Predictable fibroblast tension generation by measuring compaction of anchored collagen matrices using microscopy and optical coherence tomography.

The anchored fibroblast-populated collagen matrix (aFPCM) is an appropriate model to study fibrocontractive disease mechanisms. Our goal was to determine if aFPCM height reduction (compaction) during development is sufficient to predict tension generation. Compaction was quantified daily by both traditional light microscopy and an optical coherence tomography (OCT) system. Contraction in aFPCM was revealed by releasing them from anchorage. We found that aFPCM contraction increase was correlated to the compaction increase. Cytochalasin D treatment reversibly inhibited compaction. Therefore, we demonstrated that aFPCM height reduction efficiently measures compaction, contraction, and relative maturity of the collagen matrix during development or treatment. In addition, we showed that OCT is suitable for effectively imaging the cross-sectional morphology of the aFPCM in culture. This study will pave the way for more efficient studies on the mechanisms of (and treatments that target) migration and contraction in wound healing and Dupuytren's contracture in a tissue environment.

Effect of Collagen-Polycaprolactone Nanofibers Matrix Coating on the In Vitro Cytocompatibility and In Vivo Bone Responses of Titanium.

The objective of this study was to improve the biomechanical performance of titanium (Ti) using a biocompatible electrospun nanofiber matrix. The study is based on the hypothesis that coating a Ti surface with a nanofiber matrix (NFM) made of collagen (CG) and polycaprolactone (PCL) electrospun nanofibers could increase the mechanical fixation of Ti/bone by improving the surface and cytocompatibility properties of Ti. This study prepared Ti samples with and without CG-PCL NFM coatings. This study determined the in vitro effects of each group of Ti samples on the surface topography and cytocompatibility (osteoblast cell adhesion, proliferation, mineralization and protein adsorption) properties. This study also determined in vivo interface shear strength and bone volume fraction of each group of Ti samples with bone using a rabbit model. This study found that the CG-PCL NFM coating on Ti improved the surface roughness, osteoblast cell adhesion, proliferation, mineralization and protein adsorption properties of Ti. In vivo studies found that interface shear strength of CG-PCL NFM-coated Ti/bone samples was significantly higher compared to those values of control Ti/bone samples (p value < 0.05) due to an increase in the amount of growth of the connective tissue joining the Ti implant. Therefore, the developed CG-PCL NFM coating technique should further be investigated for its potential in clinical applications.

Use of Polycaprolactone Electrospun Nanofibers as a Coating for Poly(methyl methacrylate) Bone Cement.

Poly(methyl methacrylate) (PMMA) bone cement has limited biocompatibility. Polycaprolactone (PCL) electrospun nanofiber (ENF) has many applications in the biomedical field due to its excellent biocompatibility and degradability. The effect of coating PCL ENF on the surface topography, biocompatibility, and mechanical strength of PMMA bone cement is not currently known. This study is based on the hypothesis that the PCL ENF coating on PMMA will increase PMMA roughness leading to increased biocompatibility without influencing its mechanical properties. This study prepared PMMA samples without and with the PCL ENF coating, which were named the control and ENF coated samples. This study determined the effects on the surface topography and cytocompatibility (osteoblast cell adhesion, proliferation, mineralization, and protein adsorption) properties of each group of PMMA samples. This study also determined the bending properties (strength, modulus, and maximum deflection at fracture) of each group of PMMA samples from an American Society of Testing Metal (ASTM) standard three-point bend test. This study found that the ENF coating on PMMA significantly improved the surface roughness and cytocompatibility properties of PMMA (p < 0.05). This study also found that the bending properties of ENF-coated PMMA samples were not significantly different when compared to those values of the control PMMA samples (p > 0.05). Therefore, the PCL ENF coating technique should be further investigated for its potential in clinical applications.

Plasma nitriding of titanium alloy: Effect of roughness, hardness, biocompatibility, and bonding with bone cement.

