Preoperative latent medial laxity and correction angle are crucial factors for overcorrection in medial open-wedge high tibial osteotomy.

PURPOSE: This study aimed to determine which preoperative factors affect the postoperative change in the joint line convergence angle (JLCA) by preoperatively quantifying soft tissue laxity. METHODS: Thirty-four patients who underwent medial open-wedge high tibial osteotomy (HTO) with a navigation were analysed. The JLCA change after HTO was calculated using standing long-bone anteroposterior radiographs taken preoperatively and 6 months postoperatively. Latent soft tissue laxity was defined as the amount of soft tissue that can be extended to valgus or varus from the weight-bearing position, and calculated by subtracting the JLCA on weight-bearing standing radiographs from that on stress radiographs. Multiple linear regression was performed to determine the preoperative factors that statistically correlated with the postoperative JLCA change. RESULTS: In multiple linear regression, JLCA change had a statistically significant correlation with latent medial laxity (R = 0.6) and a statistically borderline significant correlation with correction angle (R = 0.2). These imply that the postoperative JLCA change increased by 0.6° per 1° increase in latent medial laxity, and increased by 0.2° per 1° increase in correction angle. Latent medial laxity was the most crucial factor associated with postoperative JLCA changes. CONCLUSION: The JLCA change could be larger in patients with large latent medial laxity or severe varus deformity requiring a large correction, which could lead to unexpected overcorrection in HTO. Postoperative JLCA change should be considered in preoperative surgical planning. Target point shifting within the hypomochlion point could be a strategy to prevent overcorrection, especially in patients with large latent medial laxity. LEVEL OF EVIDENCE: Level IV.

Seasonal Acclimatization in Summer versus Winter to Changes in the Sweating Response during Passive Heating in Korean Young Adult Men.

We investigated the sweating response during passive heating (partial submersion up to the umbilical line in 42±0.5℃ water, 30 min) after summer and winter seasonal acclimatization (SA). Testing was performed in July during the summer, 2011 [summer-SA; temp, 25.6±1.8℃; relative humidity (RH), 82.1±8.2%] and in January during the winter, 2012 (winter-SA; temp, -2.7±2.9℃; RH, 65.0±13.1%) in Cheonan (126°52'N, 33.38'E), Republic of Korea. All experiments were carried out in an automated climatic chamber (temp, 25.0±0.5℃: RH, 60.0±3.0%). Fifteen healthy men (age, 23.4±2.5 years; height, 175.0±5.9 cm; weight, 65.3±6.1 kg) participated in the study. Local sweat onset time was delayed during winter-SA compared to that after summer-SA (p< 0.001). Local sweat volume, whole body sweat volume, and evaporative loss volume decreased significantly after winter-SA compared to those after summer-SA (p<0.001). Changes in basal metabolic rate increased significantly after winter-SA (p< 0.001), and tympanic temperature and mean body temperature were significantly lower after summer-SA (p<0.05). In conclusion, central sudomotor acitivity becomes sensitive to summer-SA and blunt to winter-SA in Rebubic of Korea. These results suggest that the body adjusts its temperature by economically controlling the sweating rate but does not lower the thermal dissipation rate through a more effective evaporation scheme after summer-SA than that after winter-SA.

Age- and sex-related differences in sudomotor function evaluated by the quantitative sudomotor axon reflex test (QSART) in healthy humans.

The aim of the present study was to quantitatively investigate the age and sex-related differences in sudomotor function in healthy humans. The quantitative sudomotor axon reflex test (QSART) with iontophoresis (2 mA for 5 min) and 10% acetylcholine (ACh) was performed to determine axon reflex-mediated (AXR), with and without iotophoresis (AXR(1) and AXR(2), respectively), and directly activated (DIR) sweating. All experiments were conducted under thermoneutral conditions (temperature 24.0 ± 0.5°C; relative humidity 40 ± 3%). In general, men had enhanced values of onset time of AXR, sweat rates, activated sweat gland density (SGD) and activated sweat gland output (SGO) than women, but not in all cases. The onset time of AXR (r(2)  = 0.567; P < 0.001) was positively correlated with advancing age, whereas sweat rates of AXR(1) and AXR(2) (r(2)  = 0.571 and r(2)  = 0.486, respectively; P < 0.0001), DIR (r(2)  = 0.594; P < 0.0001), SGD (r(2)  = 0.496; P < 0.0001) and SGO (r(2)  = 0.551; P < 0.0001) were negatively correlated in both men and women with advancing age. The results demonstrate that an attenuation of sudomotor function occurs with aging in both sexes. Moreover, the findings showed a progressive increase in onset time and a decrease in sweat rates, SGD and SGO with increasing age in both sexes. A variation in sweat function was found between sexes, but not in all age groups.

