Hepatitis E in post‐liver transplantation: is it time to routinely consider it?

Hepatitis E, although commonly recognized in the Eastern Hemisphere, is less well recognized in the West. Particularly owing to this disease's grave impact on outcomes after liver transplantation, greater consideration of hepatitis E is necessary in the context of abnormal liver tests. Here, we review the most recent data on detecting and managing hepatitis E, both pre‐ and post‐liver transplantation, discuss major detection assay limitations, consider future directions, and propose an algorithm for the diagnosis and management of pre‐and post‐transplantation hepatitis E.     

Melatonin and maturation pace in female three-spined stickleback, Gasterosteus aculeatus

In many animals sexual maturation is controlled by the photoperiod. In mammals, the photoperiodic message is mediated via melatonin, but it is unclear whether this also applies to fishes. Administration of melatonin via the water on a schedule aimed at mimicking a short nonstimulatory photoperiod cycle has been found not to inhibit maturation in male three-spined sticklebacks, Gasterosteus aculeatus, kept under stimulatory long photoperiods. To study whether melatonin affects maturation pace, adult female sticklebacks kept under stimulatory photoperiodic regimes of Light:Dark (LD) 24:0 h (Exp. 1) or LD 16:8 h (Exp. 2) and 18 degrees were treated with melatonin (0, 20, or 80 microg/L water) via the water for 16 h per day. In addition, females were also kept under a nonstimulatory short photoperiod (LD 8:16). The time at which full maturation was achieved (running roe) was noted and the ovaries of nonovulated fish were studied histologically. Most fish under LD 24:0 and LD 16:8 matured (maturation rates in Exp. 1 and 2, respectively: control, 100 and 86%; low-dose melatonin, 83 and 93%; high-dose melatonin, 90 and 75%), whereas almost all females kept under LD 8:16 remained immature (maturation rates: 0% in Exp. 1 and 3% in Exp. 2). There was no difference in maturation pace, proportion of fish maturing, or relative ovarian weights between controls and melatonin-treated fish kept under LD 16:8. Furthermore, there was no difference in proportion of fish maturing or relative ovarian weights between controls and melatonin-treated fish kept under LD 24:0. However, LD 24:0 controls matured significantly earlier than fish receiving the high melatonin dose. Thus, there was an inhibitory effect of the high melatonin dose on maturation pace under LD 24:0. Nevertheless, this effect was small compared to the inhibitory effect of LD 8:16 treatment, suggesting that at least in this season, the major part of the photoperiodic effects in the stickleback is mediated via mechanisms other than circulating melatonin.     

Biological and clinical features of low-molecular-weight heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a common adverse effect of unfractionated heparin (UFH) therapy. In contrast, only a few patients have been reported with HIT following low-molecular-weight heparin (LMWH) therapy (LMW-HIT). To define the clinical and biological characteristics of LMW-HIT, 180 patients treated for suspected HIT at 15 French centres were investigated. Clinical history was recorded and HIT was confirmed in 59 patients with positive serotonin release assay results: 57 of them had high levels of antibodies (Abs) to heparin-platelet factor 4 complexes (H/PF4) and two had Abs to interleukin 8. Eleven patients were treated exclusively with LMWH (LMW-HIT) and 48 with UFH either alone (UF-HIT, n = 34) or combined with LMWH (UF/LMW-HIT, n = 14). The LMW-HIT and UF-HIT groups were similar with respect to sex, age, platelet count before heparin therapy, frequency of bleeding and occurrence of disseminated intravascular coagulation. The interval to onset of HIT was longer in LMW-HIT patients compared with UF-HIT patients (P = 0.03). Severe thrombocytopenia (platelets < 15 x 10(9)/l) was more frequent in the LMW-HIT group (P = 0.04). Thrombosis occurred in three of 11 LMW-HIT patients, i.e. as frequently as in UF-HIT patients. LMW-HIT is potentially severe and may be observed after longer heparin treatment compared with UF-HIT. It is highly recommended, therefore, that platelet counts be monitored carefully whenever LMWH is administered.     

Cost-Effectiveness Models for Chronic Obstructive Pulmonary Disease: Cross-Model Comparison of Hypothetical Treatment Scenarios

ObjectivesTo compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios.MethodsCOPD modeling groups simulated four hypothetical interventions with their model and compared the results with a reference scenario of no intervention. The four interventions modeled assumed 1) 20% reduction in decline in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in all-cause mortality, and 4) all these effects combined. The interventions were simulated for a 5-year and lifetime horizon with standardization, if possible, for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality due to other causes, utilities, costs, and discount rates. Furthermore, uncertainty around the outcomes of intervention four was compared.ResultsSeven out of nine contacted COPD modeling groups agreed to participate. The 5-year incremental cost-effectiveness ratios (ICERs) for the most comprehensive intervention, intervention four, was €17,000/quality-adjusted life-year (QALY) for two models, €25,000 to €28,000/QALY for three models, and €47,000/QALY for the remaining two models. Differences in the ICERs could mainly be explained by differences in input values for disease progression, exacerbation-related mortality, and all-cause mortality, with high input values resulting in low ICERs and vice versa. Lifetime results were mainly affected by the input values for mortality. The probability of intervention four to be cost-effective at a willingness-to-pay value of €50,000/QALY was 90% to 100% for five models and about 70% and 50% for the other two models, respectively.ConclusionsMortality was the most important factor determining the differences in cost-effectiveness outcomes between models.     