Titanium (Ti) alloys have been widely used in orthopedics and orthodontic surgeries as implants because of their beneficial chemical, mechanical, and biological properties. Improvement of these properties of a Ti alloy, Ti-6Al-4V Eli, is possible by the use of plasma nitriding treatment on the Ti alloy. The novelty of this study is the evaluation of a DC glow discharge nitrogen plasma treatment method on the surface, mechanical and biological properties of Ti alloy. Specifically, this study measured the chemical states, roughness, hardness, and biocompatibility of plasma nitride treated Ti-6Al-4V Eli as well as determined the effect of plasma treatment on the fracture strength between the Ti alloy and bone clement. This study hypothesized that DC glow discharge nitrogen plasma treatment may alter the surface chemical and mechanical states of the Ti alloy that may influence the fracture strength of implant/cement interfaces under static load. This study found that plasma nitride treatment on Ti alloy does not have effect on the roughness and biocompatibility (P value > 0.5), but significantly effect on the hardness and fracture strength of Ti-bone cement interfaces compared to those values of untreated Ti samples (P value < 0.5). Therefore, the DC glow discharge nitrogen plasma treated Ti alloy can potentially be used for orthopedic applications.

Peen treatment on a titanium implant: effect of roughness, osteoblast cell functions, and bonding with bone cement.

Implant failure due to poor integration of the implant with the surrounding biomaterial is a common problem in various orthopedic and orthodontic surgeries. Implant fixation mostly depends upon the implant surface topography. Micron to nanosize circular-shaped groove architecture with adequate surface roughness can enhance the mechanical interlock and osseointegration of an implant with the host tissue and solve its poor fixation problem. Such groove architecture can be created on a titanium (Ti) alloy implant by laser peening treatment. Laser peening produces deep, residual compressive stresses in the surfaces of metal parts, delivering increased fatigue life and damage tolerance. The scientific novelty of this study is the controlled deposition of circular-shaped rough spot groove using laser peening technique and understanding the effect of the treatment techniques for improving the implant surface properties. The hypothesis of this study was that implant surface grooves created by controlled laser peen treatment can improve the mechanical and biological responses of the implant with the adjoining biomaterial. The objective of this study was to measure how the controlled laser-peened groove architecture on Ti influences its osteoblast cell functions and bonding strength with bone cement. This study determined the surface roughness and morphology of the peen-treated Ti. In addition, this study compared the osteoblast cell functions (adhesion, proliferation, and differentiation) between control and peen-treated Ti samples. Finally, this study measured the fracture strength between each kind of Ti samples and bone cement under static loading. This study found that laser peen treatment on Ti significantly changed the surface architecture of the Ti, which led to enhanced osteoblast cell adhesion and differentiation on Ti implants and fracture strength of Ti-bone cement interfaces compared with values of untreated Ti samples. Therefore, the laser peen treatment method has the potential to improve the biomechanical functions of Ti implants.

CLINICAL AND COST-EFFECTIVENESS OF INSULIN DELIVERY WITH V-GO(®) DISPOSABLE INSULIN DELIVERY DEVICE VERSUS MULTIPLE DAILY INJECTIONS IN PATIENTS WITH TYPE 2 DIABETES INADEQUATELY CONTROLLED ON BASAL INSULIN.

OBJECTIVE: To compare two methods of delivering intensified insulin therapy (IIT) in patients with type 2 diabetes inadequately controlled on basal insulin ± concomitant antihyperglycemic agents in a real-world clinical setting. METHODS: Data for this retrospective study were obtained using electronic medical records from a large multicenter diabetes system. Records were queried to identify patients transitioned to V-Go(®) disposable insulin delivery device (V-Go) or multiple daily injections (MDI) using an insulin pen to add prandial insulin when A1C was >7% on basal insulin therapy. The primary endpoint was the difference in A1C change using follow-up A1C results. RESULTS: A total of 116 patients were evaluated (56 V-Go, 60 MDI). Both groups experienced significant glycemic improvement from similar mean baselines. By 27 weeks, A1C least squares mean change from baseline was -1.98% (-21.6 mmol/mol) with V-Go and -1.34% (-14.6 mmol/mol) with MDI, for a treatment difference of -0.64% (-7.0 mmol/mol; P = .020). Patients using V-Go administered less mean ± SD insulin compared to patients using MDI, 56 ± 17 units/day versus 78 ± 40 units/day (P<.001), respectively. Diabetes-related direct pharmacy costs were lower with V-Go, and the cost inferential from baseline per 1% reduction in A1C was significantly less with V-Go ($118.84 ± $158.55 per patient/month compared to $217.16 ± $251.66 per patient/month with MDI; P = .013). CONCLUSION: Progression to IIT resulted in significant glycemic improvement. Insulin delivery with V-Go was associated with a greater reduction in A1C, required less insulin, and proved more cost-effective than administering IIT with MDI. ABBREVIATIONS: A1C = glycated hemoglobin ANCOVA = analysis of covariance CI = confidence interval CSII = continuous subcutaneous insulin infusion FPG = fasting plasma glucose IIT = intensified insulin therapy LSM = least squares mean MDI = multiple daily injections T2DM = type 2 diabetes mellitus TDD = total daily dose.

