[Rheumatic pain and chronic pain in children, adolescents and young adults]. / Rheumaschmerz und chronischer Schmerz bei Kindern, Jugendlichen und jungen Erwachsenen.

BACKGROUND: Rheumatic diseases, such as juvenile idiopathic arthritis (JIA), are typically associated with acute pain mainly caused by inflammation. Chronic pain is described as pain lasting at least 3 months. In JIA patients chronic pain may occur despite successful treatment. Chronic pain and pain disorders frequently occur during the course of the disease despite successful control of inflammation. OBJECTIVE: Possible interrelations between JIA and pain disorders are presented. METHOD: Besides a review of the available literature, a retrospective cohort study was conducted, including 906 patients with a chronic pain disorder with somatic and psychological factors (CPD) and/or a complex regional pain syndrome type I (CRPS I). The frequency of pre-existing rheumatic illnesses was analyzed. RESULTS: The JIA is a risk factor for the development of a CPD. Especially polyarticular, extended oligoarticular, enthesitis-associated JIA and psoriatic arthropathy were found to be significantly associated with an increased risk for developing CPD. In contrast, an increased risk for development of CRPS I was not observed. CONCLUSION: Our study demonstrates JIA to be a risk factor for the development of chronic pain not only as a result from malpositioning or arthrosis but also as a chronic pain disorder (CPD). Further studies are necessary to clarify the relevance of disease activity and duration and also of psychological factors for the pathogenesis.

[Cushing's syndrome with subsequent tertiary adrenocortical insufficiency after simultaneous multiple intra-articular local glucocorticoid treatment : Keep an eye on hormone deficiency conditions requiring treatment after multiple administrations of local steroids]. / Cushing-Syndrom mit konsekutiver tertiärer Nebennierenrindeninsuffizienz nach simultaner multipler intraartikulärer Lokaltherapie mit Glukokortikoiden : Bei Mehrfachgabe von lokalen Steroiden behandlungsbedürftige Hormonmangelzustände im Blick behalten.

After simultaneous multiple local treatment with glucocorticoids at 46 sites a 4­year-old female patient with newly diagnosed polyarticular juvenile idiopathic arthritis (JIA) initially developed Cushing's syndrome followed by a gradual worsening of her condition and finally an acute high fever urinary tract infection. Iatrogenic adrenocortical insufficiency after multiple intra-articular glucocorticoid administration was diagnosed. The possibility of severe systemic glucocorticoid side effects after extensive local treatment should be included in the regular management of JIA patients.

[Accreditation and certification of skull base centres in Germany by the German Society for Skull Base Surgery (Gesellschaft für Schädelbasischirurgie, GSB). German version]. / Akkreditieren und Zertifizieren von Schädelbasiszentren in Deutschland durch die Gesellschaft für Schädelbasischirurgie (GSB).

The German Society for Skull Base Surgery (Gesellschaft für Schädelbasischirurgie, GSB) has developed a protocol for the certification of GSB skull base centres. The development of such a protocol has led to numerous open and sometimes controversial discussions among the GSB members. The various critical discussion points will be reviewed and the ensuing results, which will then be included in the accreditation protocol, presented. The current GSB accreditation protocol will be presented and explained in an international comparison.

Accreditation and certification of Skull Base Centres in Germany by the Society for Skull Base Surgery (Gesellschaft für Schädelbasischirurgie, GSB).

The German Society for Skull Base Surgery (Gesellschaft für Schädelbasischirurgie, GSB) has developed a protocol for the certification of GSB skull base centres. The development of such a protocol has led to numerous open and sometimes controversial discussions among the GSB members. The various critical discussion points will be reviewed and the ensuing results, which will then be included in the accreditation protocol, presented. The current GSB accreditation protocol will be presented and explained in an international comparison.

Comprehensive characterization of RB1 mutant and MYCN amplified retinoblastoma cell lines.

