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ZusammenfassungSialorrhoe, ein unkontrollierter, übermäßiger Speichelfluss aus dem Mund und in den Schlund, tritt als Begleitsymptom bei verschiedenen, v. a. neurologischen Erkrankungen im Kindes- und Erwachsenenalter auf. Mit IncobotulinumtoxinA (Xeomin, IncoBoNT/A, Merz Pharmaceuticals GmbH) steht seit 2019 ein zugelassenes Medikament für die Behandlung der Sialorrhoe zur Verfügung. Indikationsstellung, mögliche Therapieziele, Praxis der Behandlung und Management in besonderen Behandlungssituationen bilden den Schwerpunkt dieser konsentierten Praxis-Empfehlungen, die in interdisziplinärer Zusammenarbeit erfahrener Anwender entwickelt wurden. Ziel ist, den Zugang zur Therapie zu erleichtern und einen Beitrag zu einer qualifizierten Botulinumtoxin-Therapie zu leisten.

Most individuals with rare diseases initially consult their primary care physician. For a subset of rare diseases, efficient diagnostic pathways are available. However, ultra-rare diseases often require both expert clinical knowledge and comprehensive genetic diagnostics, which poses structural challenges for public healthcare systems. To address these challenges within Germany, a novel structured diagnostic concept, based on multidisciplinary expertise at established university hospital centers for rare diseases (CRDs), was evaluated in the three year prospective study TRANSLATE NAMSE. A key goal of TRANSLATE NAMSE was to assess the clinical value of exome sequencing (ES) in the ultra-rare disease population. The aims of the present study were to perform a systematic investigation of the phenotypic and molecular genetic data of TRANSLATE NAMSE patients who had undergone ES in order to determine the yield of both ultra-rare diagnoses and novel gene-disease associations; and determine whether the complementary use of machine learning and artificial intelligence (AI) tools improved diagnostic effectiveness and efficiency.ES was performed for 1,577 patients (268 adult and 1,309 pediatric). Molecular genetic diagnoses were established in 499 patients (74 adult and 425 pediatric). A total of 370 distinct molecular genetic causes were established. The majority of these concerned known disorders, most of which were ultra-rare. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were delineated, mainly in individuals with neurodevelopmental disorders.To determine the likelihood that ES will lead to a molecular diagnosis in a given patient, based on the respective clinical features only, we developed a statistical framework called YieldPred. The genetic data of a subcohort of 224 individuals that also gave consent to the computer-assisted analysis of their facial images were processed with the AI tool Prioritization of Exome Data by Image Analysis (PEDIA) and showed superior performance in variant prioritization.The present analyses demonstrated that the novel structured diagnostic concept facilitated the identification of ultra-rare genetic disorders and novel gene-disease associations on a national level and that the machine learning and AI tools improved diagnostic effectiveness and efficiency for ultra-rare genetic disorders.

Objective To investigate the frequency and characteristics of adverse drug reactions (ADRs) that occurred on the gerontopsychiatric ward of Hannover Medical School over a 6-year period. Design Retrospective monocentric cohort study. Results Six hundred thirty-four patient cases (mean age 76.6 ± 7.1 years; 67.2% female) were analysed. In total, 92 ADRs in 56 patient cases were registered in the study population. The overall ADR prevalence, the ADR prevalence upon hospital admission, and the ADR prevalence during hospitalisation were 8.8%, 6.3%, and 4.9%, respectively. The most frequent ADRs were extrapyramidal symptoms, alterations in blood pressure or heart rate, and electrolyte disturbances. Of note, two cases of asystole and one case of obstructive airway symptoms related to general anaesthesia in the context of electroconvulsive therapy (ECT) were detected. The presence of coronary heart disease was associated with an increased risk of ADR occurrence (odds ratio (OR) 2.92, 95% confidence interval (CI) 1.37–6.22), while the presence of dementia was associated with a decreased risk of ADR development (OR 0.45, 95% CI 0.23–0.89). Conclusions Type and prevalence of ADRs in the present study were largely in accordance with previous reports. By contrast, we did not observe a relationship between advanced age or female sex and ADR occurrence. We detected a risk signal for cardiopulmonary ADRs related to general anaesthesia in the context of ECT that warrants further investigation. Elderly psychiatric patients should be carefully screened for cardiopulmonary comorbidities before initiation of ECT.

