Dual Orbital Degeneracy Lifting in a Strongly Correlated Electron System.

The local structure of NaTiSi_{2}O_{6} is examined across its Ti-dimerization orbital-assisted Peierls transition at 210 K. An atomic pair distribution function approach evidences local symmetry breaking preexisting far above the transition. The analysis unravels that, on warming, the dimers evolve into a short range orbital degeneracy lifted (ODL) state of dual orbital character, persisting up to at least 490 K. The ODL state is correlated over the length scale spanning ∼6 sites of the Ti zigzag chains. Results imply that the ODL phenomenology extends to strongly correlated electron systems.

Local orbital degeneracy lifting as a precursor to an orbital-selective Peierls transition.

Fundamental electronic principles underlying all transition metal compounds are the symmetry and filling of the d-electron orbitals and the influence of this filling on structural configurations and responses. Here we use a sensitive local structural technique, x-ray atomic pair distribution function analysis, to reveal the presence of fluctuating local-structural distortions at high temperature in one such compound, CuIr2S4. We show that this hitherto overlooked fluctuating symmetry-lowering is electronic in origin and will modify the energy-level spectrum and electronic and magnetic properties. The explanation is a local, fluctuating, orbital-degeneracy-lifted state. The natural extension of our result would be that this phenomenon is likely to be widespread amongst diverse classes of partially filled nominally degenerate d-electron systems, with potentially broad implications for our understanding of their properties.

Robust Phonon-Plasmon Coupling in Quasifreestanding Graphene on Silicon Carbide.

Using inelastic electron scattering in combination with dielectric theory simulations on differently prepared graphene layers on silicon carbide, we demonstrate that the coupling between the 2D plasmon of graphene and the surface optical phonon of the substrate cannot be quenched by modification of the interface via intercalation. The intercalation rather provides additional modes like, e.g., the silicon-hydrogen stretch mode in the case of hydrogen intercalation or the silicon-oxygen vibrations for water intercalation that couple to the 2D plasmons of graphene. Furthermore, in the case of bilayer graphene with broken inversion symmetry due to charge imbalance between the layers, we observe a similar coupling of the 2D plasmon to an internal infrared-active mode, the LO phonon mode. The coupling of graphene plasmons to vibrational modes of the substrate surface and internal infrared active modes is envisioned to provide an excellent tool for tailoring the plasmon band structure of monolayer and bilayer graphene for plasmonic devices such as plasmon filters or plasmonic waveguides. The rigidity of the effect furthermore suggests that it may be of importance for other 2D materials as well.

Increased expression of receptor phosphotyrosine phosphatase-ß/ζ is associated with molecular, cellular, behavioral and cognitive schizophrenia phenotypes.

Schizophrenia is a serious and chronic mental disorder, in which both genetic and environmental factors have a role in the development of the disease. Neuregulin-1 (NRG1) is one of the most established genetic risk factors for schizophrenia, and disruption of NRG1 signaling has been reported in this disorder. We reported previously that NRG1/ErbB4 signaling is inhibited by receptor phosphotyrosine phosphatase-ß/ζ (RPTP ß/ζ) and that the gene encoding RPTPß/ζ (PTPRZ1) is genetically associated with schizophrenia. In this study, we examined the expression of RPTPß/ζ in the brains of patients with schizophrenia and observed increased expression of this gene. We developed mice overexpressing RPTPß/ζ (PTPRZ1-transgenic mice), which showed reduced NRG1 signaling, and molecular and cellular changes implicated in the pathogenesis of schizophrenia, including altered glutamatergic, GABAergic and dopaminergic activity, as well as delayed oligodendrocyte development. Behavioral analyses also demonstrated schizophrenia-like changes in the PTPRZ1-transgenic mice, including reduced sensory motor gating, hyperactivity and working memory deficits. Our results indicate that enhanced RPTPß/ζ signaling can contribute to schizophrenia phenotypes, and support both construct and face validity for PTPRZ1-transgenic mice as a model for multiple schizophrenia phenotypes. Furthermore, our results implicate RPTPß/ζ as a therapeutic target in schizophrenia.

Effect of blended carbon dioxide and erbium:YAG laser energy on preauricular and ear lobule keloid fibroblast secretion of growth factors: a serum-free study.

