Adverse effects of fillers and their histopathology.

Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options.

Late cardiac sodium current can be assessed using automated patch-clamp

The cardiac late Na (+) current is generated by a small fraction of voltage-dependent Na (+) channels that undergo a conformational change to a burst-gating mode, with repeated openings and closures during the action potential (AP) plateau. Its magnitude can be augmented by inactivation-defective mutations, myocardial ischemia, or prolonged exposure to chemical compounds leading to drug-induced (di)-long QT syndrome, and results in an increased susceptibility to cardiac arrhythmias. Using CytoPatch™ 2 automated patch-clamp equipment, we performed whole-cell recordings in HEK293 cells stably expressing human Nav1.5, and measured the late Na (+) component as average current over the last 100 ms of 300 ms depolarizing pulses to -10 mV from a holding potential of -100 mV, with a repetition frequency of 0.33 Hz. Averaged values in different steady-state experimental conditions were further corrected by the subtraction of current average during the application of tetrodotoxin (TTX) 30 μM. We show that ranolazine at 10 and 30 μM in 3 min applications reduced the late Na (+) current to 75.0 ± 2.7% (mean ± SEM, n = 17) and 58.4 ± 3.5% ( n = 18) of initial levels, respectively, while a 5 min application of veratridine 1 μM resulted in a reversible current increase to 269.1 ± 16.1% ( n = 28) of initial values. Using fluctuation analysis, we observed that ranolazine 30 μM decreased mean open probability p from 0.6 to 0.38 without modifying the number of active channels n, while veratridine 1 μM increased n 2.5-fold without changing p. In human iPSC-derived cardiomyocytes, veratridine 1 μM reversibly increased APD90 2.12 ± 0.41-fold (mean ± SEM, n = 6). This effect is attributable to inactivation removal in Nav1.5 channels, since significant inhibitory effects on hERG current were detected at higher concentrations in hERG-expressing HEK293 cells, with a 28.9 ± 6.0% inhibition (mean ± SD, n = 10) with 50 μM veratridine.

Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications

Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment.

Cage-induced stereotypies, perseveration and the effects of environmental enrichment in laboratory mice.

When kept in barren and restrictive cages, animals frequently develop stereotypic behaviour patterns that are characterized by high repetition rates, conspicuous invariance and an apparent lack of function. Although millions of animals are affected, the underlying causes and mechanisms are still unclear. Growing evidence suggests that cage-induced stereotypies may reflect pathological dysfunction within basal ganglia circuitry expressed by perseverative behaviour. In order to assess whether variation in stereotypy performance and variation in perseverative behaviour may have a common cause in ICR CD-1 mice, we assessed the effects of environmental enrichment on both phenomena. We raised 48 female ICR CD-1 mice in standard or enriched cages from three weeks to either 6 or 11 months of age and measured stereotypy level in the home cage and perseveration on an extinction task. We further examined whether enriched rearing conditions (early enrichment) protect mice from the developing stereotypies later in life and whether stereotypies developed in barren cages would persist in an enriched environment (late enrichment) by transferring standard mice to enriched cages and vice versa for 14 weeks after completion of the extinction task. We found no evidence for a causal relation between stereotypy and perseveration in mice. However, transfer to enriched cages reduced stereotypy levels significantly both at 6 and 11 months of age indicating that stereotypies had not become established yet. Finally, we found that removing enrichments at both ages did not induce higher stereotypy levels, thereby confirming earlier reports of a neuroprotective effect of early enrichment.