In retinoblastoma research tumor-derived cell lines remain an important model to investigate tumorigenesis and new therapy options, due to limited tumor material and lack of adequate animal models. A panel of 10 retinoblastoma cell lines was characterized with respect to mutation, methylation and expression of RB1 and MYCN. These established retinoblastoma cell lines represent the most frequent types of RB1 inactivation and together with the MYCN amplification status, three classes can be distinguished: RB1mut/MYCNnonA, RB1mut/MYCNA and RB1wt/MYCNA. MYCN amplification was identified in five cell lines, whereby two of them, RB522 and RB3823, harbor no aberration in RB1. Targeted sequencing of 160 genes often mutated in cancer identified only few variants in tumor-associated genes other than in RB1. None of these variants was recurrent. mRNA expression analyses of retinal markers, cell cycle regulators and members of the TP53 signaling pathway revealed a high variability between cell lines but no class-specific differences. The here presented thorough validation of retinoblastoma cell lines, including microsatellite analysis for cell line authentication, provides the basis for further in vitro studies on retinoblastoma.

Microalgae-bacteria symbiosis in microalgal growth and biofuel production: a review.

Photosynthetic microalgae can capture solar energy and convert it to bioenergy and biochemical products. In nature or industrial processes, microalgae live together with bacterial communities and may maintain symbiotic relationships. In general interactions, microalgae exude dissolved organic carbon that becomes available to bacteria. In return, the bacteria remineralize sulphur, nitrogen and phosphorous to support the further growth of microalgae. In specific interactions, heterotrophic bacteria supply B vitamins as organic cofactors or produce siderophores to bind iron, which could be utilized by microalgae, while the algae supply fixed carbon to the bacteria in return. In this review, we focus on mutualistic relationship between microalgae and bacteria, summarizing recent studies on the mechanisms involved in microalgae-bacteria symbiosis. Symbiotic bacteria on promoting microalgal growth are described and the relevance of microalgae-bacteria interactions for biofuel production processes is discussed. Symbiotic microalgae-bacteria consortia could be utilized to improve microalgal biomass production and to enrich the biomass with valuable chemical and energy compounds. The suitable control of such biological interactions between microalgae and bacteria will help to improve the microalgae-based biomass and biofuel production in the future.

Preventing involuntary admissions: special needs for distinct patient groups.

BACKGROUND: Coercive measures in psychiatry are a controversial topic and raise ethical, legal and clinical issues. Involuntary admission of patients is a long-lasting problem and indicates a problematic pathway to care situations within the community, largely because personal freedom is fundamentally covered by the UN declaration of human rights and the German constitution. METHODS: In this study, a survey on a large and comprehensive population of psychiatric in-patients in the eastern part of North Rhine-Westphalia, Germany, was carried out for the years 2004-2009, including 230.678 treatment cases. The data were collected from the dataset transferred to health insurance automatically, which, since 2004 is available in an electronic form. In addition, a wide variety of information on treatment, sociodemographic and illness-related factors were collected and analysed. Data were collected retrospectively and analyses were calculated using statistical software (IBM SPSS Statistics 19.0®). Quantitative data are presented as mean and standard deviation. Due to the unequal group sizes, group differences were calculated by means of Chi-square tests or independent sample t tests. A Bonferroni correction was applied to control for multiple comparisons. RESULTS: We found an over-representation of involuntary admissions in young men (<21 years) suffering from schizophrenia and in female patients aged over 60 with a diagnosis of dementia. Most of our results are concordant with the previous literature. Also admission in hours out of regular out-patient services elevated the risk. CONCLUSION: The main conclusion from these findings is a need for a fortification of ambulatory treatment offers, e.g. sociopsychiatric services or ward round at home for early diagnosis and intervention. Further prospective studyies are needed.

Photoinduced hole transfer in QD-phthalocyanine hybrids.

A series of CdSe quantum dot (QD)-phthalocyanine (Pc) hybrids were synthesized and their photophysics was studied using steady state and time-resolved spectroscopic methods. Emission of QDs was progressively quenched upon increasing the concentration of Pc in the hybrids. A detailed transient absorption study of the hybrids revealed that the mechanism of quenching is charge separation, resulting in the formation of hybrids with negatively charged QDs and the Pc cation. Direct photo-excitation of Pc did not show any detectable interaction between the excited state of Pc and the QD to which it is attached. An explanation is proposed, based on the suggestion that the energy of the lowest unoccupied molecular orbital (LUMO) of Pc is lower than the lower edge of the QD conduction band, while the energy of the highest occupied molecular orbital (HOMO) of Pc is sufficiently higher than the high energy edge of the QD valence band (VB), thus permitting hole transfer from the QD VB to the Pc HOMO after photo-excitation of QDs.

