Reaction of Pertechnetate in Highly Alkaline Solution: Synthesis and Characterization of the Nitridotrioxotechnetate Ba[TcO3 N].

The preparation of novel technetium oxides, their characterization and the general investigation of technetium chemistry are of significant importance, since fundamental research has so far mainly focused on the group homologues. Whereas the structure chemistry of technetium in strongly oxidizing media is dominated by the Tc O 4 - ${{\left[{\rm { Tc}}{{\rm { O}}}_{{\rm { 4}}}\right]}^{-}}$ anion, our recent investigation yielded the new Tc O 3 N 2 - ${{\left[{\rm { Tc}}{{\rm { O}}}_{{\rm { 3}}}{\rm { N}}\right]}^{{\rm { 2}}-}}$ anion. Brown single crystals of Ba[TcO3 N] were obtained under hydrothermal conditions starting from Ba(OH)2 ⋅ 8H2 O and NH4 [TcO4 ] at 200 °C. Ba [ Tc O 3 N ] ${{\rm { Ba[Tc}}{{\rm { O}}}_{{\rm { 3}}}{\rm { N]}}}$ crystallizes in the monoclinic crystal system with the space group P21 /n (a=7.2159(4) Å, b=7.8536(5) Å, c=7.4931(4) Šand ß=104.279(2)°). The crystal structure of Ba [ Tc O 3 N ] ${{\rm { Ba[Tc}}{{\rm { O}}}_{{\rm { 3}}}{\rm { N]}}}$ consists of isolated Tc O 3 N 2 - ${{\left[{\rm { Tc}}{{\rm { O}}}_{{\rm { 3}}}{\rm { N}}\right]}^{{\rm { 2}}-}}$ tetrahedra, which are surrounded by Ba2+ cations. XANES measurements complement the oxidation state +VII for technetium and Raman spectroscopic experiments on Ba[TcO3 N] single crystals exhibit characteristic Tc-O and Tc-N vibrational modes.

Hydrogel matrix presence and composition influence drug responses of encapsulated glioblastoma spheroids.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with median patient survival of 12-15 months. To facilitate treatment development, bioengineered GBM models that adequately recapitulate the in vivo tumor microenvironment are needed. Matrix-encapsulated multicellular spheroids represent such model because they recapitulate solid tumor characteristics, such as dimensionality, cell-cell, and cell-matrix interactions. Yet, there is no consensus as to which matrix properties are key to improving the predictive capacity of spheroid-based drug screening platforms. We used a hydrogel-encapsulated GBM spheroid model, where matrix properties were independently altered to investigate their effect on GBM spheroid characteristics and drug responsiveness. We focused on hydrogel degradability, tuned via enzymatically degradable crosslinkers, and hydrogel adhesiveness, tuned via integrin ligands. We observed increased cellular infiltration of GBM spheroids and increased resistance to temozolomide in degradable, adhesive hydrogels compared to spheroids in non-degradable, non-adhesive hydrogels or to free-floating spheroids. Further, a higher infiltration index was noted for spheroids in adhesive compared to non-adhesive degradable hydrogels. For spheroids in degradable hydrogels, we determined that infiltrating cells were more susceptible to temozolomide compared to cells in the spheroid core. The temozolomide susceptibility of the infiltrating cells was independent of integrin adhesion. We could not attribute differential drug responses to differential cellular proliferation or to limited drug penetration into the hydrogel matrix. Our results suggest that cell-matrix interactions guide GBM spheroid drug responsiveness and that further elucidation of these interactions could enable the engineering of more predictive drug screening platforms. STATEMENT OF SIGNIFICANCE: Glioblastoma multiforme (GBM) multicellular spheroids hold promise for drug screening and development as they better mimic in vivo cellular responses to therapeutics compared to monolayer cultures. Traditional spheroid models lack an external extracellular matrix (ECM) and fail to mimic the mechanical, physical, and biochemical cues seen in the GBM microenvironment. While embedding spheroids in hydrogel matrices has been shown to better recapitulate the tumor microenvironment, there is still limited understanding as to the key matrix properties that govern spheroid responsiveness to drugs. Here we decoupled and independently altered matrix properties such as degradability, via an enzymatically degradable peptide crosslinker, and cell adhesion, via an adhesive ligand, giving further insight into what matrix properties contribute to GBM chemoresistance.

Sequence-dependent cross-resistance of combined radiotherapy plus BRAFV600E inhibition in melanoma.

