Observation of Charge Separation and Space-Charge Region in Single-Crystal P3HT/C60 Heterojunction Nanowires.

We directly observed charge separation and a space-charge region in an organic single-crystal p-n heterojunction nanowire, by means of scanning photocurrent microscopy. The axial p-n heterojunction nanowire had a well-defined planar junction, consisted of P3HT (p-type) and C60 (n-type) single crystals and was fabricated by means of the recently developed inkjet-assisted nanotransfer printing technique. The depletion region formed at the p-n junction was directly observed by exploring the spatial distribution of photogenerated carriers along the heterojunction nanowire under various applied bias voltages. Our study provides a facile approach toward the precise characterization of charge transport in organic heterojunction systems as well as the design of efficient nanoscale organic optoelectronic devices.

Androgen receptor transcriptionally regulates µ-opioid receptor expression in rat trigeminal ganglia.

The involvement of testosterone in pain, inflammation, and analgesia has been reported, but the role of androgen receptor (AR), a steroid receptor for testosterone, is not well understood. We have previously shown that peripheral inflammation upregulates µ-opioid receptor (MOR) in rat trigeminal ganglia (TG) in a testosterone-dependent manner. In this study, we hypothesized that testosterone regulates MOR expression via transcriptional activities of AR in TG. We first examined whether AR is co-expressed with MOR in TG neurons. Our immunohistochemical experiment revealed that AR staining is detected in neurons of all sizes in TG and that a subset of AR is expressed in MOR as well as in TRPV1-positive neurons. We identified the promoter region of the rat MOR gene contains putative AR binding sites. Using chromatin immunoprecipitation assay, we demonstrated that AR directly binds to these sites in TG extracts. We confirmed with luciferase reporter assay that AR activated the MOR promoter in response to androgens in a human neuroblastoma cell line (5H-5YSY). These data demonstrated that AR functions as a transcriptional regulator of the MOR gene activity. Finally, we showed that flutamide, a specific AR antagonist, prevents complete Freund's adjuvant (CFA)-induced upregulation of MOR mRNA in TG, and that flutamide dose-dependently blocks the efficacy of DAMGO, a specific MOR agonist, on CFA-induced mechanical hypersensitivity. Our results expand the knowledge regarding the role of androgens and their receptor in pain and analgesia and have important clinical implications, particularly for inflammatory pain patients with low or compromised plasma testosterone levels.

Cross-stacked single-crystal organic nanowire p-n nanojunction arrays by nanotransfer printing.

We fabricated cross-stacked organic p-n nanojunction arrays made of single-crystal 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-PEN) and fullerene (C60) nanowires as p-type and n-type semiconductors, respectively, by using a nanotransfer printing technique. Single-crystal C60 nanowires were synthesized inside nanoscale channels of a mold and directly transferred onto a desired position of a flexible substrate by a lubricant liquid layer. In the consecutive printing process, single-crystal TIPS-PEN nanowires were grown in the same way and then perpendicularly aligned and placed onto the C60 nanowire arrays, resulting in a cross-stacked single-crystal organic p-n nanojunction array. The cross-stacked single-crystal TIPS-PEN/C60 nanowire p-n nanojunction devices show rectifying behavior with on/off ratio of ∼ 13 as well as photodiode characteristic with photogain of ∼ 2 under a light intensity of 12.2 mW/cm(2). Our study provides a facile, solution-processed approach to fabricate a large-area array of organic crystal nanojunction devices in a desired arrangement for future nanoscale electronics.

H11/HspB8 and Its Herpes Simplex Virus Type 2 Homologue ICP10PK Share Functions That Regulate Cell Life/Death Decisions and Human Disease.

Small heat shock proteins (sHsp) also known as HspB are a large family of widely expressed proteins that contain a 90 residues domain known as α-crystallin. Here, we focus on the family member H11/HspB8 and its herpes simplex virus type 2 (HSV-2) homologue ICP10PK, and discuss the possible impact of this relationship on human disease. H11/HspB8 and ICP10PK are atypical protein kinases. They share multi-functional activity that encompasses signaling, unfolded protein response (UPR) and the regulation of life cycle potential. In melanocytes H11/HspB8 causes growth arrest. It is silenced in a high proportion of melanoma prostate cancer, Ewing's sarcoma and hematologic malignancies through aberrant DNA methylation. Its restored expression induces cell death and inhibits tumor growth in xenograft models, identifying H11/HspB8 as a tumor suppressor. This function involves the activation of multiple and distinct death pathways, all of which initiate with H11/HspB8-mediated phosphorylation of transforming growth factor ß-activated kinase 1 (TAK1). Both ICP10PK and H11/HspB8 were implicated in inflammatory processes that involve dendritic cells activation through Toll-like receptor-dependent pathways and may contribute to the onset of autoimmunity. The potential evolutionary relationship of H11/HspB8 to ICP10PK, its impact on human disorders and the development of therapeutic strategies are discussed.

