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AbstractWe present three “hard” diagrams of the unknot. They require (at least) three extra crossings before they can be simplified to the trivial unknot diagram via Reidemeister moves in S2. Two of them are constructed by applying previously proposed methods. The proof of their hardness uses significant computational resources. We also determine that no small “standard” example of a hard unknot diagram requires more than one extra crossing for Reidemeister moves in S2.

AbstractGay and Kirby recently introduced the concept of a trisection for arbitrary smooth, oriented closed 4-manifolds, and with it a new topological invariant, called the trisection genus. This paper improves and implements an algorithm due to Bell, Hass, Rubinstein and Tillmann to compute trisections using triangulations, and extends it to non-orientable 4–manifolds. Lower bounds on trisection genus are given in terms of Betti numbers and used to determine the trisection genus of all standard simply connected PL 4-manifolds. In addition, we construct trisections of small genus directly from the simplicial structure of triangulations using the Budney-Burton census of closed triangulated 4-manifolds. These experiments include the construction of minimal genus trisections of the non-orientable 4-manifolds and

It is well established that even moderate levels of alcohol affect cognitive functions such as memory, self‐related information processing, and response inhibition. Nevertheless, the neural mechanisms underlying these alcohol‐induced changes are still unclear, especially on the network level. The default mode network (DMN) plays an important role in memory and self‐initiated mental activities; hence, studying functional interactions of the DMN may provide new insights into the neural mechanisms underlying alcohol‐related changes. We investigated resting‐state functional connectivity (rsFC) of the DMN in a cohort of 37 heavy drinkers at a breath alcohol concentration of 0.8 g/kg. Alcohol and saline were infused in a single‐blind crossover design. Intranetwork connectivity analyses revealed that participants showed significantly decreased rsFC of the right hippocampus and right middle temporal gyrus during acute alcohol exposure. Moreover, follow‐up analyses revealed that these rsFC decreases were more pronounced in participants who reported stronger craving for alcohol. Exploratory internetwork connectivity analyses of the DMN with other resting‐state networks showed no significant alcohol‐induced changes, but suffered from low statistical power. Our results indicate that acute alcohol exposure affects rsFC within the DMN. Functionally, this finding may be associated with impairments in memory encoding and self‐referential processes commonly observed during alcohol intoxication. Future resting‐state functional magnetic resonance imaging studies might therefore also investigate memory function and test whether DMN‐related connectivity changes are associated with alcohol‐induced impairments or craving. Our study investigated the effects of alcohol (ALC) on functional brain connectivity in 37 heavy drinkers. Compared to saline (SAL), moderate alcohol exposure (0.8 g/kg) significantly decreased the functional connectivity of two brain areas within the default mode network (DMN). The DMN is a brain system implicated in memory processes and self‐initiated mentation. It is active when we are awake but resting. Our findings help explain dysfunctions in episodic memory encoding and self‐referential processing apparent after moderate alcohol consumption.

For 3‐dimensional convex polytopes, inscribability is a classical property that is relatively well‐understood due to its relation with Delaunay subdivisions of the plane and hyperbolic geometry. In particular, inscribability can be tested in polynomial time, and for every f‐vector of 3‐polytopes, there exists an inscribable polytope with that f‐vector. For higher dimensional polytopes, much less is known. Of course, for any inscribable polytope, all of its lower dimensional faces need to be inscribable, but this condition does not appear to be very strong. We observe non‐trivial new obstructions to the inscribability of polytopes that arise when imposing that a certain inscribable face be inscribed. Using this obstruction, we show that the duals of the 4‐dimensional cyclic polytopes with at least eight vertices — all of whose faces are inscribable — are not inscribable. This result is optimal in the following sense: We prove that the duals of the cyclic 4‐polytopes with up to seven vertices are, in fact, inscribable. Moreover, we interpret this obstruction combinatorially as a forbidden subposet of the face lattice of a polytope, show that d‐dimensional cyclic polytopes with at least d+4vertices are not circumscribable, and that no dual of a neighborly 4‐polytope with eight vertices, that is, no polytope with f‐vector (20,40,28,8), is inscribable.

The Turaev–Viro invariants are a powerful family of topological invariants for distinguishing between different 3-manifolds. They are invaluable for mathematical software, but current algorithms to compute them require exponential time. The invariants are parameterized by an integer $$r \ge 3$$ r≥3 . We resolve the question of complexity for $$r=3$$ r=3 and $$r=4$$ r=4 , giving simple proofs that the Turaev–Viro invariants for $$r=3$$ r=3 can be computed in polynomial time, but computing the invariant for $$r=4$$ r=4 is #P-hard. Moreover, we describe an algorithm for arbitrary r, which is fixed-parameter tractable with respect to the treewidth of the dual graph of the input triangulation. We show through concrete implementation and experimentation that this algorithm is practical—and indeed preferable—to the prior state of the art for real computation. The algorithm generalises to every triangulated 3-manifold invariant defined from tensor network contraction.

