Combustion conditions influence toxicity of flame-generated soot to ocular (ARPE-19) cells.

Soot is a prevalent aerosol found both indoors and outdoors that has several sources, such as natural (e.g., wildfires), civilian (e.

Changes in relative histone abundance and heterochromatin in αA-crystallin and αB-crystallin knock-in mutant mouse lenses.

Objective: Understanding the mechanisms of cataract formation is important for age-related and hereditary cataracts caused by mutations in lens protein genes. Lens proteins of the crystallin gene families α-, β-, and γ-crystallin are the most abundant proteins in the lens. Single point mutations in crystallin genes cause autosomal dominant cataracts in multigenerational families.

Creatine kinase/α-crystallin interaction functions in cataract development.

Creatine kinase (CK) is an energy storage enzyme that plays an important role in energy metabolism. CK/phosphocreatine functions as an energy buffer and links ATP production sites with ATP utilization sites. Several key mutations in the αA-crystallin () and αB-crystallin () genes have been linked with autosomal-dominant, hereditary human cataracts.

Mechanism of Action of VP1-001 in cryAB(R120G)-Associated and Age-Related Cataracts.

Purpose: We previously identified an oxysterol, VP1-001 (also known as compound 29), that partially restores the transparency of lenses with cataracts. To understand the mechanism of VP1-001, we tested the ability of its enantiomer, ent-VP1-001, to bind and stabilize αB-crystallin (cryAB) in vitro and to produce a similar therapeutic effect in cryAB(R120G) mutant and aged wild-type mice with cataracts. VP1-001 and ent-VP1-001 have identical physicochemical properties.

Bioinspired Fibrillary Hydrogel with Controlled Swelling Behavior: Applicability as an Artificial Vitreous.

The vitreous humor of the eye is mainly composed of fibrillary collagen and semiflexible hyaluronic acid (HA). To mimic this macromolecular composition of the vitreous, we previously developed an injectable two-component hydrogel composed of a fibrillary gellan and a semiflexible polyelectrolyte, poly[methacrylamide--(methacrylic acid)], both endowed with thiol cross-linkers. We optimized the hydrogel formulations for optical, physical, mechanical, and transport properties approximating those of the vitreous.

interactions of histones and α-crystallin.

The aggregation of crystallins in lenses is associated with cataract formation. We previously reported that mutant crystallins are associated with an increased abundance of histones in knock-in and knockout mouse models. However, very little is known about the specific interactions between lens crystallins and histones.

Probing the changes in gene expression due to α-crystallin mutations in mouse models of hereditary human cataract.

The mammalian eye lens expresses a high concentration of crystallins (α, β and γ-crystallins) to maintain the refractive index essential for lens transparency. Crystallins are long-lived proteins that do not turnover throughout life. The structural destabilization of crystallins by UV exposure, glycation, oxidative stress and mutations in crystallin genes leads to protein aggregation and development of cataracts.

Preparation and Characterization of Biomimetic β-Lens Crystallins Using Single-Chain Polymeric Nanoparticles.

Presbyopia, the inability to focus at arm's length, and cataracts that cloud vision are associated primarily with changes in the mechanical and optical properties of the lens. The optical properties, particularly the refractive index, of the human lens originate from the cytoplasm of the lens fiber, which contains a highly concentrated solution (∼40%) of globular proteins referred to as α, β, and γ crystallins, of which β is the most abundant. In this study, we focus on the synthesis and characterization of a β-crystallin biomimetic in an effort to understand and develop treatments for presbyopia and cataract.

Biomimetic hydrogel with tunable mechanical properties for vitreous substitutes.

Unlabelled: The vitreous humor of the eye is a biological hydrogel principally composed of collagen fibers interspersed with hyaluronic acid. Certain pathological conditions necessitate its removal and replacement. Current substitutes, like silicone oils and perfluorocarbons, are not biomimetic and have known complications.

Synthesis and characterization of in situ forming anionic hydrogel as vitreous substitutes.

The natural vitreous is a biological hydrogel consisting primarily of a collagen and anionic hyaluronate. It is surgically removed in many ocular diseases and replaced with fluids, gases, or silicone oils. We have been interested in developing synthetic hydrogels as vitreous substitutes.

The effect of ankle joint immobilization on lower limb venous flow.

Background: Below-knee cast immobilization is associated with an increased risk of developing deep vein thrombosis secondary to venous stasis. We investigated the effect of weight-bearing in a below-knee cast or pneumatic walking boot on lower limb venous blood flow.

Methods: Duplex ultrasonography was used to measure venous blood flow in the popliteal vein of 10 healthy volunteers.

Comparative proteomic analysis identifies age-dependent increases in the abundance of specific proteins after deletion of the small heat shock proteins αA- and αB-crystallin.

Mice with deletion of genes for small heat shock proteins αA- and αB-crystallin (αA/αB(-/-)) develop cataracts. We used proteomic analysis to identify lens proteins that change in abundance after deletion of these α-crystallin genes. Wild-type (WT) and αA/αB(-/-) knockout (DKO) mice were compared using two-dimensional difference gel electrophoresis and mass spectrometric analysis, and protein identifications were validated by Mascot proteomic software.

