Application of magnetically induced hyperthermia on the model protozoan Crithidia fasciculata as a potential therapy against parasitic infections

Magnetic hyperthermia is currently an EU-approved clinical therapy against tumor cells that uses magnetic nanoparticles under a time varying magnetic field (TVMF). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, since therapeutic drugs available display severe side effects and drug-resistant strains. However, no applications of this strategy against protozoan-induced diseases have been reported so far. In the present study, Crithidia fasciculata, a widely used model for therapeutic strategies against pathogenic trypanosomatids, was targeted with Fe_{3}O_{4} magnetic nanoparticles (MNPs) in order to remotely provoke cell death using TVMFs. The MNPs with average sizes of d approx. 30 nm were synthesized using a precipitation of FeSO_{4}4 in basic medium. The MNPs were added to Crithidia fasciculata choanomastigotes in exponential phase and incubated overnight. The amount of uploaded MNPs per cell was determined by magnetic measurements. Cell viability using the MTT colorimetric assay and flow cytometry showed that the MNPs were incorporated by the cells with no noticeable cell-toxicity effects. When a TVMF (f = 249 kHz, H = 13 kA/m) was applied to MNP-bearing cells, massive cell death was induced via a non-apoptotic mechanism. No effects were observed by applying a TVMF on control (without loaded MNPs) cells. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. Scanning Electron Microscopy showed morphological changes after TVMF experiments. These data indicate (as a proof of principle) that intracellular hyperthermia is a suitable technology to induce the specific death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies that combat parasitic infections.Comment: 9 pages, four supplementary video file

Actividad eléctrica muscular en la marcha a distintas velocidades y en la carrera

En este estudio se analiza la actividad electromiográfica de los principales músculos de la extremidad inferior derecha: Glúteos Mayor y Medio, Recto Anterior y Vasto Interno del Cuádriceps, Isquiotibioperoneos, Gemelos y Tibial Anterior, al caminar en un tapiz rodante a distintas velocidades y en una carrera suave. Para dividir el ciclo de la marcha y la carrera en fases se utilizó un sistema de análisis tridimensional con dos cámaras de vídeo. La señal electromiográfica de cada una de estas fases se integró y se expresó en porcentaje de la actividad máxima isométrica de su músculo correspondiente. Los resultados obtenidos muestran que la participación muscular en la marcha lenta y normal es muy similar, sin embargo, en la marcha rápida aparecen aumentos importantes conservando el mismo patrón de actuación. En la carrera, no sólo existen actividades del triple de las halladas en la marcha a velocidad cómoda, sino que se modifica el patrón de actuación, presentando todos los músculos sus picos de actividad durante la fase de apoyo, momento en el que el centro de gravedad se lleva hacia delante sobre el miembro inferior

Actividad eléctrica muscular en la marcha a distintas velocidades y en la carrera

En este estudio se analiza la actividad electromiográfica de los principales músculos de la extremidad inferior derecha: Glúteos Mayor y Medio, Recto Anterior y Vasto Interno del Cuádriceps, Isquiotibioperoneos, Gemelos y Tibial Anterior, al caminar en un tapiz rodante a distintas velocidades y en una carrera suave. Para dividir el ciclo de la marcha y la carrera en fases se utilizó un sistema de análisis tridimensional con dos cámaras de vídeo. La señal electromiográfica de cada una de estas fases se integró y se expresó en porcentaje de la actividad máxima isométrica de su músculo correspondiente. Los resultados obtenidos muestran que la participación muscular en la marcha lenta y normal es muy similar, sin embargo, en la marcha rápida aparecen aumentos importantes conservando el mismo patrón de actuación. En la carrera, no sólo existen actividades del triple de las halladas en la marcha a velocidad cómoda, sino que se modifica el patrón de actuación, presentando todos los músculos sus picos de actividad durante la fase de apoyo, momento en el que el centro de gravedad se lleva hacia delante sobre el miembro inferior

Derivation of Del180 from sediment core log data\u27 Implications for millennial-scale climate change in the Labrador Sea

Sediment core logs from six sediment cores in the Labrador Sea show millennial-scale climate variability during the last glacial by recording all Heinrich events and several major Dansgaard-Oeschger cycles. The same millennial-scale climate change is documented for surface water δ18O records of Neogloboquadrina pachyderma (left coiled); hence the surface water δ18O record can be derived from sediment core logging by means of multiple linear regression, providing a paleoclimate proxy record at very high temporal resolution (70 years). For the Labrador Sea, sediment core logs contain important information about deepwater current velocities and also reflect the variable input of ice-rafted debris from different sources as inferred from grain-size analysis, the relation of density and P wave velocity, and magnetic susceptibility. For the last glacial, faster deepwater currents, which correspond to highs in sediment physical properties, occurred during iceberg discharge and lasted from several centuries to a few millennia. Those enhanced currents might have contributed to increased production of intermediate waters during times of reduced production of North Atlantic Deep Water. Hudson Strait might have acted as a major supplier of detrital carbonate only during lowered sea level (greater ice extent). During coldest atmospheric temperatures over Greenland, deepwater currents increased during iceberg discharge in the Labrador Sea, then surface water freshened shortly thereafter, while the abrupt atmospheric temperature rise happened after a larger time lag of ≥ 1 kyr. The correlation implies a strong link and common forcing for atmosphere, sea surface, and deep water during the last glacial at millennial timescales but decoupling at orbital timescales

