Hydrophobic superparamagnetic FePt nanoparticles in hydrophilic poly(N-vinylcaprolactam) microgels: a new multifunctional hybrid system.

We report the synthesis of a new multifunctional colloidal hybrid system consisting of thermoresponsive amphiphilic biocompatible poly(N-vinylcaprolactam) microgels loaded with hydrophobic superparamagnetic FePt nanoparticles (NPs). In the first step, water swellable poly(N-vinylcaprolactam) microgels were mixed with hydrophobically coated sub-10 nm superparamagnetic FePt NPs in a tetrahydrofuran (THF) solution. In the second step, changing the surrounding solvent from THF to water forces the FePt NPs to migrate into the amphiphilic microgels. These new hybrid microgels (i) are colloidally stable in water and their thermo-responsive properties in terms of volume phase transition are retained, (ii) exhibit superparamagnetic characteristics introduced by FePt NPs, (iii) show a drastically reduced cytotoxicity compared to water-soluble FePt NPs of similar size, as known from the literature. This makes the new hybrid microgels suitable e.g. as biocompatible containers for drug delivery or for imaging.

The impact of low hemoglobin levels and transfusion on critical care patients with severe ischemic stroke: STroke: RelevAnt Impact of HemoGlobin, Hematocrit and Transfusion (STRAIGHT)--an observational study.

PURPOSE: Optimal management of hemoglobin (Hb) and red blood cell transfusion (RBCT) in neurologic intensive care unit (NICU) patients has not been determined yet. Here we aimed to investigate the impact of anemia and transfusion activity in patients who had acute ischemic stroke. MATERIALS AND METHODS: A retrospective analysis of clinical, laboratory, and outcome data of patients with severe acute ischemic stroke treated on our NICU between 2004 and 2011 was performed. RESULTS: Of 109 patients, 97.2% developed anemia and 33% received RBCT. Significant correlations were found between NICU length of stay (NICU LOS) and lowest (nadir) Hb (correlation coefficient, -0.42, P < .001), Hb decrease (0.52, P < .001), nadir hematocrit (Hct; -0.43, P < .001), and Hct decrease (0.51, P < .001). Duration of mechanical ventilation (MV) was strongly associated with both nadir Hb (-0.41, P < .001) and decrease (0.42, P < .001) and nadir Hct (-0.43, P < .001) and decrease (0.40, P < .001). Red blood cell transfusion correlated with NICU LOS (0.33, P < .001) and with duration of MV (0.40, P < .001). None of these hematologic parameters correlated with in-hospital mortality or 90-day outcome. The linear regression model showed number of RBCT (0.29, P = .008), nadir Hb (-0.18, P = .049), Hb decrease (0.33, P < .001), nadir Hct (-0.18, P = .03), and Hct decrease (0.29, P < .001) to be independent predictors of NICU LOS. Duration of MV was also independently predicted by number of RBC transfusions (0.29, P < .001), nadir Hb (-0.20, P = .02), Hb decrease (0.25, P = .002), nadir Hct (-0.21, P = .015), and Hct decrease (0.26, P < .001). CONCLUSIONS: Low and further decreasing Hb and Hct levels as well as RBCT activity are associated with prolonged NICU stay and duration of MV but not with mortality or long-term outcome. Our findings do not justify using a more aggressive transfusion practice at present.

Salubrinal, an endoplasmic reticulum stress blocker, modulates sleep homeostasis and activation of sleep- and wake-regulatory neurons.

Endoplasmic reticulum (ER) stress has been associated with the regulation of sleep and wake. We have previously shown that i.c.v. administration of a specific ER stress modulator, Salubrinal (SALUB), which inhibits global protein translation by blocking the dephosphorylation of eukaryotic initiation factor 2α (p-eIF2α), increased non-rapid eye movement (NREM) sleep. Here we report on the relationship between ER stress response and sleep homeostasis by measuring the amount and intensity of homeostatic recovery sleep in response to the i.c.v. administration of SALUB in adult freely behaving rats. We have also tested the hypothesis that SALUB induces sleep by activating sleep-promoting neurons and inhibiting wake-promoting neurons in the basal forebrain (BF) and hypothalamus by quantifying the effects of SALUB treatment on c-Fos expression in those neuronal groups. The present study found that i.c.v. administration of SALUB significantly modified the homeostatic sleep response. SALUB administered during sleep deprivation increased sleep intensity, indicated by slow-wave activity (SWA), during recovery sleep, whereas its administration during recovery sleep increased the amount of recovery sleep. We also found that SALUB induced c-Fos activation of GABAergic neurons in the sleep-promoting rostral median preoptic nucleus while simultaneously reducing c-Fos activation of wake-promoting lateral hypothalamic orexin-expressing neurons and magnocellular BF cholinergic neurons. The current findings suggest that ER stress pathway plays a role in the homeostatic control of NREM sleep in response to sleep deprivation and provides a mechanistic explanation for the sleep modulation by molecules signaling the need for brain protein synthesis.