Fluorescent Nanodiamonds Embedded in Biocompatible Translucent Shells

High pressure high temperature (HPHT) nanodiamonds (NDs) represent extremely promising materials for construction of fluorescent nanoprobes and nanosensors. However, some properties of bare NDs limit their direct use in these applications: they precipitate in biological solutions, only a limited set of bio‐orthogonal conjugation techniques is available and the accessible material is greatly polydisperse in shape. In this work, we encapsulate bright 30‐nm fluorescent nanodiamonds (FNDs) in 10–20‐nm thick translucent (i.e., not altering FND fluorescence) silica shells, yielding monodisperse near‐spherical particles of mean diameter 66 nm. High yield modification of the shells with PEG chains stabilizes the particles in ionic solutions, making them applicable in biological environments. We further modify the opposite ends of PEG chains with fluorescent dyes or vectoring peptide using click chemistry. High conversion of this bio‐orthogonal coupling yielded circa 2000 dye or peptide molecules on a single FND. We demonstrate the superior properties of these particles by in vitro interaction with human prostate cancer cells: while bare nanodiamonds strongly aggregate in the buffer and adsorb onto the cell membrane, the shell encapsulated NDs do not adsorb nonspecifically and they penetrate inside the cells.     

TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients

Clinical guidelines recommend concurrent treatment of anemia in end‐stage renal disease with erythropoiesis‐stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12‐month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4‐week interval for four consecutive intervals (k ? 2, k ? 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k ? 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k ? 2, k ? 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long‐term safety of iron use to improve Hb response to ESA warrants further study.     

3D Printing of Customized Drug Delivery Systems with Controlled Architecture via Reversible Addition-Fragmentation Chain Transfer Polymerization

3D printing via reversible addition-fragmentation chain transfer (RAFT) polymerization has been recently developed to expand the scope of 3D printing technologies. A potentially high-impact but relatively unexplored opportunity that can be provided by RAFT-mediated 3D printing is a pathway toward personalized medicine through manufacturing bespoke drug delivery systems (DDSs). Herein, 3D printing of drug-eluting systems with precise geometry, size, drug dosage, and release duration/profiles is reported. This is achieved through engineering a range of 3D models with precise interconnected channel-pore structure and geometric proportions in architectural patterns. Notably, the application of the RAFT process is crucial in manufacturing materials with highly resolved macroscale features by confining curing to exposure precincts. This approach also allows spatiotemporal control of the drug loading and compositions within different layers of the scaffolds. The ratio between the polyethylene glycol units and the acrylate units in the crosslinkers is found to be a critical factor, with a higher ratio increasing swelling capacity, and thus enhancing the drug release profile, from the drug-eluting systems. This proof-of-concept research demonstrates that RAFT-mediated 3D printing enables the production of personalized drug delivery materials, providing a pathway to replace the “one-size-fits-all” approach in traditional health care.     

Demonstration of discrete secreted and membrane-bound ocular mucins in the dog

Our aims were to separate and characterize secreted canine ocular mucins, and to provide definitive evidence of membrane-bound mucins at the canine ocular surface. Mucus was collected by suction from the ocular surface of normal dogs and dispersed in guanidine hydrochloride and a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation separated secreted mucins from membranes, which were collected from the top of the gradients. Membranes were extracted with octyl glucoside and screened using lectins and anti-mucin antibodies. Gradient fractions containing secreted mucins were constituted into pools on the basis of differential lectin and antibody staining. High molecular weight material from each pool was purified by gel filtration. This material, and the membrane extract, were reduced and alkylated. Vacuum blotting of separated materials after agarose gel electrophoresis was used to compare subunit structure. Density gradient profiles indicated three principal secreted glycoprotein peaks: one staining strongly with anti-mucin antibodies. Gel filtration demonstrated that each contained high molecular weight material. Vacuum blots demonstrated the presence of two secreted glycoproteins with differently sized subunits. On the basis of buoyant density, one of these may be lipid complexed. Membrane extracted material stained with anti-mucin antibodies, and vacuum blotting of this material provided evidence for two membrane-bound components. In conclusion, we have shown that normal canine ocular mucus contains two secreted mucins, each exhibiting different subunit structure; one of these mucins may undergo lipid complexation. Normal canine ocular mucus also contains two membrane-bound mucins: one of which is unique among membrane mucins in showing subunit structure.     

Adult attachment classification and self-reported psychiatric symptomatology as assessed by the Minnesota Multiphasic Personality Inventory--2.

This study examined differences in self-reported psychiatric symptomatology on the Minnesota Multiphasic Personality Inventory-2 according to adult attachment status on the Adult Attachment Interview in first-time mothers from a high-risk poverty sample. Participants reported fairly high levels of symptomatology regardless of attachment status. The dismissing adult attachment group reported comparatively little psychiatric distress, emphasized independence, and scored the lowest on self-reported anxiety. The preoccupied group was highest on a range of indices of psychiatric symptoms indicative of self-perceived distress and relationship problems. The autonomous group's scores ranged between the scores of the other 2 groups on most scales. These different symptom patterns are consistent with adult attachment status as an index of self-representation and as a set of strategies for processing emotions and thoughts related to distress and to attachment relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of five smoking cessation pharmacotherapies on smoking cessation milestones.

