Neurotoxicology: a clinical systems-based review

Neurological disease caused by toxins is widespread but under-recognised. Despite increasing public interest and a growing number of novel potential neurotoxins, diagnosis of neurotoxic disease is often delayed or missed, resulting in poorer patient outcomes. This article discusses neurotoxic syndromes using a systems-based approach, focusing on environmental and occupational agents. We do not discuss recreational drugs, pharmaceutical agents or developmental neurotoxins in detail. We aim to provide neurologists with a working understanding of the scenarios in which a clinical presentation may be due to a neurotoxin and how to approach confirmation of the diagnosis

The Importance of CD19+ Cells from Pre-diabetic NOD Mice in Delaying Onset of Disease in an Adoptive Transfer Model of Type 1 Diabetes Mellitus

This dissertation describes a protective effect on autoimmune diabetes in NOD.scid recipients following injections of splenocytes from diabetic NOD donors in addition to purified CD19+ cells taken from pre-diabetic 6-week-old NOD female donors, compared to NOD.scid recipients receiving injections of splenocytes from diabetic NOD donors alone. Delayed progression of T1D was associated with a remarkable reduction in IL-1β plasma levels, a reduction in the severity of insulitis, and increased levels of CD19+ precursor B cells (compared to controls) likely exhibiting regulatory function upon activation and interaction with pathogenic T cells. The protective effect conferred by CD19+ cells was age specific as co-transfers of CD19+ cells from 6-week-old NOD mice exhibited a suppressive effect halting and/or significantly delaying the progression of diabetes and insulitis, while those from greater than 15-week-old NOD donors did not confer the same protective effect. Administration of a monoclonal antibody against IL-1β in NOD.scid recipients following injection of diabetic NOD splenocytes significantly delayed diabetes onset, unlike the administration of an isotype-matched antibody. In conclusion, progression to overt disease correlates with the pathogenic T cell’s escape from CD19+ cell–mediated regulation. These data provide evidence for a novel suppressive function of the regulatory B cell compartment in autoimmune diabetes. The expansion of regulatory CD19+ B cells may have therapeutic potential for T1D.PHDImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/137113/1/avonber_1.pd

Differentielle Effekte der tiefen Hirnstimulation von STN und VIM auf kognitive Komponenten der Wortproduktion