A knock-in mouse model for the R120G mutation of αB-crystallin recapitulates human hereditary myopathy and cataracts.

An autosomal dominant missense mutation in αB-crystallin (αB-R120G) causes cataracts and desmin-related myopathy, but the underlying mechanisms are unknown. Here, we report the development of an αB-R120G crystallin knock-in mouse model of these disorders. Knock-in αB-R120G mice were generated and analyzed with slit lamp imaging, gel permeation chromatography, immunofluorescence, immunoprecipitation, histology, and muscle strength assays.

Surgical anatomy of the proximal release of the gastrocnemius: a cadaveric study.

Background: The importance of isolated gastrocnemius contracture in disorders of the foot and ankle has been established in recent years. The aim of this study was to describe the proximal anatomical approach to the medial and lateral heads of gastrocnemius and to compare the sizes of the medial and lateral heads of the gastrocnemius.

Materials And Methods: 15 cadaveric extremities were dissected using a posterior approach 1 cm below the level of the skin crease.

Sciatic nerve blockade: a survey of orthopaedic foot and ankle specialists in North America and the United Kingdom.

Background: Sciatic nerve blocks are used to reduce post-operative pain and allow early discharge for patients undergoing foot and ankle surgery. This study aimed to identify the utilization of this procedure in the US and UK and to establish the standard of care with respect to the level of anesthesia that the patient is under and use of ultrasound localization when performing sciatic nerve blocks.

Materials And Methods: A survey of current committee members of AOFAS and members of BOFAS.

A facile synthesis of highly water-soluble, core-shell organo-silica nanoparticles with controllable size via sol-gel process.

A series of highly water-soluble organo-silica nanoparticles, ranging from 2 to 10nm in diameter, were synthesized by the cohydrolysis and copolycondensation reactions. omega-methoxy(polyethyleneoxy)propyltrimethoxysilane (PEG6-9) and hydroxymethyltriethoxysilane (HMTEOS) mixtures were catalyzed by sodium hydroxide in the presence of surfactant benzethonium chloride (BTC) with various ratios of PEG6-9/HMTEOS at room temperature. The synthesized organo-silica nanoparticles possess a core-shell structure with a core of organo-silica resulting from HMTEOS and a monolayer shell of PEG6-9.

Rabbit study of an in situ forming hydrogel vitreous substitute.

Purpose: An in situ forming hydrogel was evaluated as a potential vitreous substitute in rabbits.

Methods: The hydrogel used a disulfide cross-linker that was then reduced to produce an injectable thiol-containing polymer solution. The disulfide cross-links reformed by air oxidation of the thiols and produced a stable hydrogel once inside the eye.

Comparison of the behavior of natural and refilled porcine lenses in a robotic lens stretcher.

The mechanism by which the eye dynamically changes focal distance (accommodation), and the mechanism by which this ability is lost with age (presbyopia), are still contested. Due to inherent confounding factors in vivo, in vitro measurements have been undertaken using a robotic lens stretcher to examine these mechanisms as well as the efficacy of lens refilling - a proposed treatment for presbyopia. Dynamic forces, anterior and posterior curvatures, and lens thickness are all correlated for young natural and refilled porcine lenses.

Mechanism of insolubilization by a single-point mutation in alphaA-crystallin linked with hereditary human cataracts.

AlphaA-crystallin is a small heat shock protein that functions as a molecular chaperone and a lens structural protein. The R49C single-point mutation in alphaA-crystallin causes hereditary human cataracts. We have previously investigated the in vivo properties of this mutant in a gene knock-in mouse model.

Material characterization of porcine lenticular soluble proteins.

The soluble proteins present in the ocular lens impart important optical and dynamic mechanical properties on the lens. The short-range order of crystallin proteins grants transparency to a very concentrated protein solution. This unique protein system directly enables proper visual function of the eye.

In situ formation of hydrogels as vitreous substitutes: Viscoelastic comparison to porcine vitreous.

The human vitreous is a gelatinous substance predominantly composed of water (97-99%). Vitreous substitutes are needed for treatment of retinal detachments by reapproximating the retina to the back of the eye, or during vitrectomies for maintenance of ocular volume. None of the current substitutes can be used long-term due to their short retention time, toxicity, or complications such as glaucoma or cataracts.

Dynamic multi-arm radial lens stretcher: a robotic analog of the ciliary body.

We developed a dynamic lens stretching device to quantitatively determine the relationships between force, equatorial displacement, and anterior curvature. A computer-controlled four-arm lens stretcher, equipped with real-time force transducers in each arm, was designed and constructed to obtain transient force measurements during lens stretching. The force-decay spectrum was fitted with a seven-parameter viscoelastic model characterized by three time constants.

A commentary on recent water safety initiatives in the context of water utility risk management.

Over the last decade, suppliers of drinking water have recognised the limitations of relying solely on end-product monitoring to ensure safe water quality and have sought to reinforce their approach by adopting preventative strategies where risks are proactively identified, assessed and managed. This is leading to the development of water safety plans; structured 'route maps' for managing risks to water supply, from catchment to consumer taps. This paper reviews the Hazard Analysis and Critical Control Point (HACCP) procedure on which many water safety plans are based and considers its appropriateness in the context of drinking water risk management.