Effects of multiple drilling on the ischemic capital femoral epiphysis of immature piglets.

PURPOSE: This study investigated the effects of multiple drilling on the immature capital femoral epiphysis following ischemic injury in a piglet model. MATERIALS AND METHODS: Ischemic necrosis of capital femoral epiphysis was induced bilaterally in 12 piglets using a cervical ligation method. Three weeks later, medial, central, and lateral 3 drill holes were made on the left femoral head using 0.062" K-wire. At 3, 6, 9, and 12 weeks following the multiple drilling, femoral heads were harvested from each three piglets. On histologic examination, percent of revascularization, percent of osteoblast surface, capital femoral epiphyseal quotient and proximal femoral growth plate height were evaluated. Untreated right femoral heads served as control. RESULTS: While percent of revascularization of left capital femoral epiphysis with multiple drilling was significantly higher than untreated control side (p<0.001), percent of osteoblast surface, capital femoral epiphyseal quotient and proximal femoral growth plate height showed no significant difference. CONCLUSION: This study indicates that multiple drilling could promote revascularization of ischemic capital femoral epiphysis, and multiple drilling does not appear to produce bony physeal bars at short-term, if using small diameter drill. However, multiple drilling alone does not seem to prevent femoral head deformity or to promote new bone formation.

Limb angular deformity correction using Dyna-ATC: surgical technique, calculation method, and clinical outcome.

PURPOSE: Dyna-ATC is a unilateral external fixator with angulator, lengthener, and translator, which allows for angular correction and compensation of the secondary displacement during angular correction. The purpose of this study is to introduce surgical technique and calculation methods and to evaluate the clinical outcome of angular deformity correction using Dyna-ATC. MATERIALS AND METHODS: The amounts of secondary displacement were calculated with the distances between axis of correction of angulation, Center of Rotational Angulation, and osteotomy and the amount of angular deformity. The rate of angular correction was determined to distract the corticotomy at 1 mm/day. Clinical and radiographic evaluation was performed on 13 patients who underwent deformity correction using Dyna-ATC. There were 8 proximal tibia vara, 1 tibia valga, 2 varus and 4 valgus deformities on distal femur. One patient underwent pelvic support femoral reconstruction. Concomitant lengthening was combined in all femur cases. Mean age at surgery was 17.5 years (7 to 64). RESULTS: All but one achieved bony healing and normal alignment with the index procedure. Mean mechanical axis deviation improved from 31.9 mm to 3.0 mm. The average amount of angular correction was 11.0° on tibiae and 10.0° on femora. The average length gain on femora was 6.4 cm, and the healing index averaged to 1.1 mo/cm. One patient underwent quadricepsplasty and one patient had three augmentation surgeries due to poor new bone formation. CONCLUSION: We believe that Dyna-ATC is a useful alternative to bulky ring fixators for selective patients with angular deformity less than 30 degrees in the coronal plane around the knee joint.

Pulmonary manifestations in Proteus syndrome: pulmonary varicosities and bullous lung disease.

We report on two patients with Proteus syndrome (PS), with emphasis on its pulmonary manifestations. The first patient was a 6-year-old girl diagnosed with PS at 5 years of age. The pulmonary abnormalities first observed at age 3 years and included streaky densities with accentuated vascular markings detected by chest radiography. The patient had persistent abnormalities on follow-up chest radiographs. Chest computed tomography (CT) scans showed diffuse pulmonary venous dilatations. The second patient was a 10-year-old boy diagnosed with PS at age 4 years. Chest radiography and CT scans showed patchy and streaky densities intermixed with small bullae, which were interpreted as pneumonia with post-inflammatory pneumatoceles. The patient developed diffuse enlargement of air spaces of the lungs at age 10 years with severe respiratory compromise. Although pulmonary manifestations in PS are uncommon, recognition of pulmonary vein malformation and the presentation of enlarged air spaces in the lungs at an earlier age are important for accurate diagnosis. The plain radiograph findings of accentuated vascular markings seen in patients with PS may appear similar to interstitial or chronic pneumonia. This report emphasizes the features of lung involvement in children with PS and suggests that specific attention be paid to pulmonary manifestations using chest CT scans. © 2011 Wiley-Liss, Inc.