The impacts of volcanic aerosol on stratospheric ozone and the Northern Hemisphere polar vortex: separating radiative-dynamical changes from direct effects due to enhanced aerosol heterogeneous chemistry

After major volcanic eruptions the enhanced aerosol causes ozone changes due to greater heterogeneous chemistry on the particle surfaces (HET-AER) and from dynamical effects related to the radiative heating of the lower stratosphere (RAD-DYN). We carry out a series of experiments with an atmosphere–ocean–chemistry–climate model to assess how these two processes change stratospheric ozone and Northern Hemispheric (NH) polar vortex dynamics. Ensemble simulations are performed under present day and preindustrial conditions, and with aerosol forcings representative of different eruption strength, to investigate changes in the response behaviour. We show that the halogen component of the HET-AER effect dominates under present-day conditions with a global reduction of ozone (−21 DU for the strongest eruption) particularly at high latitudes, whereas the HET-AER effect increases stratospheric ozone due to N2O5 hydrolysis in a preindustrial atmosphere (maximum anomalies +4 DU). The halogen-induced ozone changes in the present-day atmosphere offset part of the strengthening of the NH polar vortex during mid-winter (reduction of up to −16 m s-1 in January) and slightly amplify the dynamical changes in the polar stratosphere in late winter (+11 m s-1 in March). The RAD-DYN mechanism leads to positive column ozone anomalies which are reduced in a present-day atmosphere by amplified polar ozone depletion (maximum anomalies +12 and +18 DU for present day and preindustrial, respectively). For preindustrial conditions, the ozone response is consequently dominated by RAD-DYN processes, while under present-day conditions, HET-AER effects dominate. The dynamical response of the stratosphere is dominated by the RAD-DYN mechanism showing an intensification of the NH polar vortex in winter (up to +10 m s-1 in January). Ozone changes due to the RAD-DYN mechanism slightly reduce the response of the polar vortex after the eruption under present-day conditions.

Effects of microbeam radiation therapy on normal and tumoral blood vessels

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT.

Interstellar Flow and Temperature Determination with IBEX: Robustness and Sensitivity to Systematic Effects

The Interstellar Boundary Explorer (IBEX) samples the interstellar neutral (ISN) gas flow of several species every year from December through late March when the Earth moves into the incoming flow. The first quantitative analyses of these data resulted in a narrow tube in four-dimensional interstellar parameter space, which couples speed, flow latitude, flow longitude, and temperature, and center values with approximately 3° larger longitude and 3 km s⁻¹ lower speed, but with temperatures similar to those obtained from observations by the Ulysses spacecraft. IBEX has now recorded six years of ISN flow observations, providing a large database over increasing solar activity and using varying viewing strategies. In this paper, we evaluate systematic effects that are important for the ISN flow vector and temperature determination. We find that all models in use return ISN parameters well within the observational uncertainties and that the derived ISN flow direction is resilient against uncertainties in the ionization rate. We establish observationally an effective IBEX-Lo pointing uncertainty of ±0°18 in spin angle and confirm an uncertainty of ±0°1 in longitude. We also show that the IBEX viewing strategy with different spin-axis orientations minimizes the impact of several systematic uncertainties, and thus improves the robustness of the measurement. The Helium Warm Breeze has likely contributed substantially to the somewhat different center values of the ISN flow vector. By separating the flow vector and temperature determination, we can mitigate these effects on the analysis, which returns an ISN flow vector very close to the Ulysses results, but with a substantially higher temperature. Due to coupling with the ISN flow speed along the ISN parameter tube, we provide the temperature Tvisn∞=8710+440/-680 K for Visn∞=26 km s⁻¹ for comparison, where most of the uncertainty is systematic and likely due to the presence of the Warm Breeze.

Fall Fertilization Timing Effects on Nitrate Leaching and Turfgrass Color and Growth

Fall season fertilization is a widely recommended practice for turfgrass. Fertilizer applied in the fall, however, may be subject to substantial leaching losses. A field study was conducted in Connecticut to determine the timing effects of fall fertilization on nitrate N (NO3-N) leaching, turf color, shoot density, and root mass of a 90% Kentucky bluegrass (Poa pratensis L.), 10% creeping red fescue (Festuca rubra L.) lawn. Treatments consisted of the date of fall fertilization: 15 September, 15 October, 15 November, 15 December, or control which received no fall fertilizer. Percolate water was collected weekly with soil monolith lysimeters. Mean log10 NO3-N concentrations in percolate were higher for fall fertilized treatments than for the control. Mean NO3-N mass collected in percolate water was linearly related to the date of fertilizer application, with higher NO3-N loss for later application dates. Applying fall fertilizer improved turf color and density but there were no differences in color or density among applications made between 15 October and 15 December. These findings suggest that the current recommendation of applying N in mid- to late November in southern New England may not be compatible with water quality goals.

