Pretreatment With Fragments of Substance-P or With Cholecystokinin Differentially Affects Recovery From Sub-Total Nigrostriatal 6-Hydroxydopamine Lesion

The neuropeptide substance P is known to have mnemogenic and reinforcing actions and can exert neurotrophic and regenerative effects in vitro as well as in vivo. Furthermore, our previous work in the rat showed that either pre- or post-lesion treatment with substance P can promote functional recovery in cases of partial nigrostriatal dopamine lesions. Other work has provided evidence that the effects of substance P might be differentially encoded by its C- and N-terminal fragments. The C-terminal fragment was found to be reinforcing, whereas the mnemogenic as well as neurotrophic properties have been ascribed to the N-terminal sequences. Given these relations, we asked here whether pre-lesion treatment with either a C- or an N-terminal fragment of substance P might differentially affect the behavioral and neurochemical outcome of nigrostriatal dopamine lesions. Therefore, either substance P1−7 or substance P5−11 (37 nmol/kg each) was administered intraperitoneally daily for eight consecutive days before unilateral 6-hydroxy-dopamine lesions of the substantia nigra. Control rats received prelesion treatment with vehicle. Furthermore, we investigated the effects of pre-treatment with Boc-cholecystokinin-4 (0.91 nmol/kg), as we had found an increase in dopamine metabolism in animals that were pre-treated with cholecystokinin-8 in a former study. In accordance with our previous work, drug treatment effects were observed when excluding animals with most severe dopamine lesions: In animals with partial lesions (residual neostriatal dopamine levels of more than 10%), lesion-dependent asymmetries in turning behavior were observed in animals that were pre-treated with vehicle-, substance P1−7 , or Boc-cholecysto-kinin–4,. whereas turning after pre-treatment with substance P5−11 was not significantly asymmetrical. Furthermore, the ipsi- and contra-lateral neostriatal dopamine levels did not differ significantly in this group. Moreover, pre treatment with substance P5−11 affected dopamine metabolism in the neostriatum and in the venral striatum, as indicated by increased ratios of dihydroxyphenyllic acid to dopamine. The data provide the first evidence that the promotive effects of substance-P treatment in the unilateral dopamine lesion model might be mediated by its C-terminal and might depend on actions on residual dopamine mechanisms

Case report of a cervical myelomalacia caused by a thoracolumbar intradural disc herniation leading to intracranial hypotension

A 50-year-old patient was admitted with symptoms of intracranial hypotension. MRI revealed a cervical myelomalacia caused by engorged epidural veins leading to a stenosis of the spinal canal. This condition is rarely described in patients with hydrocephalus and ventricular shunts suffering from chronic overdrainage. However, the reason in this patient was a CSF leak caused by an intradural disc herniation at T12/L1. After surgery, symptoms resolved and the cervical myelomalacia and the swollen epidural veins disappeared on postoperative MRI. In patients with engorged cervical epidural veins without a ventricular shunt, a CSF leak has to be considered

Twins in rotational spectroscopy: Does a rotational spectrum uniquely identify a molecule?

Rotational spectroscopy is the most accurate method for determining structures of molecules in the gas phase. It is often assumed that a rotational spectrum is a unique "fingerprint" of a molecule. The availability of large molecular databases and the development of artificial intelligence methods for spectroscopy makes the testing of this assumption timely. In this paper, we pose the determination of molecular structures from rotational spectra as an inverse problem. Within this framework, we adopt a funnel-based approach to search for molecular twins, which are two or more molecules, which have similar rotational spectra but distinctly different molecular structures. We demonstrate that there are twins within standard levels of computational accuracy by generating rotational constants for many molecules from several large molecular databases, indicating the inverse problem is ill-posed. However, some twins can be distinguished by increasing the accuracy of the theoretical methods or by performing additional experiments

Stromal cell-derived factor-1 (chemokine C-X-C motif ligand 12) and chemokine C-X-C motif receptor 4 are required for migration of gonadotropin-releasing hormone neurons to the forebrain