Objective Geriatric patients account for a significant proportion of the collective treated by psychiatric consultation service in hospitals. In the Emergency Department (ED), psychotropic drugs are frequently recommended, notwithstanding their extensive side-effect profiles. This study sought to investigate medication safety of geriatric patients referred to psychiatric consultation service in the ED. Methods Medication lists of 60 patients from the general internal medicine and trauma surgery EDs referred to psychiatric consultation service were analyzed. Utilizing PRISCUS list and Fit fOR The Aged (FORTA) classification, prescriptions of potentially inappropriate medications (PIMs) were assessed. Results 84 drugs were newly prescribed following psychiatric consultations. The total number of drugs per patient was 5.4 ± 4.2 before psychiatric consultation and 6.5 ± 4.2 thereafter ( p < .001). 22.6 % of the newly recommended drugs were PIMs according to the PRISCUS list, while 54.8 % were designated as therapeutic alternatives to PIMs. 54.8 % and 20.2 % of the newly recommended drugs were FORTA category C and D drugs, respectively. An average of 1.2 ± 1.7 drug–drug interactions (DDIs) existed before psychiatric consultation and 1.3 ± 1.9 DDIs thereafter ( p = .08). Conclusion The majority of newly recommended drugs by psychiatric consultation service in the ED were designated as suitable therapeutic alternatives to PIMs according to the PRISCUS list, but had comparatively unfavorable ratings according to the FORTA classification, demonstrating discrepancies between these two PIM classification systems. Physicians delivering psychiatric consultation services in the ED should not solely rely on one PIM classification system.

Objective The number of clinical trials for Duchenne muscular dystrophy (DMD) has increased substantially lately, therefore appropriate clinical instruments are needed to measure disease progression and drug efficacy. Jumping mechanography is a medical diagnostic method for motion analysis, which allows to quantify physical parameters. In this study, we compared mechanography with timed function tests (TFTs). Methods 41 ambulatory DMD patients performed a total of 95 chair rising tests (CRT) and a total of 76 single two-legged jumps (S2LJ) on a mechanography ground reaction force platform. The results were correlated with a 6-minute walk test (6MWT) and the time required to run 10 meters, stand up from a supine position, and climb four stairs, all performed in the same setting. Results Our measurements show a high correlation between mechanography and the TFTs: S2LJ/10-m run, r = 0.62; CRT/10-m run, r = 0.61; S2LJ/standing up from supine, r = 0.48; CRT/standing up from supine, r = 0.58; S2LJ/climb four stairs, r = 0.55; CRT/climb four stairs, r = 0.51. The correlation between mechanography and the 6MWT was only moderate with r = 0.38 for S2LJ/6MWT and r = 0.39 for CRT/6MWT. Interpretation Jumping mechanography is a reliable additional method, which can be used for physical endpoint measurements in clinical trials. We confirmed our assumption, that the method provides additional information concerning performance at movement with higher power output. We suggest using the S2LJ as a first-choice tandem tool combined with the 6MWT. In patients with higher disability, the CRT is an alternative measuring method, because with the progression of the disease this is longer feasible.

Adverse drug reactions (ADRs) constitute a frequent cause of hospitalization in older people. The risk of ADRs is increased by the prescription of potentially inappropriate medications for older people (PIMs). The PRISCUS list and the FORTA classification represent established tools to detect PIMs. The aim of the present study was to examine the prevalence and characteristics of PIM prescriptions on the gerontopsychiatric ward of a university hospital in Germany. To this aim, medication charts of 92 patients (mean age 75.9 ± 7.7 years; 66.3% female) were analyzed on a weekly basis until patient discharge by utilization of the PRISCUS list and the FORTA classification. Overall, 335 medication reviews comprising 2363 drug prescriptions were analyzed. 3.0% of the prescribed drugs were PIMs according to the PRISCUS list, with benzodiazepines and Z-drugs accounting for nearly half (49.3%) of all PIM prescriptions. 30.4% of the patients were prescribed at least one PRISCUS-PIM, while 43.5% of the study population took at least one FORTA class D drug. A considerable proportion of gerontopsychiatric patients were affected by PIMs; however, the overall number of PIM prescriptions in the study population was low. Further improvements in the quality of prescribing should target the use of sedating agents such as benzodiazepines and Z-drugs. Physicians should be aware of discrepancies between the PRISCUS list and the FORTA classification.

