Increasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson's disease. However, whether beta bursts occur during precise and ...prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson's disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson's disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.
Translational experimental approaches that help us better trace Parkinson's disease (PD) pathophysiological mechanisms leading to new therapeutic targets are urgently needed. In this article, we ...review recent experimental and clinical studies addressing abnormal neuronal activity and pathological network oscillations, as well as their underlying mechanisms and modulation. Our aim is to enhance our knowledge about the progression of Parkinson's disease pathology and the timing of its symptom's manifestation. Here, we present mechanistic insights relevant for the generation of aberrant oscillatory activity within the cortico-basal ganglia circuits. We summarize recent achievements extrapolated from available PD animal models, discuss their advantages and limitations, debate on their differential applicability, and suggest approaches for transferring knowledge on disease pathology into future research and clinical applications.
Abstract
Deciphering the physiological patterns of motor network connectivity is a prerequisite to elucidate aberrant oscillatory transformations and elaborate robust translational models of movement ...disorders. In the proposed translational approach, we studied the connectivity between premotor (PMC) and primary motor cortex (M1) by recording high-density electroencephalography in humans and between caudal (CFA) and rostral forelimb (RFA) areas by recording multi-site extracellular activity in mice to obtain spectral power, functional and effective connectivity. We identified a significantly higher spectral power in β- and γ-bands in M1compared to PMC and similarly in mice CFA layers (L) 2/3 and 5 compared to RFA. We found a strong functional β-band connectivity between PMC and M1 in humans and between CFA L6 and RFA L5 in mice. We observed that in both humans and mice the direction of information flow mediated by β- and γ-band oscillations was predominantly from PMC toward M1 and from RFA to CFA, respectively. Combining spectral power, functional and effective connectivity, we revealed clear similarities between human PMC-M1 connections and mice RFA-CFA network. We propose that reciprocal connectivity of mice RFA-CFA circuitry presents a suitable model for analysis of motor control and physiological PMC-M1 functioning or pathological transformations within this network.
HintergrundLange, wenig unterbrochene Sitzzeiten, auch am Arbeitsplatz, werden als Risikofaktor für die Gesundheit eingeschätzt. Unterschiedliche Interventionsansätze, die das Sitzverhalten am ...Arbeitsplatz adressieren, wurden überprüft und zeigen heterogene Ergebnisse.FragestellungZiel der folgenden Übersichtsarbeit ist die Zusammenfassung des vorliegenden Wissens zur Wirksamkeit der Interventionen und die Diskussion des aktuellen Forschungsbedarfs.MethodeEs wurde systematisch nach Reviews zum Thema in den Datenbanken PubMed, SportDiscus und PsycInfo recherchiert. Interventionsstrategien wurden klassifiziert und in Bezug auf ihre Wirkung auf Sitzverhalten, Energieverbrauch und Gesundheit beschrieben.ErgebnisseViele Erkenntnisse liegen zu Interventionen, die die Arbeitsumgebung adressieren, vor: Höhenverstellbare Schreibtische können Sitzzeiten bis zu etwa 2 h/Arbeitstag reduzieren, tragen jedoch im Gegensatz zu dynamischen Arbeitsplätzen, z. B. dem Laufbandschreibtisch, kaum zur Steigerung des Energieverbrauchs bei. Mit dynamischen Arbeitsplätzen können Einschränkungen der Arbeitsleistung verbunden sein. In Bezug auf die Reduktion der Sitzzeit sind auf die Arbeitsumgebung bezogene Interventionen und Multikomponenten-Interventionen gegenüber auf das Individuum bezogene edukative Maßnahmen erfolgreicher.DiskussionForschungsbedarf besteht vor allem bzgl. Interventionsstudien mit hoher Qualität und langer Beobachtungszeit zur Überprüfung der Nachhaltigkeit. Die Studien geben zurzeit noch unzureichend Aufschluss darüber, inwieweit eine durch die Intervention erreichte Veränderung des Sitz- und Bewegungsverhaltens mit der Veränderung physiologischer Parameter, z. B. dem BMI oder dem Blutdruck, verbunden ist, um einschätzen zu können, welche Strategien in Bezug auf den gesundheitlichen Benefit am aussichtsreichsten sind.
Zusammenfassung
Hintergrund
Lange, wenig unterbrochene Sitzzeiten, auch am Arbeitsplatz, werden als Risikofaktor für die Gesundheit eingeschätzt. Unterschiedliche Interventionsansätze, die das ...Sitzverhalten am Arbeitsplatz adressieren, wurden überprüft und zeigen heterogene Ergebnisse.
Fragestellung
Ziel der folgenden Übersichtsarbeit ist die Zusammenfassung des vorliegenden Wissens zur Wirksamkeit der Interventionen und die Diskussion des aktuellen Forschungsbedarfs.
Methode
Es wurde systematisch nach Reviews zum Thema in den Datenbanken PubMed, SportDiscus und PsycInfo recherchiert. Interventionsstrategien wurden klassifiziert und in Bezug auf ihre Wirkung auf Sitzverhalten, Energieverbrauch und Gesundheit beschrieben.