BACKGROUND: A serum-free in vitro model was used to determine the effect of combined carbon dioxide (CO2) and erbium (Er):YAG laser (Derma K; ESC/Sharplan Medical Systems, Yokneam, Israel) irradiation on keloid-producing fibroblasts (KFs) from 2 distinct facial sites. Transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) play an integral part in wound healing and were assayed using this model. It has always been a clinical impression that fibroblasts from different regions of the face behave differently. This is exemplified by patients prone to lobule keloid formation after ear piercing, who heal normally after a facial incision. DESIGN: Laboratory-based wound healing. METHODS: Human KF cell lines were established from operative specimens using standard explant techniques. At 48 hours after seeding, 20% of each well was exposed to 1.7 J/pulse of Er:YAG laser energy and CO2 delivered at 3 or 5 W and at a duty cycle of 25%, 50%, or 100%. Using a quantitative enzyme-linked immunosorbent assay, TGF-beta1 and bFGF were assayed from collected supernatants. RESULTS: Laser-treated ear lobule KFs demonstrated decreased TGF-beta1 production when compared with preauricular KFs. Statistical significance (P<.005) was seen in the 3-W CO2 25% duty cycle; a trend was seen in the 3-W CO2 50% duty cycle (P<.08). Preauricular KFs secreted increased bFGF when compared with lobule KFs. Significance was seen in the 3-W CO2 25% and 50% duty cycles (P<.05). Laser-treated preauricular KFs had increased bFGF secretion when compared with non-laser-treated preauricular KFs in the 3-W CO2 25%, 50%, and 100% duty cycles. CONCLUSIONS: Combined CO2 and Er:YAG laser treatment decreases the production of TGF-beta1 in preauricular and ear lobule KFs. This laser may have clinical promise in the treatment of keloids. Finally, the different growth factor profiles obtained suggest that KFs from the ear lobule and preauricular regions are different.

Midfacial osteomyelitis in a chronic cocaine abuser: a case report.

We describe the case of a 56-year-old man who was admitted for treatment of a progressive destruction of his hard palate, septum, nasal cartilage, and soft palate that had been caused by chronic cocaine inhalation. Biopsy of the bony septum revealed acute osteomyelitis and an extensive overgrowth of bacteria and Actinomyces-like organisms. There was no evidence of granuloma or neoplasm. The patient received intravenous ampicillin/sulbactam for 6 weeks, followed by lifetime oral amoxicillin. When there was no further evidence that destruction was progressing, the patient underwent nasal reconstruction with a cranial bone graft. The surgery was completed with no complications. To our knowledge, this is the first reported case of midfacial osteomyelitis associated with chronic cocaine abuse. The severity of this patient's complications, coupled with the success of his reconstructive surgery, makes this case particularly interesting. We believe that it is important for physicians to understand that septal perforation in a cocaine abuser should not be underestimated because it could result in a secondary bone infection. Nasoseptal destruction secondary to intranasal cocaine abuse is a result of cocaine's vasoconstrictive properties, and a decrease in the oxygen tension of intranasal tissue can facilitate the growth of anaerobic pathogens.

Laser skin resurfacing.

Laser skin resurfacing has become an important component of rejuvenation surgery. The two wavelengths in common use are: pulsed carbon dioxide and erbium:yttrium aluminum garnet. The principles and techniques of using these lasers for resurfacing and the practice of combining these wavelengths in sequence are described.

Microdermabrasion.

Microdermabrasion is a new skin resurfacing modality rapidly gaining popularity among the aesthetic surgery patient population. It produces a superficial wound to the skin, comparable with alpha hydroxy acid treatment clinically and histologically. Advantages include fast results, no anesthetic requirement, safety, and rapid recovery time. Equipment costs and training requirements are modest. Microdermabrasion will likely earn an important place in the skin resurfacing armamentarium.

Effect of tamoxifen on transforming growth factor beta1 production by keloid and fetal fibroblasts.

BACKGROUND: Evidence suggests that keloid scar formation may be mediated, in part, by deranged growth factor activity, including that of transforming growth factor (TGF) beta1. Tamoxifen citrate has shown promise in the treatment of keloids. OBJECTIVE: To evaluate the effect of tamoxifen on autocrine growth factor expression in keloid and fetal dermal fibroblasts, which exhibit scar-free healing. DESIGN: Serum-free cell lines of keloid and fetal dermal fibroblasts were established. Cell cultures were exposed to different concentrations of tamoxifen solution (8 and 12 or 16 micromol/L). Cell counts were performed and supernatants collected at 24, 48, and 96 hours. Cell-free supernatants were quantitatively assayed for TGF-beta1 expression. RESULTS: Keloid fibroblasts show increased per-cell TGF-beta1 production compared with fetal fibroblasts. Tamoxifen appeared to decrease per-cell TGF-beta1 production at each of the time points evaluated. CONCLUSIONS: Keloids likely arise due to locally insufficient or excessive concentrations of specific growth factors. The higher level of TGF-beta1 produced by keloid cells compared with fetal fibroblasts could be related to the aberrant wound healing seen with keloids. The addition of tamoxifen may lead to improved wound healing in keloids by decreasing the expression of TGF-beta1.