Sialorrhea, uncontrolled, excessive drooling, accompanies different, mostly neurological disorders from childhood to adulthood. With incobotulinumtoxinA (Xeomin, IncoBoNT/A, Merz Pharmaceuticals GmbH), an approved medication for the treatment of sialorrhea has been available since 2019. Patient selection, possible therapy goals, treatment and the management of specific treatment situations build the focus of this interdisciplinary expert consensus recommendations with the intent to facilitate access to treatment and to contribute to qualified botulinum toxin therapy.Sialorrhoe, ein unkontrollierter, übermäßiger Speichelfluss aus dem Mund und in den Schlund, tritt als Begleitsymptom bei verschiedenen, v. a. neurologischen Erkrankungen im Kindes- und Erwachsenenalter auf. Mit IncobotulinumtoxinA (Xeomin, IncoBoNT/A, Merz Pharmaceuticals GmbH) steht seit 2019 ein zugelassenes Medikament für die Behandlung der Sialorrhoe zur Verfügung. Indikationsstellung, mögliche Therapieziele, Praxis der Behandlung und Management in besonderen Behandlungssituationen bilden den Schwerpunkt dieser konsentierten Praxis-Empfehlungen, die in interdisziplinärer Zusammenarbeit erfahrener Anwender entwickelt wurden. Ziel ist, den Zugang zur Therapie zu erleichtern und einen Beitrag zu einer qualifizierten Botulinumtoxin-Therapie zu leisten.

Objective Psychiatric patients in general, and elderly psychiatric patients in particular, are at risk of adverse drug reactions due to comorbidities and inappropriate polypharmacy. Interdisciplinary and clinical-pharmacologist-led medication reviews may contribute to medication safety in the field of psychiatry. In this study, we reported the frequency and characteristics of clinical-pharmacological recommendations in psychiatry, with a particular focus on geriatric psychiatry. Method A clinical pharmacologist, in collaboration with the attending psychiatrists and a consulting neurologist, conducted interdisciplinary medication reviews in a general psychiatric ward with a geropsychiatric focus at a university hospital over a 25-week period. All clinical and pharmacological recommendations were recorded and evaluated. Results A total of 316 recommendations were made during 374 medication reviews. Indications/contraindications of drugs were the most frequently discussed topics (59/316; 18.7 %), followed by dose reductions (37/316; 11.7 %), and temporary or permanent discontinuation of medications (36/316; 11.4 %). The most frequent recommendations for dose reduction involvedbenzodiazepines (9/37; 24.3 %). An unclear or absent indication was the most common reason for recommending temporary or permanent discontinuation of the medication (6/36; 16.7 %). Conclusion Interdisciplinary clinical pharmacologist-led medication reviews represented a valuable contribution to medication management in psychiatric patients, particularly the elderly ones.

Background Uterine-preserving techniques are becoming increasingly popular in the last decade. This investigation evaluates a novel hysteropexy technique using a mesh in sling-alike configuration [Splentis (Promedon, Argentina)] which is attached anteriorly to the cervix and suspended to the sacrospinous ligaments bilaterally via the vaginal route in women undergoing surgery for uterine prolapse. Methods This was a single-center cohort study, evaluating women who underwent transvaginal hysteropexy with Splentis for primary uterine descent. Data have been collected prospectively as part of the quality assurance system. Primary endpoint was treatment success, defined as a combined endpoint including the absence of a vaginal bulge symptom and no retreatment of apical prolapse. A validated questionnaire to evaluate quality-of-life and prolapse symptoms was utilized. Descriptive analysis was applied. Wilcoxon signed-rank test was performed to compare paired samples. The significance level was set at 5%. Results A total of 103 women with a median age of 68.0 [IQR 11.5] years with a median apical POP-Q stage of 3 were included. The median surgery time was 22 [IQR 12] minutes and no intraoperative complication occurred. After a median follow-up time of 17 months, treatment success was achieved in 91 (89.2%) patients and quality of life and patient report outcomes improved significantly (p Conclusion Bilateral sacrospinous hysteropexy with Splentis offers an efficacious and safe alternative for apical compartment repair, incorporating the advantages of pelvic floor reconstruction via the vaginal route.