Zusammenfassung.Zielsetzung:Suchtkranke Personen und insbesondere Methamphetamin (MA) -abhängige schwangere Frauen, Mütter und Väter brauchen spezifische Hilfsangebote für sich und ihre Kinder. Am Universitätsklinikum Dresden wurde 2016 dazu das interdisziplinäre Programm „Mama denk‘ an mich“ (MAMADAM) ins Leben gerufen, dessen suchttherapeutischer Teil hier vorgestellt wird. Methode:Die Therapieaufgaben der Ärzte, Psychologen und Sozialarbeiter werden dargestellt. Spezifisch gehören dazu die MA-spezifische Gruppenpsychotherapie für schwangere Frauen und Mütter, Vorgehen beim Abstinenznachweis und bei positivem Drogentest sowie die Zusammenarbeit mit den Jugendämtern. Ergebnisse: Bislang wurden insgesamt 13 Schwangere, 49 Mütter und19 Väter vorstellig. Die Hauptsuchtmittel waren MA (65 %), Alkohol (18 %) und Cannabis (15 %). Komorbide psychiatrische Störungen lagen bei 78 % der Fälle vor, bei 56 % beinhaltete dies auch nicht suchtbezogene Störungen. 71 % waren zu Therapiebeginn überwiegend fremdmotiviert, 71 % bezogen Arbeitslosengeld II und 38 % waren vorbestraft. Die Haltequote für Patienten, die ins Therapieprogramm eingeschlossen wurden, lag bei 77 % bei einer Therapiedauer von 22 Wochen (Median). 20 Patienten wurden in stationäre Entgiftungs-/Reha-Behandlung vermittelt. Diskussion:Die behandelte Stichprobe stellt eine hoch risikobehaftete Klientel dar. Dennoch gelang es im ambulanten Setting, den überwiegenden Anteil abstinent in Therapie zu halten. Die ambulante psychiatrische Suchttherapie kann somit für Eltern eine sinnvolle Alternative zur stationären Langzeittherapie darstellen.

ABSTRACTTight triangulations are exotic, but highly regular objects in combinatorial topology. A triangulation is tight if all its piecewise linear embeddings into a Euclidean space are as convex as allowed by the topology of the underlying manifold. Tight triangulations are conjectured to be strongly minimal and proven to be so for dimensions ⩽ 3. However, in spite of substantial theoretical results about such triangulations, there are precious few examples. In fact, apart from dimension two, we do not know if there are infinitely many of them in any given dimension. In this article, we present a computer-friendly combinatorial scheme to obtain tight triangulations and present new examples in dimensions three, four, and five. Furthermore, we describe a family of tight triangulated d-manifolds, with 2d− 1⌊d/2⌋!⌊(d− 1)/2⌋! isomorphically distinct members for each dimension d⩾ 2. While we still do not know if there are infinitely many tight triangulations in a fixed dimension d> 2, this result shows that there are abundantly many.

While the utility of experimental free‐access alcohol self‐administration paradigms is well established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self‐administration studies. Timeline Follow‐back drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing 1 of 2 similar alcohol self‐administration paradigms. In study 1, 18 social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self‐infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D‐LAYA), who participated in 2 sessions of alcohol self‐infusion up to a maximum BACof 120 mg%, and a nonexposed age‐matched control group of 42 (28 females, mean age 18.4 years) subjects. In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to prestudy levels (p< 0.05, respectively). In study 2, alcohol‐exposed participants reported 7.1% and non‐alcohol‐exposed controls 6.5% fewer drinking days at poststudy measurement (p< 0.001), while percent heavy drinking days and drinks per drinking day did not differ. These data suggest that participation in intravenous alcohol self‐administration experiments does not increase subsequent real‐life drinking of young adults.

Abstract: We present a constructive proof that there exists a decomposition of the 2-skeleton of the k-dimensional cross polytope β k into closed surfaces of genus g ≤ 1, each with a transitive automorphism group given by the vertex transitive $${\mathbb{Z}_{2k}}$$ -action on β k . Furthermore we show that for each $${k \equiv 1, 5(6)}$$ the 2-skeleton of the (k − 1)-simplex is a union of highly symmetric tori and Möbius strips.

simpcomp is an extension to GAP, the well known system for computational discrete algebra. It allows the user to work with simplicial complexes. In the latest version, support for simplicial blowups and discrete normal surfaces was added. Furthermore, new functions for constructing certain infinite series of triangulations have been implemented and interfaces to other software packages have been improved to previous versions.

