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IntroductionBronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay of anti-inflammatory and proinflammatory lipid mediators could lead to the development of novel anti-inflammatory therapies for bronchiectasis.AimThe aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state.MethodsSix healthy volunteers, 10 patients with mild bronchiectasis, 15 with moderate bronchiectasis and 9 with severe bronchiectasis were recruited. All participants had 60 mL of blood taken and underwent a bronchoscopy while in the stable state. Lipidomics was done on serum and bronchoalveolar lavage fluid (BALF).ResultsIn the stable state, in serum there were significantly higher levels of prostaglandin E2(PGE2), 15-hydroxyeicosatetranoic acid (15-HETE) and leukotriene B4(LTB4) in patients with moderate–severe disease compared with healthy volunteers. There was a significantly lower level of lipoxin A4(LXA4) in severe bronchiectasis.In BALF, there were significantly higher levels of PGE2, 5-HETE, 15-HETE, 9-hydroxyoctadecadienoic acid and LTB4in moderate–severe patients compared with healthy volunteers.In the stable state, there was a negative correlation of PGE2and LTB4with % predicted forced expiratory volume in 1 s and a positive correlation with antibiotic courses.LXA4improved blood and airway neutrophil phagocytosis and bacterial killing in patients with bronchiectasis. Additionally LXA4reduced neutrophil activation and degranulation.ConclusionThere is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA4improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA4in bronchiectasis warrants further studies.

ZUSAMMENFASSUNGDie komplexe Symptomatik der Parkinsonerkrankung erfordert einen langfristigen, individuellen und umfassenden Therapieansatz. Spezialisierte Netzwerke sind eine Möglichkeit, diesem Bedarf zu begegnen. In Deutschland ist keine flächendeckende, netzwerkbasierte Versorgung Parkinsonerkrankter etabliert. Es fehlen in Netzwerken organisierte und in der Parkinsonbehandlung geschulte Physiotherapeuten. Die im Heilmittelkatalog geregelten, ambulanten Leistungen der Physiotherapie beruhen auf konzeptbasierten Therapieformen, die nicht den Inhalten der europäischen Physiotherapieleitlinie entsprechen. Im Modellvorhaben PaNTher – Parkinson Netzwerk Therapie erhalten Parkinsonpatienten im Großraum München die Möglichkeit einer spezialisierten, leitlinienbasierten Physiotherapie. Vorgestellt wird das Chronic Care Modell auf dessen Basis PaNTher darauf abzielt, die Versorgungsqualität zu verbessern. Stadien- bzw. symptomspezifische Therapieprogramme, ein strukturiertes Schulungsprogramm zur Steigerung der Expertise der Physiotherapeuten und eine sektorenübergreifende Zusammenarbeit zwischen kooperierenden Fachärzten, Therapeuten und dem Projektzentrum an der Parkinson-Fachklinik sind Komponenten des Programms. Teilnehmende Patienten werden im Selbstmanagement ihrer Erkrankung gestärkt. Die Wirksamkeit des Modellvorhabens PaNTher wird durch eine unabhängige, begleitende wissenschaftliche Evaluation untersucht.

Bronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay of anti-inflammatory and proinflammatory lipid mediators could lead to the development of novel anti-inflammatory therapies for bronchiectasis.The aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state.Six healthy volunteers, 10 patients with mild bronchiectasis, 15 with moderate bronchiectasis and 9 with severe bronchiectasis were recruited. All participants had 60 mL of blood taken and underwent a bronchoscopy while in the stable state. Lipidomics was done on serum and bronchoalveolar lavage fluid (BALF).In the stable state, in serum there were significantly higher levels of prostaglandin EThere is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA

Background Freezing of gait is a highly disabling symptom in persons with Parkinson's disease (PwP). Despite its episodic character, freezing can be reliably evaluated using the FOG score. The description of the minimal clinically relevant change is a requirement for a meaningful interpretation of its results. Objective To determine the minimal clinically relevant change of the FOG score. Methods We evaluated video recordings of a standardized freezing-evoking gait parkour, i.e., the FOG score just before and 30 minutes after the intake of a regular levodopa dose in a randomized blinded fashion. The minimal clinically relevant response was considered a value of one or more on a 7-step Likert-type response scale [-3; +3] that served as the anchor. The minimal clinically relevant change was determined by ROC analysis. Results 37 PwP (Hoehn & Yahr stages 2.5-4, 27 male, 10 female) were aged 68.2 years on average (range 45-80). Mean disease duration was 12.9 years (2-29 years). Minimum FOG score was 0 and Maximum FOG score was 29. Mean FOG scores before medication were 10.6, and 11.1 after medication intake, with changes ranging from -14.7 to +16.7. The minimal clinically relevant change (MCRC) for improvement based on expert clinician rating was three scale points with a sensitivity of 0.67 and a specificity of 0.96. Conclusions The FOG score is recognized as a useful clinical instrument for the evaluation of freezing in the clinical setting. Knowledge of the MCRC should help to define responses to interventions that are discernible and meaningful to the expert physician and to the patient.