Einleitung: Die Behandlung von Morbus Parkinson und essentiellem Tremor durch die Tiefenhirnstimulation (THS) im basalganglionären Nucleus subthalamicus (STN) und thalamischen Nucleus ventralis intermedius (VIM) führt zur Verbesserung entsprechender Bewegungsstörungen. Obwohl THS bzgl. kognitiver Nebenwirkungen als relativ sicher gilt, wurden negative Auswirkungen auf Wortflüssigkeit berichtet. Grundlagen dessen sind unklar, da Wortflüssigkeitsleistungen exekutive und lexikalische Prozesse beinhalten, deren Bezüge zu THS-Zielstrukturen unbekannt sind. Daher wurde zur Differenzierung (i) kognitiver THS- Wirkungen und (ii) Funktionen von THS-Zielstrukturen der Einfluss von STN- vs. VIM- Stimulation auf unterschiedliche Aspekte der Wortproduktion bestimmt. Methodik: Zur Analyse der Wortproduktionsleistung (mittels Regensburger Wortflüssigkeitstest) wurde die „temporale Clusteranalyse“ verwendet, die eine formale Differenzierung schneller (Cluster) vs. langsamer (Switches) Wortproduktionsphasen erlaubt. Cluster gelten als Ergebnis automatischer Aktivitätsausbreitung assoziierter lexikalischer Informationen und reflektieren somit sprachbezogene Netzwerkprozesse. Switches gelten als aufmerksamkeitsabhängige Prozesse, die Transitionen zwischen lexikalischen Assoziationsfeldern widerspiegeln. Um zu überprüfen, ob sich bisher nur im semantischen Kontext erprobte temporale Clusteranalysen auch für Untersuchungen mit Standardwortflüssigkeitsaufgaben eignen, haben wir in Studie 1 das Cluster-/Switchverhalten von 42 gesunden Probanden in einer phonematischen VF-Aufgabe analysiert. In den Studien 2/3 wurde das Cluster-/Switchverhalten von 11/13 Patienten mit STN-THS/VIM-THS im aktiven (STIM-ON-) und inaktiven (STIM-OFF) Stimulationszustand untersucht. Die Ergebnisse wurden jeweils mit den Leistungen gesunder Kontrollprobanden verglichen. Ergebnisse: Studie 1 zeigte, dass im Cluster produzierte Wörter in rein phonematischen VF- Aufgaben semantisch und phonematisch stärker verwandt waren als Switch-bezogene Wörter. Höhere phonematische Wortassoziationswerte gingen einher mit vermehrter, höhere semantische Assoziationswerte mit geringerer Wortflüssigkeitsleistung. Bezüglich THS-Wirkungen in verschiedenen subkortikalen Strukturen ergaben sich unterschiedliche Stimulationswirkungen auf das Cluster-/Switchverhalten. Studie 2 zeigte, dass im STN STIM-ON mehr Switches mit geringeren Switchzeiten generiert wurden als im STIM- OFF, während Clusterparameter unbeeinflusst blieben. In Studie 3 wurde ein gegensätzliches Muster identifiziert: im VIM war STIM-ON mit langsameren Clusterzeiten verbunden als STIM- OFF, ohne Effekte auf die Switchparameter zu haben. Verglichen mit Kontrollprobanden generierten beide Patientengruppen unabhängig vom Stimulationszustand geringere VF- Leistungen. Diskussion: Studie 1 zeigt, dass die temporale Clusteranalyse sowohl im semantischen als auch im phonematischen Kontext exekutive und lexikalische Aspekte der VF-Leistung voneinander abgrenzt. Diese Ergebnisse erweitern Annahmen zum „Semantic Default“-Modus lexikalischer Produktion (siehe Hauptteil) und legitimieren die Verwendung von Standardwortflüssigkeitsaufgaben im gegebenen Kontext. Die Patientenstudien deuten darauf hin, dass der STN keine ‚lexikalische Bedeutung‘ hat, jedoch prozedurale Wortproduktionsprozesse unterstützt, passend zur Einbettung in fronto- striatäre Netzwerke mit vermuteten Exekutivfunktionen. VIM-THS scheint mit thalamischen Funktionen automatischer lexikalischer Informationsrekrutierung zu interferieren. Die Ergebnisse werden unter konzeptuellen und klinischen Gesichtspunkten diskutiert.Introduction: Treatment of Parkinson’s disease and essential tremor via deep brain stimulation (DBS) of the basal ganglia subthalamic nucleus (STN) and the thalamic ventral intermedius nucleus (VIM) improves respective motor deficits. Although DBS is relatively safe regarding cognitive side-effects, negative effects on verbal fluency (VF) have been reported. Reasons for this finding are unclear, since VF-performance includes executive and lexical processes with unknown relation to DBS target structures. For differentiating (i) cognitive DBS-effects and (ii) functions of DBS-structures, we studied effects of STN- vs. VIM-stimulation on different aspects of VF. Method: VF-performance (tested with the standard “Regensburger Wortflüssigkeitstest”) was analysed using the ‘temporal cluster analysis’, allowing a formal distinction between faster (clusters) vs. slower (switches) word production phases. Clusters are regarded as the result of automatic activation of associated word-related information throughout lexical networks, whereas switches rather mirror attention-demanding processes for the transition from a given lexical field to another. To find out whether temporal cluster analysis, which was previously used only in semantic contexts, can be reasonably applied in standard VF-tasks, we investigated cluster and switch performance of 42 healthy subjects in a phonemic VF-task in study 1. In studies 2/3 we analysed the cluster and switch performance of 11/13 patients with STN- DBS/VIM-DBS in the stimulated (STIM-ON) and non-stimulated (STIM-OFF) DBS-condition. Results were compared to those of healthy controls. Results: Study 1 showed that in a phonemic VF-task clustered words had higher semantic and phonemic relations than switch-related words. A stronger phonemic relatedness was associated with increased, a stronger semantic relatedness with decreased VF-performance. Regarding DBS-effects in distinct subcortical structures, different stimulation-effects on cluster and switch performance were found. Study 2 showed that in the STN STIM-ON more switches with slower switch times were generated than in STIM-OFF. Cluster parameters were not affected. Study 3 revealed a contrary pattern: in VIM, STIM-ON was accompanied by slower cluster times compared to STIM-OFF, without affecting switch parameters. Compared to control subjects both patient groups had decreased VF-performances, regardless of their stimulation condition. Discussion: Study 1 indicates that temporal cluster analysis can differentiate executive and lexical aspects of VF-performance in semantic and phonemic contexts. The results extend assumptions about a “semantic default” mode of lexical production (see main text) and legitimize the use of standard VF-tasks in the given framework. The patient studies suggest that the STN has no proper “lexical relevance”; however, it seems to support procedural VF-processes, compatible with its embedding in frontostriatal networks with suggested executive functions. VIM-DBS seems to interfere with thalamic functions of automatic lexical information recruitment. Results are discussed in conceptual and clinical contexts