The in vitro and in vivo anti-tumor effect of KO-202125, a sauristolactam derivative, as a novel epidermal growth factor receptor inhibitor in human breast cancer.

Epidermal growth factor receptor (EGFR) is one of the most promising targets for cancer therapy. Here, we show the in vitro and in vivo anticancer effects and associated mechanisms of KO-202125, one of the synthesized aristolactam analogs, as a novel EGFR inhibitor, in EGFR-overexpressing cancer cell lines. KO-202125 showed more effective growth inhibition and apoptosis induction than gefitinib, a representative EGFR inhibitor, in various EGFR-overexpressing human cancers including estrogen receptor (ER)-negative MDA-MB-231 human breast cancer cells. Epidermal growth factor receptor phosphorylation at Tyr1068 was reduced and, consequently, the association of EGFR with p85 was decreased by KO-202125 treatment in MDA-MB-231 cell lines. This led to inactivation of the PI3K/Akt pathway, and consequently suppression of activation of the Wnt pathway and enhancement of the nuclear import of p27Kip1. KO-202125 treatment in nude mice injected with MDA-MB-231 cells showed inhibition of tumor growth without toxicity. Collectively, our results showed the possibility of KO-202125 as an effective therapy agent of EGFR-overexpressing cancer cells through reduced EGFR activity and downregulation of the Akt pathway.

Computed Tomography-Based Morphologic Analysis of Osteoarthritis of the Distal Radioulnar Joint Associated with Extensor Tendon Ruptures.

BACKGROUD: Although the scallop sign is considered the most important risk factor for extensor tendon ruptures (ETRs) in patients with osteoarthritis of the distal radioulnar joint (DRUJ), previous reports provide a limited understanding of the changes at DRUJ, as risk factors were examined in plain radiographs of the wrist. The aim of this study was to assess the changes of DRUJ using axial images of computed tomography (CT) in patients with DRUJ osteoarthritis and associated ETRs and to evaluate the relationship between the changes of DRUJ and ETRs. METHODS: Twelve patients with ETRs due to osteoarthritis of the DRUJ were enrolled. The changes of DRUJ were examined on axial images of CT and the following 8 parameters were measured: width of radius, anteroposterior (AP) length of radius, width of sigmoid notch (SN), AP length of SN, AP length of ulnar head, subluxation length of ulnar head, dorsal inclination of SN, and distance from Lister's tubercle to SN. Radiological parameters of the DRUJ were measured in 60 control wrists without trauma or osteoarthritis, and the patient and control groups were statistically compared. RESULTS: Statistically significant differences were observed between the patient and control groups in all the radiological parameters except for the AP length of SN and AP length of ulnar head. The width of radius, AP length of radius, width of SN, subluxation length of ulnar head, and dorsal inclination of SN were greater and the distance from Lister's tubercle to SN was smaller in the patient group than in the control group. The width of SN, dorsal inclination of SN, and distance from Lister's tubercle to SN were statistically significant risk factors among the 8 parameters. CONCLUSIONS: ETRs due to osteoarthritis of the DRUJ was related to the changes of DRUJ, especially the changes around SN of the distal radius. In addition to the existing risk factors, a decreased distance from Lister's tubercle to SN and increased dorsal inclination of SN were identified as new risk factors. Axial images of CT were effective to evaluate degenerative changes at the DRUJ.

Initial biocompatibility and enhanced osteoblast response of Si doping in a porous BCP bone graft substitute.