The effect of copper tripeptide and tretinoin on growth factor production in a serum-free fibroblast model.

OBJECTIVE: To evaluate the effect of copper tripeptide and tretinoin on normal and keloid-producing dermal fibroblasts in a serum-free in vitro model. The cellular response was described in terms of viability and secretion of basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1). METHODS: Primary cell lines were established from patient facial skin samples obtained during surgery and plated in serum-free media. At 0 hour, copper tripeptide (1 x 10 (-9) mol/L), tretinoin (1 x 10 (-5) mol/L), or appropriate control vehicle was added. Cell counts and viability were established at 24, 72, and 120 hours. Supernatants were collected at the same intervals and were assessed for bFGF and TGF-beta1 concentrations using the enzyme-linked immunosorbent assay technique. RESULTS: Cell lines showed viability between 86% and 96% (mean, 92%) throughout the experiment. Tretinoin-treated normal fibroblasts secreted more bFGF than did controls at 24 hours (P<.05). Tretinoin-treated keloid-producing fibroblasts secreted more TGF-beta1 than did controls at 120 hours (P<.05). Keloid-producing fibroblasts treated with copper tripeptide secreted less TGF-beta1 than did controls at 24 hours (P<.05); a similar trend was observed in normal fibroblasts. CONCLUSIONS: Normal fibroblasts treated with tretinoin produced more bFGF than did controls, and this might partially explain the clinically observed tightening effects of tretinoin. Normal and keloid-producing dermal fibroblasts treated with copper tripeptide secreted less TGF-beta1 than did controls, suggesting a possible clinical use for decreasing excessive scar formation.

In vivo model of histologic changes after treatment with the superpulsed CO(2) laser, erbium:YAG laser, and blended lasers: a 4- to 6-month prospective histologic and clinical study.

BACKGROUND AND OBJECTIVE: To compare the in vivo histologic effects of the pulsed carbon dioxide (CO(2)) and erbium:ytrium aluminum garnet (Er:YAG) lasers and to assess the effects of combining CO(2) and Er:YAG laser modalities during a single treatment session. We previously reported 10 patients treated with four laser regimens: CO(2) alone, CO(2)/Er:YAG, Er:YAG alone, Er:YAG/CO(2) with time points at 1 hour and 7 days between laser treatment and histologic analysis. This study found that the optimal treatment consisted of limited CO(2) laser passes followed by Er:YAG. This treatment produced less collagen injury, less thermal necrosis, and more robust epithelial and dermal fibrous tissue regeneration in the acute phase of healing. The present study examines the histologic changes resulting from the host healing response to laser treatment on long-term follow-up of 4-6 months. STUDY DESIGN/MATERIALS AND METHODS: The Stanford University Committee on Human Subjects in Medical Research approved this study. Nine patients with actinic damage and indications for rhytidectomy volunteered for this interventional study in which each patient served as both experimental and control. The right preauricular area was treated at five sites with the following: (1) CO(2), (2) CO(2) followed by Er:YAG, (3) Er:YAG, (4) blended CO(2)/Er:YAG (Derma-Ktrade mark), (5) phenol. Each was subjected to full-face or sub-unit treatment. Each patient was followed up initially daily then weekly for healing of the full-face laser and for differences in healing of the five treatment areas. Five patients were selected for histologic evaluation. At 4-6 months, these patients underwent rhytidectomy with immediate removal of laser-treated skin, which was evaluated histologically by the study dermatopathologist, who was blinded to the treatment at each site. RESULTS: CO(2) laser treatment produced the greatest thickness of neocollagen (0.27 mm; P < 0.05), the highest neocollagen density (P < 0.05), the greatest decrease in elastosis (27%), but took the longest time for healing and resolution of erythema and inflammation (up to 6 months). Er:YAG used alone produced the least collagen density, with the thinnest band of neocollagen (0.08 mm), but the most rapid resolution of erythema and inflammation (within 10 days). Combined CO(2)/Er:YAG treatments, including Derma-Ktrade mark and CO(2) followed by Er:YAG produced histologic changes that were intermediate, as well as recovery that was intermediate (resolution of erythema within 1 month); the development of neocollagen was greater in CO(2)-containing modalities than Er:YAG used alone by a statistically significant margin (P = 0.001). These histologic findings were corroborated by clinical correlation by examination of the five treatment spots in nine patients and in full-face treatments in 100 patients. CONCLUSION: Collagenesis is greatest with CO(2) and least with Er:YAG. Elastosis decreased to the greatest degree with CO(2), least with erbium, and to an intermediate extent with blended CO(2)/Er:YAG regimens (sequential and Derma-K). These changes from control are statistically significant with all regimens (P < 0.05). Blended CO(2)/Er:YAG treatments provide an optimal combination of the benefits of CO(2) but with lesser erythema and healing delay. Clinical and histologic findings change over time for different treatments. Thus, long-term histology is critical for predicting results of treatment.

