Fluorescein sodium fluorescence microscope‐integrated lymphangiography for lymphatic supermicrosurgery

Microscope‐integrated lymphangiography is a useful method in the field of lymphatic supermicrosurgery. Fluorescence based on indocyanine green (ICG) is the most commonly used. Fluorescein sodium is a fluorescent tracer used for retinal and neurosurgical angiography but not yet for lymphatic supermicrosurgery. In this report, we present a case in which the fluorescein sodium fluorescence microscope‐integrated lymphangiography was used for assessment of lymphatic drainage pathway and patency in a patient treated for secondary lymphedema by lymphaticovenular anastomoses. Fluorescein sodium fluorescence microscope‐integrated lymphangiography was evaluated in a 67‐year‐old female presented for a Campisi clinical stage IV lymphedema of the upper limb. Transcutaneous guidance and vascular fluorescence were assessed. A comparison with ICG fluorescence was made intraoperatively. Two lymphaticovenular anastomoses were performed and their patency were checked by lymphangiography. Transcutaneous signal was found higher with fluorescein sodium fluorescence. Intraluminal visualization was possible with fluorescein sodium coloration during lymphaticovenular anastomoses. No adverse reaction occurred. The circumferential differential reduction rate of affected limb was 8.1% 3 months after lymphaticovenular anastomoses. The use of fluorescence microscope‐integrated lymphangiography with fluorescein sodium may be superior to ICG fluorescence in assistance of lymphaticovenular anastomoses. © 2015 Wiley Periodicals, Inc. Microsurgery 35:407–410, 2015.     

Graphene nanomaterials as biocompatible and conductive scaffolds for stem cells: impact for tissue engineering and regenerative medicine

The discovery of the interesting intrinsic properties of graphene, a two‐dimensional nanomaterial, has boosted further research and development for various types of applications from electronics to biomedicine. During the last decade, graphene and several graphene‐derived materials, such as graphene oxide, carbon nanotubes, activated charcoal composite, fluorinated graphenes and three‐dimensional graphene foams, have been extensively explored as components of biosensors or theranostics, or to remotely control cell–substrate interfaces, because of their remarkable electro‐conductivity. To date, despite the intensive progress in human stem cell research, only a few attempts to use carbon nanotechnology in the stem cell field have been reported. Interestingly, most of the recent in vitro studies indicate that graphene‐based nanomaterials (i.e. mainly graphene, graphene oxide and carbon nanotubes) promote stem cell adhesion, growth, expansion and differentiation. Although cell viability in vitro is not affected, their potential nanocytoxicity (i.e. nanocompatibility and consequences of uncontrolled nanobiodegradability) in a clinical setting using humans remains unknown. Therefore, rigorous internationally standardized clinical studies in humans that would aim to assess their nanotoxicology are requested. In this paper we report and discuss the recent and pertinent findings about graphene and derivatives as valuable nanomaterials for stem cell research (i.e. culture, maintenance and differentiation) and tissue engineering, as well as for regenerative, translational and personalized medicine (e.g. bone reconstruction, neural regeneration). Also, from scarce nanotoxicological data, we also highlight the importance of functionalizing graphene‐based nanomaterials to minimize the cytotoxic effects, as well as other critical safety parameters that remain important to take into consideration when developing nanobionanomaterials. Copyright © 2014 John Wiley & Sons, Ltd.     

From the Cover: Warming enabled upslope advance in western US forest fires

Increases in burned area and large fire occurrence are widely documented over the western United States over the past half century. Here, we focus on the elevational distribution of forest fires in mountainous ecoregions of the western United States and show the largest increase rates in burned area above 2,500 m during 1984 to 2017. Furthermore, we show that high-elevation fires advanced upslope with a median cumulative change of 252 m (−107 to 656 m; 95% CI) in 34 y across studied ecoregions. We also document a strong interannual relationship between high-elevation fires and warm season vapor pressure deficit (VPD). The upslope advance of fires is consistent with observed warming reflected by a median upslope drift of VPD isolines of 295 m (59 to 704 m; 95% CI) during 1984 to 2017. These findings allow us to estimate that recent climate trends reduced the high-elevation flammability barrier and enabled fires in an additional 11% of western forests. Limited influences of fire management practices and longer fire-return intervals in these montane mesic systems suggest these changes are largely a byproduct of climate warming. Further weakening in the high-elevation flammability barrier with continued warming has the potential to transform montane fire regimes with numerous implications for ecosystems and watersheds.

