Innovations in functional and rehabilitative knee bracing.

New knee brace designs are available that have the potential to improve patient outcomes relative to traditional bracing. For the indications of post-knee injury/surgery recovery, conservative management of knee osteoarthritis (OA), total knee arthroplasty (TKA) pre-habilitation, and the treatment of post-surgical extension deficits/flexion contractures, innovative new bracing designs merit review and discussion. The researchers requested information from industry brace manufacturers, and from the information received, have selected those products considered significant improvements over traditional functional brace designs for review in this article.

Zn-binding in the glutamate-rich region of the intrinsically disordered protein prothymosin-alpha.

Prothymosin-α is a small, multifunctional intrinsically disordered protein associated with cell survival and proliferation which binds multiple Zn ions and undergoes partial folding. The interaction between prothymosin-α and at least two of its protein targets is significantly enhanced in the presence of Zn ions, suggesting that Zn binding plays a role in the protein's function. The primary sequence of prothymosin-α is highly acidic, with almost 50% comprised of Asp and Glu, and is unusual for a Zn-binding protein as it lacks Cys and His residues.

Effect of 28-mm Cryoballoon Ablation on Major Atrial Ganglionated Plexi.

Objectives: The authors intended to investigate if 28-mm cryoballoon (CB) ablation also modifies the 4 major atrial ganglionaated plexi (GP).

Background: The major atrial GP facilitate the initiation and maintenance of atrial fibrillation (AF). The 28-mm CB covers a large surface area of the left atrium and probably the GP areas.

Home is where the future is: The BrightFocus Foundation consensus panel on dementia care.

Introduction: A national consensus panel was convened to develop recommendations on future directions for home-based dementia care (HBDC).

Methods: The panel summarized advantages and challenges of shifting to HBDC as the nexus of care and developed consensus-based recommendations.

Results: The panel developed five core recommendations: (1) HBDC should be considered the nexus of new dementia models, from diagnosis to end of life in dementia; (2) new payment models are needed to support HBDC and reward integration of care; (3) a diverse new workforce that spans the care continuum should be prepared urgently; (4) new technologies to promote communication, monitoring/safety, and symptoms management must be tested, integrated, and deployed; and (5) targeted dissemination efforts for HBDC must be employed.

The effectiveness of the bone bridge transtibial amputation technique: A systematic review of high-quality evidence.

Background: This literature review was undertaken to determine if commonly held views about the benefits of a bone bridge technique are supported by the literature.

Methods: Four databases were searched for articles pertaining to surgical strategies specific to a bone bridge technique of the transtibial amputee. A total of 35 articles were identified as potential articles.

A Simple Dewar/Cryostat for Thermally Equilibrating Samples at Known Temperatures for Accurate Cryogenic Luminescence Measurements.

The design and operation of a simple liquid nitrogen Dewar/cryostat apparatus based upon a small fused silica optical Dewar, a thermocouple assembly, and a CCD spectrograph are described. The experiments for which this Dewar/cryostat is designed require fast sample loading, fast sample freezing, fast alignment of the sample, accurate and stable sample temperatures, and small size and portability of the Dewar/cryostat cryogenic unit. When coupled with the fast data acquisition rates of the CCD spectrograph, this Dewar/cryostat is capable of supporting cryogenic luminescence spectroscopic measurements on luminescent samples at a series of known, stable temperatures in the 77-300 K range.

A Potent d-Protein Antagonist of VEGF-A is Nonimmunogenic, Metabolically Stable, and Longer-Circulating in Vivo.

Polypeptides composed entirely of d-amino acids and the achiral amino acid glycine (d-proteins) inherently have in vivo properties that are proposed to be near-optimal for a large molecule therapeutic agent. Specifically, d-proteins are resistant to degradation by proteases and are anticipated to be nonimmunogenic. Furthermore, d-proteins are manufactured chemically and can be engineered to have other desirable properties, such as improved stability, affinity, and pharmacokinetics.

How much gene flow is needed to avoid inbreeding depression in wild tiger populations?

The number and size of tiger populations continue to decline owing to habitat loss, habitat fragmentation and poaching of tigers and their prey. As a result, tiger populations have become small and highly structured. Current populations have been isolated since the early 1970s or for approximately seven generations.

