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.

[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.

[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.

[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.

Clinical Accuracy of 3D-Planned Maxillary Positioning Using CAD/CAM-Generated Splints in Combination With Temporary Mandibular Fixation in Bimaxillary Orthognathic Surgery.

STUDY DESIGN: The aim of this study was to evaluate the accuracy of 3-dimensional (3D)-planned maxillary positioning by using computer-assisted design (CAD)/computer-assisted manufacturing (CAM) splints combined with temporary mandibular fixation in bimaxillary orthognathic surgery. In orthognathic surgery, customized splints work sufficiently well to transfer preoperative planning into the operation site for transverse und sagittal positioning of the maxilla. The vertical positioning is more difficult due to the non-fixed mandibular reference. Therefore, the combined use of CAD/CAM splints and temporary mandibular fixation to the zygomatic region was applied for transferring the 3D-planned maxillary position into the operation site from 2012 until 2015 in our hospital. OBJECTIVE: In addition to the general accuracy, the precision should therefore be checked especially in the vertical plane compared to axial and sagittal plane. METHODS: In this retrospective study, we calculated the deviation of 5 occlusal landmarks of the maxilla in 35 consecutive patients by fusing preoperative 3D planning images and postoperative computed tomography scans after bimaxillary surgery. RESULTS: The overall median deviation of maxillary positioning between plan and surgical result was 0.99 mm. The accuracy of left-right positioning was median 0.96 mm. Anterior-posterior positioning of the maxilla showed a median accuracy of 0.94 mm. Just slightly higher values were determined for the upward-downward positioning (median 1.06 mm). CONCLUSIONS: This demonstrates the predictability of maxillary positioning by using CAD/CAM splints in combination with temporary mandibular fixation in all 3 axes.

Custom wave-shaped CAD/CAM orbital wall implants for the management of post-enucleation socket syndrome.

The satisfactory management of post-enucleation socket syndrome is a major challenge. In addition to enophthalmos and hypophthalmos, the appearance of the supratarsal fold is frequently unsatisfactory. Using a combination of orbital volume reduction by means of custom wave-shaped CAD/CAM implants (1), the implantation of a dermis-fat graft (2), and the fitting of an acrylic eye prothesis (3), an algorithm has been developed that has led to considerable long-term improvements. 10 patients have already been treated by this method. The most important step is the reduction of orbital volume by means of custom wave-shaped CAD/CAM implants. These move the intraorbital soft tissue in an anterior and cranial direction. This considerably reduces the required volume of additional dermis-fat grafts, which are always subject to resorption. The use of an acrylic eye prothesis facilitates the aesthetic and functional correction of this condition and exerts less pressure on the lower eyelid due to its low weight. The method presented here leads to stable and aesthetically pleasing results with a minimum risk of complications. One problem is the exact predictability of the necessary orbital volume reduction by the custom wave-shaped CAD/CAM implants. Further studies and a larger number of cases are required to address this problem.

Invasion windows for a global legume invader are revealed after joint examination of abiotic and biotic filters.

Successful alien plant invasion is influenced by both climate change and plant-plant interactions. We estimate the single and interactive effects of competition and extreme weather events on the performance of the global legume invader Lupinus polyphyllus (Lindl.). In three experimental studies we assessed (i) the stress tolerance of seedling and adult L. polyphyllus plants against extreme weather events (drought, fluctuating precipitation, late frost), (ii) the competitive effects of L. polyphyllus on native grassland species and vice versa, and (iii) the interactive effects of extreme weather events and competition on the performance of L. polyphyllus. Drought reduced growth and led to early senescence of L. polyphyllus but did not reduce adult survival. Fluctuating precipitation events and late frost reduced the length of inflorescences. Under control conditions, interspecific competition reduced photosynthetic activity and growth of L. polyphyllus. When subjected to competition during drought, L. polyphyllus conserved water while simultaneously maintaining high assimilation rates, demonstrating increased water use efficiency. Meanwhile, native species had reduced performance under drought. In summary, the invader gained an advantage under drought conditions through a smaller reduction in performance relative to its native competitors but was competitively inferior under control conditions. This provides evidence for a possible invasion window for this species. While regions of high elevation or latitude with regular severe late frost events might remain inaccessible for L. polyphyllus, further spread across Europe seems probable as the predicted increase in drought events may favour this non-native legume over native species.

Effectiveness of botulinum neurotoxin type A injections in naïve and previously-treated patients suffering from Torti- or Laterocollis or -caput: Results from a German-Austrian open-label prospective post-marketing surveillance study.

AbobotulinumtoxinA (aboBoNT-A; Dysport®) is an effective treatment for cervical dystonia (CD) with a well-established safety profile. In this prospective, multicentre, non-interventional study (NCT01840462) the primary objective was effectiveness (Tsui score) of aboBoNT-A in botulinum neurotoxin type A (BoNT-A) treatment-naïve and previously-treated (>2 yrs) patients after two injection cycles (at visit 3). Secondary objectives included the effectiveness of aboBoNT-A overall visits and quality of life (CDQ-24) in different CD subtypes. Observation time was 12-16 months, including 5 visits and 4 injection cycles (each 3-4 months). In the analysis population 273 patients from 41 centres across Germany and Austria were included. At baseline, 62.6% were previously-treated with BoNT-A. The major primary components of CD were torticollis (64.5%) and torticaput (17.6%). Previously-treated patients showed a slight reduction of the Tsui scores, whereas BoNT-A-naïve patients had a more severe baseline Tsui score and improved much more over all cycles. Results were similar for CDQ-24. Interestingly, improvements mainly occurred in the Tsui subscore A (amplitude of sustained posture). Marked differences between CD subtypes regarding effectiveness could not be determined. To our knowledge this is the first large multi-centre study investigating the effectiveness of BoNT-A in different primary subtypes of CD over several injection cycles.

