressant used, treatment duration, liver function tests and viral markers before, during and after each immunosuppressant. Logistic and Cox regression analysis were used to identify predictors of outcome.
162 patients were included; 104 had HBV markers (25 HBsAg positive) and 74 had HCV markers (51 HCV-RNA positive), and 16 patients had markers of both infections. Liver dysfunction was observed in 9 of 25 HBsAg positive patients (36%), 6 of whom developed hepatic failure. Liver dysfunction in HCV was observed in 8 of 51 HCV-RNA positive patients (15.7%), and only one developed hepatic failure. The frequency and severity of liver dysfunction was significantly higher in HBV-infected patients than in HCV-infected patients (p=0.045 and p=0.049, respectively). Treatment with ≥2 immunosuppressants was an independent predictor of HBV reactivation (OR 8.75; 95% CI 1.16 to 65.66). The majority of patients without reactivation received only one immunosuppressant for a short period and/or prophylactic antiviral treatment. No definite HBV reactivations were found in anti-HBc positive patients lacking HBsAg.
Liver dysfunction in patients with IBD treated with immunosuppressants is more frequent and severe in those with HBV than in HCV carriers and is associated with combined immunosuppression.
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