Use of V-Go® Insulin Delivery Device in Patients with Sub-optimally Controlled Diabetes Mellitus: A Retrospective Analysis from a Large Specialized Diabetes System.

INTRODUCTION: Tight glycemic control and timely treatment can improve outcomes in patients with diabetes yet many remain sub-optimally controlled. The objective of the current study was to evaluate the effect of switching patients with sub-optimally controlled diabetes to the V-Go® (Valeritas Inc., Bridgewater, NJ, USA) Disposable Insulin Delivery device. METHODS: A retrospective analysis of electronic medical records was conducted to assess patients with sub-optimal glycemic control defined as a glycated hemoglobin (HbA1c) >7%, switched to V-Go. Blood glucose control defined as change from baseline in HbA1c, prescribed insulin doses, body weight, concomitant anti-hyperglycemic agents, and reported hypoglycemia were collected prior to switching to V-Go and during V-Go use. RESULTS: Two-hundred and four patients were evaluated during the study period. Overall, there was a significant decrease in HbA1c after switching to V-Go at the 14- and 27-week follow-up visits. The least-squares mean (LSM) change in HbA1c (95% confidence interval) from baseline to 14 weeks was -1.53% (-1.69% to -1.37%; P < 0.001), and from baseline to 27 weeks was -1.79% (-1.97% to -1.61%; P < 0.001). Significant reductions in mean HbA1c were achieved at both visits in all patient subsets: Patients with type 2 and type 1/latent autoimmune diabetes in adults (LADA); patients using insulin at baseline and patients naïve to insulin at baseline. Patients administering insulin at baseline required significantly less insulin on V-Go (86-99 LSM units/day at baseline to 58 LSM units/day at 27 weeks; P < 0.001). Across all patients, reported hypoglycemic events were no more frequent on V-Go than on previous therapy. CONCLUSION: V-Go is safe and effective in patients with sub-optimally controlled diabetes requiring insulin therapy. Glycemic control improved significantly, less insulin was required, and hypoglycemic events were similar after patients switched to insulin delivery by V-Go. FUNDING: Valeritas, Inc.

Effect of additive particles on mechanical, thermal, and cell functioning properties of poly(methyl methacrylate) cement.

The most common bone cement material used clinically today for orthopedic surgery is poly(methyl methacrylate) (PMMA). Conventional PMMA bone cement has several mechanical, thermal, and biological disadvantages. To overcome these problems, researchers have investigated combinations of PMMA bone cement and several bioactive particles (micrometers to nanometers in size), such as magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica. A study comparing the effect of these individual additives on the mechanical, thermal, and cell functional properties of PMMA would be important to enable selection of suitable additives and design improved PMMA cement for orthopedic applications. Therefore, the goal of this study was to determine the effect of inclusion of magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica additives in PMMA on the mechanical, thermal, and cell functional performance of PMMA. American Society for Testing and Materials standard three-point bend flexural and fracture tests were conducted to determine the flexural strength, flexural modulus, and fracture toughness of the different PMMA samples. A custom-made temperature measurement system was used to determine maximum curing temperature and the time needed for each PMMA sample to reach its maximum curing temperature. Osteoblast adhesion and proliferation experiments were performed to determine cell viability using the different PMMA cements. We found that flexural strength and fracture toughness were significantly greater for PMMA specimens that incorporated silica than for the other specimens. All additives prolonged the time taken to reach maximum curing temperature and significantly improved cell adhesion of the PMMA samples. The results of this study could be useful for improving the union of implant-PMMA or bone-PMMA interfaces by incorporating nanoparticles into PMMA cement for orthopedic and orthodontic applications.