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.

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.

Taraxacum officinale extract shows antitumor effects on pediatric cancer cells and enhance mistletoe therapy.

OBJECTIVES: While Taraxacum officinale (dandelion) extracts showed antitumor effects on adult cancer cells, effects on pediatric tumor cells as a single agent or in combination with mistletoe extracts are hitherto unknown. MATERIAL AND METHODS: The anti-proliferative effects of an aqueous fermented Taraxacum officinale extract (Taraxacum) on a pediatric cancer cell line panel were assessed by cell viability assays (MTT). In two neuroblastoma cell lines, SH-SY5Y and Kelly, the effects on cell cycle distribution (PI staining), mitochondrial integrity (MitoTracker staining), invasion (Boyden chamber assay) and migration (Scratch-assay) as well as the synergistic effects of the co-treatment of Taraxacum and mistletoe preparations (Iscucin® Tiliae or Iscucin® Pini) were investigated. RESULTS: All tested cancer cell lines were more susceptible to Taraxacum than the normal human fibroblast cell line, NHDF-C. In neuroblastoma cell lines Taraxacum caused apoptosis and loss of mitochondrial integrity as well as an inhibition of invasion and migration. The simultaneous therapy of Taraxacum and the mistletoe extracts revealed synergistic effects. CONCLUSION: This preclinical data support the use of Taraxacum as a potential adjuvant application in pediatric oncology.

Validity of sentinel node biopsy in early oral and oropharyngeal carcinoma.

PURPOSE: This study investigates the possibility and sensibility of using sentinel node biopsy (SNB) during surgery for oropharyngeal carcinomas with clinically and radiographically unremarkable cervical lymph nodes. MATERIALS AND METHODS: A total of 36 patients who were treated for early oral and oropharyngeal carcinoma and unremarkable cervical lymph nodes were included in this study. After lymphoscintigraphy for detecting sentinel lymph nodes (SLN), the SLN were excised first. Thereafter elective neck dissection was performed. Histopathological and immunochemical examinations were used to examine the SLN and all other lymph nodes. RESULTS: The preoperative SLN detection rate was 97.2% (35 of 36). SLN in level V were detected in four patients (11.1%). Metastases were found in 33.3% of the patients (12 of 36). All metastases were in the marked SLN. No skip metastases could be detected. A specificity of 100% and a sensitivity of 94.4% were identified for the SNB. CONCLUSION: The study confirms that SNB is a precise diagnostic procedure for assessing the nodal status of cervical lymph nodes. Further studies are needed to determine whether SNB without elective neck dissection for clinically and radiologically unremarkable cervical lymph nodes can become a reliable course of treatment for carcinomas of the head and neck region.

Under-reporting bicycle accidents to police in the COST TU1101 international survey: Cross-country comparisons and associated factors.

Police crash reports are often the main source for official data in many countries. However, with the exception of fatal crashes, crashes are often underreported in a biased manner. Consequently, the countermeasures adopted according to them may be inefficient. In the case of bicycle crashes, this bias is most acute and it probably varies across countries, with some of them being more prone to reporting accidents to police than others. Assessing if this bias occurs and the size of it can be of great importance for evaluating the risks associated with bicycling. This study utilized data collected in the COST TU1101 action "Towards safer bicycling through optimization of bicycle helmets and usage". The data came from an online survey that included questions related to bicyclists' attitudes, behaviour, cycling habits, accidents, and patterns of use of helmets. The survey was filled by 8655 bicyclists from 30 different countries. After applying various exclusion factors, 7015 questionnaires filled by adult cyclists from 17 countries, each with at least 100 valid responses, remained in our sample. The results showed that across all countries, an average of only 10% of all crashes were reported to the police, with a wide range among countries: from a minimum of 0.0% (Israel) and 2.6% (Croatia) to a maximum of a 35.0% (Germany). Some factors associated with the reporting levels were type of crash, type of vehicle involved, and injury severity. No relation was found between the likelihood of reporting and the cyclist's gender, age, educational level, marital status, being a parent, use of helmet, and type of bicycle. The significant under-reporting - including injury crashes that do not lead to hospitalization - justifies the use of self-report survey data for assessment of bicycling crash patterns as they relate to (1) crash risk issues such as location, infrastructure, cyclists' characteristics, and use of helmet and (2) strategic approaches to bicycle crash prevention and injury reduction.

Involvement of obliquus capitis inferior muscle in dystonic head tremor.

INTRODUCTION: Head tremor is a common feature in cervical dystonia (CD) and often less responsive to botulinum neurotoxin (BoNT) treatment than dystonic posturing. Ultrasound allows accurate targeting of deeper neck muscles. METHODS: In 35 CD patients with dystonic head tremor the depth and thickness of the splenius capitis (SPL), semispinalis capitis and obliquus capitis inferior muscles (OCI) were assessed using ultrasound. Ultrasound guided EMG recordings were performed from the SPL and OCI. RESULTS: Burst-like tremor activity was present in both OCI in 25 and in one in 10 patients. In 18 patients, tremor activity was present in one SPL and in 2 in both SPL. Depth and thickness of OCI, SPL and semispinalis capitis muscles were very variable. CONCLUSION: Muscular activity underlying tremulous CD is most commonly present in OCI. Due to the variability of muscle thickness, we suggest ultrasound guided BoNT injections into OCI.

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.