Objective: Most smoking cessation studies have used long-term abstinence as their primary outcome measure. Recent research has suggested that long-term abstinence may be an insensitive index of important smoking cessation mechanisms. The goal of the current study was to examine the effects of 5 smoking cessation pharmacotherapies using Shiffman et al.'s (2006) approach of examining the effect of smoking cessation medications on 3 process markers of cessation or smoking cessation milestones: initial abstinence, lapse, and the lapse–relapse transition. Method: The current study (N = 1,504; 58.2% female and 41.8% male; 83.9% Caucasian, 13.6% African American, 2.5% other races) examined the effect of 5 smoking cessation pharmacotherapy treatments versus placebo (bupropion, nicotine lozenge, nicotine patch, bupropion + lozenge, patch + lozenge) on Shiffman et al.'s smoking cessation milestones over 8 weeks following a quit attempt. Results: Results show that all 5 medication conditions decreased rates of failure to achieve initial abstinence and most (with the exception of the nicotine lozenge) decreased lapse risk; however, only the nicotine patch and bupropion + lozenge conditions affected the lapse–relapse transition. Conclusions: These findings demonstrate that medications are effective at aiding initial abstinence and decreasing lapse risk but that they generally do not decrease relapse risk following a lapse. The analysis of cessation milestones sheds light on important impediments to long-term smoking abstinence, suggests potential mechanisms of action of smoking cessation pharmacotherapies, and identifies targets for future treatment development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A taxonomy of effect size measures for the differential functioning of items and scales.

[Correction Notice: An erratum for this article was reported in Vol 95(5) of Journal of Applied Psychology (see record 2010-18410-004). There was an error in Formula 6 on page 731 for the pooled standard deviation of the ESSD index. The correct formula is given in the erratum. Related to this, in Table 8 on page 739, the ETSSD statistic should have been .094 for the cross cultural comparison and .001 for the Administration Format example.] Much progress has been made in the past 2 decades with respect to methods of identifying measurement invariance or a lack thereof. Until now, the focus of these efforts has been to establish criteria for statistical significance in items and scales that function differently across samples. The power associated with tests of differential functioning, as with all significance tests, is affected by sample size and other considerations. Additionally, statistical significance need not imply practical importance. There is a strong need as such for meaningful effect size indicators to describe the extent to which items and scales function differently. Recently developed effect size measures show promise for providing a metric to describe the amount of differential functioning present between groups. Expanding upon recent developments, this article presents a taxonomy of potential differential functioning effect sizes; several new indices of item and scale differential functioning effect size are proposed and illustrated with 2 data samples. Software created for computing these indices and graphing item- and scale-level differential functioning is described. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do neuropsychological tests have the same meaning in Spanish speakers as they do in English speakers?

Objective: The purpose of this study was to examine whether neuropsychological tests translated into Spanish measure the same cognitive constructs as the original English versions. Method: Older adult participants (N = 2,664), who did not exhibit dementia from the Washington Heights Inwood Columbia Aging Project (WHICAP), a community-based cohort from northern Manhattan, were evaluated with a comprehensive neuropsychological battery. The study cohort includes both English (n = 1,800) and Spanish speakers (n = 864) evaluated in their language of preference. Invariance analyses were conducted across language groups on a structural equation model comprising four neuropsychological factors (memory, language, visual-spatial ability, and processing speed). Results: The results of the analyses indicated that the four-factor model exhibited partial measurement invariance, demonstrated by invariant factor structure and factor loadings but nonequivalent observed score intercepts. Conclusion: The finding of invariant factor structure and factor loadings provides empirical evidence to support the implicit assumption that scores on neuropsychological tests are measuring equivalent psychological traits across these two language groups. At the structural level, the model exhibited invariant factor variances and covariances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heat Shock Alters the Proteomic Profile of Equine Mesenchymal Stem Cells

The aim of this research was to determine the impact of heat stress on cell differentiation in an equine mesenchymal stem cell model (EMSC) through the application of heat stress to primary EMSCs as they progressed through the cell specialization process. A proteomic analysis was performed using mass spectrometry to compare relative protein abundances among the proteomes of three cell types: progenitor EMSCs and differentiated osteoblasts and adipocytes, maintained at 37 °C and 42 °C during the process of cell differentiation. A cell-type and temperature-specific response to heat stress was observed, and many of the specific differentially expressed proteins were involved in cell-signaling pathways such as Notch and Wnt signaling, which are known to regulate cellular development. Furthermore, cytoskeletal proteins profilin, DSTN, SPECC1, and DAAM2 showed increased protein levels in osteoblasts differentiated at 42 °C as compared with 37 °C, and these cells, while they appeared to accumulate calcium, did not organize into a whorl agglomerate as is typically seen at physiological temperatures. This altered proteome composition observed suggests that heat stress could have long-term impacts on cellular development. We propose that this in vitro stem cell culture model of cell differentiation is useful for investigating molecular mechanisms that impact cell development in response to stressors.     