Ergebnisse
Viele Erkenntnisse liegen zu Interventionen, die die Arbeitsumgebung adressieren, vor: Höhenverstellbare Schreibtische können Sitzzeiten bis zu etwa 2 h/Arbeitstag reduzieren, tragen jedoch im Gegensatz zu
dynamischen Arbeitsplätzen
, z. B. dem Laufbandschreibtisch, kaum zur Steigerung des Energieverbrauchs bei. Mit dynamischen Arbeitsplätzen können Einschränkungen der Arbeitsleistung verbunden sein. In Bezug auf die Reduktion der Sitzzeit sind auf die Arbeitsumgebung bezogene Interventionen und Multikomponenten-Interventionen gegenüber auf das Individuum bezogene edukative Maßnahmen erfolgreicher.
Diskussion
Forschungsbedarf besteht vor allem bzgl. Interventionsstudien mit hoher Qualität und langer Beobachtungszeit zur Überprüfung der Nachhaltigkeit. Die Studien geben zurzeit noch unzureichend Aufschluss darüber, inwieweit eine durch die Intervention erreichte Veränderung des Sitz- und Bewegungsverhaltens mit der Veränderung physiologischer Parameter, z. B. dem BMI oder dem Blutdruck, verbunden ist, um einschätzen zu können, welche Strategien in Bezug auf den gesundheitlichen Benefit am aussichtsreichsten sind.
The pharmacokinetics of a new potent beta-adrenoceptor blocking drug, bis-4-(2-hydroxy-3-isopropylamino-propoxy)-2-methyl indole sulphate (LF 17-895), have been studied in 5 volunteers after single ...oral (10 mg) and intravenous (4 mg) doses in a cross-over design. Following oral administration adsorption was rapid with peak plasma concentrations recorded after 3 h. Following the intravenous dose a biphasic decline of the plasma level curve was observed. The half-life of plasma elimination during beta-phase was 4.6 +/- 0.7 (p.o.) and 4.7 +/- 0.3 (i.v.) h, respectively. Absorption of the drug was 88.3 +/- 9.6% comparing the areas under the curve. 28.4 +/- 2.2% of the dose given i.v. was excreted in urine unchanged. When the pharmacokinetic data obtained with LF 17-895 were compared with those of pindolol, which differs only in lacking one methyl group in position 2 at the indole ring, only minor differences were seen: absorption of pindolol as well as plasma elimination were slightly faster.
Summary
Cow's milk is a common cause of food allergy in children. Children usually outgrow cow's milk allergy by the age of 3–5 years, but some will have persistent symptoms beyond childhood. We ...performed a systematic review of randomized controlled trials (RCTs) and observational studies to assess the evidence supporting the use of oral immunotherapy in IgE‐mediated cow's milk allergy to inform the World Allergy Organization guidelines. Of 1034 screened articles published until May 2011, five RCTs and five observational studies fulfilled a priori specified inclusion criteria. RCTs including 218 patients showed that oral immunotherapy, compared to elimination diet alone, increased the likelihood of achieving full tolerance of cow's milk relative risk: 10.0 (95% CI: 4.1–24.2). Adverse effects of immunotherapy include frequent local symptoms (16% of doses), mild laryngospasm relative risk: 12.9 (1.7–98.6), mild asthma rate ratio: 3.8 (2.9–5.0), reactions requiring oral glucocorticosteroids relative risk: 11.3 (2.7–46.5) or intramuscular epinephrine injection rate ratio 5.8 (1.6–21.9). Results of observational studies were consistent with those of RCTs. Despite the availability of RCTs, the overall low quality of evidence leaves important uncertainty about anticipated effects of immunotherapy due to very serious imprecision of the estimates of effects and the likelihood of publication bias for some of the critical outcomes. A potentially large benefit of oral immunotherapy in patients with cow's milk allergy may be counterbalanced by frequent and sometimes serious adverse effects. Additional, larger RCTs measuring all patient‐important outcomes are still needed.
Radiocarbon (14C) analysis is a unique tool to distinguish fossil/nonfossil sources of carbonaceous aerosols. We present 14C measurements of organic carbon (OC) and total carbon (TC) on highly time ...resolved filters (3–4 h, typically 12 h or longer have been reported) from 7 days collected during California Research at the Nexus of Air Quality and Climate Change (CalNex) 2010 in Pasadena. Average nonfossil contributions of 58% ± 15% and 51% ± 15% were found for OC and TC, respectively. Results indicate that nonfossil carbon is a major constituent of the background aerosol, evidenced by its nearly constant concentration (2–3 μgC m−3). Cooking is estimated to contribute at least 25% to nonfossil OC, underlining the importance of urban nonfossil OC sources. In contrast, fossil OC concentrations have prominent and consistent diurnal profiles, with significant afternoon enhancements (~3 μgC m−3), following the arrival of the western Los Angeles (LA) basin plume with the sea breeze. A corresponding increase in semivolatile oxygenated OC and organic vehicular emission markers and their photochemical reaction products occurs. This suggests that the increasing OC is mostly from fresh anthropogenic secondary OC (SOC) from mainly fossil precursors formed in the western LA basin plume. We note that in several European cities where the diesel passenger car fraction is higher, SOC is 20% less fossil, despite 2–3 times higher elemental carbon concentrations, suggesting that SOC formation from gasoline emissions most likely dominates over diesel in the LA basin. This would have significant implications for our understanding of the on‐road vehicle contribution to ambient aerosols and merits further study.
Key Points
Nonfossil carbon concentrations in Pasadena are constant throughout the day
Fossil afternoon increase after arrival of the western Los Angeles basin plume
Fossil increase is mainly due to fresh SOA formed in the LA basin plume