Upper Limb Spasticity: The Quality of Online Patient Resources.

OBJECTIVE: The aim of the study is to assess the quality, readability, content, accessibility, and structure of online resources for patients with upper limb spasticity. DESIGN: This was a cross sectional study examined Internet searches across three search engines related to patient resources for upper limb spasticity. Search phrases for either hand or upper limb spasticity were used. The top 20 Websites from each search were evaluated using the four readability metrics and the DISCERN scale for quality assessment. YouTube videos with exact search phrases were evaluated using DISCERN. Descriptive statistical analyses were performed using SPSS software. RESULTS: Thirty-six Websites and 33 videos met the inclusion criteria for this study. The average Flesh-Kincaid Grade Level of the Websites was 11.7 ± 3.1, showing low Website readability. According to this index, only two Websites were written at the suggested sixth-grade level (5.4%). With a maximum score of 75, the mean DISCERN score for both Websites and videos scored in the "good" range (53.5 ± 8 and 50.5 ± 6.6), respectively. CONCLUSIONS: Current online resources for upper limb spasticity are good in quality but are written above the health literacy level of American citizens. Organizations should consider reviewing their present materials and developing high-quality patient education materials that are easier to understand.

Structure, mechanism and inhibition of anthranilate phosphoribosyltransferase.

Anthranilate phosphoribosyltransferase catalyses the second reaction in the biosynthesis of tryptophan from chorismate in microorganisms and plants. The enzyme is homodimeric with the active site located in the hinge region between two domains. A range of structures in complex with the substrates, substrate analogues and inhibitors have been determined, and these have provided insights into the catalytic mechanism of this enzyme. Substrate 5-phospho-d-ribose 1-diphosphate (PRPP) binds to the C-terminal domain and coordinates to Mg2+, in a site completed by two flexible loops. Binding of the second substrate anthranilate is more complex, featuring multiple binding sites along an anthranilate channel. This multi-modal binding is consistent with the substrate inhibition observed at high concentrations of anthranilate. A series of structures predict a dissociative mechanism for the reaction, similar to the reaction mechanisms elucidated for other phosphoribosyltransferases. As this enzyme is essential for some pathogens, efforts have been made to develop inhibitors for this enzyme. To date, the best inhibitors exploit the multiple binding sites for anthranilate. This article is part of the theme issue 'Reactivity and mechanism in chemical and synthetic biology'.

Wafer-Scale Full-Coverage Self-Limiting Assembly of Particles on Flexible Substrates.

Self-limiting assembly of particles represents the state-of-the-art controllability in nanomanufacturing processes where the assembly stops at a designated stage, providing a desirable platform for applications requiring delicate thickness control such as optics, electronics, and catalytic systems. Most successes in self-limiting assembly are limited to self-assembled monolayers (SAMs) of small molecules on inorganic, chemically homogeneous rigid substrates (e.g., Au and SiO2) through surface-interaction mechanisms. Similar mechanisms, however, cannot achieve a uniform assembly of particles on flexible polymer substrates. The complex configurations and conformations of polymer chains create a surface with nonuniform distributions of chemical groups and phases. In addition, most assembly mechanisms require good solvent wettability, where many desirable but hard-to-wet particles and polymer substrates are excluded. Here, we demonstrate a collision-based self-limiting assembly (CSA) to achieve wafer-scale, full-coverage, close-packed monolayers of hydrophobic particles on hydrophobic polymer substrates in aqueous solutions. The kinetic assembly and self-limiting processes are facilitated and controlled by the combined acoustic and shear fields. We envision many applications in functional coatings and showcase their feasibility in structural coloration. Importantly, such functional coatings can be repaired using CSA, and both particles and polymer substrate can be recycled.

A Low Redundancy Wavelet Entropy Edge Detection Algorithm.

Fast edge detection of images can be useful for many real-world applications. Edge detection is not an end application but often the first step of a computer vision application. Therefore, fast and simple edge detection techniques are important for efficient image processing. In this work, we propose a new edge detection algorithm using a combination of the wavelet transform, Shannon entropy and thresholding. The new algorithm is based on the concept that each Wavelet decomposition level has an assumed level of structure that enables the use of Shannon entropy as a measure of global image structure. The proposed algorithm is developed mathematically and compared to five popular edge detection algorithms. The results show that our solution is low redundancy, noise resilient, and well suited to real-time image processing applications.