A pragmatist approach to the hope discourse in health care research

Hope is a central concept in nursing and other fields of health care. However, there is no consensus about the concept of hope. We argue that seeking consensus is futile given the multifaceted and multidimensional nature of the concept, but instead we encourage in‐depth studies of the assumptions behind talk about hope in specific contexts. Our approach to the ‘science of hope’ is inspired by philosophical pragmatism. We argue that hope is a concept that opens different rooms for action in different contexts and that accordingly, all hope interventions are contextually sensitive. Careful attention to how the relative positions and power of nurses and patients influence what can be inferred from their different ways of talking about hope may make hopeful conversations more meaningful in health care relationships.     

High-intensity intermittent cycling increases purine loss compared with workload-matched continuous moderate intensity cycling

Purpose

Exercise at 50–60 % of peak oxygen consumption (VO_{2 peak}) stimulates maximal fat oxidation rates. Despite a lower estimated work performed; high-intensity intermittent exercise (HIIE) training produces greater fat mass reductions when compared with workload-matched continuous (CON) steady state exercise. No metabolic basis has been documented nor mechanisms offered to explain this anomaly. This study investigated the physiological and metabolic responses of two different workload-matched exercise protocols.

Methods

On separate occasions and at least 1 week apart, eight apparently healthy males cycled for 30 min at either 50 % VO_{2 peak} (CON) or performed repeated 20 s bouts of supramaximal exercise at 150 %VO_{2 peak} separated by 40 s rest (HIIE).

Results

The average heart rate, oxygen consumption, plasma glycerol and free fatty acid concentrations were not different during exercise and recovery between the trials. Plasma lactate and hypoxanthine (Hx) concentrations were elevated and urinary excretion rates of Hx and uric acid were greater following HIIE as compared to CON (P < 0.05).

Conclusion

Exercise-induced plasma Hx accumulation and urinary purine excretion are greater following HIIE and indirectly represents a net loss of adenosine triphosphate (ATP) from the muscle. The subsequent restorative processes required for intramuscular de novo replacement of ATP may contribute to a negative energy balance and in part, account for the potential accelerated fat loss observed with HIIE when compared with CON training programs.     

The origin of volatile elements in the Earth–Moon system

The origin of volatile species such as water in the Earth–Moon system is a subject of intense debate but is obfuscated by the potential for volatile loss during the Giant Impact that resulted in the formation of these bodies. One way to address these topics and place constraints on the temporal evolution of volatile components in planetary bodies is by using the observed decay of ⁸⁷Rb to ⁸⁷Sr because Rb is a moderately volatile element, whereas Sr is much more refractory. Here, we show that lunar highland rocks that crystallized ∼4.35 billion years ago exhibit very limited ingrowth of ⁸⁷Sr, indicating that prior to the Moon-forming impact, the impactor commonly referred to as “Theia” and the proto-Earth both must have already been strongly depleted in volatile elements relative to primitive meteorites. These results imply that 1) the volatile element depletion of the Moon did not arise from the Giant Impact, 2) volatile element distributions on the Moon and Earth were principally inherited from their precursors, 3) both Theia and the proto-Earth probably formed in the inner solar system, and 4) the Giant Impact occurred relatively late in solar system history.

Understanding the formation of the Moon has long been a topic of intense interest, although hard constraints on this event only developed after the Apollo program returned lunar samples to Earth. Based on the thousands of lunar rocks that have been studied to date, arguably one of the most stringent of these constraints is that the Moon is strongly depleted in volatile elements relative to the solar photosphere, primitive meteorites, and Earth. Recognition of such a depletion of volatile elements, combined with the orbital mechanics of the Moon and geochemical evidence that it differentiated from a mostly molten state, led to the now widely accepted “Giant Impact” hypothesis, in which the Moon accreted from a volatile element–depleted debris disk produced by an impact between a Mars-sized body (Theia) and the proto-Earth (1). Yet, the formation of the Moon through such an impact scenario raises questions about the composition of the proto-Earth and Theia and their respective contributions to the makeup and subsequent evolution of the Earth–Moon system. Of particular interest is how and when the Moon and Earth obtained their present allotments of volatile components, including, and most importantly, water. Did the Moon and Earth form with their current allotments of volatile elements, or were these elements lost during the Giant Impact and reintroduced to Earth by later accretion of volatile element–laden materials? Here, we address this issue using the Rb–Sr isotopic systematics of lunar samples to provide time constraints on the history and distribution of volatile elements in the Earth–Moon system.