INTRODUCTION: Treatment of patients with metastatic melanoma is hampered by drug-resistance and often requires combination with radiotherapy as last-resort option. However, also after radiotherapy, clinical relapses are common. METHODS & RESULTS: Our preclinical models indicated a higher rate of tumour relapse when melanoma cells were first treated with BRAFV600E inhibition (BRAFi) followed by radiotherapy as compared to the reverse sequence. Accordingly, retrospective follow-up data from 65 stage-IV melanoma patients with irradiated melanoma brain metastases confirmed a shortened duration of local response of mitogen-activated protein kinase (MAPK)-inhibitor-pretreated compared with MAPK-inhibitor-naïve intracranial metastases. On the molecular level, we identified JARID1B/KDM5B as a cellular marker for cross-resistance between BRAFi and radiotherapy. JARID1Bhigh cells appeared more frequently under upfront BRAFi as compared with upfront radiation. JARID1B favours cell survival by transcriptional regulation of genes controlling cell cycle, DNA repair and cell death. CONCLUSION: The level of cross-resistance between combined MAPK inhibition and radiotherapy is dependent on the treatment sequence. JARID1B may represent a novel therapy-overarching resistance marker.

TDM-controlled ring resonator arrays for fast, fixed-wavelength optical biosensing.

A novel control concept for serial ring resonator arrays based on a time-division multiplex (TDM) approach is presented. It allows fast sampling rates in terms of biological kinetics. The novelty consists of using both thermal tuning of the effective refractive index and thermo-optical multiplexing for the silicon-on-insulator (SOI) ring resonator arrays, without the need for a tunable laser source. Using a fixed wavelength, fast read-out rates of 100 Hz are demonstrated for each ring.

[Osteochondritis Dissecans of the Talus - A Critical Review]. / Osteochondrosis dissecans tali ­ eine kritische Übersicht.

The etiology remains unclear. Mechanical factors seem to play an important role. Most histologies report clefts between the cartilage and bone and necrotic areas. Several classifications have been published based on observations from imaging techniques or on intraoperative findings. Clinical symptoms are unspecific. Imaging techniques are of great importance: X-rays of the ankle joint enable a quick diagnostic overview. MRT is the imaging-technique of choice for diagnosing OCDT-lesions. Regarding treatment, a tremendous number of retrospective publications exist. Only a few are classified as level I or II papers. Patients with open physes and low-grade lesions have good results with conservative therapy. Adults do not profit from a longer conservative procedure. Where surgery is necessary, the procedure depends on the stage of the lesion and on the state of the cartilage. With intact cartilage, retrograde procedures or transchondral drilling are to be favoured. Where the cartilage is damaged, several techniques can be used: while techniques such as drilling and microfracturing, or matrix-associated microfracturing produces repair cartilage, other techniques reconstruct the defect with osteochondral grafts or cell-based procedures such as chondrocyte transplantation. Regarding the outcome, it is difficult to make a precise, scientifically-based recommendation which has been confirmed by more than one prospective study. Only limited recommendations are possible: In juveniles with intact cartilage, initially conservative treatment is indicated. If there is no improvement, conservative invasive techniques such as drilling may help. In adults conservative therapy should be limited to a few weeks. Regarding the surgical treatment options, there is a tendency towards better results with procedures which reconstruct the bone and the cartilage and there is also a trend towards better long-term results when co-morbidities are treated. Severe grades of osteoarthrosis are rare.

Gait analysis in tumor patients after distal femoral resection and implantation of a megaprosthesis.

We analysed nine patients who had had a megaprosthesis implanted into the distal femur and knee joint for treatment of sarcomas. Data obtained from the leg operated on were compared with those from the contralateral side and healthy volunteers. Gait data, kinematics, ground reaction forces and the EMG from five muscles around the knee joint were analysed by means of a video-based analysis system recording data from reflection markers ; a Kistler-plate recorded the GRF and a ten channel surface EMG the muscle activity. Muscle around the knee showed a cocontraction between the extensor and flexor muscles in the thigh and the calf in the operated leg as well as contralaterally. Gait characteristics exhibited a reduced speed, -cadence, and a shorter step. This correlated with a reduced flexion in the hip and knee joint. The GRF exhibited significant changes in the data representing the reduced gait dynamic.

[Oncological healthcare research in urology - perspectives]. / Onkologische Versorgungsforschung in der Urologie - ein Ausblick.

