There are relatively few nanotechnologies that can produce nanocomposite scaffolds for cell growth. Electrospinning has emerged as the foremost method of producing nanofibrous biomimetic scaffolds ...for tissue engineering applications. In this study diamond nanoparticles were integrated into a polymer solution to develop a nanocomposite scaffold containing poly(lactide-co-glycolide) (PLGA) loaded with diamond nanoparticles. To investigate the effect of adding diamond nanoparticles to PLGA scaffolds, primary human mesenchymal stem cells (hMSCs) were seeded on the scaffolds. The cytocompatibility results showed that addition of diamond nanoparticles did not impinge upon cell proliferation, nor was there a cytotoxic cellular response after 9 days in culture. Scanning electron microscopy, transmission electron microscopy, atomic force microscopy and confocal microscopy enabled qualitative characterization of the fibres and revealed cell morphology and number. Furthermore, surface roughness was measured to evaluate diamond nanoparticle modifications, and no significant difference was found between the diamond nanocomposite and pure polymer scaffolds. On the other hand, bright spots on phase images performed by atomic force microscopy suggested a higher hardness at certain points on fibers of the PLGA-nanodiamond composites, which was supported by nanoindentation measurements. This study shows that PLGA nanofibers can be reinforced with nanodiamond without adversely affecting cell behaviour, and thus it sets the foundation for future application of these scaffolds in bone tissue engineering.
This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell ...lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life.
Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC).
Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life.
In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.
GJ 758 B is a cold (~600 K) companion to a Sun-like star at 29 AU projected separation, which was recently detected with high-contrast imaging. Here, we present photometry of the companion in seven ...photometric bands from Subaru/HiCIAO, Gemini/NIRI, and Keck/NIRC2, providing a rich sampling of the spectral energy distribution in the 1-5 Delta *mm wavelength range. A clear detection at 1.58 Delta *mm combined with an upper limit at 1.69 Delta *mm shows methane absorption in the atmosphere of the companion. The mass of the companion remains uncertain, but an updated age estimate indicates that the most likely mass range is ~30-40 M jup. In addition, we present an updated astrometric analysis that imposes tighter constraints on GJ 758 B's orbit and identifies the proposed second candidate companion, 'GJ 758 C,' as a background star.
Purpose: Pregabalin (PGB) is an α2‐δ ligand with demonstrated efficacy in epilepsy, neuropathic pain, and anxiety disorders. PGB is highly efficacious as adjunctive therapy in patients with ...refractory partial seizures.
Methods: Given its efficacy as adjunctive therapy, the potential for interaction of PGB with other antiepileptic drugs (AEDs) was assessed in patients with partial epilepsy in open‐label, multiple‐dose studies. Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ).
Results: Trough steady‐state concentrations of CBZ (and its epoxide metabolite), PHT, LTG, and VPA were unaffected by concomitant PGB administration. Likewise, PGB steady‐state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone. The PGB–AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug–drug interactions.
Background and importance6-mercaptopurine (6-MP) is an anticancer and immunosuppressive agent used as part of the therapeutic strategy in acute lymphoblastic leukaemia (ALL), in the induction, ...consolidation and maintenance phases. However, it may cause life threatening myelotoxicity that is commonly associated with polymorphisms in genes involved in its metabolism (thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15)).Aim and objectivesTo describe the clinical case of a Caucasian girl, aged 2 years, diagnosed with B-ALL (intermediate risk of hyperdiploidy in cytogenetics (DNI index 1.27) and MRD on day +15 of 1.4%, CNS-1) that presented prolonged myelotoxicity under the LAL-SEHOP-PETHEMA-2013 treatment protocol.Material and methodsDuring the induction phase, prolonged spinal cord aplasia occurred with the complication of sepsis due to Staphylococcus epidermidis, which required