Significant molecular and systemic adaptations after repeated sprint training in hypoxia

While intermittent hypoxic training (IHT) has been reported to evoke cellular responses via hypoxia inducible factors (HIFs) but without substantial performance benefits in endurance athletes, we hypothesized that repeated sprint training in hypoxia could enhance repeated sprint ability (RSA) performed in normoxia via improved glycolysis and O(2) utilization. 40 trained subjects completed 8 cycling repeated sprint sessions in hypoxia (RSH, 3000 m) or normoxia (RSN, 485 m). Before (Pre-) and after (Post-) training, muscular levels of selected mRNAs were analyzed from resting muscle biopsies and RSA tested until exhaustion (10-s sprint, work-to-rest ratio 1ratio2) with muscle perfusion assessed by near-infrared spectroscopy. From Pre- to Post-, the average power output of all sprints in RSA was increased (p<0.01) to the same extent (6% vs 7%, NS) in RSH and in RSN but the number of sprints to exhaustion was increased in RSH (9.4+/-4.8 vs. 13.0+/-6.2 sprints, p<0.01) but not in RSN (9.3+/-4.2 vs. 8.9+/-3.5). mRNA concentrations of HIF-1alpha (+55%), carbonic anhydrase III (+35%) and monocarboxylate transporter-4 (+20%) were augmented (p<0.05) whereas mitochondrial transcription factor A (-40%), peroxisome proliferator-activated receptor gamma coactivator 1alpha (-23%) and monocarboxylate transporter-1 (-36%) were decreased (p<0.01) in RSH only. Besides, the changes in total hemoglobin variations (Delta[tHb]) during sprints throughout RSA test increased to a greater extent (p<0.01) in RSH. Our findings show larger improvement in repeated sprint performance in RSH than in RSN with significant molecular adaptations and larger blood perfusion variations in active muscles.

Results of the 2nd scientific workshop of the ECCO (III): basic mechanisms of intestinal healing.

The second scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal healing for the disease course of inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms, markers for disease prediction, detection and monitoring of intestinal healing, impact of intestinal healing on the disease course of IBD as well as therapeutic strategies. The results of this workshop are presented in four separate manuscripts. This section describes basic mechanisms of intestinal healing, identifies open questions in the field and provides a framework for future studies.

Role of the HCF-1 basic region in sustaining cell proliferation.

BACKGROUND: The human herpes simplex virus-associated host cell factor 1 (HCF-1) is a conserved human transcriptional co-regulator that links positive and negative histone modifying activities with sequence-specific DNA-binding transcription factors. It is synthesized as a 2035 amino acid precursor that is cleaved to generate an amino- (HCF-1(N)) terminal subunit, which promotes G1-to-S phase progression, and a carboxy- (HCF-1(C)) terminal subunit, which controls multiple aspects of cell division during M phase. The HCF-1(N) subunit contains a Kelch domain that tethers HCF-1 to sequence-specific DNA-binding transcription factors, and a poorly characterized so called "Basic" region (owing to a high ratio of basic vs. acidic amino acids) that is required for cell proliferation and has been shown to associate with the Sin3 histone deacetylase (HDAC) component. Here we studied the role of the Basic region in cell proliferation and G1-to-S phase transition assays. METHODOLOGY/PRINCIPAL FINDINGS: Surprisingly, much like the transcriptional activation domains of sequence-specific DNA-binding transcription factors, there is no unique sequence within the Basic region required for promoting cell proliferation or G1-to-S phase transition. Indeed, the ability to promote these activities is size dependent such that the shorter the Basic region segment the less activity observed. We find, however, that the Basic region requirements for promoting cell proliferation in a temperature-sensitive tsBN67 cell assay are more stringent than for G1-to-S phase progression in an HCF-1 siRNA-depletion HeLa-cell assay. Thus, either half of the Basic region alone can support G1-to-S phase progression but not cell proliferation effectively in these assays. Nevertheless, the Basic region displays considerable structural plasticity because each half is able to promote cell proliferation when duplicated in tandem. Consistent with a potential role in promoting cell-cycle progression, the Sin3a HDAC component can associate independently with either half of the Basic region fused to the HCF-1 Kelch domain. CONCLUSIONS/SIGNIFICANCE: While conserved, the HCF-1 Basic region displays striking structural flexibility for controlling cell proliferation.

Ombres et lumières de l'accès public a la défibrillation [Public access defibrillation]

La stratégie d'accès public à la défibrillation (APD) comprend l'installation de défibrillateurs automatiques externes (DAE) dans les lieux publics et l'entraînement de sauveteurs non professionnels à la réanimation cardio pulmonaire et à la défibrillation (RCP-D). Cette approche est recommandée pour le traitement des arrêts cardiaques (ACR) dans les lieux publics. Beaucoup d'études d'observation, mais peu d'études randomisées s'intéressant à cette approche ont été publiées. Cet article résume les différentes approches proposées dans le cadre d'APD. A notre avis, l'installation de DAE dans des lieux publics ou le choix d'une stratégie alternative doivent être précédés d'une étude de la démographie locale des ACR et de l'entraînement du plus grand nombre possible de laïcs à la reconnaissance des signes précurseurs d'ACR et au massage cardiaque externe. Placement of automated external defibrillators (AED) in public facilities and training of the lay persons in basic life support-defibrillation (BLS-D) was recommended by the American Heart Association for the treatment of out-of-hospital cardiac arrest (OHCA). Immediate use of AED result in increase of survival to hospital discharge. Many observation and much less randomized trials describe clinical efficacy of this approach. However, "negative" trials have also been published and some recent data suggest that public access defibrillation (PAD) will have a minimal impact on population survival. In this article various PAD strategies were briefly reviewed. In our opinion installation of AED in public places should be based on the long-term study of local OHCA demography and preceded by widespread BLS training of lay population.