Healthcare research has become established as an interdisciplinary self-contained field of research. It has now arrived in oncology and also provides important knowledge on healthcare events and for analysis of healthcare quality in urology. Because healthcare research covers a broad range both methodologically and in content, it is not always easy to maintain an overview of the many concurrently occurring developments. This article describes three current developments, which will probably be come of great importance for oncological healthcare research in the coming years and will also play a role in urology.

[Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the Clinical Tissue Regeneration Study Group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic Surgery]. / Nachbehandlung bei der autologen Chondrozytentransplantation: Eine Bestandsaufnahme und Empfehlung der AG Klinische Geweberegeneration der DGU/DGOOC.

BACKGROUND: Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. MATERIAL AND METHODS: Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. RESULTS: There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. CONCLUSIONS: This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).

Design rules for p-i-n diode carriers sweeping in nano-rib waveguides on SOI.

In this paper we present a detailed analysis of the carrier lifetime for a p-i-n junction on silicon nano-rib waveguides. Several factors determining efficiency of carriers removal from the waveguiding region will be discussed. We compare different structure geometries and spacings between p and n doped regions to show the way to optimize electrons and holes sweeping for CW nonlinear optical devices.

[Methods of health economic evaluation for health services research]. / Methoden der gesundheitsökonomischen Evaluation in der Versorgungsforschung.

On August 30, 2010, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal [Gesundheitswesen 2010; 72: 739-748]. The present paper focuses on methodological issues of economic evaluation of health care technologies. It complements the Memorandum III "Methods for Health Services Research", part 2. First, general methodological principles of the economic evaluations of health care technologies are outlined. In order to adequately reflect costs and outcomes of health care interventions in the routine health care, data from different sources are required (e. g., comparative efficacy or effectiveness studies, registers, administrative data, etc.). Therefore, various data sources, which might be used for economic evaluations, are presented, and their strengths and limitations are stated. Finally, the need for methodological advancement with regard to data collection and analysis and issues pertaining to communication and dissemination of results of health economic evaluations are discussed.

Perfusion culture system: Synovial fibroblasts modulate articular chondrocyte matrix synthesis in vitro.

OBJECTIVE: To investigate the interactions of chondrocyte metabolism by synovial cells and synovial supernatants in a new perfusion co-culture system. METHODS: Chondrocytes and synovial fibroblasts were obtained from knee joints of slaughtered adult cattle. For experimental studies chondrocytes and synovial fibroblasts were placed together into a perfusion chamber (co-culture) or were placed into two different perfusion culture containers, which were connected by a silicone tube (culturing of chondrocytes with synovial supernatants). A control setup was used without synovial cells. Chondrocyte proliferation was shown by measurement of DNA content. The proteoglycan synthesis was quantified using (35)SO(4)(2-)-labelling and the dimethylmethylene blue assay. (3)H-proline incorporation was used to estimate the protein biosynthesis. Type II collagen synthesis was measured by ELISA, furthermore extracellular matrix deposition was monitored immunohistochemically (collagen types I/II). Regarding to the role of reactive oxygen species LDH release before and after stimulation with hydrogen peroxide was measured. RESULTS: The proliferation of chondrocytes shows an increase in monoculture as well as in co-culture or in culture with synovial supernatants more than fivefold within 12 days. (3)H-proline incorporation as a marker for chondrocytes biosynthetic activity decreases in co-culture system and in culture with synovial supernatants. A similar effect is seen measuring total proteoglycan content as well as the (35)SO(4)(2-) incorporation in chondrocytes. Co-culturing and culturing with synovial supernatants lead to a significant decrease of proteoglycan release and content. Quantification of collagen type II by ELISA shows significant lower amounts of native collagen type II in the extracellular matrix of co-cultured chondrocytes as well as in culture with synovial supernatants. The membrane damage of chondrocytes by hydrogen peroxide is reduced when chondrocytes are co-cultured with synovial fibroblasts. CONCLUSION: The co-culture perfusion system is a new tool to investigate interactions of different cell types with less artificial interferences. Our results suggest that synovial supernatants and synovial fibroblasts modulate the biosynthetic activity and the matrix deposition of chondrocytes as well as the susceptibility to radical attack of reactive oxygen species.

The use of CT derived solid modelling of the pelvis in planning cancer resections.