Dopant-Bound Spinons in Cu_(1-x)Zn_xGeO_3

Polarized inelastic light scattering experiments on Cu_(1-x)Zn_xGeO_3 (0<= x 0 a new distinct mode at nearly half the energy of the singlet response below the spin-Peierls transition. The temperature, magnetic field, polarization, and doping dependencies of this mode are similar to those of the singlet bound state. The data are interpreted in terms of a spinon-assisted light scattering process. Position and form of the peak provide strong evidence for the presence of dopant-bound spinons in Cu_(1-x)Zn_xGeO_3.Comment: 4 pages, Latex with 3 figures, including EPL style files, Eur. Phys. Lett. in pres

Impact of a silver layer on the membrane of tap water filters on the microbiological quality of filtered water

<p>Abstract</p> <p>Background</p> <p>Bacteria in the hospital's drinking water system represent a risk for the acquisition of a nosocomial infection in the severely immunocompromised host. Terminal tap water filters may be used to prevent nosocomial Legionnaires' disease. We present data from water samples using an improved kind of tap water filters.</p> <p>Methods</p> <p>In a blinded study on an intermediate care unit of the thoracic surgery department, a modified type of the Germlyser water filter (Aqua-Free Membrane Technology) with a newly-introduced silver layer on the filtration membrane was compared to its preceding type without such a layer on 15 water outlets. We determined growth of <it>Legionella</it>, other pathogenic bacteria, and the total heterotrophic plate count in unfiltered water and filtered water samples after filter usage intervals of 1 through 4 weeks.</p> <p>Results</p> <p>A total of 299 water samples were tested. Twenty-nine of the 60 unfiltered water samples contained <it>Legionella </it>of various serogroups (baseline value). In contrast, all samples filtered by the original water filter and all but one of the water samples filtered by the modified filter type remained <it>Legionella</it>-free. No other pathogenic bacteria were detected in any filtered sample. The total plate count in water samples increased during use of both kinds of filters over time. However, for the first 7 days of use, there were significantly fewer water samples containing >100 CFU per mL when using the new filter device compared with the older filters or taps with no filter. No advantage was seen thereafter.</p> <p>Conclusion</p> <p>The use of this type of terminal water filter is an appropriate method to protect immunocompromised patients from water-borne pathogens such as <it>Legionella</it>.</p