Granular shape biphasic calcium phosphate (BCP) bone grafts with and without doping of silicon cations were evaluated in regards to biocompatibility and MG-63 cellular response. To do this we studied Cellular cytotoxicity, cellular adhesion and spreading behavior and cellular differentiation with alizarin red S staining. Gene expression in MG-63 cells on the implanted bone substitutes was also examined at different time points using RT-PCR. In comparison, the Si-doped BCP granule showed more cellular viability than the BCP granule without doping in MTT assay. Moreover, cell proliferation was much higher when Si doping was employed. The cells grown on the silicon-doped BCP substitutes had more active filopodial growth with cytoplasmic webbing that proceeded to the flattening stage, which was indicative of well cellular adhesion. When these cells were exposed to Si-doped BCP granules for 14 days, well differentiated MG-63 cells were observed. Osteonectin and osteopontin genes were highly expressed in the late stage of differentiation (14 days), whereas collagen type I mRNA were found to be highly expressed during the early stage (day 3). These combined results of this study demonstrate that silicon-doped BCP enhanced osteoblast attachment/spreading, proliferation, differentiation and gene expression.

Extensor Tendon Rupture Due to Advanced Kienböck's Disease: Two Case Reports and a Review of Literature.

Extensor tendon rupture of the finger is a very rare complication of Kienböck's disease. However, advanced Kienböck's disease can cause an attritional rupture of extensor tendons due to displaced lunate fragment. An extensor tendon of the thumb is frequently damaged in the distal radial fracture, and an extensor tendon of the fifth finger is mainly ruptured in arthritis of distal radio-ulnar joint. On the other hand, the extensor tendons of the 2nd, 3rd and 4th fingers are usually ruptured in advanced Kienböck's disease. We report two elderly patients diagnosed with advanced Kienböck's disease after non-traumatic rupture of extensor tendon of the fingers. Since the extensor tendon rupture in Kienböck's disease present as a loss of active extension of metacarpophalangeal joint in the central fingers, these patients should undergo imaging of the wrist joints to ascertain concomitant Kienböck's disease.

Comparison of small bowel findings using capsule endoscopy between Crohn's disease and intestinal tuberculosis in Korea.

BACKGROUND: Little is known about capsule endoscopy (CE) findings in patients with intestinal tuberculosis who exhibit small bowel lesions. The aim of the present study was to distinguish between Crohn's disease (CD) and intestinal tuberculosis based on CE findings. METHODS: Findings from 55 patients, who underwent CE using PillCam SB CE (Given Imaging, Yoqneam, Israel) between February 2003 and June 2015, were retrospectively analyzed. RESULTS: CE revealed small bowel lesions in 35 of the 55 patients: 19 with CD and 16 with intestinal tuberculosis. The median age at diagnosis for patients with CD was 26 years and 36 years for those with intestinal tuberculosis. On CE, three parameters, ≥10 ulcers, >3 involved segments and aphthous ulcers, were more common in patients with CD than in those intestinal tuberculosis. Cobblestoning was observed in five patients with CD and in none with intestinal tuberculosis. The authors hypothesized that a diagnosis of small bowel CD could be made when the number of parameters in CD patients was higher than that for intestinal tuberculosis. The authors calculated that the diagnosis of either CD or intestinal tuberculosis would have been made in 34 of the 35 patients (97%). CONCLUSION: The number of ulcers and involved segments, and the presence of aphthous ulcers, were significantly higher and more common, respectively, in patients with CD than in those with intestinal tuberculosis. Cobblestoning in the small bowel may highly favor a diagnosis of CD on CE.

Tropical Malaysians and temperate Koreans exhibit significant differences in sweating sensitivity in response to iontophoretically administered acetylcholine.