Uncoupling Molecular Testing for SARS-CoV-2 From International Supply Chains.

The rapid global rise of COVID-19 from late 2019 caught major manufacturers of RT-qPCR reagents by surprise and threw into sharp focus the heavy reliance of molecular diagnostic providers on a handful of reagent suppliers. In addition, lockdown and transport bans, necessarily imposed to contain disease spread, put pressure on global supply lines with freight volumes severely restricted. These issues were acutely felt in New Zealand, an island nation located at the end of most supply lines. This led New Zealand scientists to pose the hypothetical question: in a doomsday scenario where access to COVID-19 RT-qPCR reagents became unavailable, would New Zealand possess the expertise and infrastructure to make its own reagents onshore? In this work we describe a review of New Zealand's COVID-19 test requirements, bring together local experts and resources to make all reagents for the RT-qPCR process, and create a COVID-19 diagnostic assay referred to as HomeBrew (HB) RT-qPCR from onshore synthesized components. This one-step RT-qPCR assay was evaluated using clinical samples and shown to be comparable to a commercial COVID-19 assay. Through this work we show New Zealand has both the expertise and, with sufficient lead time and forward planning, infrastructure capacity to meet reagent supply challenges if they were ever to emerge.

Phase II study of bi-weekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma.

PURPOSE: Bevacizumab is an active anti-angiogenic agent in the treatment of recurrent glioblastoma. Temozolomide can prolong survival in patients with newly diagnosed glioblastoma. At recurrence, alternate dosing of temozolomide has shown to further deplete methyl-guanine-methyltransferase (MGMT) conferring added activity for patients who have progressed on the standard dosing regimen. In this study, bevacizumab plus biweekly temozolomide was evaluated for efficacy in adult patients with recurrent glioblastoma. METHODS: Thirty patients with recurrent glioblastoma were treated with bevacizumab on (10 mg/kg i.v.) days 1 and 15 of a 28-day cycle combined with temozolomide (100 mg/m2) on days 1-5 and 15-19 on a 28-day cycle. Responses were assessed at week 4 and then every 8 weeks. MGMT status and quality of life measures were also assessed. RESULTS: Overall response rate from diagnosis was 51 weeks, the 6-month progression-free survival was 52%, and median time to tumor progression was 5.5 months. CONCLUSION: Bevacizumab plus bi-weekly temozolomide was well tolerated and may be a salvage regimen to be considered in a subset of patients with recurrent glioblastoma.

Fluorescent Hexose Conjugates Establish Stringent Stereochemical Requirement by GLUT5 for Recognition and Transport of Monosaccharides.

The specificity characteristics of transporters can be exploited for the development of novel diagnostic therapeutic probes. The facilitated hexose transporter family (GLUTs) has a distinct set of preferences for monosaccharide substrates, and while some are expressed ubiquitously (e.g., GLUT1), others are quite tissue specific (e.g., GLUT5, which is overexpressed in some breast cancer tissues). While these differences have enabled the development of new molecular probes based upon hexose- and tissue-selective uptake, substrate design for compounds targeting these GLUT transporters has been encumbered by a limited understanding of the molecular interactions at play in hexose binding and transport. Four new fluorescently labeled hexose derivatives have been prepared, and their transport characteristics were examined in two breast cancer cell lines expressing mainly GLUTs 1, 2, and 5. Our results demonstrate, for the first time, a stringent stereochemical requirement for recognition and transport by GLUT5. 6-NBDF, in which all substituents are in the d-fructose configuration, is taken up rapidly into both cell lines via GLUT5. On the other hand, inversion of a single stereocenter at C-3 (6-NBDP), C-4 (6-NBDT), or C-5 (6-NDBS) results in selective transport via GLUT1. An in silico docking study employing the recently published GLUT5 crystal structure confirms this stereochemical dependence. This work provides insight into hexose-GLUT interactions at the molecular level and will facilitate structure-based design of novel substrates targeting individual members of the GLUT family and forms the basis of new cancer imaging or therapeutic agents.

Interrupting the Nazarov Cyclization with Bromine.