Fertilización foliar con macronutrientes a plantas de naranja Valencia late (Citrus sinensis (L.) Osbeck) y tangor Murcott (Citrus reticulata Blanco x Citrus sinensis (L.) Osbeck)

El objetivo de este trabajo fue analizar el efecto de diferentes dosis de fertilizantes foliares con macronutrientes en plantas de naranja Valencia y de tangor Murcott. Los experimentos fueron realizados durante tres campañas consecutivas en Corrientes Argentina. El diseño experimental fue en bloques completos al azar con cuatro repeticiones y parcelas experimentales de cuatro plantas. Los tratamientos ensayados fueron T1 control; T2 N (12%) 2 L.ha-1; T3 N (12%) 4 L.ha-1; T4 N (9%) y P (2,6%) 2 L ha- 1; T5 N (9%) y P (2,6%) 4 L.ha-1; T6 N (9,3%), P (2,6%) y K (2,1%) 2 L.ha-1; T7 N (9,3%), P (2,6%) y K (2,1%) 4 L.ha-1, de fertilizante foliar formulados en base a sales de sulfato de amonio, fosfato monoamónico y nitrato de potasio según tratamiento. Los mismos fueron aplicados por campaña en prefloración, plena floración y en otoño. Se midieron las concentraciones foliares de N, P y K en hojas de otoño de ramas fructíferas y al momento de cosecha se determinó rendimiento total, diámetro de fruta, porcentaje de jugo, sólidos solubles, acidez y relación sólidos solubles/acidez. En Valencia late todos los tratamientos incrementaron el contenido de P foliar en comparación con el control. El tratamiento T7 incrementó un 38,7% el rendimiento respecto de T1, aunque los frutos presentaron menor diámetro. En "Murcott" todos los tratamientos incrementaron el rendimiento comparados con T1, y las máximas producciones se observaron en los tratamientos T7 (64,9% mayor) y T6 (43,8% mayor) además T7 incrementó el contenido de P foliar y disminuyó el contenido de sólidos solubles en comparación con el control. La fertilización foliar con macronutrientes incrementó la productividad en naranja Valencia late y tangor Murcott. Este trabajo muestra la utilidad de la fertilización foliar con macronutrientes como una herramienta complementaria en los programas de fertilización diseñados para optimizar el rendimiento.

(Table 1) Trace element/Ca ratios of Orbulina universa shells from late Neogene Mediterranean samples

A Mediterranean composite sedimentary record was analyzed for Ba/Ca ratios on carbonate shells of Orbulina universa planktonic foraminifer (Ba/Ca)carb providing the opportunity to study and assess the extent of freshwater inputs on the basin and possible impacts on its dynamics during the Tortonian to Recent period. A number of scanning electron microscope analyses and auxiliary trace element measurements (Mn, Sr, and Mg), obtained from the same samples, exclude important diagenetic effects on the studied biogenic carbonates and corroborate the reliability of (Ba/Ca)carb ratios in foraminifera calcite as indicators of seawater source components during the studied interval. A long-term trend with (Ba/Ca)carb values shifting from ~7 to 3 µmol/mol from the base of the Tortonian to the top of the Messinian is observed. The interval of the late Messinian salinity crisis, where biogenic carbonates are missing or strongly diagenized, represents a crucial passage not monitored in our record. At the base of the Pliocene, up to about 4.7 Ma, the (Ba/Ca)carb record shows a decreasing trend from ~4 µmol/mol stabilizing itself to an about constant value of 0.9 ± 0.3 µmol/mol for the whole Plio-Pleistocene interval. These results suggest a dramatic change in the continental runoff values, up to ~3-16 times higher during part of the late Neogene (Tortonian-early Pliocene), with a possible profound modification in the physical dynamics of the Mediterranean basin. First-order mass balance equations used to estimate barium and salinity budgets in the Mediterranean Sea during the late Miocene-early Pliocene interval support the hypothesis of an active connection of the basin with the Paratethys region and of a definitive restriction at the base of the Pliocene after about 0.7 Ma from the well-known Messinian Lagomare phase. They also open intriguing scenarios on possible circulation shifts during the Neogene.