Natives of the tropics are able to tolerate high ambient temperatures. This results from their long-term residence in hot and often humid tropical climates. This study was designed to compare the peripheral mechanisms of thermal sweating in tropical natives with that of their temperate counterparts. Fifty-five healthy male subjects including 20 native Koreans who live in the temperate Korean climate (Temperate-N) and 35 native tropical Malaysian men that have lived all of their lives in Malaysia (Tropical-N) were enrolled in this study after providing written informed consent to participate. Quantitative sudomotor axon reflex testing after iontophoresis (2 mA for 5 min) with 10% acetylcholine (ACh) was used to determine directly activated (DIR) and axon reflex-mediated (AXR) sweating during ACh iontophoresis. The sweat rate, activated sweat gland density, sweat gland output per single gland activated, and oral and skin temperature changes were measured. The sweat onset time of AXR (nicotinic-receptor-mediated) was 56 s shorter in the Temperate-N than in the Tropical-N subjects (P < 0.0001). The nicotinic-receptor-mediated sweating activity AXR (1), and the muscarinic-receptor-mediated sweating activity DIR, in terms of sweat volume, were 103% and 59% higher in the Temperate-N compared to the Tropical-N subjects (P < 0.0001). The Temperate-N group also had a 17.8% (P < 0.0001) higher active sweat gland density, 35.4% higher sweat output per gland, 0.24 degrees C higher resting oral temperature, and 0.62 degrees C higher resting forearm skin temperature compared to the Tropical-N subjects (P < 0.01). ACh iontophoresis did not influence oral temperature, but increased skin temperature near where the ACh was administered, in both groups. These results suggest that suppressed thermal sweating in the Tropical-N subjects was, at least in part, due to suppressed sweat gland sensitivity to ACh through both recruitment of active sweat glands and the sweat gland output per each gland. This physiological trait guarantees a more economical use of body fluids, thus ensuring more efficient protection against heat stress.

Reliability of the EOS Imaging System for Assessment of the Spinal and Pelvic Alignment in the Sagittal Plane.

BACKGROUND: The sagittal alignment of the spine and pelvis is not only closely related to the overall posture of the body but also to the evaluation and treatment of spine disease. In the last few years, the EOS imaging system, a new low-dose radiation X-ray device, became available for sagittal alignment assessment. However, there has been little research on the reliability of EOS. The purpose of this study was to evaluate the intrarater and interrater reliability of EOS for the sagittal alignment assessment of the spine and pelvis. METHODS: Records of 46 patients were selected from the EOS recording system between November 2016 and April 2017. The exclusion criteria were congenital spinal anomaly and deformity, and previous history of spine and pelvis operation. Sagittal parameters of the spine and pelvis were measured by three examiners three times each using both manual and EOS methods. Means comparison t-test, Pearson bivariate correlation analysis, and reliability analysis by intraclass correlation coefficients (ICCs) for intrarater and interrater reliability were performed using R package "irr." RESULTS: We found excellent intrarater and interrater reliability of EOS measurements. For intrarater reliability, the ICC ranged from 0.898 to 0.982. For interrater reliability, the ICC ranged from 0.794 to 0.837. We used a paired t-test to compare the values measured by manual and EOS methods: there was no statistically significant difference between the two methods. Correlation analysis also showed a statistically significant positive correlation. CONCLUSIONS: EOS showed excellent reliability for assessment of the sagittal alignment of the spine and pelvis.

HAp granules encapsulated oxidized alginate-gelatin-biphasic calcium phosphate hydrogel for bone regeneration.

Bone repair in the critical size defect zone using 3D hydrogel scaffold is still a challenge in tissue engineering field. A novel type of hydrogel scaffold combining ceramic and polymer materials, therefore, was fabricated to meet this challenge. In this study, oxidized alginate-gelatin-biphasic calcium phosphate (OxAlg-Gel-BCP) and spherical hydroxyapatite (HAp) granules encapsulated OxAlg-Gel-BCP hydrogel complex were fabricated using freeze-drying method. Detailed morphological and material characterizations of OxAlg-Gel-BCP hydrogel (OGB00), 25wt% and 35wt% granules encapsulated hydrogel (OGB25 and OGB35) were carried out for micro-structure, porosity, chemical constituents, and compressive stress analysis. Cell viability, cell attachment, proliferation and differentiation behavior of rat bone marrow-derived stem cell (BMSC) on OGB00, OGB25 and OGB35 scaffolds were confirmed by MTT assay, Live-Dead assay, and confocal imaging in vitro experiments. Finally, OGB00 and OGB25 hydrogel scaffolds were implanted in the critical size defect of rabbit femoral chondyle for 4 and 8 weeks. The micro-CT analysis and histological studies conducted by H&E and Masson's trichrome demonstrated that a significantly higher (***p<0.001) and earlier bone formation happened in case of 25% HAp granules encapsulated OxAlg-Gel-BCP hydrogel than in OxAlg-Gel-BCP complex alone. All results taken together, HAp granules encapsulated OxAlg-Gel-BCP system can be a promising 3D hydrogel scaffold for the healing of a critical bone defect.