[Computer-aided reconstruction of the facial skeleton : Planning and implementation in clinical routine]. / Computerassistierte Gesichtsschädelrekonstruktion : Planung und Umsetzung in der klinischen Routine.

In computer-aided reconstruction of the facial skeleton, a workflow has been established involving the following steps: > diagnosis → planning and simulation → surgical procedure → validation and quality control <. In addition to clinical findings, the focus of diagnosis is on three-dimensional (3D) imaging, particularly computed tomography. Planning and simulation involves creation of a virtual model of the desired surgical outcome using special planning software. The accuracy of implant fit can be virtually verified before surgery. 3D models and virtual reconstructions can be used for manufacturing patient-specific implants. During the surgical procedure, planning must be transferred to the surgical site as accurately as possible. A number of techniques are available for this purpose, e. g., closed reduction, open reduction with the placement of anatomically preformed or patient-specific implants in combination with surgical guides, and the additional use of navigation. Validation and quality control require postprocedural 3D imaging. After reconstructions of the midface, 3D imaging should be performed even before surgery is completed. Malpositions can thus be directly corrected and unnecessary open reconstructions avoided. Mobile 3D c-arms are particularly useful for intraoperative 3D imaging. Whereas intraoperative imaging makes postoperative imaging after midface reconstruction unnecessary in many cases, postoperative 3D imaging in addition to intraoperative imaging may still be recommended after complex reconstructions of the facial skeleton.

Lithography-free oxide patterns as templates for self-catalyzed growth of highly uniform GaAs nanowires on Si(111).

We report self-catalyzed growth of GaAs nanowires (NWs) on Si/SiOx patterns fabricated by a lithography-free method. The patterns are defined using droplet epitaxy of GaAs nanocrystals, spontaneous oxidation, and thermal annealing. We investigate the influence of the size and density of the nucleation sites on the NW growth process and show that this approach enables the fabrication of highly uniform GaAs NWs with controllable density. The pattern fabrication and NW growth process are studied and discussed in relation to the surface morphology and chemical properties of the Si/SiOx patterns. Furthermore, the optical quality of the NWs is investigated by photoluminescence experiments performed for GaAs­AlGaAs core­shell NWs.

Adjuvant therapeutic decisions in elderly breast cancer patients: the role of chemotherapy in a retrospective analysis.

PURPOSE: Decisions on the type of adjuvant treatment in older breast cancer patients are challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty on the basis of studies usually excluding patients over 69 years. To aid this decision, we analyzed a database of 6000 unselected patients and of those evaluated elderly primary breast cancer patients with hormone receptor-negative tumors from 1963 until 2003 in respect of survival data depending on adjuvant treatment. METHODS: A total of 131 elderly (i.e., >65 years) patients were observed retrospectively for a median of 72 months. Patients received breast-conserving therapy or mastectomy and adjuvant radiotherapy, chemotherapy, and endocrine therapy. Data were collected from a hospital-intern database. RESULTS: Median age at diagnosis was 72 years. Mostly, tumors were small (81 % T1, 17 % T2) but of unfavorable grading (40 % G2, 35 % G3). Lymph nodes were positive in 42 %. Mastectomy was performed in 65 %. While 42 % of patients received radiotherapy, only 10 % were treated with chemotherapy. Patients with G2 and G3 tumors (p = 0.027), younger women (p = 0.012), and patients with positive lymph node status (p < 0.0001) more likely received chemotherapy. Recurrence-free survival was longer in patients without chemotherapy (37 vs. 29 months, p = 0.234). Overall survival was non-significantly shorter in patients who received chemotherapy (59 vs. 81 months, p = 0.131). CONCLUSIONS: In this analysis, adjuvant chemotherapy was not associated with improved survival, presumably caused by an a priori poor prognosis of these patients. For an aging society more data are urgently needed to help selecting and personalizing adjuvant treatment within subgroups of breast cancer in older women.