The generation of dibrominated cyclopentenones via an interrupted Nazarov cyclization is reported. The installation of two bromine atoms occurs at the α and α' positions of the cyclopentenyl scaffold via successive nucleophilic and electrophilic bromination of the 2-oxidocyclopentenyl cation and its resulting enolate. Notably, the reaction proceeds with good diastereoselectivity, favoring the symmetrical product.

Forty-three-Year Follow-up of Salvage Knee Reconstruction Using the Patella to Replace Lost Tibial Articular Surface: A Case Report.

CASE: A 19-year-old soldier presented with sudden onset of left knee pain and giving-way while running. Evaluation showed a pathologic fracture through a radiolucent lesion of the tibial metaphysis. Excision of a giant cell tumor of bone entailed removal of much of the lateral tibial articular surface. The joint surface was replaced by transposition of the patella, which was transfixed in position with an ASIF (Association for the Study of Internal Fixation) condylar blade plate. This technique resulted in satisfactory knee function that has persisted for 43 years. CONCLUSION: When excision of a tumor of the tibia results in removal of a substantial portion of the articular surface, the defect can be replaced by transposition of the patella to provide long-lasting satisfactory knee function.

Diastereoselective synthesis of 5-hydroxy-8-methoxy-1-oxaspiro[5,5]undeca-7,10-diene-9-one.

A short five steps synthesis of the title compound from vanillin is described. The racemic spiroether 7 was obtained in 61% yield and in >99% diastereomeric excess (by 1H-NMR) from the corresponding phenolic derivative 3 by oxidation with lead (IV) acetate.

Diastereoselective spiroannulation of phenolic substrates: advances towards the asymmetric formation of the manumycin m-C7N core skeleton.

The asymmetric syntheses of two new spirolactones prepared in optically pure form from L-3-nitrotyrosine are described. The key step, an oxidative spiroannulation, was carried out on the optically active phenols 11a and 11b and afforded the new spirolactones 5a and 5b in 85% and 83% yields, respectively, as mixtures (3:1 dr) of diastereomers. The major diastereomers from these mixtures could be isolated in optically pure form by trituration using acetone-hexanes as the solvent. Thus, the optically active spirolactones (+)-5a (+ 92.8 degrees, c=0.125 acetone) and (+)-5b (+112.0 degrees, c= 0.125 acetone) were obtained after four synthetic steps from L-3-nitrotyrosine in 41% and 43% yield, respectively.

New directions in Medicare managed care.

The new Medicare Prescription Drug, Improvement, and Modernization Act of 2003 offers the most sweeping reforms to the Medicare program since its inception. The managed care benefit formerly offered by Medicare+Choice is greatly improved under Medicare Advantage. Now the nation's senior citizens in urban and rural areas alike can participate in PPOs that provide care-management programs and protection against catastrophic costs. They also receive the same kind of private health insurance options that have been available to the nation's work force.

Thomas A. Scully and the Centers for Medicare and Medicaid Services. Interview by Kevin C. Park and Wanda Bishop.

Thomas A. Scully became the administrator of the Centers for Medicare and Medicaid Services (CMS; previously the Health Care Financing Administration) in 2001. Before that, he was the president and chief executive officer of the Federation of American Hospitals, the trade association representing the nation's 1,700 privately owned and managed community hospitals and health systems. Before joining the federation, Mr. Scully was a partner in the Washington, DC, law firm of Patton Boggs, LLP, where his practice focused on regulatory and legislative work in healthcare. Before joining the law firm, Mr. Scully worked at the White House as deputy assistant to the President and counselor to the director of the Office of Management and Budget (OMB) and as associate director of OMB for Human Resources, Veterans and Labor. In these positions, he oversaw the fiscal policy and regulatory review of the Departments of Health and Human Services, Education, Labor, and Veterans Affairs. He also advised former President Bush on healthcare policy and Medicare and Medicaid payment reform. Mr. Scully has served on the board of directors of Oxford Health Plans and of DaVita Corporation, two of the nation's largest healthcare service providers. Mr. Scully holds a Juris Doctor from Catholic University of America and a bachelor's degree from the University of Virginia.

A call to excellence.

Health care improvement affects us all and is not optional. For change to occur, consumers must demand excellence from their providers and clinicians. Patient safety is part of a broader set of health care quality issues. Championing this view will not be easy, for it means fundamental change to the myriad interrelated systems that make up U.S. health care. HHS is taking the lead on patient safety through a number of initiatives and activities.