High Payload Dual Therapeutic-Imaging Nanocarriers for Triggered Tumor Delivery

The in vitro and in vivo characterization of an optimized formulation of nanoparticles (NPs) loaded with a high content of dexamethasone palmitate (DEX-P), a chemotherapeutic adjuvant that decreases interstitial fluid pressure in tumors, and 111In, a signaling agent, is described. These NPs are uniform in size and composition. Single photon emission computed tomography imaging demonstrates significant tumor uptake of 111In-labeled DEX-P NPs in tumor-bearing mice. As with many nanoparticle-based drug delivery systems, significant liver accumulation is observed. Assessment of liver histology and blood tests show no apparent hepatic or renal toxicity of the DEX-P NPs. Conversion of DEX-P to DEX occurs when DEX-P NPs are incubated with mouse plasma, human tumor homogenate and ascites from tumor bearing mice, but not with human plasma. This conversion is slower in plasma from Es1e(−/−)/SCID mice, a potential alternative animal model that better mimics humans; however, plasma from these mice are not completely devoid of esterase activity. The difference between blood and tumor esterase activity in humans facilitates the delivery of DEX-P NPs to tumors and the release of dexamethasone by an esterase trigger

Single Transconjunctival Incision and Two-point Fixation for the Treatment of Noncomminuted Zygomatic Complex Fracture

The ultimate goal in treating zygomatic complex fracture is to obtain an accurate, stable reduction while minimizing external scars and functional deformity. The present authors present our experiences with a single transconjunctival incision and two-point (inferior orbital rim and frontozygomatic suture) fixation in 53 patients with zygomatic complex fracture which were not comminuted. All patients had transconjunctival approaches with lateral canthal extensions, and six out of 53 patients also had an additional small (about less than 2 cm) gingivobuccal incision to achieve an accurate reduction. There were 3 minor complications, and the overall esthetics and functional results were satisfactory with a long term follow-up. Our method has the following advantages in the reduction of zygomatic complex fracture; It leaves only an inconspicuous lateral canthal scar. In addition, it provides excellent simultaneous visualization of the inferior orbital rim and frontozygomatic suture area. Hence, two-point fixation through a single incision can be performed with a satisfactory stability

Algorithmic Complexity for Short Binary Strings Applied to Psychology: A Primer

Since human randomness production has been studied and widely used to assess executive functions (especially inhibition), many measures have been suggested to assess the degree to which a sequence is random-like. However, each of them focuses on one feature of randomness, leading authors to have to use multiple measures. Here we describe and advocate for the use of the accepted universal measure for randomness based on algorithmic complexity, by means of a novel previously presented technique using the the definition of algorithmic probability. A re-analysis of the classical Radio Zenith data in the light of the proposed measure and methodology is provided as a study case of an application.Comment: To appear in Behavior Research Method

The Association between Kidney Function, Coronary Artery Disease, and Clinical Outcome in Patients Undergoing Coronary Angiography

To characterize the association between chronic kidney disease (CKD), mortality, severity of coronary artery disease (CAD), treatment modality of CAD, and type of coronary stents among patients undergoing coronary angiography (CAG), we retrospectively reviewed the electronic medical records of the patients who underwent CAG at Seoul National University Bundang Hospital in Korea between May 2003 and January 2006. CKD was staged using an estimated glomerular filtration rate (eGFR) from the creatinine value prior to CAG. There were 3,637 patients included. The presence of CAD was 48% in CKD stage 1, 61% in stage 2, 73% in stage 3, 87% in stage 4, and 81% in stage 5. Survival rate gradually diminished for patients with decreasing renal function. No significant differences in all-cause and cardiac mortality were observed by medical treatment, PCI or CABG, in CKD patients with an eGFR less than 60 mL/min/1.73 m2. CKD patients with drug-eluting stents showed significantly lower all-cause mortality (5.4% vs. 13.3%) and incidence of myocardial infarction (1.7% vs. 10%) than those with bare metal stents. In conclusion, an eGFR is a strong independent prognostic marker among patients undergoing CAG and the severity of CAD increases progressively with worsening renal function

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference