A Recombinant System and Reporter Viruses for Papiine Alphaherpesvirus 2

Primate simplex viruses, including Herpes simplex viruses 1 and 2, form a group of closely related herpesviruses, which establish latent infections in neurons of their respective host species. While neuropathogenic infections in their natural hosts are rare, zoonotic transmission of Macacine alphaherpesvirus 1 (McHV1) from macaques to humans is associated with severe disease. Human infections with baboon-derived Papiine alphaherpesvirus 2 (PaHV2) have not been reported, although PaHV2 and McHV1 share several biological properties, including neuropathogenicity in mice. The reasons for potential differences in PaHV2 and McHV1 pathogenicity are presently not understood, and answering these questions will require mutagenic analysis. Here, we report the development of a recombinant system, which allows rescue of recombinant PaHV2. In addition, we used recombineering to generate viruses carrying reporter genes (Gaussia luciferase or enhanced green fluorescent protein), which replicate with similar efficiency as wild-type PaHV2. We demonstrate that these viruses can be used to analyze susceptibility of cells to infection and inhibition of infection by neutralizing antibodies and antiviral compounds. In summary, we created a recombinant system for PaHV2, which in the future will be invaluable for molecular analyses of neuropathogenicity of PaHV2.     

Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience

BackgroundMigraine frequency increases after the cessation of successful preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs). In this study, we aimed to evaluate the course of migraine after treatment resumption.MethodsPatients with migraine, who started treatment with the same CGRP(-R) mAb after a three-month drug holiday were included in this analysis. We collected headache data at four prospective visits: 1) during the four weeks before the initial mAb treatment (baseline); 2) during the four weeks before the last mAb injection; 3) in weeks 13–16 of the drug holiday; 4) in weeks 9–12 after treatment restart. Outcomes were the changes in monthly migraine days (MMD), monthly headache days (MHD), monthly days with acute medication use (AMD) and Headache Impact Test-6 (HIT-6) scores across the observation period.ResultsThis study included 39 patients (erenumab n = 16; galcanezumab/ fremanezumab n = 23). MMD decreased from 12.3 ± 6.3 at the end of the drug holiday to 7.8 ± 5.5 three months after treatment restart (p = 0.001). The improvement after treatment resumption was similar to the response in the initial treatment period (baseline: 12.3 ± 6.3 MMD vs. 7.5 ± 5.2 MMD before treatment interruption). MHD and AMD showed a significant improvement after treatment restart. HIT-6 scores decreased, indicating a diminished impact of headache on everyday life.ConclusionsReinitiation of treatment with CGRP(-R) mAbs after a drug holiday leads to a significant reduction of migraine frequency and medication use as well as improvement in quality of life.     

Injuries in Professional Male Soccer Players in the Netherlands: A Prospective Cohort Study

Context:Injuries are a major adverse event in a soccer player''s career. Reducing injury incidence requires a thorough knowledge of the epidemiology of soccer injuries.Objective:To investigate the incidence and characteristics of injuries in the Dutch premier soccer league.Design:Cohort study.Setting:The Dutch premier soccer league.Results:A total of 286 injuries were recorded, affecting 62.7% of the players. The overall injury incidence was 6.2 injuries per 1000 player-hours, 2.8 in training sessions and 32.8 in matches. Most of the recorded injuries were acute (68.5%). Eight percent of the injuries were classified as recurrent. Injuries were most likely to be located in the lower extremities (82.9%). Injury time loss ranged from 1 to 752 days, with a median of 8 days. Knee injuries had the greatest consequences in terms of days of absence from soccer play (on average, 45 days). The most common diagnosis was muscle/tendon injury of the lower extremities (32.9%).Conclusions:Injury risk in the Dutch premier soccer league is high, especially during matches. Preventive measures should focus on the most common diagnoses, namely, muscle/tendon injuries of the lower extremities.Key Words: football, incidence, epidemiology, elite athletes

Key Points

• Injury risk in the Dutch premier soccer league is high; during 1 season, 62.7% of the players sustained an injury.
• Injuries most often affected the lower extremities (groin, posterior thigh, knee, lower leg/Achilles tendon, and ankle).
• Recurrent injuries caused longer absences than did first-time injuries, and knee injuries had the greatest consequences in time lost from soccer play.
• Preventive measures should focus on the most common diagnoses, namely, muscle/tendon injuries of the lower extremities.