Modeling, characterizing, and accommodating static birefringence in circular and linear dichroism spectroscopy.

Nearly all circular dichroism (CD) and linear dichroism (LD) spectrometers use a photoelastic modulator (PEM) in which an optical element is stressed using a high-tension voltage (HT) signal to induce birefringence. The birefringence consequently produces a phase difference between perpendicular polarization states of light passing through the PEM that is appropriate to CD or LD measurements. However, even without external stress (i.

Novel technique for improvement in calibration of the photoelastic modulator in circular and linear dichroism spectroscopy.

Both the voltage-induced and the inherent (static) birefringence of a photoelastic modulator (PEM) affect the phase difference between orthogonal components of light passing through the PEM. This phase difference determines the polarization state of the light and is essential for determining true circular and linear dichroism (CD and LD, respectively) spectroscopy. Presented here are a more complete theoretical model of CD and LD and a new technique to determine the phase difference and static birefringence of a PEM in CD and LD.

Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.

Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A.

CsSnI3: Semiconductor or metal? High electrical conductivity and strong near-infrared photoluminescence from a single material. High hole mobility and phase-transitions.

CsSnI(3) is an unusual perovskite that undergoes complex displacive and reconstructive phase transitions and exhibits near-infrared emission at room temperature. Experimental and theoretical studies of CsSnI(3) have been limited by the lack of detailed crystal structure characterization and chemical instability. Here we describe the synthesis of pure polymorphic crystals, the preparation of large crack-/bubble-free ingots, the refined single-crystal structures, and temperature-dependent charge transport and optical properties of CsSnI(3), coupled with ab initio first-principles density functional theory (DFT) calculations.

Noise characterization in circular dichroism spectroscopy.

Circular dichroism (CD), defined as the difference in absorption between left and right circularly polarized light, is used to spectroscopically study the structures of chiral materials. In this article, various methodologies are presented for characterizing the performance of CD spectrometers to determine (1) experimental conditions for optimal data collection, (2) noise characteristics dependent on machine parameters, (3) the relative significance of spectral data as a function of detector gain, and (4) stray light and dark current as a function of wavelength. The results of case studies of two commercial CD spectrometers (specifically, Jasco J810 and J815) are described.

Ligand binding assays in the 21st century laboratory: recommendations for characterization and supply of critical reagents.

Critical reagents are essential components of ligand binding assays (LBAs) and are utilized throughout the process of drug discovery, development, and post-marketing monitoring. Successful lifecycle management of LBA critical reagents minimizes assay performance problems caused by declining reagent activity and can mitigate the risk of delays during preclinical and clinical studies. Proactive reagent management assures adequate supply.

Calorimetric investigation of copper(II) binding to Aβ peptides: thermodynamics of coordination plasticity.

Metal ions have been shown to play a critical role in β-amyloid (Aβ) neurotoxicity, thus prompting an intense investigation into the formation of metal-Aβ complexes. Isothermal titration calorimetry (ITC) has been widely used to determine binding constants (K) for a variety of metal-protein interactions, including those in metal-Aβ complexes. In this study, ITC was used to more fully quantify the thermodynamics (K, ΔG, ΔH, and TΔS) of Cu(2+) binding to Aβ16, N-acetyl-Aβ16, Aβ28, N-acetyl-Aβ28, and Aβ28 variants (H6A, H13A, H14A) at pH 7.

Characterization of amyloidogenic intermediate states through a combined use of CD and NMR spectroscopy.

Characterization of amyloidogenic intermediate states is of central importance in understanding the molecular mechanism of amyloid formation. In this study, we utilized CD and NMR spectroscopy to investigate secondary structure of the monomeric amyloidogenic intermediate of a beta-structured SH3 domain, which was induced by trifluoroethanol (TFE). The combined biophysical studies showed that the native state SH3 domain is gradually converted to the amyloidogenic intermediate state at TFE concentrations of 20-26% (v/v) and the aggregation-prone state contains substantial amount of the beta-sheet conformation ( approximately 30%) with disordered (54%) and some helical characters (16%).

Genetic organization, length conservation, and evolution of RNA polymerase II carboxyl-terminal domain.