ZusammenfassungHypersalivation bezeichnet einen übermäßigen Speichelfluss, der durch insuffiziente orofaziale Fähigkeiten, verminderte zentralnervöse Kontrolle und Koordination oder gestörte Schluckabläufe entstehen kann. Die Aktualisierung der S2k-Leitlinie soll den neuen diagnostischen und therapeutischen Kenntnisstand berücksichtigen.Die Diagnostik- und Therapiemaßnahmen sollten multidisziplinär erfolgen. Schwerpunkte sind die Abklärung von Schluckstörungen mit Speichelaspiration. Hier sind klinische Screeninguntersuchungen und die fiberendoskopische Schluckuntersuchung (FEES) hervorzuheben.Bei fast allen Ursachen sind die schlucktherapeutischen Übungsmaßnahmen zur Aktivierung und zum Erlernen von Kompensationsmechanismen unverzichtbar. Insbesondere bei Kindern mit hypotoner orofazialer Muskulatur sind myofunktionelle Therapiekonzepte indiziert, allerdings ist die Kompetenz zur Mitarbeit entscheidend. Zusätzlich können orale Stimulationsplatten durch die Veränderung der Zungenpositionierung zu einer Symptomreduktion führen. Sinnvolle medikamentöse Therapien sind insbesondere die verschiedenen Applikationsformen von Glycopyrrolat, von denen Sialanar® (Glycopyrronium) als Saft eine Genehmigung zur Behandlung bei Kindern ab 3 Jahren und Jugendlichen erhalten hat. Die Injektion von Botulinumtoxin in die Kopfspeicheldrüsen hat sich als effektive und sichere Behandlungsform mit einer langanhaltenden Speichelreduktion erwiesen. Für Incobotulinumtoxin A ist die Phase III-Studie bei Erwachsenen aktuell abgeschlossen und führte in den USA bereits zur Zulassungserweiterung bei Hypersalivation. Chirurgische Eingriffe der Speicheldrüsen bleiben Einzelfällen vorbehalten. Die Bestrahlung der Speicheldrüsen ist, insbesondere wenn sie in moderner 3-D-konformaler Technik zur Gewebeschonung durchgeführt wird, eine sichere und effektive Therapie. In einer regelhaften Nachsorge sind Therapieeffekte und mögliche Nebenwirkungen zu erfassen; insbesondere bei neurodegenerativen Erkrankungen ist die individuelle Dynamik der Symptomverschlechterung zu berücksichtigen.

Facade greening has great potential to combat problems in modern cities, such as urban heat islands. However, it is not used extensively inter alia due to its high maintenance efforts. In this paper a prototype of an under constrained parallel driven Robot for Vertical Green maintenance is presented. First the concept of cable driven robots is compared with other possible solutions. Afterwards the concept of a robot held by four cables and driven by two motors is explained for the given task with a large and flat work space. This configuration leads to two uncontrolled degrees of freedom. The rolling movement of the robot should be measured and counteracted by the swivel head for the tools. The distance perpendicular to the facade is planned to be measured with a laser level detector and controlled by a pair of actuated propellers. The work in progress on the robot and the results of the first field tests are shown. The robotic concept seems to be suitable for vertical green maintenance and other tasks with a comparable workspace.

Summary Background Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. Methods For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. Findings We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. Interpretation In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations. Funding Else Kroner-Fresenius-Stiftung, Technische Universitat Munchen, Helmholtz Zentrum Munchen, Medizinische Universitat Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.

Microbial valorization of plant biomass is a key target in bioeconomy. A promising candidate for consolidated bioprocessing is the dimorphic fungus Ustilago maydis. It harbors hydrolytic enzymes to degrade biomass components and naturally produces valuable secondary metabolites like itaconic acid, malic acid or glycolipids. However, hydrolytic enzymes are mainly expressed in the hyphal form. This type of morphology should be prevented in industrial fermentation processes. Genetic activation of these enzymes can enable growth on cognate substrates also in the yeast form. Here, strains were engineered for growth on polygalacturonic acid as major component of pectin. Besides activation of intrinsic enzymes, supplementation with heterologous genes for potent enzymes was tested. The presence of an unconventional secretion pathway allowed exploiting fungal and bacterial enzymes. Growth of the engineered strains was evaluated by a recently developed method for online determination of residual substrates based on the respiration activity. This enabled the quantification of the overall consumed substrate as a key asset for the assessment of the enzyme degradation potential even on polymeric substrates. Co-fermentation of endo- and exo-polygalacturonase overexpression strains resulted in efficient growth on polygalacturonic acid. In the future, the approach will be extended to establish efficient degradation and valorization of pectin. Previous article in issue