Axial deformities such as camptocormia or Pisa syndrome in people with Parkinson’s disease (PwP) are poorly understood. The scarcity of information may result from the shortage of reliable and responsive evaluation instruments. We evaluated the body height loss (BHL) as a new measure for PwP with axial deformities. 50 PwP with axial deformity defined by an UPDRS item 28 value of at least 2 were included in this mono-center study. We measured body height while lying supine and after 1 min of standing, providing a percentage value of BHL, and compared this measure to other clinical variables. BHL depended on the Hoehn and Yahr clinical stage and correlated with clinical scales for function and mobility, but not with timely measures of the axial disorder such as age at diagnosis or duration of disease. ANOVA showed that only lumbar flexion explained the variability of BHL (F = 21.0, p

ZusammenfassungTrotz wachsender Möglichkeiten in der Pharmakotherapie und der tiefen Hirnstimulation können bei der Mehrzahl der Parkinson-Patienten im Verlauf wesentliche Funktionen wie Gleichgewicht, Gehen, Sprechen, Schlucken und Kognition langfristig nur unzureichend gebessert werden. Den aktivierenden Therapien wie Physio-, Sprech-, Schluck- und Ergotherapie kommt hierbei eine zunehmen de Rolle zu. Der Empfehlungsgrad in den S3-Leitlinien erreicht für die Haupttherapie-formen Level A (Physiotherapie) und B (Logopädie, Schlucktherapie, Ergotherapie). Für die Physiotherapie finden sich die meisten Studien. Neue Ansätze mit Krafttraining, Tanzen, Tai Chi sowie gerätegestützte Ansätze wie Laufbandtraining kombiniert mit neuen Entwicklungen wie virtueller Realität und Spielkonsolen („Exergaming“) weisen eine gute Studienevidenz auf. Die S3-Leitlinie der DGN fordert für alle Patienten in allen Stadien Zugang zu einer zeitlich ausreichenden Physiotherapie. Dieser CME Artikel fasst den Stand der aktivierenden Therapien in der Langzeitversorgung von Parkinson-Patienten zusammen.

Menschen mit idiopathischem Parkinson-Syndrom erleben in fortgeschrittenen Erkrankungsstadien bedeutsame Alltagseinschrankungen. Defizite der Balance, dadurch bedingte Sturzgefahr und Sturze begrunden Mobilitatsverluste. Sturze resultieren haufig in rumpfnahen Frakturen und erfordern Krankenhauseinweisungen. Physiotherapeutisch angeleitete Ubungsprogramme sind erfolgreich und konnen kurz- und langfristig die ansteigenden Krankheitskosten dampfen.

Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid., Highlights • Dietary fibre gives both short chain fatty acids and phenolic acids in the colon. • Ferulic acid is partially taken into cells by the transporter MCT1. • Ferulic acid is effluxed basolaterally by the transporter MCT4. • Butyrate upregulates transporters of phenolic acids in a colonic model. • A short chain fatty acid can regulate phenolic acid absorption.

Menschen mit Parkinson fallt es schwer, ihr Bewegungsverhalten richtig einzuschatzen. Das standardisierte Amplitudentraining LSVT BIG hilft ihnen, ihre Bewegungsamplitude zu vergrosern. Es wirkt gezielt auf die bei Parkinson auftretende Hypo- und Bradykinese.