Improved in vitro biocompatibility of surface-modified hydroxyapatite sponge scaffold with gelatin and BMP-2 in comparison against a commercial bone allograft.

This study aims to demonstrate the morphology and in vitro biocompatibility of neat and surface-modified hydroxyapatite sponge scaffold (SM-HASS) which was fabricated using a sponge replica method, and compared with the commercially available demineralized freeze-dried bone allograft (DFDBA). Surface-modifications were done by coating the surface area of the neat hydroxyapatite sponge scaffold (HASS) with either gelatin alone (HASS/G) or gelatin and BMP-2 growth factor (HASS/G+B). Scanning electron microscope (SEM), Fourier transform infrared (FTIR), porosity, pore size distribution, and compressive strength analyses showed that the addition of gelatin in HASS/G produced a morphologically and structurally similar scaffold to that of the allograft. The addition of BMP-2 improved the biocompatibility of the HASS/G+B in vitro using MC3T3-E1 cells which showed better cell viability, proliferation, and cell adhesion than on the allograft. Therefore, hydroxyapatite scaffold coated with gelatin polymer and gelatin with BMP-2 growth factor showed comparable performance against commercially available DFDBA from cadaver with regards to structure and in vitro biocompatibility.

Nanoparticle biphasic calcium phosphate loading on gelatin-pectin scaffold for improved bone regeneration.

Biphasic calcium phosphate (BCP) nanoparticles were loaded with porous gelatin-pectin (GE-P) scaffolds. The biodegradable gelatin-pectin-BCP scaffolds were produced as miscible mixtures with well-defined interconnected pores to facilitate osteoconductivity and enhance bone formation. It was observed that the compressive strength increased with the loading of BCP nanoparticles. From in vitro results, cell adhesion, viability, and proliferation were found in the GE-P-10 scaffolds in comparison with those without BCP, resulting in high alkaline phosphate (ALP), and osteopontin (OPN) expression at 21 days. Micro-computed tomography data, hematoxylin and eosin staining, and immunohistochemistry (OPN, OCN, COL I, and COL II) confirmed rapid new bone formation in rabbit models. Our results provide a novel and simple method to provide an adequate scaffold, and thus GE-P-BCP porous scaffolds may be appropriate candidates for bone tissue engineering.

Bone Regeneration Using Hydroxyapatite Sponge Scaffolds with In Vivo Deposited Extracellular Matrix.

There is currently an increased interest in studying the extracellular matrix (ECM) and its potential applications for tissue engineering and regenerative medicine. The ECM plays an important role by providing adhesive substrates to cells during migration, morphogenesis, differentiation, and homeostasis by signaling biochemical and biomechanical cues to cells. In this study, the ECM was incorporated into hydroxyapatite by implanting sponge replica scaffolds in subcutaneous pockets in rats, and the implants were tested for bone regeneration potential. The resulting scaffolds were characterized using scanning electron microscopy, confocal microscopy, DNA and RNA quantification, tissue staining, energy dispersive X-ray spectroscopy analysis, compressive strength testing, porosity, and pore size distribution analysis using bare scaffolds as a control reference. Biocompatibility was assessed using MC3T3-E1 preosteoblast cells and in vivo studies were carried out by implanting decellularized scaffolds in 11 mm radial defects in New Zealand rabbits for 4 and 8 weeks to determine the effect of the in vivo deposited ECM. Material characterization indicated that a 2-week decellularized scaffold was the best among the samples, with an evenly distributed ECM visible on hematoxylin and eosin-stained tissue sections, a compressive strength of 2.53 ± 0.68 MPa, a porosity of 58.08 ± 3.32% and a pore size distribution range of 10-150 µm. In vivo results showed no severe inflammation, with increased cell infiltration followed by dense matrix deposition after 4 weeks and new bone formation at 8 weeks. The results indicate that incorporation of an in vivo deposited ECM into ceramic scaffolds can potentially improve bone regeneration.

