Preventing Plasmon Coupling between Gold Nanorods Improves the Sensitivity of Photoacoustic Detection of Labeled Stem Cells in Vivo

© 2016 American Chemical Society.Gold nanorods are excellent contrast agents for imaging technologies which rely on near-infrared absorption such as photoacoustic imaging. For cell tracking applications, the cells of interest are labeled with the contrast agent prior to injection. However, after uptake into cells by endocytosis, the confinement and high concentration in endosomes leads to plasmon band broadening and reduced absorbance. This would limit the potential of multispectral optoacoustic tomography in terms of spectral processing and, consequently, sensitivity. Here, we show that steric hindrance provided by silica coating of the nanorods leads to the preservation of their spectral properties and improved photoacoustic sensitivity. This strategy allowed the detection and monitoring of as few as 2 × 104 mesenchymal stem cells in mice over a period of 15 days with a high spatial resolution. Importantly, the silica-coated nanorods did not affect the viability or differentiation potential of the transplanted mesenchymal stem cells

CyberKnife® enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures

<p>Abstract</p> <p>Introduction</p> <p>With conventional radiation technique alone, it is difficult to deliver radical treatment (≥ 60 Gy) to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma.</p> <p>Methods</p> <p>Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem) were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy). Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife^®image-guided radiosurgical system. The majority of patients (88%) received concurrent and/or adjuvant Temozolmide.</p> <p>Results</p> <p>During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients.</p> <p>Conclusion</p> <p>We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study.</p

Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy

Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation contributes to seizure generation in animal models. However, further work is required to understand the role of HMGB1 and its isoforms in epileptogenesis and drug resistance. Using a combination of animal models and sera from clinically well-characterized patients, we have demonstrated that there are dynamic changes in HMGB1 isoforms in the brain and blood of animals undergoing epileptogenesis. The pathologic disulfide HMGB1 isoform progressively increased in blood before epilepsy onset and prospectively identified animals that developed the disease. Consistent with animal data, we observed early expression of disulfide HMGB1 in patients with newly diagnosed epilepsy, and its persistence was associated with subsequent seizures. In contrast with patients with well-controlled epilepsy, patients with chronic, drug-refractory epilepsy persistently expressed the acetylated, disulfide HMGB1 isoforms. Moreover, treatment of animals with antiinflammatory drugs during epileptogenesis prevented both disease progression and blood increase in HMGB1 isoforms. Our data suggest that HMGB1 isoforms are mechanistic biomarkers for epileptogenesis and drug-resistant epilepsy in humans, necessitating evaluation in larger-scale prospective studies

GRB 021211 as a Faint Analogue of GRB 990123: Exploring the Similarities and Differences in their Optical Afterglows

We present B, V, Rc, J, H, and Ks photometry of the optical afterglow of the gamma-ray burst GRB 021211 taken at the Magellan, MMT, and WIYN observatories between 0.7 and 50 days after the burst. We find an intrinsic spectral slope at optical and near-infrared wavelengths of 0.69 +/- 0.14 at 0.87 days. The optical decay during the first day is almost identical to that of GRB 990123 except that GRB 021211's optical afterglow was intrinsically approximately 38 times fainter, and the transition from the reverse shock to the forward shock may have occurred earlier than it did for GRB 990123. We find no evidence for a jet break or the cooling break passing through optical frequencies during the first day after the burst. There is weak evidence for a break in the J-band decay between 0.89 and 1.87 days which may be due to a jet. The optical and infrared data are consistent with a relativistic fireball where the shocked electrons are in the slow cooling regime and the electron index is 2.3 +/- 0.1. The forward shock appears to have been expanding in a homogeneous ambient medium during the first day after the burst. Our analysis suggests that the jet of GRB 021211 may have a small opening angle and that the total gamma-ray energy is likely to be much less than the canonical value of 1.33E+51 erg. If this is the case then it is possible that most of the energy of the burst is in another form such as a frozen magnetic field, supernova ejecta, or a second jet component. The host galaxy of GRB 021211 is subluminous and has a star formation rate of at least one Solar mass per year.Comment: 24 pages, 4 figures, LaTex using AASTeX v5.2, to the Nov 2004 Astronomical Journal. Some minor changes have been made to the paper in accordance with the referee's repor

In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

RationaleThe sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.MethodsNuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.ResultsNuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.ConclusionsThe molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions

A Mysterious Island in the Digital Age: Technology and Musical Life in Ulleungdo, South Korea

This paper contributes to the growing body of ethnomusicological research about music-making on small islands, focusing on the remote South Korean island of Ulleungdo (literally, ‘Mysterious Island’). Historically, a number of factors have conspired to present serious obstacles to the Ulleungdo islanders' musical aspirations. However, since the early 1990s, enterprising amateurs have managed to generate and maintain a variety of musical activities in spite of these obstacles: church ensembles, karaoke, saxophone clubs, and more. Paralleling other island music studies, this paper seeks to show how the condition of being an Ulleungdo islander—entailing a complex of varied experiences, values, and relationships—has informed music-making over the years. However, here, the discussion remains firmly focused upon the islanders' use of technology since an acute reliance on technology has come to permeate Ulleungdo's musical life, with certain electronic devices commonly regarded as essential facilitators of musical expression. Drawing from the islanders' own testimonies, studies of Ulleungdo's cultural history, and works addressing technology's applications within and effects upon local communities, the authors explore how and why this condition of musical techno-reliance developed, how it is manifest in the present-day, and its broader implications for the island's music culture and identity