Summary Cellular redox homeostasis and signalling are important in progression of the eukaryotic cell cycle. In animals, the low-molecular-weight thiol tripeptide glutathione (GSH) is recruited into the nucleus early in the cell proliferation cycle. To determine whether a similar process occurs in plants, we studied cell proliferation in Arabidopsis thaliana. We show that GSH co-localizes with nuclear DNA during the proliferation of A. thaliana cells in culture. Moreover, GSH localization in the nucleus was observed in dividing pericycle cells of the lateral root meristem. There was pronounced accumulation of GSH in the nucleus at points in the growth cycle at which a high percentage of the cells were in G1 phase, as identified by flow cytometry and marker transcripts. Recruitment of GSH into the nucleus led to a high abundance of GSH in the nucleus (GSHn) and severe depletion of the cytoplasmic GSH pool (GSHc). Sequestration of GSH in the nucleus was accompanied by significant decreases in transcripts associated with oxidative signalling and stress tolerance, and an increase in the abundance of hydrogen peroxide, an effect that was enhanced when the dividing cells were treated with salicylic acid. Total cellular GSH and the abundance of GSH1 and GSH2 transcripts increased after the initial recruitment of GSH into the nucleus. We conclude that GSH recruitment into the nucleus during cell proliferation has a profound effect on the whole-cell redox state. High GSHn levels trigger redox adjustments in the cytoplasm, favouring decreased oxidative signalling and enhanced GSH synthesis.

Festination and freezing of gait (FOG) are sudden episodic inabilities to initiate or sustain locomotion mostly experienced during the later stages of Parkinson's disease (PD) or other higher-level gait disorders. The aim of this study was to develop a clinical rating instrument for short-interval rating of festination and FOG. Foot movements of 33 patients were video taped and rated during 12 episodes in a standardized course on a four-level interval scale according to severity. Motor blocks were provoked in four situations and by three levels of dual-tasking (tasks). Addition of the item scores produced a FOG score. The assessment requires less than 15 min. The inter-rater and re-test reliability of the FOG score is high (Kendall kappa = 0.85-0.92, P < 0.0001). Variability of the item scale due to situations and tasks can be attributed to unidimensional group factors (Cronbach's alpha 0.84 and 0.94). Group comparisons and a logistic regression model show significant effects for both situations and tasks on the item scale (Friedman test: "situation": P < 0.0001, "task": P < 0.0001). Six patients with PD have significantly different scores during mobile (practical ON; 6.2 +/- 3.9) and immobile (practical OFF; 15.8 +/- 4.6) medication states (P < 0.05). The FOG score correlates with the 10 m number of steps (rho = 0.58; P = 0.001) and with the self-evaluation of FOG (rho = 0.51; P < 0.01). Our results encourage the further use of the FOG score to evaluate festination and FOG.

ZusammenfassungMotorische Blockaden während des Gehens sind als eine episodisch auftretende Störung der Ganginitiierung und des Lokomotionserhalts bei Parkinsonsyndromen und zentralen Gangstörungen definiert. Phänomenologisch werden Festination, trembling-in-place und total akinesia als Freezing-Formen unterschieden. Fünf differente Gangsituationen wurden als klassische Provokatoren für Freezing-Episoden benannt. Um eine Testung durch einen Beobachter klinisch einfach und aussagekräftig durchführen zu können, haben wir ein neues Testinstrument, den Freezing-ofgait-Score (FOG-Score) entwickelt, der im klinischen Alltag erprobt wird. Freezing bei Parkinsonpatienten ist meist dopasensitiv, kann aber auch im On-Zustand des Patienten auftreten und ist dann schwer zu therapieren.Wir diskutieren standardisierte Therapieschemata für Patienten mit On-Freezing, die wir an unserem Zentrum entwickelt haben.

Festgefroren am Boden – so scheint es, wenn Menschen am Freezing of Gait (FOG) leiden. Dieses Symptom kann Patientenmit einem Parkinson-Syndrom erheblich in ihrer Selbstständigkeit einschränken. Der Einsatz externer Signale, sogenannter Cues, hilft, auftretende motorische Blockadenzu überwinden. Die Autorinnen haben aktuelle Studien zum Thema gesichtet undzeigen, welche akustischen und visuellen Cues Patienten einsetzen sollten.

Freezing of gait (FOG) is a common disturbance in Parkinson's disease (PD) and other higher-level gait disorders. It appears most often during the later stages of PD but is seen also during the initial phases before oral substitution of levodopa has started. The disorder has its own pathophysiology and differs from bradykinesia. It can occur both on and off medication. It interferes with activities of daily life, reduces mobility, and is an important risk factor for falling. While patients with FOG during medication do not reliably respond to pharmacotherapy or deep brain stimulation, external cues have been demonstrated that influence FOG effectively. They are applied as auditory, visual, tactile, or mental cues. This article discusses available pharmacological and physiotherapeutic approaches to the treatment of FOG.