intensive care unit support. Subsequently, she presented sepsis due to Pseudomonas, a granuloma in the reservoir area that requires channelling of a peripheral access central catheter type PICC. TPMT polymorphisms (*2, *3A, *3B and *3C) were studied without alterations. Therefore, the consolidation phase continued, and she presented with aplasia, febrile neutropenia, respiratory infection and central venous catheter infection. The dose of 6-MP was reduced to 10%. In the reinduction phase she also showed aplasia, febrile neutropenia and mucocutaneous infection by Candida dubliniensis. During maintenance, methotrexate and 6-MP were suspended several times, and 6-MP was resumed at 3% of the dose. She received multiple transfusions of red blood cells and platelets.To understand the toxicity manifested by the patient and considering the update of the pharmacogenetic guide for thiopurines of the Clinical Pharmacogenetics Implementation Consortium, real time PCR genotyping by Taqman was performed for NUDT15-rs116855232 gene polymorphism.ResultsAlthough initial genetic testing revealed that the patient carried the TPMT wild-type allele, the patient had prolonged spinal cord aplasia and multiple infectious complications. Subsequent analysis revealed that the patient carried the rs116855232-TT genotype (frequency in Europeans 0.000004). This polymorphism is associated with potentially fatal myelosuppression (evidence level 1A), which explains the toxicity manifested.Conclusion and relevanceThis case shows the relevance of implementing pharmacogenetics studies (TPMT and NUDT15 gene polymorphisms) in daily clinical practice that allows the early detection of patients treated with 6-MP with a higher risk of myelosuppression.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and importanceMethotrexate (MTX) is widely used in paediatric chemotherapy treatment and is effective. However, it presents with significant toxicity. Myelopathy is a rare but serious ...complication, usually related to mechanical damage caused by multiple lumbar punctures and the administration of drugs by this route. The main symptoms are loss of sensitivity, alteration of motor neurons, root pain and sphincter incontinence.Aim and objectivesWe present a clinical case of a Caucasian girl with precursor B cell lymphoblastic lymphoma, stage IV, that affected the CNS type 3. She presented with neurotoxicity after administration of intrathecal MTX. She received treatment under the EURO-LB02 protocol.Material and methodsAfter seven doses of intrathecal triple (TIT) the patient began to experience distal tremor with numbness in the feet and slight ataxia. Gradually, the numbness increased and she developed areflexic paraparesis with static and kinetic ataxia that prevented her from walking. There was no cognitive impairment. MRI showed areas of leucoencephalopathy and homogeneous hyperintensity in the posterior segment from T1 to T12, suggesting dorsal myelitis. Folic acid and vitamin B12 levels were normal. Lymphoblastic invasion of the CNS was eradicated. To treat myelitis, she received methylprednisolone, dextromethorphan, s-adenosylmethionine, folinate, cyanocobalamin and intensive rehabilitation. Due to the patient‘s condition, we analysed 22 single nucleotide polymorphisms (SNPs) associated with the MTX metabolic pathway by TaqMan real time PCR.Results10 altered SNPs were found, mainly in genes encoding transport proteins (ABCB1 and ABCG2) and enzymes in the folate pathway (MTHFR) that could explain the toxicity manifested. However, there was low level evidence to support it. During subsequent cycles of chemotherapy, MTX was discontinued from TIT and intravenous MTX was gradually titrated to full doses. Currently, the patient is in the reinduction phase and has shown partial recovery from myelitis. She was rescued with leucovorin after intravenous MTX and levels of MTX were always within the normal range without notable toxicity.Conclusion and relevanceMTX may cause spinal cord dysfunction in children, especially when the intrathecal route is used. SNPs in enzymes involved in pharmacokinetics and pharmacodynamics may be the cause. However, more studies are needed to confirm these findings and translate them into information applicable to clinical practice.References and/or acknowledgementsConflict of interestNo conflict of interest
Are bio-telemetric devices a drag? Vandenabeele, S. P.; Shepard, E. L. C.; Grémillet, D. ...
