At elevated levels, homocysteine (Hcy, 1) is a risk factor for cardiovascular diseases, Alzheimer's disease, neural tube defects, and osteoporosis. Both 1 and cysteine (Cys, 3) are linked to neurotoxicity. The biochemical mechanisms by which 1 and 3 are involved in disease states are relatively unclear. Herein, we describe simple methods for detecting either Hcy or Cys in the visible spectral region with the highest selectivity reported to date without using biochemical techniques or preparative separations. Simple methods and readily available reagents allow for the detection of Cys and Hcy in the range of their physiologically relevant levels. New HPLC postcolumn detection methods for biological thiols are reported. The potential biomedical relevance of the chemical mechanisms involved in the detection of 1 is described.

The synthesis of new benzo[a]- and [b]xanthene dye frameworks is described. A unique benzo[a]xanthene, seminaphtho[a]fluorone (SNAFR-1), is studied in a variety of media. The optimization of solution parameters and excitation wavelengths allows SNAFR-1 to display red, green, and blue emission bands of approximately equal intensities and also to produce white light. Ratiometric red (anion) and green (neutral) emissions are observed upon varying solution pH. A pH-independent violet-blue emission band is due to the addition of nucleophiles to the benzylic carbon of SNAFR-1.

Level III, comparative case series.

A readily accessible new class of near infrared (NIR) molecular probes has been synthesized and evaluated. Specific fluorophores in this unique xanthene based regioisomeric seminaphthofluorone dye series exhibit a combination of desirable characteristics including (i) low molecular weight (339 amu), (ii) aqueous solubility, and (iii) dual excitation and emission from their fluorescent neutral and anionic forms. Importantly, systematic changes in the regiochemistry of benzannulation and the ionizable moieties afford (iv) tunable deep-red to NIR emission from anionic species and (v) enhanced Stokes shifts. Anionic SNAFR-6, exhibiting an unusually large Stokes shift of Ϸ200 nm (5,014 cm ؊1 ) in aqueous buffer, embodies an unprecedented fluorophore that emits NIR fluorescence when excited in the blue/green wavelength region. The successful use of SNAFR-6 in cellular imaging studies demonstrates proof-of-concept that this class of dyes possesses photophysical characteristics that allow their use in practical applications. Notably, each of the new fluorophores described is a minimal template structure for evaluation of their basic spectral properties, which may be further functionalized and optimized yielding concomitant improvements in their photophysical properties.NIR dyes ͉ xanthenes D yes active in the near infrared (NIR) region (Ͼ700 nm) have been under development since the first discovery of dyes with such spectral properties in the early twentieth century. NIR dyes have found wide applicability in optical recording, thermal writing displays, laser printers, laser filters, infrared photography, photodynamic therapy, and numerous other applications (1). More recently, NIR dyes have attracted considerable attention for biological and biomedical applications (2) because of inherent advantages, such as minimal interfering absorption and fluorescence from biological samples, inexpensive laser diode excitation, reduced scattering, and enhanced tissue penetration depth. Surprisingly, only a relatively few classes of NIR dyes, such as the phthalocyanines, cyanines, and squaraines, are available for use in these fields. Each of these classes of dyes has its own distinct advantages and disadvantages; moreover, common limitations include relatively small Stokes shifts and incompatibility with common f luorophores for multiplexing applications. Clearly, there is a strong need and interest in enriching the available pool of NIR fluorophores.Annulation has proven to be quite successful for effecting bathochromic shifts through extension of the conjugated system of various dye architectures (3-4). Lee et al. (3) first synthesized the red-shifted type [c] naphthofluorescein framework nearly two decades ago. In addition, seminaphthofluorescein (SNAFL) and seminaphthorhodafluor (SNARF) with type [c] annulations, as developed by Haugland and coworkers (4), are in wide use today. These dyes primarily display red-shifted emissions that have maxima in the red spectral region. Importantly, although the use of type [c] annulation ha...

Level IV, retrospective case series.

We present ABCD, an integrated drug discovery informatics platform developed at Johnson & Johnson Pharmaceutical Research & Development, L.L.C. ABCD is an attempt to bridge multiple continents, data systems, and cultures using modern information technology and to provide scientists with tools that allow them to analyze multifactorial SAR and make informed, data-driven decisions. The system consists of three major components: (1) a data warehouse, which combines data from multiple chemical and pharmacological transactional databases, designed for supreme query performance; (2) a state-of-the-art application suite, which facilitates data upload, retrieval, mining, and reporting, and (3) a workspace, which facilitates collaboration and data sharing by allowing users to share queries, templates, results, and reports across project teams, campuses, and other organizational units. Chemical intelligence, performance, and analytical sophistication lie at the heart of the new system, which was developed entirely in-house. ABCD is used routinely by more than 1000 scientists around the world and is rapidly expanding into other functional areas within the J&J organization.

This international consensus derived from leaders in the field will assist clinicians with debridement, curettage and bone marrow stimulation as a treatment strategy for osteochondral lesions of the talus.

BackgroundA key point to surgical treatment of chronic lateral ankle instability is choosing a suitable surgical procedure. The purpose of this meta-analysis was to compare different surgical techniques for management of chronic lateral ankle instability.MethodsWe searched the Cochrane Library, MEDLINE, and EMBASE. All identified randomized and quasi-randomized controlled trials of operative treatment for chronic lateral ankle instability were included. Two review authors independently extracted data from each study and assessed risk of bias. Where appropriate, results of comparable studies were pooled.ResultsSeven randomized controlled trials were included for analysis. They fell in five clearly distinct groups.One study comparing two different kinds of non-anatomic reconstruction procedures (dynamic and static tenodesis) found two clinical outcomes favoring static tenodesis: better clinical satisfaction and fewer subsequent sprains.Two studies compared non-anatomic reconstruction versus anatomic repairment. In one study, nerve damage was more frequent in non-anatomic reconstruction group; the other one reported that radiological measurement of ankle laxity showed that non-anatomic reconstruction provided higher reduction of talar tilt angle.Two studies comparing two anatomic repairment surgical techniques (transosseous suture versus imbrication) showed no significant difference in any clinical outcome at the follow-up except operation time.One study compared two different anatomic repairment techniques. They found that the double anchor technique was superior with respect to the reduction of talar tilt than single anchor technique.One study compared an anatomic reconstruction procedure with a modified Brostrom technique. Primary reconstruction combined with ligament advanced reinforcement system results in better patient-scored clinical outcome, at 2 years post-surgery, than the modified Brostrom procedure.ConclusionsThere is limited evidence to support any one surgical technique over another surgical technique for chronic lateral ankle instability, but based on the evidence, we could still get some conclusions: (1) There are limitations to the use of dynamic tenodesis, which obtained poor clinical satisfaction and more subsequent sprains. (2) Non-anatomic reconstruction abnormally increased inversion stiffness at the subtalar level as compare with anatomic repairment. (3) Multiple types of modified Brostrom procedures could acquire good clinical results. (4) Anatomic reconstruction is a better procedure for some specific patients.Electronic supplementary materialThe online version of this article (10.1186/s13018-018-0870-6) contains supplementary material, which is available to authorized users.