Ankle valgus deformity secondary to proximal migration of the fibula in tibial lengthening with use of the Ilizarov external fixator.

BACKGROUND: Ankle valgus deformity secondary to proximal migration of the fibula following an Ilizarov tibial lengthening has not been discussed in detail in the literature. The purposes of this study were to determine the underlying mechanism of and to identify factors associated with proximal migration of the fibula that caused ankle valgus deformity after an Ilizarov tibial lengthening. METHODS: We reviewed the outcome of seventy-four bilateral Ilizarov tibial lengthenings for short stature in thirty-seven patients. The mean age at the time of surgery was 21.7 years (range, thirteen to thirty-one years), and the mean duration of follow-up was forty-five months. Proximal migration of the fibula was assessed with changes in the malleolar tip distance. A valgus change of ≥ 5° in the tibiotalar angle was regarded as ankle valgus deformity following tibial lengthening. RESULTS: The average length gain was 6.9 cm (range, 4.7 to 11.5 cm), and the average lengthening index was 1.5 mo/cm. Valgus deformity developed in six ankles (8%) and fibular nonunion developed in ten (14%). Proximal migration of the lateral malleolus of ≥ 5 mm was related to valgus talar tilting. Bifocal tibial lengthening, rapid distraction rate of the fibula (>1 mm per day), and development of a fibular nonunion were factors associated with proximal migration of the distal end of the fibula of ≥ 5 mm, which suggests that regenerated bone of poor quality in the distraction gap may cause proximal migration of the distal end of the fibula following tibial lengthening. CONCLUSIONS: Proximal migration of the distal end of the fibula following tibial lengthening may occur even with the use of an Ilizarov ring fixator. This migration seems to be caused by collapse of regenerated bone of poor quality or fibular nonunion. Proximal migration of ≥ 5 mm is associated with the risk of valgus talar tilting. Surgeons should consider earlier intervention with bone-grafting if there are conditions that compromise regenerated bone formation in the fibular distraction gap, such as can occur with extensive tibial lengthening by bifocal corticotomy.

Combined therapy of orthopedic surgery after deep brain stimulation in cerebral palsy mixed type - a case report -.

Dystonia is a symptom defined by involuntary and irregular contractions of the muscles, which cause movement disorders and postural problems. Deep brain stimulation (DBS) in globus pallidus interna (GPi) is a good option for controlling dystonia. DBS has already been shown to have significant effects on primary dystonia as well as Parkinson's disease. Dystonia is very difficult to manage, as seen in cerebral palsy (CP) mixed with spasticity. As CP patients grow, their musculoskeletal problems may require orthopedic surgery. However, the outcome of orthopedic surgery is not usually suitable due to dystonia. Therefore, we attempted to control dystonia through DBS initially and perform orthopedic surgery to correct musculoskeletal deformities after treatment of dystonia. Herein, we report a case that showed remarkable improvement in terms of the dystonia rating scale and gait pattern after combined therapy of DBS and orthopedic surgery.

Altered synthesis of cartilage-specific proteoglycans by mutant human cartilage oligomeric matrix protein.

BACKGROUND: The mechanism by which mutant cartilage oligomeric matrix protein (COMP) induces a pseudoachondroplasia phenotype remains unknown, and the reason why a mutation of a minor protein of the growth plate cartilage causes total disruption of endochondral bone formation has not yet been determined. The current study was performed to investigate the effects of mutated COMP on the synthesis of the cartilage-specific major matrix proteins of Swarm rat chondrosarcoma chondrocytes. METHODS: The Swarm rat chondrosarcoma chondrocytes transfected with a chimeric construct, which consisted of a mutant gene of human COMP and an amino acid FLAG tag sequence, were cultured in agarose gel. Formation of extracellular proteoglycan and type-II collagen by the cells was evaluated by immunohistochemical staining and measuring the (35)S-sulfate incorporation. RESULTS: No difference was observed for the detection of type-II collagen among the cell lines expressing mutant COMP and the control cell lines. Histochemical staining of sulfated proteoglycans with safranin-O showed that lesser amounts of proteoglycans were incorporated into the extracellular matrix of the chondrocytes transfected with the mutant gene. (35)S-sulfate incorporation into the cell/matrix fractions demonstrated markedly lower radiolabel incorporation, as compared to that of the control cells. CONCLUSIONS: Mutation of COMP has an important impact on the processing of proteoglycans, rather than type-II collagen, in the three-dimensional culture of Swarm rat chondrosarcoma chondrocytes.