Marine ecology. Progress series (Halstenbek),
01/2015, Letnik:
519
Journal Article
Recenzirano
Odprti dostop
Externally attached remote-sensing devices used to study animals in their environment are a possible source of disturbance, notably in terms of drag, for diving species. The aim of the present study ...was to assess the possible effect of device-induced drag on the diving performance of great cormorants Phalacrocorax carbo. Based on wind-tunnel measurements, we assessed the effect of device size on drag and derived a formula to predict how drag changes as a function of both swim speed and device cross-sectional area. Tests on captive cormorants indicated that drag had an effect on the energy expenditure (using dynamic body acceleration as a proxy) during the dive. Wind tunnel-derived drag metrics were combined with data from the literature to construct a model predicting the power consumption of diving cormorants according to device size. Applying the model to dive data from 6 free-living great cormorants (recorded using implanted time-depth recorders) indicated that a device constituting only ca. 3% of the bird’s cross-sectional area could cause a 1.7% increase in power consumption when swimming. However, if a bird maintains constant power underwater, e.g. by decreasing foraging speed with increasing drag, this would result in a 7.1% reduction in the distance travelled during the bottom (active hunting) phase of the dive. Device-related increases in drag are also likely to reduce the maximum speeds achievable by these pursuit predators. The present study highlights the interaction between both drag coefficient and swim speed for diving animals with externally attached devices.
Reaching population immunity against COVID‐19 is proving difficult even in countries with high vaccination levels. Thus, it is critical to identify limits of control and effective measures against ...future outbreaks. The effects of nonpharmaceutical interventions (NPIs) and vaccination strategies are analyzed with a detailed community‐specific agent‐based model (ABM). The authors demonstrate that the threshold for population immunity is not a unique number, but depends on the vaccination strategy. Prioritizing highly interactive people diminishes the risk for an infection wave, while prioritizing the elderly minimizes fatalities when vaccinations are low. Control over COVID‐19 outbreaks requires adaptive combination of NPIs and targeted vaccination, exemplified for Germany for January–September 2021. Bimodality emerges from the heterogeneity and stochasticity of community‐specific human–human interactions and infection networks, which can render the effects of limited NPIs uncertain. The authors' simulation platform can process and analyze dynamic COVID‐19 epidemiological situations in diverse communities worldwide to predict pathways to population immunity even with limited vaccination.
The limits of control and the effect of measures against future COVID‐19 outbreaks are identified using a detailed community‐specific ABM. The demographic and geographic structure of assessed communities influence the pattern of infection spreading and the resulting R‐values. Stochastic community dynamics and limited vaccination can lead to bimodal outcomes, rendering predictions about infection spreading and effects of nonpharmaceutical interventions uncertain.
Lucky Imaging of M subdwarfs Lodieu, N.; Zapatero Osorio, M. R.; Martín, E. L.
Astronomy and astrophysics (Berlin),
06/2009, Letnik:
499, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Context. The knowledge of the binary properties of metal-poor and solar-metallicity stars can shed light on the potential differences between the formation processes responsible for both types of ...objects. Aims. The aim of the project is to determine the binary properties (separation, mass ratio, frequency of companions) for M subdwarfs, the low-metallicity counterparts of field M dwarfs, and investigate any potential differences between both populations. Methods. We have obtained high-resolution imaging in the optical for a sample of 24 early-M subdwarfs and nine extreme subdwarfs with the “Lucky Imaging” technique using the AstraLux instrument on the Calar Alto 2.2-m telescope. Results. We are sensitive to companions at separations larger than 0.1 arcsec and differences of ~2 mag at 0.1 arcsec and ~5 mag at 1 arcsec. We have found no companion around the 24 subdwarfs under study and one close binary out of nine extreme subdwarfs. A second image of LHS 182 taken three months later with the same instrument confirms the common proper motion of the binary separated by about 0.7 arcsec. Moreover, we do not confirm the common proper motion of the faint source reported by Riaz and collaborators at ~2 arcsec from LHS 1074. Conclusions. We derive a binary frequency of 3±3% for M subdwarfs from our sample of 33 objects for separations larger than about five astronomical units. Adding to our sample the additional 28 metal-poor early-M dwarfs observed with the Hubble Space Telescope by Riaz and collaborators, we infer a binary fraction of 3.7±2.6% (with a 1σ confidence limit), significantly lower than the fraction of resolved binary M dwarfs (~20%) over the same mass and separation ranges. This result suggests a sharp cut-off in the multiplicity fraction from G to M subdwarfs, indicating that the metallicity plays a role at lower masses and/or an environmental effect governing the formation of metal-poor M dwarfs compared to their metallicity counterparts.
In comatose patients after out-of-hospital cardiac arrest, the incidence of death or severe disability was similar regardless of whether a restrictive or a liberal oxygenation strategy was used.
PDF
