Is hypoxia training good for muscles and exercise performance?

Altitude training has become very popular among athletes as a means to further increase exercise performance at sea level or to acclimatize to competition at altitude. Several approaches have evolved during the last few decades, with "live high-train low" and "live low-train high" being the most popular. This review focuses on functional, muscular, and practical aspects derived from extensive research on the "live low-train high" approach. According to this, subjects train in hypoxia but remain under normoxia for the rest of the time. It has been reasoned that exercising in hypoxia could increase the training stimulus. Hypoxia training studies published in the past have varied considerably in altitude (2300-5700 m) and training duration (10 days to 8 weeks) and the fitness of the subjects. The evidence from muscle structural, biochemical, and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available performance capacity data such as maximal oxygen uptake (Vo(2)max) and (maximal) power output, hypoxia as a supplement to training is not consistently found to be advantageous for performance at sea level. Stronger evidence exists for benefits of hypoxic training on performance at altitude. "Live low-train high" may thus be considered when altitude acclimatization is not an option. In addition, the complex pattern of gene expression adaptations induced by supplemental training in hypoxia, but not normoxia, suggest that muscle tissue specifically responds to hypoxia. Whether and to what degree these gene expression changes translate into significant changes in protein concentrations that are ultimately responsible for observable structural or functional phenotypes remains open. It is conceivable that the global functional markers such as Vo(2)max and (maximal) power output are too coarse to detect more subtle changes that might still be functionally relevant, at least to high-level athletes.

Training in hypoxia and its effects on skeletal muscle tissue

It is well established that local muscle tissue hypoxia is an important consequence and possibly a relevant adaptive signal of endurance exercise training in humans. It has been reasoned that it might be advantageous to increase this exercise stimulus by working in hypoxia. However, as long-term exposure to severe hypoxia has been shown to be detrimental to muscle tissue, experimental protocols were developed that expose subjects to hypoxia only for the duration of the exercise session and allow recovery in normoxia (live low-train high or hypoxic training). This overview reports data from 27 controlled studies using some implementation of hypoxic training paradigms. Hypoxia exposure varied between 2300 and 5700 m and training duration ranged from 10 days to 8 weeks. A similar number of studies was carried out on untrained and on trained subjects. Muscle structural, biochemical and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available data on global estimates of performance capacity such as maximal oxygen uptake (VO2max) and maximal power output (Pmax), hypoxia as a supplement to training is not consistently found to be of advantage for performance at sea level. There is some evidence mainly from studies on untrained subjects for an advantage of hypoxic training for performance at altitude. Live low-train high may be considered when altitude acclimatization is not an option.

Loss of the high-affinity pentamidine transporter is responsible for high levels of cross-resistance between arsenical and diamidine drugs in African trypanosomes

Treatment of many infectious diseases is under threat from drug resistance. Understanding the mechanisms of resistance is as high a priority as the development of new drugs. We have investigated the basis for cross-resistance between the diamidine and melaminophenyl arsenical classes of drugs in African trypanosomes. We induced high levels of pentamidine resistance in a line without the tbat1 gene that encodes the P2 transporter previously implicated in drug uptake. We isolated independent clones that displayed very considerable cross-resistance with melarsen oxide but not phenylarsine oxide and reduced uptake of [(3)H]pentamidine. In particular, the high-affinity pentamidine transport (HAPT1) activity was absent in the pentamidine-adapted lines, whereas the low affinity pentamidine transport (LAPT1) activity was unchanged. The parental tbat1(-/-) line was sensitive to lysis by melarsen oxide, and this process was inhibited by low concentrations of pentamidine, indicating the involvement of HAPT1. This pentamidine-inhibitable lysis was absent in the adapted line KO-B48. Likewise, uptake of the fluorescent diamidine 4',6-diamidino-2-phenylindole dihydrochloride was much delayed in live KO-B48 cells and insensitive to competition with up to 10 muM pentamidine. No overexpression of the Trypanosoma brucei brucei ATP-binding cassette transporter TbMRPA could be detected in KO-B48. We also show that a laboratory line of Trypanosoma brucei gambiense, adapted to high levels of resistance for the melaminophenyl arsenical drug melarsamine hydrochloride (Cymelarsan), had similarly lost TbAT1 and HAPT1 activity while retaining LAPT1 activity. It seems therefore that selection for resistance to either pentamidine or arsenical drugs can result in a similar phenotype of reduced drug accumulation, explaining the occurrence of cross-resistance.

Pseudovacuoles--immobilized by high-pressure freezing--are associated with blebbing in walker carcinosarcoma cells

By applying high pressure freezing and freeze-substitution, we observed large inclusions of homogeneous appearance in the front of locomoting Walker carcinosarcoma cells that have not been described earlier. Live cell imaging revealed that these inclusions were poor in lipids and nucleic acids but had a high lysine (and hence protein) content. Usually one such structure 2-5 mum in size was present at the front of motile Walker cells, predominantly in the immediate vicinity of newly forming blebs. By correlating the lysine-rich areas in fixed and embedded cells with electron microscopic pictures, inclusions could be assigned to confined, faintly stained cytoplasmic areas that lacked a surrounding membrane; they were therefore called pseudovacuoles. After high-pressure freezing and freeze substitution, pseudovacuoles appeared to be filled with 20 nm large electron-transparent patches surrounded by 12 and 15 nm large particles. The heat shock protein Hsp90 was identified by peptide sequencing as a major fluorescent band on SDS-PAGE of lysine-labelled Walker cell extracts. By immunofluorescence, Hsp90 was found to be enriched in pseudovacuoles. Colocalization of the lysine with a potassium-specific dye in living cells revealed that pseudovacuoles act as K+ stores in the vicinity of forming blebs. We propose that pseudovacuoles might support blebbing by locally regulating the intracellular hydrostatic pressure.