CLINICAL PROBLEM: Resection of malignant tumors of the pelvis is demanding. To avoid disabling hemipelvectomies, years ago internal hemipelvectomy combined with partial pelvic replacements had become a surgical procedure. To achieve adequate reconstructions custom-made replacements were recommended. In early stages of the surgical procedure using megaprostheses, individual pelvic models were manufactured. AIM OF THE STUDY: Since little is known about the accuracy of such models we analysed the charts of 24 patients (25 models) for whom an individual model of the osseous pelvis had been manufactured. RESULTS: Two patients refused surgery. In 23 patients partial resection of the bony pelvis was performed followed by a partial pelvic replacement (13x), hip transposition procedure (5x), ilio-sacral resection (4x), or revision surgery. In all patients who received a partial pelvic replacement, the fit of the replacement was optimal. No major unplanned resection was necessary. The same was observed in patients who received a hip transposition procedure or an ilio-sacral resection. Oncologically, in most of the patients we achieved wide resection margins (14x). In 5 patients the margins were marginal (4x) or intralesional (1x). In two cases the aim was a palliative resection because of a metastatic disease (1x) or benign entity (1x). CONCLUSION: Pelvic models are helpful tools to planning the manufacture of partial pelvic replacements and ensuring optimal osseous resection of the involved bone. Further attempts have to be made to evaluate the aim of navigational techniques regarding the accuracy of the osseous and soft-tissue resection.

Limb-salvage reconstruction with MUTARS hemipelvic endoprosthesis: a prospective multicenter study.

BACKGROUND: Limb-sparing surgery with hemipelvic megaprosthetic replacement is often limited by the high rate of associated complications. The aim of this evaluation was to assess clinical and oncological findings with respect to type, treatment and outcome of post-operative complications. METHODS: First results of 40 patients treated with individual MUTARS hemipelvic endoprostheses were evaluated in a prospective multicenter study. RESULTS: The mean follow-up period of the 27 male and 13 female patients was 24 months (range 1-61). The diagnosis was, in 29 cases, a primary bone or soft tissue sarcoma, in 11 patients, a metastasis. Clinical evaluation showed a mean Enneking score of 50% (range 10-70%). The oncological outcome revealed 25 patients (62.5%) alive with no evidence of disease. Seventeen of them had a primary tumour, eight a metastatic malignancy. Seven patients (17.5%) had died of their disease and eight (20%) were still alive but had developed a metastases and/or had had a recurrence of the primary tumour. The one- and two-year overall survival rate of the patients was 89% (+/- 0.10) and 81% (+/- 0.19), respectively. Post-operative complications occurred in 75% of the patients, predominantly wound-related disorders. The rate of implant revision was 22.5% with three septic and six aseptic cases of implant loosening. The estimated three-year-survival rate of the implant was 61.4% [CI95%: 0.36;0.87]. CONCLUSIONS: Periacetabular endoprosthetic replacement showed an acceptable functional and oncological outcome but had a high complication rate owing, predominantly, to infection. The indication for hemipelvic prosthesis in patients with a metastatic disease must be considered seriously.

Unilateral hypopharyngitis, cellulitis, and a multinodular goiter: a triad of findings suggestive of acute suppurative thyroiditis.

Acute suppurative thyroiditis is an uncommon disorder, which has been associated with pre-existing thyroid disease, especially a multinodular goiter. We describe a case of a woman who presented clinically with an acute inflammatory condition of the neck. On CT examination, she had a triad of a multinodular goiter, a unilateral hypopharyngitis, and a surrounding cellulitis. We suggest that the constellation of these imaging findings should alert the radiologist to the diagnosis of acute thyroiditis.

[Pigmented villo-nodular synovitis and teno-synovial giant-cell tumors]]. / Pigmentierte villonoduläre Synovialitis und tenosynovialer Riesenzelltumor.

Pigmented villo-nodular synovitis (PVS) and teno-synovial giant-cell tumors (TSGCT) are rare diseases of joints, tendon-sheaths and other synovial structures. Regarding PVS the knee joint is the most often involved joint and TSGCT are mostly located in the tendon-sheaths of fingers. Both diseases mostly occur in adults but are also observed in children. Symptoms of both diseases are non-specific. Optimal diagnosis includes an X-ray of the involved structure and a MRI. For PVS optimal therapy is a complete synovectomy, whereas, in TSGCT tumors resection of the tumor itself within marginal margins is sufficient. Because of the high rate of recurrence (up to 50 %) in cases suffering from PVS adjuvant therapeutical strategies such as postoperative radiation or radio-synoviorthesis are recommended. Although there are no significant analyses confirming the effect of an adjuvant therapy on the rate of recurrence scientifically at least there is a tendency that these strategies may reduce the rate of recurrence. Malignant dedifferentiation is rarely seen. The prognosis of the mostly benign disease depends on the extent of the disease, the involved structure, additional bony involvement and still existing degenerative changes. In TSGCT no severe sequelae are known. In contrast, PVS in the hip regularly is followed by a secondary osteoarthrosis, in other joints degenerative changes are depending on the still existing changes at the date of diagnosis. Data on the long-term prognosis are rare and only analysed retrospectively.