Growth of tissue-engineered human nasoseptal cartilage in simulated microgravity.

OBJECTIVE: To evaluate the feasibility of in vitro fabrication of tissue-engineered cartilage from human nasoseptal chondrocytes for autologous reconstruction. DESIGN: Hyaline cartilage was reconstituted from chondrocyte-polyglycolic acid scaffolding constructs in a 3-dimensional mammalian cell culture cascade. This included monolayer cellular amplification, cell seeding in the spinner flask, and tissue growth in simulated microgravity. RESULTS: The quality of the fabricated cartilage analogue was found to depend on the initial cell density, duration of incubation, and bioreactor type. Dynamic seeding was nearly completed within the first 10 hours of inoculation regardless of the cell source (cryogenically preserved vs fresh chondrocytes) or presence of serum. A duration of incubation in excess of 4 weeks was required for complete matrix biosynthesis at low seeding densities in the spinner flasks. Seeding densities greater than 2.3x10(6) chondrocytes per scaffold were required for early hyaline cartilage formation as well as longer-time mature matrix regeneration. In addition, maintaining the structural integrity of the unreinforced scaffold, which is necessary for continued mature matrix regeneration, was achievable through postseeding tissue growth in simulated microgravity. CONCLUSION: Once combined with polyglycolic acid scaffolds in the bioreactor cascades that allow efficient seeding and quiescent tissue growth, human septal chondrocytes become a valuable source of reproducible ex vivo cartilage regeneration in the laboratory.

The effect of superpulsed carbon dioxide laser energy on keloid and normal dermal fibroblast secretion of growth factors: a serum-free study.

An in vitro model was used to determine the effect of superpulsed CO2 laser energy on normal dermal and keloid-producing fibroblast proliferation and release of growth factors. Growth factors assayed included basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1). bFGF is mitogenic, inhibits collagen production, and stabilizes cellular phenotype. TGF-beta1 stimulates growth and collagen secretion and is thought to be integral to keloid formation. Growth in a serum-free medium allowed measurement of these growth factors without confounding variables. Keloid and normal dermal fibroblasts cell lines were established from facial skin samples using standard explant techniques. Samples consisted of three separate keloid and three separate normal dermal fibroblast cell lines. Cells were used at passage 4 to seed 24-well trays at a concentration of 6 x 10(4) cells per milliliter in serum-free medium. At 48 hours, 18.8 percent of each cell well was exposed to a fluence of 2.4, 4.7, and 7.3 J/cm2 using the superpulsed CO2 laser. Cell viability and counts were established at four time points: 0 (time of superpulsed CO2 laser treatment), 24, 72, and 120 hours. Supernatants were collected and assessed for bFGF and TGF-beta1 using a sandwich enzyme immunoassay. All cell lines demonstrated logarithmic growth through 120 hours (conclusion of experiment), with a statistically significant shorter population doubling time for keloid fibroblasts (p < 0.05). Use of the superpulsed CO2 laser shortened population doubling times relative to that of controls; the differences were statistically significant in keloid dermal fibroblasts when fluences of 2.4 and 4.7 J/cm2 were used (p < 0.05 and 0.01, respectively). bFGF was present in greater levels in normal dermal fibroblasts than in keloid dermal fibroblasts. Application of superpulsed CO2 demonstrated a trend toward increased bFGF secretion in both fibroblast types; the increase was significant in the keloid group at 4.7J/cm2. A consistent trend in suppression of TGF-beta1 was seen in both groups exposed to superpulsed CO2, with the maximal effect occurring at 4.7 J/cm2. Serum-free culture sustains logarithmic cell growth and allows growth factor measurement without confounding variables from serum-containing media. Superpulsed CO2 enhances fibroblast replication and seems to stimulate bFGF secretion and to inhibit TGF-beta1 secretion. Given the function of these growth factors, the application of superpulsed CO2 may support normalized wound healing. These findings may explain the beneficial effects of laser resurfacing on a cellular level and support the use of superpulsed CO2 in the management of keloid scar tissue.