A late Quaternary planktonic foraminifer faunal record of rapid climatic changes of sediment core GIK17938-2

A high-resolution planktonic foraminifer record from a core recovered from the South China Sea (SCS) (Sonne 17938-2: 19°47.2'N, 117° 32.3E; 2840 m; Delta t c. 250-1000 years) shows rapid millennial-scale changes in the western Pacific marginal sea climate during the last 30,000 years. The SCS is the largest western Pacific marginal sea off the southeast Asian continent, the area today dominated by seasonal monsoon changes. Quantitative analyses of planktonic foraminifer faunal abundance data frorn the core indicate large downcore variations in the relative abundances of the dominant taxa since about 30,000 years ago in the isotope stage 3. Further analyses indicate that the abundance of G. inflata, a good indicator species for cold SST (~13°-19°C) and deep MLD (~100-125 m) waters shows abrupt shifts. During stages 2 and 3, the abundance record of G. infiata tends to be punctuated by quasi-periodie short intervals (~2000-3000 yrs) where its abundance reaches 15% or greater, superimposed on generally low (5-10%) background values. This pattern suggests an instability of surface ocean conditions of the SCS during the past 30,000 years. The abrupt abundance changes of G. infiata correlate well with similar climatic changes observed from a GISP2 ice core 8180, and North Atlantic core DSDP 609 N. pachyderma (s.) and lithic grain abundances during 'Heinrich evcnts'. These results suggest that the millennial-scale variability of climate is not peculiar to the Atlantic region. Apparently, the rapid SCS climatic changes during Heinrich events are driven by effective mechanisms, of particularly the effects of shifts in the latitudinal position of the Siberia High Pressure System.

Stable carbon and oxygen isotope composition of Late Cretaceous benthic foraminifera from the southern South Atlantic

The stable carbon and oxygen isotope composition of different benthic foraminiferal species of the latest Campanian and earliest Maastrichtian from Ocean Drilling Project Hole 690C (Weddell Sea, southern South Atlantic, ~1800 m paleowater depth) have been investigated. The total range of measured isotope values of all samples exceeds ~4 per mil for delta 13C and 1.1 per mil for delta 18O. Carbon isotope values of proposed deep infaunal species are generally similar or only slightly lower when compared to proposed epifaunal to shallow infaunal species. Interspecific differences vary between samples probably reflecting temporal changes in organic carbon fluxes to the sea floor. Constantly lower delta 13C values for Pullenia marssoni and Pullenia reussi suggest the deepest habitat for these species. The strong depletion of delta 13C values by up to 3 per mil within lenticulinids may be attributed to a deep infaunal microhabitat, strong vital effects, or different feeding strategy when compared to other species or modern lenticulinids. The mean delta 18O values reveal a strong separation of epifaunal to shallow infaunal and deep infaunal species. Epifaunal to shallow infaunal species are characterized by low delta 18O values, deep infaunal species by higher values. This result possibly reflects lower metabolic rates and longer life cycles of deep infaunal species or the operating of a pore water [CO3]2- effect on the benthic foraminiferal stable isotopes. Pyramidina szajnochae shows an enrichment of oxygen isotopes with test size comprising a total of 0.6 per mil between 250 and 1250 µm shell size. Although delta 13C lacks a corresponding trend these data likely represent the presence of changes in metabolic rates during ontogenesis. These results demonstrate the general applicability of multi-species stable isotope measurements of pristine Cretaceous benthic foraminifera to reconstruct past microhabitats and to evaluate biological and environmental effects on the stable isotope composition.