Tibial lengthening over an intramedullary nail with use of the Ilizarov external fixator for idiopathic short stature.

BACKGROUND: The details regarding bone formation and complication rates associated with tibial lengthening over an intramedullary nail with use of the Ilizarov external fixator have not been reported, to our knowledge. The purpose of this study was to review our experiences with this procedure, performed in individuals with idiopathic short stature. In addition, we compared the results of lengthening over a nail, in terms of the observed bone formation and the complications, with those of the conventional Ilizarov method. METHODS: Eighty-eight tibiae in forty-four individuals with a mean preoperative height (and standard deviation) of 153.7 +/- 7.2 cm were included in the study. Thirty-two tibial lengthening procedures were performed with the conventional method and fifty-six, with a nail. The increase in the length of the tibia, the external fixation index, the healing index, and complications were assessed. Three specific concerns, including mobility during the lengthening procedure, the time interval before the patient could return to previous activities after completion of the lengthening, and physical activities at the time of final follow-up, were also assessed. RESULTS: The mean final height was 160.1 +/- 7.0 cm, and the mean gain in tibial length was 6.2 cm (20.0%). There was no difference in the mean gain in tibial length or the healing index between the groups; however, the external fixation index was lower and there were fewer complications per tibia in the group treated with the lengthening over a nail. The individuals treated with lengthening over a nail coped better with outdoor activities during the treatment period than the individuals treated with the conventional Ilizarov method; however, there was no difference in the time until the individual returned to previous activities or in the ability to carry out physical activities at the time of final follow-up between the groups. CONCLUSIONS: Tibial lengthening with use of the Ilizarov external fixator over an intramedullary nail results in new bone formation of a quality equal to that obtained with the conventional Ilizarov method; however, it reduces the duration of external fixation and the rate of complications.

Changes in dynamic foot pressure after surgical treatment of valgus deformity of the hindfoot in cerebral palsy.

BACKGROUND: Calcaneal lengthening osteotomy and extra-articular arthrodesis of the subtalar joint are two methods used for the correction of valgus deformity of the heel and forefoot abduction. The purpose of this study was to compare the operative results of these procedures in patients with cerebral palsy who were able to walk. We focused primarily on changes in radiographic parameters and how altered mobility of the subtalar joint by the two operative methods would modify pressure distribution over the plantar surface of the foot. METHODS: A total of eighty-one feet in forty-seven patients were included in the study. The mean age at the time of surgery was eight years and one month, and the mean follow-up period was thirty-nine months. The subjects were divided into two groups; Group I consisted of thirty-seven feet in twenty-two patients who underwent a calcaneal lengthening osteotomy, and Group II comprised forty-four feet in twenty-five patients who underwent an extra-articular subtalar arthrodesis. Preoperative and final follow-up radiographs and dynamic pedobarographs were used to evaluate the results. RESULTS: The feet in both groups were found to be similarly deformed before surgery, by radiographic measurements and dynamic foot-pressure analysis. Both operative procedures led to improved radiographic indices; however, calcaneal pitch failed to improve after the subtalar arthrodesis. After surgery, the relative vertical impulse was decreased for the hallux, first metatarsal head, and medial aspect of the midfoot in both groups, while it was increased for the lateral aspect of the midfoot and calcaneus. On the other hand, postoperatively, the relative vertical impulse of the medial aspect of the midfoot was higher and the relative vertical impulse of the first through fourth metatarsal heads was lower in the group that had subtalar arthrodesis compared with the group that had a calcaneal lengthening osteotomy and the normal control subjects. CONCLUSIONS: Extra-articular subtalar arthrodesis appears to be an effective means to achieve predictable correction of severe valgus deformity of the heel in patients with cerebral palsy who are able to walk; however, supination deformity of the forefoot remains and calcaneal equinus is not corrected. On the other hand, we believe that the calcaneal lengthening osteotomy is the treatment of choice because postoperative foot-pressure distribution more closely approximates the normal foot-pressure distribution.

Trochanteric advancement in patients with Legg-Calvé-Perthes disease does not improve pain or limp.