This study aims to evaluate the effectiveness of a prefabricated carbon-composite ankle foot orthoses (c-AFOs) on gait parameters in children with unilateral spastic cerebral palsy (USCP) exhibiting a drop foot pattern.Sixteen ambulatory children with USCP and a drop foot pattern were included (mean age: 9 years; gross motor function classification system: I = 14, II = 2) and three-dimensional gait analysis was applied under randomly assigned conditions (barefoot; shoe; c-AFO). Kinematics, kinetics, time-distance parameters and gait indices were investigated.Effects on the drop foot pattern were investigated while the children walked in shoes only. The shoes already increased the maximum ankle dorsiflexion in swing (p= 0.004) and initiated more knee flexion during single support (p⩽ 0.013). Compared to shoe walking, the c-AFO led to additional benefits regarding further ankle dorsiflexion during swing (p⩽ 0.001) and initial contact (p0.001), ankle movement during loading response (p= 0.002), improved the sole angle during initial contact (p0.001) and during mid stance (p= 0.015). Plantarflexion and ankle power generation during push-off decreased when wearing the c-AFO (p⩽ 0.008).Investigated c-AFOs are beneficial for improving drop foot patterns in children with USCP. Significant effects on pathological barefoot pattern were already achieved with the child's regular shoes. This could be considered in clinical decision processes. In comparison to shoe walking, c-AFO additionally improved foot clearance and normalized initial heel contact. The third rocker deteriorates with the c-AFO. Since kinematics improved with the orthoses during swing and early stance phase, c-AFOs might reduce tripping and falling caused by a drop foot during long distance walking.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation.Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes in order to activate compensation mechanisms as long compliances is given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (SialanarHypersalivation bezeichnet einen übermäßigen Speichelfluss, der durch insuffiziente orofaziale Fähigkeiten, verminderte zentralnervöse Kontrolle und Koordination oder gestörte Schluckabläufe entstehen kann. Die Aktualisierung der S2k-Leitlinie soll den neuen diagnostischen und therapeutischen Kenntnisstand berücksichtigen.Die Diagnostik- und Therapiemaßnahmen sollten multidisziplinär erfolgen. Schwerpunkte sind die Abklärung von Schluckstörungen mit Speichelaspiration. Hier sind klinische Screeninguntersuchungen und die fiberendoskopische Schluckuntersuchung (FEES) hervorzuheben.Bei fast allen Ursachen sind die schlucktherapeutischen Übungsmaßnahmen zur Aktivierung und zum Erlernen von Kompensationsmechanismen unverzichtbar. Insbesondere bei Kindern mit hypotoner orofazialer Muskulatur sind myofunktionelle Therapiekonzepte indiziert, allerdings ist die Kompetenz zur Mitarbeit entscheidend. Zusätzlich können orale Stimulationsplatten durch die Veränderung der Zungenpositionierung zu einer Symptomreduktion führen. Sinnvolle medikamentöse Therapien sind insbesondere die verschiedenen Applikationsformen von Glycopyrrolat, von denen Sialanar

A bulk acoustic wave gas sensor system based on high temperature stable piezoelectric transducers and thin metal oxide sensor films is developed. The simultaneous determination of changes in electrical and gravimetric properties of tin oxide (SnO 2 ), titanium oxide (TiO 2 ) and praseodymium doped ceria (PCO, Pr x Ce 1-x O 2 with x = 0.1 and 0.2) sensor films enables to distinguish methane and ethylene in inert gas atmospheres (argon) at temperatures up to 900 °C.

A protocol for the synthesis of thus far inaccessible bromo vinyl triflimides is presented. Our previously reported concept of assisted vinyl cation formation was engaged to achieve both a protonation of relatively electron poor bromo alkynes and a reaction with high regio- and stereoselectivity. To the best of our knowledge, this is the first stereoselective addition of an N-nucleophile to an open β-halovinyl cation.

Purpose To assess the impact of vertigo on health-related quality of life (HrQoL) of children/adolescents and to assess if the impact on HrQoL varies by age group, gender, and type of vertigo diagnoses. Methods A retrospective analysis was performed on the clinical and HrQoL data of children and adolescents referred to the German Center of Vertigo and Balance Disorders (n = 32; male = 17; female = 15; age range: 8–18 years), using the KIDSCREEN-52 questionnaire. For each scale, means of the Z-scores with 95% confidence intervals of the study and norm sample were compared. By nonparametric Kruskal–Wallis statistics differences between diagnostic groups were assessed. To assess the gender- and age-specific impact of vertigo on quality of life, Wilcoxon signed-rank test was used. Results The means of the physical well-being, psychological well-being, autonomy scale, and the general HrQoL index of patients were considerably lower than the means of the norm sample. The physical well-being seemed to be most affected by vertigo. The reduction of HrQoL was not related to gender and vertigo types but seemed to be higher in children suffering from vertigo aged 12 to 18 years than children aged 8 to 11 years. Conclusion These are the first data to demonstrate impaired HrQoL in children with chronic vertigo.

