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.

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.

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.

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.

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.

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.

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.