Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide. Our previous results indicate that the reduced oxidative stress capacity of sickle erythrocytes may be caused by decreased expression of NRF2 (Nuclear factor (erythroid-derived 2)-like 2), an oxidative stress regulator. We found that activation of NRF2 with sulforaphane (SFN) in erythroid progenitors significantly increased the expression of NRF2 targets HMOX1, NQO1, and HBG1 (subunit of fetal hemoglobin) in a dose-dependent manner. Therefore, we hypothesized that NRF2 activation with SFN may offer therapeutic benefits for SCD patients by restoring oxidative capacity and increasing fetal hemoglobin concentration. To test this hypothesis, we performed a Phase 1, open-label, dose-escalation study of SFN, contained in a broccoli sprout homogenate (BSH) that naturally contains SFN, in adults with SCD. The primary and secondary study endpoints were safety and physiological response to NRF2 activation, respectively. We found that BSH was well tolerated, and the few adverse events that occurred during the trial were not likely related to BSH consumption. We observed an increase in the mean relative whole blood mRNA levels for the NRF2 target HMOX1 (p = 0.02) on the last day of BSH treatment, compared to pre-treatment. We also observed a trend toward increased mean relative mRNA levels of the NRF2 target HBG1 (p = 0.10) from baseline to end of treatment, but without significant changes in HbF protein. We conclude that BSH, in the provided doses, is safe in stable SCD patients and may induce changes in gene expression levels. We therefore propose investigation of more potent NRF2 inducers, which may elicit more robust physiological changes and offer clinical benefits to SCD patients.Trial Registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01715480","term_id":"NCT01715480"}}NCT01715480     

Theoretical insight into three disease-related benefits of migration

Migration (seasonal round-trip movement across relatively large distances) is common within the animal kingdom. This behaviour often incurs extreme costs in terms of time, energy, and/or survival. Climate, food, predation, and breeding are typically suggested as factors favouring the evolution of migration. Although disease regulation has also been considered, few studies consider it as the primary selective pressure for migration. Our aim was to determine, theoretically, under what conditions migration could reduce the long-term disease prevalence within a population, assuming the only benefits of migration are infection-related. We created two mathematical models, one where the population migrates annually and one where the entire population remains on the breeding ground year-round. In each we simulated disease transmission (frequency-dependent and density-dependent) and quantified eventual disease prevalence. In the migration model we varied the time spent migrating, disease-related migration mortality, and the overall migration mortality. When we compared results from the two models, we found that migration generally lowered disease prevalence. We found a population was healthier if it: (1) spent more time migrating (assuming no disease transmission during migration), (2) had higher disease-induced migration mortality, and (3) had an overall higher mortality when migrating (compared to not migrating). These results provide support for two previously proposed mechanisms by which migration can reduce disease prevalence (migratory escape and migratory cull), and also demonstrate that non-selective mortality during migration is a third mechanism. Our findings indicate that migration may be evolutionarily advantageous even if the only migratory benefit is disease control.     

Influence of Nematode Parasitism,Body Size,Temperature, and Diel Period on the Flight Capacity of <Emphasis Type="Italic">Sirex noctilio</Emphasis> F. (Hymenoptera: Siricidae)

Sirex noctilio F. (Hymenoptera: Siricidae) is a woodwasp of pine trees that has recently invaded and established in North American forests. Although S. noctilio has had a limited impact in North America to date, there is some concern that it could have a significant impact on pine plantations, especially in the southeastern U.S.A. Moreover, there are few data on the flight capacity of male S. noctilio. We found no association between parasitism by D. siricidicola and whether or not S. noctilio initiated flight on the flight mill. Male wasps that were parasitized by nematodes were heavier than non-parasitized males, but there was no significant difference in mass between parasitized and non-parasitized females. We also examined the flight capacity of male and female S. noctilio in relation to nematode parasitism, body mass, temperature (for only males), and diel period. Body mass, temperature, and diel period affected flight in S. noctilio such that wasps were generally observed to fly faster, farther, and more frequently if they were heavier, flying at warmer temperatures, and flying during the photoperiod. The fact that nematode-parasitized male wasps were found to fly farther than the non-parasitized males is consistent with the hypothesis that nematode parasitism does not negatively affect the flight capacity of S. noctilio.     

Apps can help bridge restoration science and restoration practice

Scientists need to find innovative ways to communicate their findings with restoration practitioners in an era of global change. Apps are a promising bridge between restoration science and practice because they apply broad scientific concepts to specific situations. For example, habitat connectivity promotes ecological function, but practitioners lack ways to incorporate connectivity into decision‐making. We created an app where users calculate how habitat restoration or loss affects connectivity. By providing our app as an example and discussing the benefits and challenges in creating apps for practitioners, we encourage other restoration ecologists to similarly create apps that bridge science with practice.     

The what and where of primate field research may be failing primate conservation

With approximately 30% of nonhuman primate species listed as critically endangered, the window of opportunity to conserve primates is closing fast. In this article, we focus on the degree to which publications in field primatology are biased in favor of particular taxa and field sites. We examined more than 29,000 peer‐reviewed articles and identified 876 field visits to 349 field sites. We found a highly clumped distribution by site and species. We also examined publication ethical statements and the extent to which they acknowledged local human communities (<5%). Due to a lack of consistency across publications, we provide recommendations for improving ethical statements and for evaluating research impact. Given the plight of primate biodiversity, these results suggest broader coverage of primate species and geographies, as well as more attention to the local human communities whose support is necessary if the intent is to have primate species in the wild in the 22nd century.     

Current perspectives on biosimilars

In this work, an overview of the biosimilars market, pipeline and industry targets is discussed. Biosimilars typically have a shorter timeline for approval (8 years) compared to 12 years for innovator drugs and the development cost can be 10–20% of the innovator drug. The biosimilar pipeline is reviewed as well as the quality management system (QMS) that is needed to generate traceable, trackable data sets. One difference between developing a biosimilar compared to an originator is that a broader analytical foundation is required for biosimilars and advances made in developing analytical similarity to characterize these products are discussed. An example is presented on the decisions and considerations explored in the development of a biosimilar and includes identification of the best process parameters and methods based on cost, time, and titer. Finally factors to consider in the manufacture of a biosimilar and approaches used to achieve the target-directed development of a biosimilar are discussed.