Der Schlaganfall bei Kinder und Jugendlichen tritt selten auf, ist aber immer ein kinderneurologischer Notfall. Fur das Outcome sind eine fruhzeitige Diagnostik und Therapieeinleitung, eine adaquate Rezidivpravention und speziell auf die Bedurfnisse jedes einzelnen Kindes und seine Entwicklung abgestimmte rehabilitative Masnahmen entscheidend.

α-Carbonyl cations were found to drive 1,2-carbon shift reactions with excellent selectivity. As opposed to traditional guidelines, this selectivity is based not on the electronic and steric properties of the migrating substituent but determined by the nature of the substituent remaining in the migrant carrying remnant. Therefore, the selectivity trend is reversed, which allowed us to realize a first example for a cation-driven selective migration favoring an alkynyl over an aryl substituent

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes to activate compensation mechanisms as long compliances are given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (Sialanar®) is now indicated for hypersalivation within the EU. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long-lasting saliva reduction. Here, a phase III trial is completed for incobotulinum toxin A and, in the US, is indicated for the treatment of adult patients with chronic hypersalivation. Surgical treatment should be reserved for isolated cases. External radiation is judged as a safe and effective therapy when using modern 3D techniques to minimize tissue damage. Therapy effects and symptom severity have to be followed, especially in cases with underlying neurodegenerative disease.

Motion analysis of infants is used for early detection of movement disorders like cerebral palsy. For the development of automated methods, capturing the infant's pose accurately is crucial. Our system for predicting 3D joint positions is based on a recently introduced pixelwise body part classifier using random ferns, to which we propose multiple enhancements. We apply a feature selection step before training random ferns to avoid the inclusion of redundant features. We introduce a kinematic chain reweighting scheme to identify and to correct misclassified pixels, and we achieve rotation invariance by performing PCA on the input depth image. The proposed methods improve pose estimation accuracy by a large margin on multiple recordings of infants. We demonstrate the suitability of the approach for motion analysis by comparing predicted knee angles to ground truth angles.

We present a petrographic, petrological, geochemical, and geochronological study (U–Pb/Lu–Hf) on granulite-facies paragneisses of the Mahamba Gneiss Complex in central Swaziland, eastern Kaapvaal Craton. Our data suggest that prograde metamorphism occurred at c . 3.07 Ga. Dating of detrital zircons of a metapelite in combination with geochronological and ambiguous structural relationships with granitoid gneisses suggests two possible scenarios: (1) the time of deposition of the sedimentary protoliths is prior to c . 3.58 Ga; (2) c . 3.58 Ga granitoid crust was the basement for the sedimentary protoliths. Furthermore, enrichment in Ni and Cr in the Mahamba metasediments may originate from erosion of a greenstone terrane similar in composition to the dominantly mafic and ultramafic lithologies of the Barberton Greenstone Belt or Dwalile supracrustal belt. Evidence for an older crustal basement is provided by the oldest detrital zircons, which yield ages up to c . 3.7 Ga. Because the metamorphic conditions of metapelitic rocks have no similarity to P–T paths of modern subduction–collision tectonic settings we conclude that the metamorphic history of the Mahamba Gneiss Complex cannot be explained by this model. We propose that deformation and metamorphism occurred through intracratonic contraction and a thermal event possibly related to Mpuluzi batholith emplacement. Supplementary material: Sample localities, mineral chemistry, analytical methods, and mineral equilibria modelling method are available at www.geolsoc.org.uk/SUP18786.