Effect of Local Sustainable Release of BMP2-VEGF from Nano-Cellulose Loaded in Sponge Biphasic Calcium Phosphate on Bone Regeneration.

Bone regeneration is a coordinated process mainly regulated by multiple growth factors. Vascular endothelial growth factor (VEGF) stimulates angiogenesis and bone morphogenetic proteins (BMPs) induce osteogenesis during bone healing process. The aim of this study was to investigate how these growth factors released locally and sustainably from nano-cellulose (NC) simultaneously effect bone formation. A biphasic calcium phosphate (BCP)-NC-BMP2-VEGF (BNBV) scaffold was fabricated for this purpose. The sponge BCP scaffold was prepared by replica method and then loaded with 0.5% NC containing BMP2-VEGF. Growth factors were released from NC in a sustainable manner from 1 to 30 days. BNBV scaffolds showed higher cell attachment and proliferation behavior than the other scaffolds loaded with single growth factors. Bare BCP scaffolds and BNBV scaffolds seeded with rat bone marrow mesenchymal stem cells were implanted ectopically and orthotopically in nude mice for 4 weeks. No typical bone formation was exhibited in BNBV scaffolds in ectopic sites. BMP2 and VEGF showed positive effects on new bone formation in BNBV scaffolds, with and without seeded stem cells, in the orthotopic defects. This study demonstrated that the BNBV scaffold could be beneficial for improved bone regeneration. Stem cell incorporation into this scaffold could further enhance the bone healing process.

Preformed chitosan cryogel-biphasic calcium phosphate: a potential injectable biocomposite for pathologic fracture.

The increasing interest in chitosan-based biomaterials stems from its desirable physicochemical properties. Although calcium phosphates have been mixed with chitosan to form injectable scaffolds, its application for bone tissue engineering has been limited and is still being explored to improve its clinical translatability. We report a biocomposite comprised of preformed chitosan cryogel with dispersed biphasic calcium phosphate that can flow under moderate pressure allowing passage through a small gauge needle, while maintaining sufficient integrity and strength during injection for gel recovery. The formed samples were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction analysis and protein adsorption measurements. Composite with 1% w/v biphasic calcium phosphate (CSG1) resulted in a homogeneous and rigid final structure. Injectable composite cryogel CSG1 (2.5 ± 0.2 N, 23G needle) exhibited good protein adsorption and biocompatibility. Results of subcutaneous implantation in rats reveal relatively high presence of polymorphonuclear cells but with no fibrous encapsulation with the composites, allowing further infiltration of cells within the sample implants. The biocomposite system presents a less-invasive delivery of bone filling material for stabilizing pathologic fractures.

Bone formation of a porous Gelatin-Pectin-biphasic calcium phosphate composite in presence of BMP-2 and VEGF.

A composite scaffold of gelatin (Gel)-pectin (Pec)-biphasic calcium phosphate (BCP) was fabricated for the successful delivery of growth factors. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) were coated on the Gel-Pec-BCP surface to investigate of effect of them on bone healing. Surface morphology was investigated by scanning electron microscopy, and BCP dispersion in the hydrogel scaffolds was measured by energy dispersive X-ray spectroscopy. The results obtained from Fourier transform infrared spectroscopy showed that BMP-2 and VEGF were successfully coated on Gel-Pec-BCP hydrogel scaffolds. MC3T3-E1 preosteoblasts were cultivated on the scaffolds to investigate the effect of BMP-2 and VEGF on cell viability and proliferation. VEGF and BMP-2 loaded on Gel-Pec-BCP scaffold facilitated increased cell spreading and proliferation compared to Gel-Pec-BCP scaffolds. In vivo, bone formation was examined using rat models. Bone formation was observed in Gel-Pec-BCP/BMP-2 and Gel-Pec-BCP/VEGF scaffolds within 4 weeks, and was greatest with Gel-Pec-BCP/BMP-2 scaffolds. In vitro and in vivo results suggest that Gel-Pec-BCP/BMP-2 and Gel-Pec-BCP/VEGF scaffolds could enhance bone regeneration.

Bioactive glass incorporation in calcium phosphate cement-based injectable bone substitute for improved in vitro biocompatibility and in vivo bone regeneration.