Size-dependent properties of single InAs quantum dots grown in nanoimprint lithography patterned GaAs pits.

We report on the structural and optical properties of single InAs quantum dots (QDs) formed in etched GaAs pits with different dimensions. The site-controlled QDs were fabricated by molecular beam epitaxy on GaAs(001) surfaces patterned by nanoimprint lithography. We show that the properties of the QDs can be modified by varying the dimensions of the etched GaAs pits. Increasing the pit size resulted in larger QDs and thus in longer photoluminescence wavelengths. However, the fine structure splitting remained unaffected. A photoluminescence linewidth of 41 µeV and average fine structure splitting of 15.7 µeV were obtained for exciton recombination in the single site-controlled QDs.

Targeted Therapy for Neuroblastoma: ALK Inhibitors.

Treatment for neuroblastoma, the most common extracranial childhood tumor, spans a broad range of aggressiveness that mirrors the risk profiles of disease subtypes, with high-risk neuroblastoma still presenting a clinical challenge. Currently, most patients with relapsed neuro-blastoma die of disease and present a major challenge for treatment. New therapeutic options are urgently needed to improve patient survival. Activating mutations in the gene encoding the anaplastic lymphoma kinase (ALK) remain the most frequent druggable mutations identified in neuroblastomas to date. Preclinical data support an oncogene addiction of neuroblastoma cells to mutated ALK and demonstrate that ALK inhibitory therapy strongly combats tumor models. Most recently, pediatric phase I testing has been completed for the first approved ALK inhibitor, Crizotinib, showing very encouraging antitumoral results in neuroblastoma patients. Subsequently, an international phase I study with the second generation ALK inhibitor, LDK-378, will be launched that makes ALK inhibitory therapy also available to pediatric patients in Germany.

[Human papillomavirus in squamous cell cancer of the head and neck. A study at the Ulm Military Hospital, Germany]. / Humane Papillomavirusinfektionen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs. Eine Untersuchung am Krankengut des Bundeswehrkrankenhauses Ulm.

There is increasing evidence worldwide that human papillomavirus is a major risk factor for head and neck cancer. Only few studies on this association have been performed in Germany to date. For the purposes of the present study, tumor specimens from 223 patients with squamous cell cancer of the oral cavity, oropharynx, hypopharynx and larynx were analyzed for HPV DNA and p16INK4a expression. The prevalence of HPV genotype 16 (HPV16) DNA in the study population was 17.5%. Further high-risk HPV types were not detected. All HPV16-positive tumors showed intense p16INK4a expression. HPV16 prevalence was highest in tonsillar carcinoma (37.5%) and lowest in laryngeal cancer (2.8%). We observed a significantly higher incidence of cervical lymph node metastases in patients with HPV16-positive tonsillar carcinoma in comparison to HPV-negative tumors (p < 0.016). Tobacco and/or alcohol consumption was significantly lower in patients with HPV-positive tumors (p < 0.0001).

Determinants of Microscale pH in In Situ-Grown Dental Biofilms.

Dental biofilm pH is the most important determinant of virulence for the development of caries lesions. Confocal microscopy-based pH ratiometry allows monitoring biofilm pH with high spatial resolution. Experiments performed on simplified biofilm models under static conditions identified steep pH gradients as well as localized acidogenic foci that promote enamel demineralization. The present work used pH ratiometry to perform a comprehensive analysis of the effect of whole saliva flow on the microscale pH in complex, in situ-grown 48-h and 96-h biofilms (n = 54) from 9 healthy participants. pH was monitored in 12 areas at the biofilm bottom and top, and saliva flow with film thicknesses corresponding to those in the oral cavity was provided by an additively manufactured microfluidic flow cell. Biofilm pH was correlated to the bacterial composition, as determined by 16S rRNA gene sequencing. Biofilm acidogenicity varied considerably between participants and individual biofilms but also between different areas inside one biofilm, with pH gradients of up to 2 units. pH drops were more pronounced in 96-h than in 48-h biofilms (P = 0.0121) and virtually unaffected by unstimulated saliva flow (0.8 mm/min). Stimulated flow (8 mm/min) raised average biofilm pH to near-neutral values but it did not equilibrate vertical and horizontal pH gradients in the biofilms. pH was significantly lower at the biofilm base than at the top (P < 0.0001) and lower downstream than upstream (P = 0.0046), due to an accumulation of acids along the flow path. pH drops were positively correlated with biofilm thickness and negatively with the thickness of the saliva film covering the biofilm. Bacterial community composition was significantly different between biofilms with strong and weak pH responses but not their species richness. The present experimental study demonstrates that stimulated saliva flow, saliva film thickness, biofilm age, biofilm thickness, and bacterial composition are important modulators of microscale pH in dental biofilms.