Fracture toughness of titanium-cement interfaces: effects of fibers and loading angles.

Ideal implant-cement or implant-bone interfaces are required for implant fixation and the filling of tissue defects created by disease. Micron- to nanosize osseointegrated features, such as surface roughness, fibers, porosity, and particles, have been fused with implants for improving the osseointegration of an implant with the host tissue in orthopedics and dentistry. The effects of fibers and loading angles on the interface fracture toughness of implant-cement specimens with and without fibers at the interface are not yet known. Such studies are important for the design of a long-lasting implant for orthopedic applications. The goal of this study was to improve the fracture toughness of an implant-cement interface by deposition of micron- to nanosize fibers on an implant surface. There were two objectives in the study: 1) to evaluate the influence of fibers on the fracture toughness of implant-cement interfaces with and without fibers at the interfaces, and 2) to evaluate the influence of loading angles on implant-cement interfaces with and without fibers at the interfaces. This study used titanium as the implant, poly(methyl methacrylate) (PMMA) as cement, and polycaprolactone (PCL) as fiber materials. An electrospinning unit was fabricated for the deposition of PCL unidirectional fibers on titanium (Ti) plates. The Evex tensile test stage was used to determine the interface fracture toughness (KC) of Ti-PMMA with and without PCL fibers at 0°, 45°, and 90° loading angles, referred to in this article as tension, mixed, and shear tests. The study did not find any significant interaction between fiber and loading angles (P>0.05), although there was a significant difference in the KC means of Ti-PMMA samples for the loading angles (P<0.05). The study also found a significant difference in the KC means of Ti-PMMA samples with and without fibers (P<0.05). The results showed that the addition of the micron- to nanosize PCL fibers on Ti improved the quality of the Ti-PMMA union. The results of the study are essential for fatigue testing and finite-element analysis of implant-cement interfaces to evaluate the performance of orthopedic and orthodontic implants.

A new bioassay identifies proliferation ratios of fibroblasts and myofibroblasts.

Myofibroblasts are resident cells of wound healing, contractures and fibroses; these tissues are often referred to as fibroproliferative. Whether myofibroblasts themselves proliferate is of interest. Since many in vitro cultures are heterogeneous, staining in situ is required to identify the myofibroblast. We have tested a newly available fluorescent staining kit using ethynyl deoxyuridine (EdU) and click chemistry to identify EdU incorporation into the replicated DNA of proliferative cells. The proliferation stain was combined with the definitive myofibroblast immunostain for alpha smooth muscle actin (α-sma). Fibroblasts were grown on coverslips and within attached collagen lattices. Cultures were pulsed with EdU 4 h prior to fixation. Different standard methods of fixation and permeabilization were used to test the effects of these variables on EdU and α-sma labeling. Images of the stained samples were quantified as the total percentage of proliferative cells, as well as the proportion of fibroblasts and myofibroblasts that were proliferating. Proliferative myofibroblasts were identified in both culture conditions and with all preparation methods tested. Proliferation within the fibroblast population was greater than within the myofibroblast population in both culture conditions. Fixation and permeabilization had little effect on EdU or α-sma labeling. This method of identifying proliferative myofibroblasts will be useful in future studies of myofibroblast proliferation within heterogeneous populations.

Micro and nano MgO particles for the improvement of fracture toughness of bone-cement interfaces.

The objective of this study was to determine whether inclusion of magnesium oxide (MgO) in micro and nanoparticulate forms in poly methyl methacrylate (PMMA) cement has any influence on the fracture toughness of bone-cement interfaces. An interfacial fracture mechanics technique was used to compare the values of fracture toughness (KIC) among bone-PMMA, bone-PMMA with micro MgO particles and bone-PMMA with nano MgO particles interfaces. This study found that the values of KIC of bone-PMMA with micro MgO particles and bone-PMMA with nano MgO particles interfaces were significantly higher when compared to the values of KIC of the bone-PMMA interface (p<0.0001). Results indicated that the addition of the micro and nano MgO particles to PMMA improved the quality of bone-cement union.