Gonadotropin-releasing hormone (GnRH) neurons migrate from the vomeronasal organ (VNO) in the nasal compartment to the basal forebrain in mice, beginning on embryonic day 11 (E11). These neurons use vomeronasal axons as guides to migrate through the nasal mesenchyme. Most GnRH neurons then migrate along the caudal branch of the vomeronasal nerve to reach the hypothalamus. We show here that stromal cell-derived factor-1 [SDF-1, also known as chemokine C-X-C motif ligand 12 (CXCL12)] is expressed in the embryonic nasal mesenchyme from as early as E10 in an increasing rostral to caudal gradient that is most intense at the border of the nasal mesenchyme and the telencephalon. Chemokine C-X-C motif receptor 4 (CXCR4), the receptor for SDF-1, is expressed by neurons in the olfactory epithelium and VNO. Cells derived from these sensory epithelia, including migrating GnRH neurons and ensheathing glial precursors of the migrating mass (MM), also express CXCR4, suggesting that they may use SDF-1 as a chemokine. In support of this, most GnRH neurons of CXCR4-/- mice fail to exit the VNO at E13, and comparatively few GnRH neurons reach the forebrain. There is also a significant decrease in the total number of GnRH neurons in CXCR4-/- mice and an increase in cell death within the VNO relative to controls. The MM is smaller in CXCR4-/- mice, suggesting that some MM cells also require SDF-1/CXCR4 function for migration and survival

Live view of gonadotropin-releasing hormone containing neuron migration

Neurons that synthesize GnRH control the reproductive axis and migrate over long distances and through different environments during development. Prior studies provided strong clues for the types of molecules encountered and movements expected along the migratory route. However, our studies provide the first real-time views of the behavior of GnRH neurons in the context of an in vitro preparation that maintains conditions comparable to those in vivo. The live views provide direct evidence of the changing behavior of GnRH neurons in their different environments, showing that GnRH neurons move with greater frequency and with more changes in direction after they enter the brain. Perturbations of guiding fibers distal to moving GnRH neurons in the nasal compartment influenced movement without detectable changes in the fibers in the immediate vicinity of moving GnRH neurons. This suggests that the use of fibers by GnRH neurons for guidance may entail selective signaling in addition to mechanical guidance. These studies establish a model to evaluate the influences of specific molecules that are important for their migration

Position paper on the use of mandibular advancement devices in adults with sleep-related breathing disorders: A position paper of the German Society of Dental Sleep Medicine (Deutsche Gesellschaft Zahnaerztliche Schlafmedizin, DGZS)

Custom-made mandibular advancement devices are an effective treatment option for snoring, upper airway resistance syndrome, and obstructive sleep apnea (OSA). Evidence-based data indicates their efficacy, and international sleep societies recommend oral appliance (OA) therapy for patients with sleep-related breathing disorders. The following position paper by the German Society of Dental Sleep Medicine (DGZS) is to guide the interdisciplinary team (sleep physician and sleep disorder dentist) in detail when to prescribe oral appliances. This position paper supports the responsible use of OA as an effective treatment option for patients with sleep-related breathing disorders. The paper advises of proper indication regarding OSA severity, body mass index (BMI), and dentition. It emphasizes the interdisciplinary approach of oral appliance therapy and suggests treatment under the guidance of dentists trained in dental sleep medicine

A Parallel Autonomy Research Platform

We present the development of a full-scale “parallel autonomy” research platform including software and hardware. In the parallel autonomy paradigm, the control of the vehicle is shared; the human is still in control of the vehicle, but the autonomy system is always running in the background to prevent accidents. Our holistic approach includes: (1) a driveby-wire conversion method only based on reverse engineering, (2) mounting of relatively inexpensive sensors onto the vehicle, (3) implementation of a localization and mapping system, (4) obstacle detection and (5) a shared controller as well as (6) integration with an advanced autonomy simulation system (Drake) for rapid development and testing. The system can operate in three modes: (a) manual driving, (b) full autonomy, where the system is in complete control of the vehicle and (c) parallel autonomy, where the shared controller is implemented. We present results from extensive testing of a full-scale vehicle on closed tracks that demonstrate these capabilities

Die Subanalyse von Rheuma-VOR zeigt den erheblichen Bedarf der rheumatologischen Versorgung auf