With a simple tandem iterated sequence, the carboxyl terminal domain (CTD) of eukaryotic RNA polymerase II (RNAP II) serves as the central coordinator of mRNA synthesis by harmonizing a diversity of sequential interactions with transcription and processing factors. Despite intense research interest, many key questions regarding functional and evolutionary constraints on the CTD remain unanswered; for example, what selects for the canonical heptad sequence, its tandem array across organismal diversity, and constant CTD length within given species and finally and how a sequence-identical, repetitive structure can orchestrate a diversity of simultaneous and sequential, stage-dependent interactions with both modifying enzymes and binding partners? Here we examine comparative sequence evolution of 58 RNAP II CTDs from diverse taxa representing all six major eukaryotic supergroups and employ integrated evolutionary genetic, biochemical, and biophysical analyses of the yeast CTD to further clarify how this repetitive sequence must be organized for optimal RNAP II function. We find that the CTD is composed of indivisible and independent functional units that span diheptapeptides and not only a flexible conformation around each unit but also an elastic overall structure is required.

Structural disorder in silk proteins reveals the emergence of elastomericity.

Spider silks combine basic amino acids into strong and versatile fibers where the quality of the elastomer is attributed to the interaction of highly adapted protein motifs with a complex spinning process. The evaluation, however, of the interaction has remained elusive. Here, we present a novel analysis to study silk formation by examining the secondary structures of silk proteins in solution.

Fesselin is a natively unfolded protein.

Fesselin is a heat stable proline-rich actin binding protein. The stability, amino acid composition, and ability to bind to several proteins suggested that fesselin may be unfolded under native conditions. While the complete sequence of fesselin is unknown an analysis of a closely related protein, synaptopodin 2 from Gallus gallus, indicates that fesselin consists of a series of unstructured regions interspersed between short folded regions.

Beta-silks: enhancing and controlling aggregation.

It appears that fiber-forming proteins are not an exclusive group but that, with appropriate conditions, many proteins can potentially aggregate and form fibrils; though only certain proteins, for example, amyloids and silks, do so under normal physiological conditions. Even so, this suggests a ubiquitous aggregation mechanism in which the protein environment is at least as important as the sequence. An ideal model system in which forced and natural aggregation has been observed is silk.

Characterizations of distinct amyloidogenic conformations of the Abeta (1-40) and (1-42) peptides.

Major constituents of the amyloid plaques found in the brain of Alzheimer's patients are the 39-43 residue beta-amyloid (Abeta) peptides. Extensive in vitro as well as in vivo biochemical studies have shown that the 40- and 42-residue Abeta peptides play major roles in the neurodegenerative pathology of Alzheimer's disease. Although the two Abeta peptides share common aggregation properties, the 42-residue peptide is more amyloidogenic and more strongly associated with amyloid pathology.

Domestic violence: a complex health care issue for dentistry today.

As a natural outgrowth of the dental professional's role in recognizing and reporting child abuse the topic has been broadened in recent years to domestic violence, that is child, spouse/intimate partner, disabled and elder abuse. Forty years ago in the US there were 662 cases of child abuse reported to authorities. Today that reported number is in excess of 3 million per year [D.

Moment analysis method as applied to the 2S --> 2P transition in cryogenic alkali metal/rare gas matrices.

The moment analysis method (MA) has been tested for the case of 2S --> 2P ([core]ns1 --> [core]np1) transitions of alkali metal atoms (M) doped into cryogenic rare gas (Rg) matrices using theoretically validated simulations. Theoretical/computational M/Rg system models are constructed with precisely defined parameters that closely mimic known M/Rg systems. Monte Carlo (MC) techniques are then employed to generate simulated absorption and magnetic circular dichroism (MCD) spectra of the 2S --> 2P M/Rg transition to which the MA method can be applied with the goal of seeing how effective the MA method is in re-extracting the M/Rg system parameters from these known simulated systems.

Conformational polymorphism, stability and aggregation in spider dragline silks proteins.

Spider silk is spun in a complex and unique process, thought to depend on a hydrophobic conversion of a predominantly disordered to a beta-sheet rich protein structures. To test this hypothesis we monitored the effect of cationic (DOTAC) and anionic (alkyl sulfate) detergents and of (ii) solvent polarity using a series of alcohols on the secondary structure transition in dilute solutions of native spidroin. Our results showed that the detergents hydrophilic head charge and hydrophobic tail length cooperatively induced either a transition to the beta-sheet rich form or a stable helical state.