UDP-glucuronosyltransferases (UGTs) are highly expressed in liver, intestine and kidney, and catalyze the glucuronic acid conjugation of both endogenous compounds and xenobiotics. Using recombinant human UGT isoforms, we show that glucuronic acid conjugation of the model substrate, (−)-epicatechin, is catalyzed mainly by UGT1A8 and UGT1A9. In HepG2 cells, pretreatment with polyunsaturated fatty acids increased substrate glucuronidation. In the intestinal Caco-2/HT29-MTX co-culture model, overall relative glucuronidation rates were much higher than in HepG2 cells, and (−)-epicatechin was much more readily conjugated when applied to the basolateral side of the cell monolayer. Under these conditions, 95% of the conjugated product was effluxed back to the site of application, and none of the other phase 2-derived metabolites followed this distribution pattern. HT29-MTX cells contained >1000-fold higher levels of UGT1A8 mRNA than Caco-2 or HepG2 cells. Gene expression of UGT1A8 increased after treatment of cells with docosahexaenoic acid, as did UGT1A protein levels. Immunofluorescence staining and Western blotting showed the presence of UGT1A in the basal and lateral parts of the plasma membrane of HT29-MTX cells. These results suggest that some of the UGT1A8 enzyme is not residing in the endoplasmic reticulum but spans the plasma membrane, resulting in increased accessibility to compounds outside the cell. This facilitates more efficient conjugation of substrate and is additionally coupled with rapid efflux by functionally associated basolateral transporters. This novel molecular strategy allows the cell to carry out conjugation without the xenobiotic entering into the interior of the cell.

Jeder Physiotherapeut, der Patienten nach einem Apoplex behandelt, kennt sie – die spastischen Tonuserhöhungen. Diese treten meist vier bis sechs Wochen nach dem Schlaganfall auf und führen zu Fehlstellungen an Hand und Fuß. Je früher man sie behandelt, desto größer ist die Chance, dass man sie in den Griff bekommt.

Ataxie tritt auf, wenn Muskeln nicht mehr koordiniert zusammenspielen, beispielsweise bei Multipler Sklerose, nach Hirnblutungen oder Hirninfarkten. Bei der zerebellären Ataxie ist das Kleinhirn geschädigt oder die zuführenden Bahnen. Lesen Sie, wie sich die Schädigung auf Motorik, Testung und Therapie auswirkt.

Objective: To investigate the efficacy of a two-week programme of repetitive exercise with cueing and movement strategies upon freezing of gait in people with Parkinson’s disease. Design: Randomized cross-over trial. Setting: Specialist clinic for Parkinson’s disease. Subjects: A total of 22 patients with Parkinson’s disease and freezing while other symptoms had favorably responded to dopaminergic treatment. Intervention: Patients were randomized into a four-week cross-over trial, and received either treatment (Group 1) or no treatment (Group 2) during Period 1, and switched during Period 2. Treatment consisted of a two-week programme during which the patients exercised cueing, and movement strategies together with a physiotherapist. Main measure: The primary outcome measure was a freezing score assessed from blinded and random ratings of video recordings. The secondary outcome measure was a patient-reported freezing questionnaire. Mean differences between the treatment periods (treatment arms) were evaluated for treatment (period) effects. Sums of treatment periods were evaluated for carry-over effects. Results: The programme led to a significant treatment effect in the freezing score of 3.0 improvement (95% confidence interval 0.9–5.0; p < 0.01). No carry-over or period effects were detected. The questionnaire revealed a period effect, so groups were compared after Period 1, where a significant difference was found (15.0 vs. 11.7; p < 0.05). Conclusions: The two-week physiotherapy programme reduced the severity of freezing in patients with Parkinson’s disease.

Kapitel C befasst sich mit 'Übergängen am Arbeitsmarkt und Qualität von Beschäftigung'. Parallel zur günstigeren Arbeitsmarktentwicklung hat sich die Polarisierung des deutschen Arbeitsmarktes verschärft: Die Spreizung des Lohngefüges hat sich deutlich verstärkt, 'atypische' Beschäftigungsverhältnisse wie Leiharbeit, befristete Beschäftigung, Teilzeit- und Mini-Jobs haben stark an Bedeutung gewonnen. Die Autorinnen und Autoren dieses Kapitels analysieren die Entwicklung atypischer Beschäftigungsverhältnisse in den vergangenen Jahren und gehen der Frage nach, inwieweit diese Erwerbsformen eine Brücke in stabile und existenzsichernde Beschäftigung bilden.