Fire is an integral component of most forested lands and provides significant ecological services (1). However, burned area, fire size, the number of large fires, and the length of fire season have increased in the western United States in recent decades (2, 3). Increasing fire activity and the expansion of wildland urban interface (4) collectively amplified direct and indirect fire-related loss of life and property (5, 6) and contributed to escalating fire suppression costs (7). While increased biomass due to a century of fire exclusion efforts is hypothesized to have partially contributed to this trend (8), climate change is also implicated in the rise of fire activity in the western United States (9–11).Although increases in forest fire activity are evident in all major forested lands in the western United States (2, 12, 13), an abundance of moisture—due to snowpack persistence, cooler temperatures, and delayed summer soil and fuel drying—provides a strong buffer of fire activity (13) and longer fire-return intervals (14) at high elevations. Recent studies, however, point to changing fire characteristics across many ecoregions of the western United States (15), including high-elevation areas of the Sierra Nevada (16), Pacific Northwest, and Northern Rockies (12, 17). These studies complement documented changes in montane environments including amplified warming with elevation (18), widespread upward elevational shift in species (19), and increased productivity in energy-limited high-elevation regions that enhance fuel growth and connectivity (20). These changes have been accompanied by longer snow-free periods (21), increased evaporative demand (9), and regional declines in fire season precipitation frequency (11) across the western United States promoting increased fuel ignitability and flammability that have well-founded links to forest burned area. A warmer climate is also conducive to a higher number of convective storms and more frequent lightning strikes (22).In this study, we explore changes in the elevational distribution of burned forest across the western United States and how changes in climate have affected the mesic barrier for high-elevation fire activity. We focus on changes in high-elevation forests that have endured fewer direct anthropogenic modifications compared to drier low-elevation forests that had frequent low-severity fires prior to European colonization and have been more subject to changes in settlement patterns as well as fire suppression and harvest (23, 24); we also pose the following questions: 1) Has the elevational distribution of fire in the western US forests systematically changed? and 2) What changes in biophysical factors have enabled such changes in high-elevation fire activity? We explore these questions across 15 mountainous ecoregions of the western United States using records from large fires (>405 ha) between 1984 and 2017 [Monitoring Trends in Burn Severity (MTBS) (25)], a 10-m–resolution digital elevation model, and daily high-spatial–resolution surface meteorological data [gridMET (26)].We focus on the trends in Z₉₀—defined as the 90th percentile of normalized annual elevational distribution of burned forest in each ecoregion. Here, the term “normalized” essentially refers to the fraction of forest area burned by elevation. We complement this analysis by examining trends in burned area by elevational bands and using quantile regression of normalized annual forest fire elevation. We then assess the interannual relationships between Z₉₀ and vapor pressure deficit (VPD) and compare the upslope advance in montane fire to elevational climate velocity of VPD during 1984 to 2017. Specifically, we use VPD trends and VPD–high-elevation fire regression to estimate VPD-driven changes in Z₉₀ and BA₉₀— defined as annual burned area above the 90th percentile of forest elevational distribution in each ecoregion—during 1984 to 2017.     