Vectorial capacity, basic reproduction number, force of infection and all that: formal notation to complete and adjust their classical concepts and equations

A dimensional analysis of the classical equations related to the dynamics of vector-borne infections is presented. It is provided a formal notation to complete the expressions for the Ross' Threshold Theorem, the Macdonald's basic reproduction "rate" and sporozoite "rate", Garret-Jones' vectorial capacity and Dietz-Molineaux-Thomas' force of infection. The analysis was intended to provide a formal notation that complete the classical equations proposed by these authors.

L' Aula de Teatre de la Universitat de Vic (ATUV) : una aproximació a la seva trajectòria

El present treball de recerca explora i descriu alguns dels aspectes més rellevants del que ha estat la trajectòria de l’Aula de Teatre de la UVic (ATUV) al llarg dels anys. Consta de dues parts diferenciades. En la primera, presento de forma breu alguns dels elements bàsics de caràcter històric que configuren la relació del teatre amb l’educació, fent una especial referència al teatre universitari a l’estat espanyol i a Catalunya. La segona part del treball es desdobla, a la vegada, en dues perspectives. En una, dono compte de l’evolució realitzada per l’Aula de Teatre de la Universitat de Vic, des del punt de vista de la seva organització, característiques i funcionament, i produccions. S’ha fet una memòria descriptiva dels 18 anys de trajectòria de l’ATUV. La segona perspectiva aporta la visió del conjunt de persones (estudiants i exestudiants) que han passat per l’ATUV i que fan, a partir d’un qüestionari tramès prèviament, una valoració dels objectius de dinamització cultural de la Universitat que es proposa l’aula, així com dels aspectes de formació humanística que comprenen el treball de valors, d’habilitats i d’actituds com a procés de creixement personal que han viscut en la seva experiència a l’ATUV..

A new training set-up for trans-apical aortic valve replacement.

Trans-apical aortic valve replacement (AVR) is a new and rapidly growing therapy. However, there are only few training opportunities. The objective of our work is to build an appropriate artificial model of the heart that can replace the use of animals for surgical training in trans-apical AVR procedures. To reduce the necessity for fluoroscopy, we pursued the goal of building a translucent model of the heart that has nature-like dimensions. A simplified 3D model of a human heart with its aortic root was created in silico using the SolidWorks Computer-Aided Design (CAD) program. This heart model was printed using a rapid prototyping system developed by the Fab@Home project and dip-coated two times with dispersion silicone. The translucency of the heart model allows the perception of the deployment area of the valved-stent without using heavy imaging support. The final model was then placed in a human manikin for surgical training on trans-apical AVR procedure. Trans-apical AVR with all the necessary steps (puncture, wiring, catheterization, ballooning etc.) can be realized repeatedly in this setting.

Getting ready for malaria elimination: a check list of critical issues to consider

In recent years, a renewed interest in malaria elimination and eradication has emerged and seems to be rooting in the minds of the scientific community, public health specialists, funding bodies, policy makers and politicians. Malaria eradication will certainly benefit from improved and innovative tools; notwithstanding novel knowledge in fields ranging from basic science to mathematical modelling and health systems research. However, the elimination of malaria also encompasses a broad range of essential aspects that countries and other actors need to consider when thinking of embarking on such an adventure, including the implementation of innovative strategies, the ability to incorporate the most up-to-date evidence into policy, the integration of malaria into the broader health agenda, the strengthening of surveillance and health systems, capacity building, funding, advocacy and, very importantly, research. While in some cases this enthusiasm is clearly justified, some countries are still a long way from realistically advancing towards elimination. This paper attempts to provide guidance on all the necessary issues that should be considered when initiating a malaria elimination program.

Unison or cacophony: postgraduate training in pathology in Europe.

With the free movement of people in the European Union, medical mobility has increased significantly. This is notably the case for disciplines for which shortage of well-trained staff has occurred. Pathology is among those specialties and effectively the discipline is confronted with a striking increase in mobility among trainees and qualified specialists. The presumption underlying unlimited mobility is that the competencies of the medical specialists in the European countries are more or less equal, including significant similarities in the postgraduate training programs. In order to assess whether reality corresponds with this presumption, we conducted a survey of the content and practice requirements of the curricula in the EU and affiliated countries. The results indicate a striking heterogeneity in the training program content and practice requirements. To name a few elements: duration of the training program varied between 4 and 6 years; the number of autopsies required varied between none at all and 300; the number of biopsies required varied between none at all and 15,000. We conclude that harmonization of training outcomes in Europe is a goal that needs to be pursued. This will be difficult to reach through harmonization of training programs, as these are co-determined by political, cultural, and administrative factors, difficult to influence. Harmonization might be attained by defining the general and specific competencies at the end of training and subsequent testing them through a test to which all trainees in Europe are subjected.

CoDaPack. An Excel and Visual Basic based software of compositional data analysis. Current version and discussion form upcoming versions

In the eighties, John Aitchison (1986) developed a new methodological approach for the statistical analysis of compositional data. This new methodology was implemented in Basic routines grouped under the name CODA and later NEWCODA inMatlab (Aitchison, 1997). After that, several other authors have published extensions to this methodology: Marín-Fernández and others (2000), Barceló-Vidal and others (2001), Pawlowsky-Glahn and Egozcue (2001, 2002) and Egozcue and others (2003). (...)