Oral levodopa has been proposed to be one of the more effective medications to alleviate freezing of gait, but there is limited data on its efficacy. We evaluated the gait phenomenology of 20 Parkinson's disease patients with freezing of gait before and 60 min after a standardized levodopa dose using a rating scale based on the assumption that festination and akinetic freezing share a common pathophysiology. Levodopa abolished festination and freezing in 20% of patients (p 0.0001), and reduced the freezing sum score from a median of 15 (IQR 6.75-27.5) to 3.5 (1-11.25), p 0.001) in all but one of the remainder. Pre-dose ratings correlated with post-dose ratings, in that those patients with lower pre-dose item-scores also showed lower post-dose outcome scores. Levodopa's effect on both festination and akinetic freezing was linear, thereby supporting the concept that festination and freezing are variants on a continuity of episodic gait disorders in PD.

Die Zeitarbeit boomt, in Deutschland noch mehr als in anderen Landern. Allein in der vergangenen Dekade hat sich die Zahl der Leiharbeiternehmer fast verdreifacht. Die wachsende Bedeutung des Zeitarbeitssektors wird offentlich auserst kontrovers diskutiert. Fur die Protagonisten der Zeitarbeit hat sich die umfassende Deregulierung im Zuge der Hartz-Reformen gelohnt. In einer globalisierten Welt, in der es immer mehr darauf ankommt, schnell auf Nachfrageimpulse oder Produktionsanderungen reagieren zu konnen, hat sie den Betrieben ein Instrument an die Hand gegeben, das hohe Flexibilitat beim Personaleinsatz erlaubt. Damit konnen Wettbewerbspositionen verbessert und Marktanteile ausgebaut werden. Zeitarbeit verringert die Such- und Fluktuationskosten. Zugleich ermoglicht sie die Heranfuhrung auch wettbewerbsschwacher oder stigmatisierter Gruppen und schafft einen Zugang zum Arbeitsmarkt. Fur die Gegner ist Zeitarbeit Teufelswerk. Sie sei ein Einfallstor fur eine Verschlechterung der Arbeitsbedingungen und fur „Lohndumping“. Zeitarbeit trage zur Prekarisierung der Beschaftigung bei und verdrange „gute“ Arbeit, also unbefristete Jobs mit annehmbaren Arbeitsbedingungen und stabiler Perspektive. Anstatt zur Integration fuhre sie auf dem Arbeitsmarkt zu Drehtureffekten und in der Gesellschaft zur Exklusion. Zudem werde durch die Zeitarbeit Beschaftigung in den Entleihbetrieben ersetzt. Vermutlich wurde ein neutraler auserirdischer Beobachter nach einer kuhlen Analyse zu dem Urteil kommen, dass beide Seiten ein Stuck weit recht haben.

Parkinson's disease (PD) is a degenerative neurological disorder. Patients suffer from different movement disturbances. Amongst others, freezing of gait (FOG) is a common and disabling feature. A new method for FOG detection using a garment with integrated accelerometers, the MiMed-Pants, is presented and evaluated. MiMed-Pants are loose fitting washable pants for measuring movements and were previously developed. The accelerations of shanks and belt of 6 patients were recorded while walking on two standardized courses. The occurrence of FOG were detected and documented both by the new method and by a physician. Those recordings were then compared afterwards to determine the new method's sensitivity and specificity. With this wearable measurement device FOG could be detected without the distracting effects of an extensive measurement installation.

Cellular redox homeostasis and signalling are important in progression of the eukaryotic cell cycle. In animals, the low-molecular-weight thiol tripeptide glutathione (GSH) is recruited into the nucleus early in the cell proliferation cycle. To determine whether a similar process occurs in plants, we studied cell proliferation in Arabidopsis thaliana. We show that GSH co-localizes with nuclear DNA during the proliferation of A. thaliana cells in culture. Moreover, GSH localization in the nucleus was observed in dividing pericycle cells of the lateral root meristem. There was pronounced accumulation of GSH in the nucleus at points in the growth cycle at which a high percentage of the cells were in G(1) phase, as identified by flow cytometry and marker transcripts. Recruitment of GSH into the nucleus led to a high abundance of GSH in the nucleus (GSHn) and severe depletion of the cytoplasmic GSH pool (GSHc). Sequestration of GSH in the nucleus was accompanied by significant decreases in transcripts associated with oxidative signalling and stress tolerance, and an increase in the abundance of hydrogen peroxide, an effect that was enhanced when the dividing cells were treated with salicylic acid. Total cellular GSH and the abundance of GSH1 and GSH2 transcripts increased after the initial recruitment of GSH into the nucleus. We conclude that GSH recruitment into the nucleus during cell proliferation has a profound effect on the whole-cell redox state. High GSHn levels trigger redox adjustments in the cytoplasm, favouring decreased oxidative signalling and enhanced GSH synthesis.