Review of closed dressings after laser resurfacing.

BACKGROUND: Laser skin resurfacing has become an accepted technique for the treatment of facial rhytides and associated solar skin damage. Achieving a successful result is directly related to proper postoperative wound care during the reepithelialization process. There are open and closed approaches to the treatment of the post-laser resurfacing patient with distinct advantages and disadvantages. OBJECTIVE: To review the most commonly used closed dressings after facial laser skin resurfacing and compare their advantages and disadvantages. To compare clinical findings with a group of patients treated exclusively with an open technique. METHODS: Review of composite foams, polymer film, polymer mesh, and hydrogel products and prospective observations of clinical outcomes of patients treated with each dressing category after facial laser skin resurfacing. We perform a retrospective chart review of a group of patients treated exclusively with an open technique comparing crust formation, comfort, and pruritus with the prospective group of patients treated with closed dressings. RESULTS: The closed dressings available today each have unique structural configurations and adhesive properties intended to maintain an occlusive wound environment. Patient acceptance of these dressings was favorable, with improved comfort compared to the open dressing group. Complications of bacterial infections and contact dermatitis were not observed when closed dressings were used with a protocol for dressing changes performed at 48 hours. Rates of reepithelialization did not vary according to dressing category. Crust formation and postoperative pruritus occurred less frequently when closed occlusive dressings were worn by patients. CONCLUSIONS: When used properly, these dressings improve patient comfort, simplify their postoperative wound care, and do not increase the risk of infection or contact dermatitis. Overall satisfaction was highest with perforated mesh and polymer dressings for full-face wounds.

Growth of keloid-producing fibroblasts in commercially available serum-free media.

The purpose of this study was to update our in vitro serum-free keloid fibroblast (KF) model by use of commercially available media. Prior evaluations of fibroblast characteristics in vitro, especially that of growth factor measurement, have been confounded by the presence of serum-containing media. KFs were obtained from patients undergoing facial keloid removal. The 4 commercially available serum-free media evaluated were AIM-V (Gibco, Grand Island, NY), Fibroblast Growth Medium (FGM; Clonetics, San Diego, CA), HB GRO (Irvine Scientific, Santa Ana, CA), and UltraCULTURE (BioWhittaker Inc, Walkersville, MD). The main outcome measures were sustained KF growth and viability as compared with serum-based models. The KFs in UltraCULTURE had a higher viability but did not grow as well as in FGM. The KFs in HB GRO and AIM-V demonstrated significantly decreased viability. Because of FGM's satisfactory proliferative support and viability comparable with serum-based medium, it is recommended for the in vitro propagation of keloid-producing fibroblasts.

Delayed radionecrosis of the larynx.

Radiation has been used to treat carcinoma of the larynx for more than 70 years. Radionecrosis is a well-known complication of this modality when treating head and neck neoplasms. It has been described in the temporal bone, midface, mandible, and larynx. Laryngeal radionecrosis is manifested clinically by dysphagia, odynophagia, respiratory obstruction, hoarseness, and recurrent aspiration. The vast majority of patients who develop laryngeal radionecrosis present with these symptoms within 1 year of treatment; however, delayed presentations have been reported up to 25 years after radiotherapy. We present, in a retrospective case analysis, an unusual case of laryngeal radionecrosis in a patient who presented more than 50 years after treatment with radiotherapy for carcinoma of the larynx. The cases of delayed laryngeal necrosis in the literature are presented. This represents the longest interval between treatment and presentation in the literature. The details of the presentation, clinical course, and diagnostic imaging are discussed. The pathogenesis, clinical features, and treatment options for this rare complication are reviewed. Early stage (Chandler I and II) laryngeal radionecrosis may be treated conservatively and often observed. Late stage (Chandler III and IV) cases are medical emergencies, occasionally resulting in significant morbidity or mortality. Aggressive diagnostic and treatment measures must be implemented in these cases to improve outcome. This case represents the longest interval between initial treatment and presentation of osteoradionecrosis in the literature. A structured diagnostic and therapeutic approach is essential in managing this difficult problem.