Synthetic applications of nonmetal catalysts for homogeneous oxidations

Nonmetal oxidation catalysts have gained much attention in recent years. The reason for this surge in activity is 2-fold: On one hand, a number of such catalysts has become readily accessible; on the other hand, such catalysts are quite resistant toward self-oxidation and compatible under aerobic and aqueous reaction conditions. In this review, we have focused on five nonmetal catalytic systems which have attained prominence in the oxidation field in view of their efficacy and their potential for future development; stoichiometric cases have been mentioned to provide overview and scope. Such nonmetal oxidation catalysts include the alpha-halo carbonyl compounds 1, ketones 2, imines 3, iminium salts 4, and nitroxyl radicals 5. In combination with a suitable oxygen source (H2O2, KHSO5, NaOCl), these catalysts serve as precursors to the corresponding oxidants, namely, the perhydrates I, dioxiranes II, oxaziridines III, oxaziridinium ions IV, and finally oxoammonium ions V. A few of the salient features about these nonmetal, catalytic systems shall be reiterated in this summary. The first class entails the alpha-halo ketones, which catalyze the oxidation of a variety of organic substrates [figure: see text] by hydrogen peroxide as the oxygen source. The perhydrates I, formed in situ by the addition of hydrogen peroxide to the alpha-halo ketones, are quite strong electrophilic oxidants and expectedly transfer an oxygen atom to diverse nucleophilic acceptors. Thus, alpha-halo ketones have been successfully employed for catalytic epoxidation, heteroatom (S, N) oxidation, and arene oxidation. Although high diastereoselectivities have been achieved by these nonmetal catalysts, no enantioselective epoxidation and sulfoxidation have so far been reported. Consequently, it is anticipated that catalytic oxidations by perhydrates hold promise for further development, especially, and should ways be found to transfer the oxygen atom enantioselectively. The second class, namely, the dioxiranes, has been extensively used during the last two decades as a convenient oxidant in organic synthesis. These powerful and versatile oxidizing agents are readily available from the appropriate ketones by their treatment [figure: see text] with potassium monoperoxysulfate. The oxidations may be performed either under stoichiometric or catalytic conditions; the latter mode of operation is featured in this review. In this case, a variety of structurally diverse ketones have been shown to catalyze the dioxirane-mediated epoxidation of alkenes by monoperoxysulfate as the oxygen source. By employing chiral ketones, highly enantioselective (up to 99% ee) epoxidations have been developed, of which the sugar-based ketones are so far the most effective. Reports on catalytic oxidations by dioxiranes other than epoxidations are scarce; nevertheless, fructose-derived ketones have been successfully employed as catalysts for the enantioselective CH oxidation in vic diols to afford the corresponding optically active alpha-hydroxy ketones. To date, no catalytic asymmetric sulfoxidations by dioxiranes appear to have been documented in the literature, an area of catalytic dioxirane chemistry that merits attention. A third class is the imines; their reaction with hydrogen peroxide or monoperoxysulfate affords oxaziridines. These relatively weak electrophilic oxidants only manage to oxidize electron-rich substrates such as enolates, silyl enol ethers, sulfides, selenides, and amines; however, the epoxidation of alkenes has been achieved with activated oxaziridines produced from perfluorinated imines. Most of the oxidations by in-situ-generated oxaziridines have been performed stoichiometrically, with the exception of sulfoxidations. When chiral imines are used as catalysts, optically active sulfoxides are obtained in good ee values, a catalytic asymmetric oxidation by oxaziridines that merits further exploration. The fourth class is made up by the iminium ions, which with monoperoxysulfate lead to the corresponding oxaziridinium ions, structurally similar to the above oxaziridine oxidants except they possess a much more strongly electrophilic oxygen atom due to the positively charged ammonium functionality. Thus, oxaziridinium ions effectively execute besides sulfoxidation and amine oxidation the epoxidation of alkenes under catalytic conditions. As expected, chiral iminium salts catalyze asymmetric epoxidations; however, only moderate enantioselectivities have been obtained so far. Although asymmetric sulfoxidation has been achieved by using stoichiometric amounts of isolated optically active oxaziridinium salts, iminium-ion-catalyzed asymmetric sulf-oxidations have not been reported to date, which offers attractive opportunities for further work. The fifth and final class of nonmetal catalysts concerns the stable nitroxyl-radical derivatives such as TEMPO, which react with the common oxidizing agents (sodium hypochlorite, monoperoxysulfate, peracids) to generate oxoammonium ions. The latter are strong oxidants that chemoselectively and efficiently perform the CH oxidation in alcohols to produce carbonyl compounds rather than engage in the transfer of their oxygen atom to the substrate. Consequently, oxoammonium ions behave quite distinctly compared to the previous four classes of oxidants in that their catalytic activity entails formally a dehydrogenation, one of the few effective nonmetal-based catalytic transformations of alcohols to carbonyl products. Since less than 1 mol% of nitroxyl radical is required to catalyze the alcohol oxidation by the inexpensive sodium hypochlorite as primary oxidant under mild reaction conditions, this catalytic process holds much promise for future practical applications.