Soccer is the sport with the greatest participation globally.¹ More than 200 million people from 203 nations are members of the Federation of International Football Associations (FIFA), while the Union of European Football Associations (UEFA) has 23 million members in 51 countries.² Outdoor soccer was played by 2635 clubs and approximately 60 500 teams in the Netherlands during the 2011–2012 season. There are currently more than 1.2 million licensed members of the Royal Netherlands Football Association, 45% of whom are adult males.³To obtain a good ranking in competition, soccer players have to be talented, well trained, and healthy, so injuries are a major adverse event in a soccer player''s career. Medical and surgical treatment and rehabilitation interrupt the player''s activity for a period ranging from a few weeks to several months.² If many injuries are sustained, team results can suffer.⁴ Reducing the injury incidence and increasing player safety requires a thorough knowledge of the epidemiology of soccer injuries.⁵ One major problem in the epidemiologic assessment of soccer injuries, however, is the methodologic inconsistency among studies. For example, injury definitions and methods for data collection and recording often differ considerably among studies.^6,7Investigations that describe injury risk and injury patterns in professional soccer have typically been conducted during tournaments,^8–11 have involved only teams at the highest European level,^10,12 have covered only part of a season,¹³ or were related to only 1 team.^14,15 Limited published research has included data on injuries within 1 national professional male soccer competition and involving multiple teams. Hence, little is known about the differences among countries in injury risk and injury patterns in professional male soccer players. During the last 10 years, acute and overuse injuries during matches and training sessions within national professional male soccer competitions have been recorded in Denmark¹³ and Sweden.^16–18 In view of the differences in performance level, medical support, match frequencies, and climate, it is plausible that the incidence and severity of soccer injuries may differ between Scandinavian and other European soccer leagues.¹⁸ Therefore, our study aimed to prospectively record injuries in the Dutch premier soccer league to investigate the incidence and characteristics of injuries in male professional soccer players during 1 entire soccer season.     

Biome boundary maintained by intense belowground resource competition in world’s thinnest-rooted plant community

Recent findings point to plant root traits as potentially important for shaping the boundaries of biomes and for maintaining the plant communities within. We examined two hypotheses: 1) Thin-rooted plant strategies might be favored in biomes with low soil resources; and 2) these strategies may act, along with fire, to maintain the sharp boundary between the Fynbos and Afrotemperate Forest biomes in South Africa. These biomes differ in biodiversity, plant traits, and physiognomy, yet exist as alternative stable states on the same geological substrate and in the same climate conditions. We conducted a 4-y field experiment to examine the ability of Forest species to invade the Fynbos as a function of growth-limiting nutrients and belowground plant–plant competition. Our results support both hypotheses: First, we found marked biome differences in root traits, with Fynbos species exhibiting the thinnest roots reported from any biome worldwide. Second, our field manipulation demonstrated that intense belowground competition inhibits the ability of Forest species to invade Fynbos. Nitrogen was unexpectedly the resource that determined competitive outcome, despite the long-standing expectation that Fynbos is severely phosphorus constrained. These findings identify a trait-by-resource feedback mechanism, in which most species possess adaptive traits that modify soil resources in favor of their own survival while deterring invading species. Our findings challenge the long-held notion that biome boundaries depend primarily on external abiotic constraints and, instead, identify an internal biotic mechanism—a selective feedback among traits, plant–plant competition, and ecosystem conditions—that, along with contrasting fire regime, can act to maintain biome boundaries.