In this work, we fabricated injectable bone substitutes modified with the addition of bioactive glass powders synthesized via ultrasonic energy-assisted hydrothermal method to the calcium phosphate-based bone cement to improve its biocompatibility. The injectable bone substitutes was initially composed of a powder component (tetracalcium phosphate, dicalcium phosphate dihydrate and calcium sulfate dehydrate) and a liquid component (citric acid, chitosan and hydroxyl-propyl-methyl-cellulose) upon which various concentrations of bioactive glass were added: 0%, 10%, 20% and 30%. Setting time and compressive strength of the injectable bone substitutes were evaluated and observed to improve with the increase of bioactive glass content. Surface morphologies were observed via scanning electron microscope before and after submersion of the samples to simulated body fluid and increase in apatite formation was detected using x-ray diffraction machine. In vitro biocompatibility of the injectable bone substitutes was observed to improve with the addition of bioactive glass as the proliferation/adhesion behavior of cells on the material increased. Human gene markers were successfully expressed using real time-polymerase chain reaction and the samples were found to promote cell viability and be more biocompatible as the concentration of bioactive glass increases. In vivo biocompatibility of the samples containing 0% and 30% bioactive glass were evaluated using Micro-CT and histological staining after 3 months of implantation in male rabbits' femurs. No inflammatory reaction was observed and significant bone formation was promoted by the addition of bioactive glass to the injectable bone substitute system.

In vitro and in vivo studies of BMP-2-loaded PCL-gelatin-BCP electrospun scaffolds.

To confirm the effect of recombinant human bone morphogenetic protein-2 (BMP-2) for bone regeneration, BMP-2-loaded polycaprolactone (PCL)-gelatin (Gel)-biphasic calcium phosphate (BCP) fibrous scaffolds were fabricated using the electrospinning method. The electrospinning process to incorporate BCP nanoparticles into the PCL-Gel scaffolds yielded an extracellular matrix-like microstructure that was a hybrid system composed of nano- and micro-sized fibers. BMP-2 was homogeneously loaded on the PCL-Gel-BCP scaffolds for enhanced induction of bone growth. BMP-2 was initially released at high levels, and then showed sustained release behavior for 31 days. Compared with the PCL-Gel-BCP scaffold, the BMP-2-loaded PCL-Gel-BCP scaffold showed improved cell proliferation and cell adhesion behavior. Both scaffold types were implanted in rat skull defects for 4 and 8 weeks to evaluate the biological response under physiological conditions. Remarkable bone regeneration was observed in the BMP-2/PCL-Gel-BCP group. These results suggest that BMP-2-loaded PCL-Gel-BCP scaffolds should be considered for potential bone tissue engineering applications.

Long distance runners present upregulated sweating responses than sedentary counterparts.

Relatively few studies have investigated peripheral sweating mechanisms of long-distance runners. The aim of this study was to compare peripheral sweating mechanisms in male long-distance runners, and sedentary counterparts. Thirty six subjects, including 20 sedentary controls and 16 long-distance runners (with 7-12 years of athletic training, average 9.2±2.1 years) were observed. Quantitative sudomotor axon reflex testing (QSART) with iontophoresis (2 mA for 5 min) and 10% acetylcholine (ACh) were performed to determine axon reflex-mediated and directly activated (DIR, muscarinic receptor) sweating. Sweat onset time, sweat rate, number of activated sweat glands, sweat output per gland and skin temperature were measured at rest while maximum oxygen uptake (VO2max) were measured during maximal cycling. Sweat rate, activated sweat glands, sweat output per gland, skin temperature and VO2max were significantly higher in the trained runners than in the sedentary controls. Sweat onset time was significantly shorter for the runners. In the group of long-distance runners, significant correlations were found between VO2max and sweat onset time (r2 = 0.543, P<0.01, n = 16), DIR sweat rate (r2 = 0.584, P<0.001, n = 16), sweat output per gland (r2 = 0.539, P<0.01, n = 16). There was no correlation between VO2max and activated sweat glands. These findings suggest that habitual long-distance running results in upregulation of the peripheral sweating mechanisms in humans. Additional research is needed to determine the molecular mechanism underlying these changes. These findings complement the existing sweating data in long-distance runners.