Cementless fixation of megaprostheses using a conical fluted stem in the treatment of bone tumours.

We reviewed 25 patients in whom a MUTARS megaprosthesis with a conical fluted stem had been implanted. There were three types of stem: a standard stem was used in 17 cases (three in the proximal femur, nine in the distal femur and five proximal tibia), a custom-made proximal femoral stem in four cases and a custom-made distal femoral stem in four cases. The mean age of the patients was 40.1 years (17 to 70) and the mean follow-up was for 2.5 years (0.9 to 7.4). At follow-up two patients had died from their disease: one was alive with disease and 22 were disease-free. One of 23 prostheses had been removed for infection and another revised to a cemented stem. The mean Musculoskeletal Tumor Society score was 24.9 (12 to 30) and the mean Karnofsky index was 82% (60% to 100%). There was no radiological evidence of loosening or subsidence. Stem stress shielding was seen in 11 patients and was marked in five of these. There were five complications, rupture of the extensor mechanism of the knee after extra-articular resection in two patients, deep venous thrombosis in one, septic loosening in one, and dislocation of the hip in one. The survival rate after seven years was 87% (95% confidence interval (CI) 83 to 91) for the patients and 95% (95% CI 91 to 99) for the megaprosthesis. A longer follow-up is needed to confirm these encouraging results.

[Osteochondritis dissecans of the knee joint]. / Osteochondrosis dissecans des Kniegelenkes.

Osteochondritis dissecans is a disorder with a prevalence of 0.01 to 0.06 %. Men between 16 and 36 years of age are most commonly affected by it. In the western hemisphere, the knee is affected by this progressive disorder in 75 % of the cases, specifically the medial femoral condyle (70 - 80 %). The etiology is uncertain, although genetic defects, micro-trauma, ossification disorders and ischemia have been implicated. Pathogenetically, Osteochondritis dissecans is classified in four stages, whereas in stage one, there is merely a subchondrial edema. Without therapy this could lead to stage 4, with a free osteochondral joint fragment. Treatment is analogous with the stage of the disorder. Whereas conservative treatment may yield full recovery during stage 1, starting in stage 2, invasive treatment should be considered. When the cartilage surface remains intact retrograde procedures are indicated. If the cartilage is injured anterograde therapies, like the chondral or osteochondral transplantation, should be used.

Dedifferentiated chondrosarcoma--a fatal disease.

BACKGROUND: We report on 13 patients with dedifferentiated chondrosarcomas. The mean age of the patients at diagnosis was 59.8 years. Nine patients were classified as stage IIB and four as stage III. METHODS: In 11/13 cases surgery was performed. Mostly, limb salvage with tumour resection and implantation of a megaprosthesis was done; three patients needed amputation or disarticulation. In one out of three patients with a pelvic tumour resection was followed by implantation of a pelvic replacement; the other two patients received tumour resection with autologous stabilisation of the pelvis. Surgical margins were wide in six patients, marginal in two and intralesional in three. Adjuvant chemotherapy was given to five patients. RESULTS: Recurrence was detected in 5/11 of the patients operated on: in two with wide, in one with marginal, and in two with intralesional resection. No recurrence was seen in 5/11 patients: in four after wide and in one after marginal resection. In one patient the stage was unknown. At follow-up 11 patients were dead of disease (DOD), one dead of unknown reason (DOU) and one alive with disease (AWD). The mean survival time was 9.7 months. Metastasis to different anatomical sites was evident after a period of 10 months. CONCLUSIONS: Our results resemble those reported in the literature. DDCS is rare and is the primary malignant bone tumour with the worst prognosis. Surgery is the most important procedure, although it is unclear whether a radical resection improves the long-term results. Information regarding neoadjuvant and/or adjuvant therapy with chemotherapy is very limited.