Recent findings (1) have demonstrated striking differences in plant rooting strategies across biomes worldwide, spawning the hypothesis that belowground competition for soil resources may be critical for maintaining biome boundaries (1, 2). This idea differs fundamentally from the historical notion that biomes primarily are delineated by extrinsic abiotic factors such as climate, geological parent material, or topography (3–8), or the more recent recognition that aboveground plant adaptations can promote fire-determined plant communities (9, 10).Belowground competition introduces a biotic mechanism that is intrinsic to the plant community, emerges from plant–plant contest for resources, and may help explain the puzzling observation that biome boundaries can persist independent of climate–geological factors (4, 10).Of central importance is Ma et al.’s (1) recent observation that root traits that are associated with resource uptake appear to differ across biomes with differing soil resource dynamics. Specifically, Ma et al. hypothesized that thin-rooted plant strategies may be favored in biomes with permanently or seasonally low soil resources. They reasoned that, in those conditions, natural selection would favor absorptive roots [i.e., first-order roots (1, 11)] with low diameter and high specific root length (i.e., root length per unit photosynthetic carbon invested), which, in turn, are traits that allow high root surface area and efficient exploration of resource-poor soils. Conversely, thick roots and low specific root length may remain competitive traits in biomes with abundant soil resources, despite reduced root surface area and less efficient soil exploration.Here we test Ma et al.’s hypothesis (1) using a unique study of root traits and plant–plant resource competition across the boundary of two distinct biomes within the Cape Floristic Region of South Africa: Fynbos and Afrotemperate Forest. We show in Fig. 1 and 12, 13), by slow decomposition and nutrient recycling (14), and by low stores of soil organic matter (15). In contrast, the Afrotemperate Forest biome is defined by a substantial accumulation of soil organic matter and organic-bound nutrients, which, in turn, supports high rates of plant–soil–nutrient recycling. Based on Ma et al.’s hypothesis, we would expect that these sharp differences in soil resource conditions would result in divergent belowground root traits across the biome boundary.Open in a separate windowFig. 1.Sharp differences in biodiversity, aboveground plant traits, and ecosystem properties across the South African Fynbos–Forest boundary. (A) Two neighboring biomes of the Cape Floristic Region—the Fynbos (62) and the Afrotemperate Forest (63)—form a sharp boundary despite perching on the same geological parent material (39). (B) Biodiversity: The hyperdiverse Fynbos harbors >7,000 plant species, of which the majority are endemic to South Africa (64). The Afrotemperate Forest, on the other hand, contains >450 species with less endemism (63). (C) Aboveground plant traits: Fynbos species generally possess thick and small leaves with a high carbon-to-nitrogen (C:N) ratio while Afrotemperate Forest species display thinner and larger leaves with a lower C:N ratio. In addition, Fynbos plant species possess traits that either enhance (e.g., waxes) or resist (e.g., thick bark) fire. For example, Fynbos vegetation contains high concentrations of flammable organic compounds (e.g., crude fat content) that can facilitate very hot fires (65). In contrast, Afrotemperate Forest species tend to be sensitive to fire and possess traits that suppress fire (e.g., high water content). (D) Ecosystem properties: Fynbos soils are exceedingly poor in soil carbon, nitrogen, and phosphorus contents. In contrast, the Afrotemperate Forest soil is characterized by a developed layer rich in carbon, nitrogen, and phosphorus, which facilitates active cycling of nutrients between plant and soil pools (66, 67).Table 1.Comparison of neighboring Fynbos and Afrotemperate Forest

Virtual Resection: A New Tool for Preparing for Nephron-Sparing Surgery in Wilms Tumor Patients

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome.     

Cubic Iron Core–Shell Nanoparticles Functionalized to Obtain High-Performance MRI Contrast Agents

Nanoparticles with SiO 2 coating were synthesized to have a cubic iron core. These were found to have saturation magnetization very close to the highest possible value of any iron-containing nanoparticles and the bulk iron saturation magnetization. The in vitro toxicology studies show that they are highly biocompatible and possess better MRI contrast agent potential than iron oxide NPs.     

Incommensurate antiferromagnetism in a pure spin system via cooperative organization of local and itinerant moments

Materials with strong correlations are prone to spin and charge instabilities, driven by Coulomb, magnetic, and lattice interactions. In materials that have significant localized and itinerant spins, it is not obvious which will induce order. We combine electrical transport, X-ray magnetic diffraction, and photoemission studies with band structure calculations to characterize successive antiferromagnetic transitions in GdSi. GdSi has both sizable local moments and a partially nested Fermi surface, without confounding contributions from orbital effects. We identify a route to incommensurate order where neither type of moment dominates, but is rooted in cooperative feedback between them. The nested Fermi surface of the itinerant electrons induces strong interactions between local moments at the nesting vector, whereas the ordered local moments in turn provide the necessary coupling for a spin-density wave to form among the itinerant electrons. This mechanism echoes the cooperative interactions between electrons and ions in charge-density–wave materials, and should be germane across a spectrum of transition-metal and rare-earth intermetallic compounds.