Exon-level expression analyses identify MYCN and NTRK1 as major determinants of alternative exon usage and robustly predict primary neuroblastoma outcome.

BACKGROUND: Using mRNA expression-derived signatures as predictors of individual patient outcome has been a goal ever since the introduction of microarrays. Here, we addressed whether analyses of tumour mRNA at the exon level can improve on the predictive power and classification accuracy of gene-based expression profiles using neuroblastoma as a model. METHODS: In a patient cohort comprising 113 primary neuroblastoma specimens expression profiling using exon-level analyses was performed to define predictive signatures using various machine-learning techniques. Alternative transcript use was calculated from relative exon expression. Validation of alternative transcripts was achieved using qPCR- and cell-based approaches. RESULTS: Both predictors derived from the gene or the exon levels resulted in prediction accuracies >80% for both event-free and overall survival and proved as independent prognostic markers in multivariate analyses. Alternative transcript use was most prominently linked to the amplification status of the MYCN oncogene, expression of the TrkA/NTRK1 neurotrophin receptor and survival. CONCLUSION: As exon level-based prediction yields comparable, but not significantly better, prediction accuracy than gene expression-based predictors, gene-based assays seem to be sufficiently precise for predicting outcome of neuroblastoma patients. However, exon-level analyses provide added knowledge by identifying alternative transcript use, which should deepen the understanding of neuroblastoma biology.

The influence of post-growth annealing on the optical properties of InAs quantum dot chains grown on pre-patterned GaAs(100).

We report on the effect of post-growth thermal annealing of [011]- ,[011(-)]-, and [010]-oriented quantum dot chains grown by molecular beam epitaxy on GaAs(100) substrates patterned by UV-nanoimprint lithography. We show that the quantum dot chains experience a blueshift of the photoluminescence energy, spectral narrowing, and a reduction of the intersubband energy separation during annealing. The photoluminescence blueshift is more rapid for the quantum dot chains than for self-assembled quantum dots that were used as a reference. Furthermore, we studied polarization resolved photoluminescence and observed that annealing reduces the intrinsic optical anisotropy of the quantum dot chains and the self-assembled quantum dots.

Large array of single, site-controlled InAs quantum dots fabricated by UV-nanoimprint lithography and molecular beam epitaxy.

We present the growth of single, site-controlled InAs quantum dots on GaAs templates using UV-nanoimprint lithography and molecular beam epitaxy. A large quantum dot array with a period of 1.5 µm was achieved. Single quantum dots were studied by steady-state and time-resolved micro-photoluminescence experiments. We obtained single exciton emission with a linewidth of 45 µeV. In time-resolved experiments, we observed decay times of about 670 ps. Our results underline the potential of nanoimprint lithography and molecular beam epitaxy to create large-scale, single quantum dot arrays.

[The hybrid operating room. Home of high-end intraoperative imaging]. / Der Hybridoperationssaal. Zentrum intraoperativer Bildgebung.

A hybrid operating room must serve the medical needs of different highly specialized disciplines. It integrates interventional techniques for cardiovascular procedures and allows operations in the field of orthopaedic surgery, neurosurgery and maxillofacial surgery. The integration of all steps such as planning, documentation and the procedure itself saves time and precious resources. The best available imaging devices and user interfaces reduce the need for extensive personnel in the OR and facilitate new minimally invasive procedures. The immediate possibility of postoperative control images in CT-like quality enables the surgeon to react to problems during the same procedure without the need for later revision.