UNLABELLED: Premature closure of the proximal epiphysis in patients with Legg-Calvé-Perthes disease can cause overgrowth of the greater trochanter. We asked whether distal transfer of the greater trochanter relieved pain and improved limp and whether the operation changed frontal plane kinematic and kinetic parameters of the hip and pelvis in the gait analysis. We reviewed 15 patients (15 hips) with an average age of 16.9 years (range, 13-26 years) who had the operation and were followed for a minimum of 28 months (average, 42 months; range, 28-54 months). The Iowa hip score increased from 85.0 (range, 75.5-87.0) before surgery to 89.1 (range, 83.0-97.0) at the final followup. Only three patients had no pain and Trendelenburg sign postoperatively. Pelvic obliquity angle of affected and contralateral normal hips in ipsilateral stance and contralateral swing phases remained unchanged after surgery. Hip adduction angle and abductor moment during single stance phase of affected and contralateral normal hips were not changed. We concluded trochanteric advancement does little to relieve pain and improve limp in patients with relative overgrowth of the greater trochanter and Legg-Calvé-Perthes disease. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Interlocking telescopic rod for patients with osteogenesis imperfecta.

BACKGROUND: Intramedullary fixation with use of a telescopic rod with a T-piece is one of the standard methods for long-bone stabilization in growing children with osteogenesis imperfecta. However, installation and removal of this device can cause substantial damage to the distal joint, which limits its use, especially in the tibia. We devised a modification of the telescopic rod system--the interlocking telescopic rod--in which the obturator is a simple rod with a hole, instead of a T-piece, at its distal end. METHODS: The clinical and radiographic outcomes were evaluated more than two years following treatment of thirty-two limb segments (twenty-three tibiae and nine femora) with this new rod system in fifteen patients with osteogenesis imperfecta. RESULTS: All rods were inserted without an arthrotomy of the distal joint, and all telescoped successfully. The interlocking pin used in the first five limb segments backed out between five and thirty-three months postoperatively. A revised fixation technique was used in the remaining twenty-seven limb segments, and the interlocking pin had not backed out at an average 3.1 years postoperatively. Proximal migration of the obturator was observed in four tibiae after 2.5 years. The cumulative survival rate of the rod at four years postoperatively was 88.7%. CONCLUSIONS: Both insertion and removal of an interlocking telescopic rod are much less invasive than insertion and removal of a conventional telescopic rod with a T-piece anchor. The interlocking pin at the distal epiphysis provides effective anchorage for telescoping. Our interim results showed survival of the device to be comparable with, or better than, that of the conventional telescopic rod.

Proximal tibial lengthening by distraction osteogenesis in congenital pseudarthrosis of the tibia.

The purposes of this study were to investigate the outcome of distraction osteogenesis (DO) at the proximal tibial metaphysis in congenital pseudarthrosis of the tibia (CPT) patients and to identify the risk factors of poor regenerate bone formation. Twenty-seven cases of DO in 22 patients with CPT, with average age of 7 years, were divided into 2 groups. Group 1 contained those cases in which the target length was achieved with a healing index (HI) of 65 d/cm or less, and group 2 contained those with an HI of more than 65 d/cm and those that received additional procedures to achieve bone healing. Clinical and radiological parameters were analyzed and compared between the 2 groups using the Mann-Whitney U test or Fisher exact test. Ten cases were assigned to group 1, with a mean HI of 39 d/cm, and 17 to group 2 with a mean HI of 117 d/cm. Autogenous bone grafting was additionally performed in 12 cases, bone marrow injection in 4 cases, and demineralized bone matrix insertion in 1 case in group 2. Those cases showing proximal tibial dysplasia on radiograms (11 cases) or that underwent repeated lengthening (6 cases) belonged to group 2. The HI was significantly smaller in cases having neither of these 2 factors as compared with those having any of these factors. The present study shows that proximal tibial lengthening by DO in CPT can be safely performed if the proximal tibia is not dysplastic and has not been lengthened previously and that lengthening at a dysplastic proximal tibial segment or at a previously lengthened segment renders delayed healing and may require additional procedure(s) to promote bone healing. Physeal distraction or DO through subphyseal osteotomy may be justified to gain length in this high-risk group.

The role of the sympathetic nervous system in moxibustion-induced immunomodulation in rats.

The effects of chemical sympathectomy on moxibustion-induced changes in splenic natural killer (NK) cell cytotoxicity, T and B cell proliferation were studied. Direct moxibustion was applied to the unilateral Zusanli region. NK cell cytotoxicity was suppressed by moxibustion in both vehicle-treated rats and sympathectomized rats. T cell proliferation was not affected by moxibustion. B cell proliferation showed no significant change in vehicle-treated rats, but an increase was seen in sympathectomized rats treated with moxibustion. Sympathectomy alone induced an augmentation of NK cell cytotoxicity and a suppression of T cell proliferation. These results suggest that the sympathetic nervous system (SNS) has no significant role in the mechanism of moxibustion-induced immunomodulation.