From the Cover: The precise temporal calibration of dinosaur origins

Dinosaurs have been major components of ecosystems for over 200 million years. Although different macroevolutionary scenarios exist to explain the Triassic origin and subsequent rise to dominance of dinosaurs and their closest relatives (dinosauromorphs), all lack critical support from a precise biostratigraphically independent temporal framework. The absence of robust geochronologic age control for comparing alternative scenarios makes it impossible to determine if observed faunal differences vary across time, space, or a combination of both. To better constrain the origin of dinosaurs, we produced radioisotopic ages for the Argentinian Chañares Formation, which preserves a quintessential assemblage of dinosaurian precursors (early dinosauromorphs) just before the first dinosaurs. Our new high-precision chemical abrasion thermal ionization mass spectrometry (CA-TIMS) U–Pb zircon ages reveal that the assemblage is early Carnian (early Late Triassic), 5- to 10-Ma younger than previously thought. Combined with other geochronologic data from the same basin, we constrain the rate of dinosaur origins, demonstrating their relatively rapid origin in a less than 5-Ma interval, thus halving the temporal gap between assemblages containing only dinosaur precursors and those with early dinosaurs. After their origin, dinosaurs only gradually dominated mid- to high-latitude terrestrial ecosystems millions of years later, closer to the Triassic–Jurassic boundary.The Triassic Period (252.2–201.3 Ma) is a key interval of earth history that witnessed the origin of many faunal and floral components of modern terrestrial ecosystems, and was punctuated by at least two large-scale environmental perturbations, the end-Permian and end-Triassic mass extinctions (1). These events frame the evolutionary history of nonmarine tetrapod communities during the Triassic, resulting in a long-recognized threefold division: (i) lineages that survived the end-Permian mass extinction; (ii) a wide variety of new Triassic lineages that did not survive the end-Triassic mass extinction; and (iii) the first representatives of lineages that dominated later Mesozoic and Cenozoic ecosystems (2, 3). Among the third group is arguably the most contentious of Mesozoic macroevolutionary events: the origin and rise of dinosaurs (4–8).Although dinosaurs have often been cited as a classic case of an evolutionary radiation, many disparate hypotheses have been proposed for their origin and subsequent rapid rise to global dominance (4–8). One of the major difficulties with testing these hypotheses has been the lack of precise biostratigraphically independent age constraints for early dinosaur-bearing assemblages, which would provide a firm temporal basis for comparing origin scenarios across time and space (9).Robust analysis of macroevolutionary patterns requires well-documented assemblages with fossil specimens examined in a phylogenetic context, as well as an independent, accurate, and precise geochronologic framework. As recently pointed out, analyses of the origin and early diversification of dinosaurs have suffered from an overreliance on low-resolution (both stratigraphic and taxonomic) vertebrate biostratigraphy that obscures real faunal differences in time and space (10). This situation is particularly problematic for Triassic nonmarine communities, where tetrapod composition across Pangea appears to be particularly heterogeneous (11–13). Without precise independent age control (other than vertebrate biostratigraphic correlations), it is impossible to determine if these faunal differences vary across time, space, or a combination of both.Among the many uncertainties regarding dinosaur evolution is the timing of the origin and subsequent radiation of this clade and their closest relatives (early dinosauromorphs). Contrasting hypotheses suggest they appeared anywhere between soon after the end-Permian extinction (∼252 Ma) to very close in time to the first dinosaurs (∼231 Ma) (14). This question has been put to the fore by recent discoveries of African dinosauromorphs (15) from strata thought to be early Middle Triassic in age, ∼245–242 Ma. Nonetheless, the significance of these fossils for understanding the early evolutionary history of the group is unclear as they lack a precise time framework, with the age of the strata based solely on vertebrate correlations among unconnected Gondwanan basins. This problem has been exacerbated by the recent recognition that these vertebrate index taxa may differ in age across Gondwana (16). To resolve these outstanding major issues, we examined the Agua de la Peña succession of the Ischigualasto–Villa Unión Basin in northwestern Argentina, which contains an extensive dinosaur and dinosaur-precursor record for investigating the timing of the origin and early diversification of dinosauromorphs (Fig. 1).Open in a separate windowFig. 1.Geological map of the Chañares–Gualo area in Talampaya National Park (La Rioja Province). The main fossiliferous localities are the Romer locality and Río Gualo. The latter locality is where the detailed section (SI Appendix) was measured. (Right) Generalized stratigraphic column from Río Gualo showing the sampled levels. For additional references, see SI Appendix.     

Fusobacterium nucleatum infection mimicking metastatic cancer

A 48-year-old man presented with fevers, chills, weight loss, multiple liver masses, and several superficial and deep venous thromboses in lower extremities. Cancer work up was negative. A liver biopsy grew Fusobacterium nucleatum. To our knowledge, F. nucleatum infection presenting with multiple liver masses and Trousseau-like syndrome has not been reported earlier.