Size-related stable isotope changes in Late Cretaceous and Recent planktic foraminifera from the western tropical Atlantic

The paleoecology of Cretaceous planktic foraminifera during the Late Cenomanian to Coniacian period (~95-86 Ma) remains controversial since much of the tropical marine record is preserved as chalk and limestone with uncertain geochemical overprints. Here we present delta13C and delta18O data from sieve size fractions of monospecific samples of exceptionally well preserved planktic foraminifera recovered during Ocean Drilling Program Leg 207 (Demerara Rise, western tropical Atlantic). Our results suggest that all species studied (Hedbergella delrioensis, Heterohelix globulosa, Marginotruncana sinuosa, Whiteinella baltica) grew primarily in surface waters and did not change their depth habitat substantially during their life cycle. Comparison of size-related ontogenetic trends in delta13C in Cretaceous and modern foraminifera further suggests that detection of dinoflagellate photosymbiosis using delta13C is confounded by physiological effects during the early stages of foraminifer growth, raising doubts about previous interpretations of photosymbiosis in small foraminifera species. We propose that obligate photosymbiosis involving dinoflagellates may not have evolved until the Campanian or Maastrichtian since our survey of Cenomanian-Coniacian species does not find the delta18O and delta13C size-related trends observed in modern foraminifer-dinoflagellate symbioses.

Characterization of late Campanian and Maastrichtian planktonic foraminiferal depth habitats and vital activities based on stable isotopes

Depth habitats of 56 late Cretaceous planktonic foraminiferal species from cool and warm climate modes were determined based on stable isotope analyses of deep-sea samples from the equatorial Pacific DSDP Sites 577A and 463, and South Atlantic DSDP Site 525A. The following conclusions can be reached: Planoglobulina multicamerata (De Klasz) and Heterohelix rajagopalani (Govindan) occupied the deepest plankton habitats, followed by Abathomphalus mayaroensis (Bolli), Globotruncanella havanensis (Voorwijk), Gublerina cuvillieri Kikoine, and Laeviheterohelix glabrans (Cushman) also at subthermocline depth. Most keeled globotruncanids, and possibly Globigerinelliodes and Racemiguembelina species, lived at or within the thermocline layer. Heterohelix globulosa (Ehrenberg) and Rugoglobigerina, Pseudotextularia and Planoglobulina occupied the subsurface depth of the mixed layer, and Pseudoguembelina species inhabited the surface mixed layer. However, depth ranking of some species varied depending on warm or cool climate modes, and late Campanian or Maastrichtian age. For example, most keeled globotruncanids occupied similar shallow subsurface habitats as Rugoglobigerina during the warm late Campanian, but occupied the deeper thermocline layer during cool climatic intervals. Two distinct types of "vital effect" mechanisms reflecting photosymbiosis and respiration effects can be recognized by the exceptional delta13C signals of some species. (1) Photosymbiosis is implied by the repetitive pattern of relatively enriched delta13C values of Racemiguembelina (strongest), Planoglobulina, Rosita and Rugoglobigerina species, Pseudoguembelina excolata (weakest). (2) Enriched respiration 12C products are recognized in A. mayaroensis, Gublerina acuta De Klasz, and Heterohelix planata (Cushman). Isotopic trends between samples suggest that photosymbiotic activities varied between localities or during different climate modes, and may have ceased under certain environmental conditions. The appearance of most photosymbiotic species in the late Maastrichtian suggests oligotrophic conditions associated with increased water-mass stratification.