Sexual abuse prevention: a training program for developmental disabilities service providers.

Persons with developmental disabilities are at an increased risk for becoming victims of sexual abuse. Research has revealed that the largest group of identified perpetrators of sexual abuse is developmental disability service providers. The purpose of the present study was to develop, implement, and evaluate the effectiveness of a sexual abuse prevention training program. Participants were administered a survey assessing knowledge and attitudes before and after the training workshop. Small improvements in knowledge and attitudes about sexual abuse and the sexuality of persons with developmental disabilities were found; however, ge-neral attitudes about individuals with developmental disabilities did not change. Suggestions for future directions in this area are provided.

The interplay of sleep disturbance, anxiety, and depression in children.

OBJECTIVE: To review and critically evaluate the association between sleep, anxiety, and depression in children and provide recommendations for future research. METHODS: A literature search was conducted using MEDLINE and PsychINFO computerized databases and bibliographies of relevant articles. RESULTS: A surprisingly small but growing research base exists on the relation between sleep disturbance, anxiety, and depression in pediatric populations. Existing research indicates a significant symptom overlap between anxiety, depression, and sleep. This overlap may complicate proper assessment and treatment of children with these disorders. CONCLUSIONS: Future research should ensure adequate assessment for symptoms of anxiety and depression when examining sleep disturbance in children. Likewise, research on anxiety and depression should include assessment for symptoms of disturbed sleep. Bridging the gap between these literatures should provide further insights into the etiologies of these disorders, increase symptom detection, and improve the clinical care of children and their families.

College dating and social anxiety: using the Internet as a means of connecting to others.

With the advent and widespread use of the Internet, various online media are being used to connect and maintain social relationships in individuals of all ages. Social relationships are vital to healthy development, and individuals with social and/or dating anxiety may have marked difficulty in establishing appropriate, supportive relationships because of fear of negative evaluation by others. For these individuals, the Internet may open avenues of communication and provide an outlet through which relationships can be formed and preserved. This study investigated the characteristics of computer and Internet use in young adults to determine whether individuals who were high in social/dating anxiety symptoms were more likely to make and maintain social relationships online. To further understand the patterns of these behaviors, several measures of social and dating anxiety were collected and analyzed along with demographic, computer use, and relationship characteristics. Results indicated differences between high and low social/dating anxiety with respect to media use and relationship formation. Limitations and future directions are discussed.

Visual impairment and eye abnormalities in Oklahoma Indians.

OBJECTIVE: To determine the prevalence of visual impairment and eye abnormalities in Oklahoma Indians. METHODS: The cross-sectional study included 1019 Oklahoma Indians, aged 48 to 82 years; 60.2% were women. All participants gave a personal interview, and all underwent an eye examination, including the determination of best-corrected visual acuity and an ophthalmoscopic examination. In addition, two 45 degrees fundus photographs were taken of each eye, and these photographs were graded by the Fundus Photography Reading Center at the University of Wisconsin, Madison. RESULTS: Among the 1019 participants, 77.4% had a visual acuity of 20/20 or better, 19.5% and 2.5% had visual acuities of between 20/25 and 20/40 and between 20/50 and 20/190, respectively; and 0.6% were legally blind, all in the better eye. Cataract was the most frequent contributing cause and age-related macular degeneration the second most frequent contributing cause of visual impairment. The overall prevalence proportions of age-related macular degeneration, cataract, diabetic retinopathy, and definite glaucoma were 33.6%, 39.6%, 20.1%, and 5.6%, respectively. Most of the other eye abnormalities were rare in the study participants, except for pinguecula (42.4%) and dermatochalasis (30.1%). CONCLUSIONS: Oklahoma Indians have a higher prevalence of visual impairment, age-related macular degeneration, and diabetic retinopathy than other ethnic groups. The implementation of adequate treatment and prevention programs for eye diseases is indicated.