Infection prevention strategies in a stem cell transplant unit: impact of change of care in isolation practice and routine use of high dose intravenous immunoglobulins on infectious complications and transplant related mortality

OBJECTIVE: Nursing in 'live islands' and routine high dose intravenous immunoglobulins after allogeneic hematopoietic stem cell transplantation were abandoned by many teams in view of limited evidence and high costs. METHODS: This retrospective single-center study examines the impact of change from nursing in 'live islands' to care in single rooms (SR) and from high dose to targeted intravenous immunoglobulins (IVIG) on mortality and infection rate of adult patients receiving an allogeneic stem cell or bone marrow transplantation in two steps and three time cohorts (1993-1997, 1997-2000, 2000-2003). RESULTS: Two hundred forty-eight allogeneic hematopoetic stem cell transplantations were performed in 227 patients. Patient characteristics were comparable in the three cohorts for gender, median age, underlying disease, and disease stage, prophylaxis for graft versus host disease (GvHD) and cytomegalovirus constellation. The incidence of infections (78.4%) and infection rates remained stable (rates/1000 days of neutropenia for sepsis 17.61, for pneumonia 6.76). Cumulative incidence of GvHD and transplant-related mortality did not change over time. CONCLUSIONS: Change from nursing in 'live islands' to SR and reduction of high dose to targeted IVIG did not result in increased infection rates or mortality despite an increase in patient age. These results support the current practice.

High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral cortex: EEG topography during waking and subsequent sleep.

Repetitive transcranial magnetic stimulation (rTMS) is a novel research tool in neurology and psychiatry. It is currently being evaluated as a conceivable alternative to electroconvulsive therapy for the treatment of mood disorders. Eight healthy young (age range 21-25 years) right-handed men without sleep complaints participated in the study. Two sessions at a 1-week interval, each consisting of an adaptation night (sham stimulation) and an experimental night (rTMS in the left dorsolateral prefrontal cortex or sham stimulation; crossover design), were scheduled. In each subject, 40 trains of 2-s duration of rTMS (inter-train interval 28 s) were applied at a frequency of 20 Hz (i.e. 1600 pulses per session) and at an intensity of 90% of the motor threshold. Stimulations were scheduled 80 min before lights off. The waking EEG was recorded for 10-min intervals approximately 30 min prior to and after the 20-min stimulations, and polysomnographic recordings were obtained during the subsequent sleep episode (23.00-07.00 h). The power spectra of two referential derivations, as well as of bipolar derivations along the antero-posterior axis over the left and right hemispheres, were analyzed. rTMS induced a small reduction of sleep stage 1 (in min and percentage of total sleep time) over the whole night and a small enhancement of sleep stage 4 during the first non-REM sleep episode. Other sleep variables were not affected. rTMS of the left dorsolateral cortex did not alter the topography of EEG power spectra in waking following stimulation, in the all-night sleep EEG, or during the first non-REM sleep episode. Our results indicate that a single session of rTMS using parameters like those used in depression treatment protocols has no detectable side effects with respect to sleep in young healthy males.

A climatological analysis of high-precipitation events in Dronning Maud Land, Antarctica, and associated large-scale atmospheric conditions

The link between high precipitation in Dronning Maud Land (DML), Antarctica, and the large-scale atmospheric circulation is investigated using ERA-Interim data for 1979–2009. High-precipitation events are analyzed at Halvfarryggen situated in the coastal region of DML and at Kohnen Station located in its interior. This study further includes a comprehensive comparison of high precipitation in ERA-Interim with precipitation data from the Antarctic Mesoscale Prediction System (AMPS) and snow accumulation measurements from automatic weather stations (AWSs), with the limitations of such a comparison being discussed. The ERA-Interim and AMPS precipitation data agree very well. However, the correspondence between high precipitation in ERA-Interim and high snow accumulation at the AWSs is relatively weak. High-precipitation events at both Halvfarryggen and Kohnen are typically associated with amplified upper level waves. This large-scale atmospheric flow pattern is preceded by the downstream development of a Rossby wave train from the eastern South Pacific several days before the precipitation event. At the surface, a cyclone located over the Weddell Sea is the main synoptic ingredient for high precipitation both at Halvfarryggen and at Kohnen. A blocking anticyclone downstream is not a requirement for high precipitation per se, but a larger share of blocking occurrences during the highest-precipitation days in DML suggests that these blocks strengthen the vertically integrated water vapor transport (IVT) into DML. A strong link between high precipitation and the IVT perpendicular to the local orography suggests that IVT could be used as a “proxy” for high precipitation, in particular over DML's interior.

Religion as Culture? How European and American High Courts Endorse Majority Religion

This paper examines a trend in European and American High Courts to endorse majority religion by transforming it into “culture”, and thus by secularizing it. To dissociate religion and state is the hallmark of the liberal state. However, no state has ever managed a perfect separation, not even the American. Under conditions of mounting religious pluralism and ongoing secularization, there is pressure on the state to live up to its “neutrality”. A main strategy to square the circle of neutrality and incomplete dissociation from religion is to declare it “culture”, which gives the state the license to associate or even identify with it (as guardian of nationhood). The paper compares recent American and European High Court rules on religious symbols (especially crucifixes) that exhibits this strategy, addressing similarities and differences as well as the limits and pitfalls of “culturalizing” religion.