Bulk single-crystalline aluminum nitride (AlN) is potentially a key component for low-loss high-temperature piezoelectric devices. However, the incorporation of electrically active impurities and defects during growth of AlN may adversely affect the performance of piezoelectric resonators especially at high temperatures. The electrical conductivity and electromechanical losses in bulk AlN single crystals are analyzed in the temperature range of 300–1200 K with respect to various contents of growth-related impurities in them. For AlN with [O]/[C] ≤ 1, an increase of electrical conductivity due to thermal activation of charge carriers in the temperature range of 850–1200 K has been observed and was determined to be a major contribution to electromechanical losses Q−1 rising up to maximum values of about 10−3 at 1200 K. As the oxygen content in AlN increased, the magnitude and the activation energy of high-temperature electrical conductivity increased. In oxygen-dominated AlN, two major thermally activated contributions to electromechanical losses were observed, namely, the anelastic relaxations of point defects at temperatures of 400–800 K and electrical conductivity at T > 800 K.

BACKGROUND AND PURPOSE: Loss of integrity in nonlesional white matter occurs as a fundamental feature of multiple sclerosis in adults. The purpose of our study was to evaluate DTI-derived measures of white matter microstructure in children with MS compared with age- and sex-matched controls by using tract-based spatial statistics. MATERIALS AND METHODS: Fourteen consecutive pediatric patients with MS (11 female/3 male; mean age, 15.1 1.6 years; age range, 12–17 years) and age- and sex-matched healthy subjects (11 female/3 male; mean age, 14.8 1.7 years) were included in the study. After we obtained DTI sequences, data processing was performed by using tract-based spatial statistics. RESULTS: Compared with healthy age- and sex-matched controls, children with multiple sclerosis showed a global decrease in mean fractional anisotropy (P .001), with a concomitant increase in mean (P .001), radial (P .05), and axial diffusivity (P .001). The most pronounced fractional anisotropy value decrease in patients with MS was found in the splenium of the corpus callosum (P .001). An additional decrease in fractional anisotropy was identified in the right temporal and right and left parietal regions (P .001). Fractional anisotropy of the white matter skeleton was related to disease duration and may, therefore, serve as a diagnostic marker. CONCLUSIONS: The microstructure of white matter is altered early in the disease course in childhood multiple sclerosis. ABBREVIATIONS: AD axial diffusivity; FA fractional anisotropy; MD mean diffusivity; RD radial diffusivity; TBSS tract-based spatial statistics

The first trans-selective [3 + 2]-cycloaddition of a new type of donor-acceptor cyclopropane with aldehydes is presented. 2,2-Disubstituted cyclopropanes, bearing an alkyne moiety as the sole donor entity, were transformed to highly substituted tetrahydrofurans in the presence of a catalytic amount of Ca(NTf2)2/Bu4NPF6. The protocol allows for an easy access to tetrahydrofurans bearing a versatile alkyne substituent at the quarternary 2-position under very mild reaction conditions.

Introduction: Deep brain stimulation of the globus pallidus internus (GPi-DBS) can be effective in patients with dyskinetic cerebral palsy (CP), but outcome in terms of dystonia severity is often less pronounced and more variable compared to patients with inherited monogenic dystonia. A few published case series encompassing retrospective data have shown that GPi-DBS is associated with favorable quality of life outcomes, even in patients without changes in the BFMDRS, suggesting that the sole use of clinical rating scales may not reflect the full effects of DBS, especially not in patients with acquired forms of dystonia such as dyskinetic CP. However, there is no prospective data on DBS effects in children. We hypothesize an improvement in quality of life by GPi-DBS. Therefore, the mean change in the CPCHILD questionnaire from baseline to 12 months is chosen as the primary outcome parameter. Secondary outcome parameters encompass dystonia severity, motor function, speech, mood, cognition, pain, and quality of life of the carers before and up to 36 months after implantation. Methods: This is a prospective single-arm study to investigate the effects of GPi-DBS in young patients with dyskinetic CP. 20 patients aged 7-18 years will be recruited in a multicenter setting. 12 months after lead implantation patients are randomized by a double-blind cross-over into two groups: One group starts with ongoing stimulation, in the other group stimulation is turned off. After 24 h they switch stimulation settings. Dystonia severity will be assessed at the end of each phase. We hypothesize an improvement in quality of life by GPi-DBS. Therefore, the mean change in the CPCHILD questionnaire from baseline to 12 months is chosen as the primary outcome parameter. Secondary outcome parameters encompass dystonia severity, motor function, speech, mood, cognition, pain, and quality of life of the carers before and up to 36 months after implantation. Discussion: This is the first prospective trial investigating the effects of GPi-DBS on motor and non-motor outcome in a cohort of exclusively pediatric patients in a multicenter setting. Furthermore, long-term data on effects and side effects of GPi-DBS in young patients with dyskinetic cerebral palsy will be generated.