Magnetic-Responsive Release Controlled by Hot Spot Effect

Magnetically triggered drug delivery nanodevices have attracted great attention in nanomedicine, as they can feature as smart carriers releasing their payload at clinician's will. The key principle of these devices is based on the properties of magnetic cores to generate thermal energy in the presence of an alternating magnetic field. Then, the temperature increase triggers the drug release. Despite this potential, the rapid heat dissipation in living tissues is a serious hindrance for their clinical application. It is hypothesized that magnetic cores could act as hot spots, this is, produce enough heat to trigger the release without the necessity to increase the global temperature. Herein, a nanocarrier has been designed to respond when the temperature reaches 43 degrees C. This material has been able to release its payload under an alternating magnetic field without the need of increasing the global temperature of the environment, proving the efficacy of the hot spot mechanism in magnetic-responsive drug delivery devices

El abordaje transapofisario en las fracturas complejas del extremo distal femoral y proximal tibial

Los autores presentan las ventajas e inconvenientes, así como los distintos pasos de la técnica quirúrgica en el abordaje transapofisario, para resolver aquellas fracturas complejas tanto del extremo distal femoral como del extremo proximal tibial, en donde una amplia exposición del foco fracturario es imprescindible para lograr la restauración lo más anatómica posible de la superficie articular, que le permita a los pacientes reiniciar una movilización articular precoz. Consideran a este tipo de abordaje quirúrgico como muy beneficioso e imprescindible en estas fracturas tan complejas, presentando su experiencia al respecto.The authors show the advantages and disadvantages, as well as somo differents points of the surgical technique at the transapophyseal approach, for complex fractures of the distal end of the femur and proximal tibial plateau, when an extensible exposur e is essential to obtain an anatomic restitution of the articular surface, and to allow to the patient to mobilize the joint at once. They consider this type of surgical approach as very beneficial and essentia] in these fractures so complex. They present their experience

Functional proteomics outlines the complexity of breast cancer molecular subtypes

Breast cancer is a heterogeneous disease comprising a variety of entities with various genetic backgrounds. Estrogen receptor-positive, human epidermal growth factor receptor 2-negative tumors typically have a favorable outcome; however, some patients eventually relapse, which suggests some heterogeneity within this category. In the present study, we used proteomics and miRNA profiling techniques to characterize a set of 102 either estrogen receptor-positive (ER+)/progesterone receptorpositive (PR+) or triple-negative formalin-fixed, paraffin-embedded breast tumors. Protein expressionbased probabilistic graphical models and flux balance analyses revealed that some ER+/PR+ samples had a protein expression profile similar to that of triple-negative samples and had a clinical outcome similar to those with triple-negative disease. This probabilistic graphical model-based classification had prognostic value in patients with luminal A breast cancer. This prognostic information was independent of that provided by standard genomic tests for breast cancer, such as MammaPrint, OncoType Dx and the 8-gene Score

Subarctic Front migration at the Reykjanes Ridge during the mid- to late Holocene:Evidence from planktic foraminifera

Expansion of fresh and sea-ice loaded surface waters from the Arctic Ocean into the sub-polar North Atlantic is suggested to modulate the northward heat transport within the North Atlantic Current (NAC). The Reykjanes Ridge south of Iceland is a suitable area to reconstruct changes in the mid- to late Holocene fresh and sea-ice loaded surface water expansion, which is marked by the Subarctic Front (SAF). Here, shifts in the location of the SAF result from the interaction of freshwater expansion and inflow of warmer and saline (NAC) waters to the Ridge. Using planktic foraminiferal assemblage and concentration data from a marine sediment core on the eastern Reykjanes Ridge elucidates SAF location changes and thus, changes in the water-mass composition (upper ˜200 m) during the last c. 5.8 ka BP. Our foraminifer data highlight a late Holocene shift (at c. 3.0 ka BP) in water-mass composition at the Reykjanes Ridge, which reflects the occurrence of cooler and fresher surface waters when compared to the mid-Holocene. We document two phases of SAF presence at the study site: from (i) c. 5.5 to 5.0 ka BP and (ii) c. 2.7 to 1.5 ka BP. Both phases are characterized by marked increases in the planktic foraminiferal concentration, which coincides with freshwater expansions and warm subsurface water conditions within the sub-polar North Atlantic. We link the SAF changes, from c. 2.7 to 1.5 ka BP, to a strengthening of the East Greenland Current and a warming in the NAC, as identified by various studies underlying these two currents. From c. 1.5 ka BP onwards, we record a prominent subsurface cooling and continued occurrence of fresh and sea-ice loaded surface waters at the study site. This implies that the SAF migrated to the southeast of our core site during the last millennium

A Robust, Multisite Holocene History of Drift Ice off Northern Iceland: Implications for North Atlantic Climate

An important indicator of Holocene climate change is provided by evidence for variations in the extent of drift ice. A proxy for drift ice in Iceland waters is provided by the presence of quartz. Quantitative xray diffraction analysis of the \u3c 2 mm sediment fraction was undertaken on 16 cores from around Iceland. The quartz weight (wt.)% estimates from each core were integrated into 250-yr intervals between −0.05 and 11.7 cal. ka BP. Median quartz wt.% varied between 0.2 and 3.4 and maximum values ranged between 2.8 and 11.8 wt.%. High values were attained in the early Holocene and minimum values were reached 6–7 cal. ka BP. Quartz wt.% then rose steadily during the late Holocene. Our data exhibit no correlation with counts on haematite-stained quartz (HSQ) grains from VM129-191 west of Ireland casting doubt on the ice-transport origin. A pilot study on the provenance of Fe oxide grains in two cores that cover the last 1.3 and 6.1 cal. ka BP indicated a large fraction of the grains between 1 and 6 cal. ka BP were from either Icelandic or presently unsampled sources. However, there was a dramatic increase in Canadian and Russian sources from the Arctic Ocean ~1 cal. ka BP. These data may indicate the beginning of an Arctic Oscillation-like climate mode