Background: Early diagnosis and treatment of inflammatory rheumatic diseases can prevent consequential damage such as permanently limited mobility and joint or organ damage. Simultaneously, there is an increasing deficit in medical care owing to the lack of rheumatological capacity. Rural regions are particularly affected. Objectives: The available unconfirmed diagnoses of the study Rheuma-VOR were analysed regarding another definitive inflammatory rheumatic disease. Materials and methods: The returned questionnaires of the rheumatologists participating in Rheuma-VOR were screened for definitive inflammatory rheumatic diseases other than the required diagnosis of rheumatoid arthritis, psoriatic arthritis or spondyloarthritis. Results: Of 910 unconfirmed diagnoses, in 245 patients another definitive diagnosis could be confirmed. A total of 29.8% of the diagnoses corresponded to degenerative joint changes or chronic pain syndrome, whereas 26.1% involved different forms of inflammatory arthritis. The majority of diagnoses (40.5%) were collagenosis or vasculitis, Discussion: The available data show that a rheumatological presentation was indicated for the majority of patients. Owing to the increasing deficits in medical care a prior selection of the patients is crucial to make optimal use of restricted rheumatological capacities.Hintergrund: Eine frühe Diagnose und Behandlung entzündlich-rheumatischer Erkrankungen kann Folgeschäden wie dauerhafte Einschränkungen der Mobilität und Gelenk- oder Organschäden verhindern. Gleichzeitig besteht ein größer werdendes Versorgungsdefizit aufgrund fehlender rheumatologischer Kapazitäten. Betroffen sind besonders die ländlichen Regionen. Ziel der Arbeit: Die vorliegenden nicht bestätigten Diagnosen der Studie Rheuma-VOR wurden hinsichtlich des Vorliegens einer anderen definitiven entzündlich-rheumatischen Erkrankung analysiert. Material und Methoden: Die eingegangenen Fragebögen der an der Rheuma-VOR-Studie teilnehmenden Rheumatolog:innen wurden nach Vermerken anderer entzündlich-rheumatischer Erkrankungen als der geforderten Diagnose einer rheumatoiden Arthritis, Psoriasis-Arthritis oder Spondyloarthritis gescreent. Ergebnisse: Von 910 „nicht bestätigten“ Diagnosen waren bei 245 Patient:innen andere gestellte Diagnosen auszuwerten. Insgesamt 29,8 % der Diagnosen entsprechen degenerativen Gelenkveränderungen oder chronischen Schmerzsyndromen, bei 26,1 % lagen verschiedene Formen entzündlicher Arthritiden vor. Der Großteil der Diagnosen (40,5 %) entfiel auf Kollagenosen und Vaskulitiden, wobei die Polymyalgia rheumatica mit 20 % am häufigsten diagnostiziert wurde (49 Patient:innen). Diskussion: Die vorliegenden Daten zeigen, dass bei einem Großteil der Patient:innen die rheumatologische Vorstellung indiziert war. Aufgrund der ambulanten Versorgungsdefizite ist eine vorherige Selektion des Patientenguts essenziell, um die eingeschränkten Kapazitäten bestmöglich zu nutzen

Yardstick Competition in German Municipalities

Does increasing transparency improve fiscal policy behavior of local governments? One way this could take place is via Yardstick Competition between incumbents of neighboring municipalities. This paper contributes to the literature by introducing a simple model which employs probabilistic voting to show the effect of Yardstick Competition on the amount of political rents diverted from the tax revenue. Since additional rents lower the probability of being reelected, the incumbent will reduce equilibrium rents if voters use information on fiscal performance in similar municipalities to evaluate the incumbent's quality. I test this hypothesis on a panel dataset of municipal budget and electoral data in the german state of Northrine-Westphalia. I show evidence for Yardstick Competition in the local business and property tax rates.Kann zunehmende Transparenz im kommunalen Budgetprozess die fiskalpolitische Disziplin der politischen Entscheidungsträger verbessern? In dieser Arbeit wird ein positiver Modellrahmen entwickelt, anhand dessen die Wirkungsweise von steigen - der Transparenz auf das Entscheidungsverhalten von Kommunalpolitikern durch den Yardstick Competition Effekt dargestellt werden kann. Politiker reduzieren die Veruntreuung finanzieller Mittel, wenn ihr Verhalten von den Wählern relativ zur Leistung von Politikern in benachbarten Kommunen bewertet wird. Unter Anwendung von Methoden der räumlichen Ökonometrie auf kommunale Haushalts- und Wahldaten der Jahre 1989 bis 2004 wird gezeigt, dass die räumliche Korrelation in den Gewerbe- und Grundsteuerhebesätzen in Nordrhein-Westfalen auf die Existenz von Yardstick Competition zurückzuführen ist