The 4-dimensional abstract Kummer variety K4with 16 nodes leads to the K3 surface by resolving the 16 singularities. Here we present a simplicial realization of this minimal resolution. Starting with a minimal 16-vertex triangulation of K4, we resolve its 16 isolated singularities—step by step—by simplicial blowups. As a result we obtain a 17-vertex triangulation of the standard PL K3 surface. A key step is the construction of a triangulated version of the mapping cylinder of the Hopf map from real projective 3-space onto the 2-sphere with the minimum number of vertices. Moreover, we study simplicial Morse functions and the changes of their levels between the critical points. In this way we obtain slicings through the K3 surface of various topological types.

simpcomp [4] is an extension (a so called package) to GAP [6], the well known system for computational discrete algebra. The package enables the user to compute numerous properties of (abstract) simplicial complexes, provides functions to construct new complexes from existing ones and an extensive library of triangulations of manifolds. For an introduction to the field of piecewise linear (PL) topology see the books [16] and [11]. The authors acknowledge support by the DFG: simpcomp has partly been developed within the DFG projects Ku 1203/5-2 and Ku 1203/5-3.

ABSTRACTToll-like receptors (TLRs) are crucial pattern recognition receptors in innate immunity that are expressed in microglia, the resident macrophages of the brain. TLR2, -4, and -9 are important in the responses against Streptococcus pneumoniae, the most common agent causing bacterial meningitis beyond the neonatal period. Murine microglial cultures were stimulated with agonists for TLR1/2 (Pam3CSK4), TLR4 (lipopolysaccharide), and TLR9 (CpG oligodeoxynucleotide) for 24 h and then exposed to either the encapsulated D39 (serotype 2) or the nonencapsulated R6 strain of S. pneumoniae. After stimulation, the levels of interleukin-6 and CCL5 (RANTES [regulated upon activation normal T-cell expressed and secreted]) were increased, confirming microglial activation. The TLR1/2, -4, and -9 agonist-stimulated microglia ingested significantly more bacteria than unstimulated cells (P< 0.05). The presence of cytochalasin D, an inhibitor of actin polymerizaton, blocked >90% of phagocytosis. Along with an increased phagocytic activity, the intracellular bacterial killing was also increased in TLR-stimulated cells compared to unstimulated cells. Together, our data suggest that microglial stimulation by these TLRs may increase the resistance of the brain against pneumococcal infections.

Toll-like receptors (TLRs) are crucial pattern recognition receptors in innate immunity that are expressed in microglia, the resident macrophages of the brain. TLR2, -4, and -9 are important in the responses against Streptococcus pneumoniae, the most common agent causing bacterial meningitis beyond the neonatal period. Murine microglial cultures were stimulated with agonists for TLR1/2 (Pam3CSK4), TLR4 (lipopolysaccharide), and TLR9 (CpG oligodeoxynucleotide) for 24 h and then exposed to either the encapsulated D39 (serotype 2) or the nonencapsulated R6 strain of S. pneumoniae. After stimulation, the levels of interleukin-6 and CCL5 (RANTES [regulated upon activation normal T-cell expressed and secreted]) were increased, confirming microglial activation. The TLR1/2, -4, and -9 agonist-stimulated microglia ingested significantly more bacteria than unstimulated cells (P < 0.05). The presence of cytochalasin D, an inhibitor of actin polymerizaton, blocked >90% of phagocytosis. Along with an increased phagocytic activity, the intracellular bacterial killing was also increased in TLR-stimulated cells compared to unstimulated cells. Together, our data suggest that microglial stimulation by these TLRs may increase the resistance of the brain against pneumococcal infections.

Gelastic epilepsy due to hypothalamic hamartomas is usually a severe condition encompassing both epileptic seizures and an epileptic encephalopathy associated with behavioral and cognitive impairments. Here we report the effects of interstitial radiosurgery in the treatment of this generally pharmacoresistant epilepsy syndrome.

Despite effective antibiotic treatment, neuronal injury is frequent among children and adults with bacterial meningitis resulting in a high rate of death and neurologic sequelae. The hematopoietic cytokine erythropoietin (EPO) provides neuroprotection in models of acute and chronic neurologic diseases. We studied whether recombinant EPO (rEPO) reduces neuronal damage in a rabbit model of Escherichia colimeningitis. Inflammation within the central nervous system (CNS) was monitored by measurement of bacterial load, pleocytosis, protein, and lactate in the cerebrospinal fluid (CSF). Neuronal damage was measured by quantification of the density of apoptotic neurons in the hippocampal dentate gyrus and the concentration of the global neuronal destruction marker neuron-specific enolase (NSE) in CSF. To increase clinical relevance, rEPO was applied as adjunctive therapy from the beginning of antibiotic therapy 12 h after infection. EPO treatment applied as an intravenous injection at a dose of 1000 IU/kg body weight resulted in plasma concentrations of 6993 ± 1406 mIU/mL, CSF concentrations of 1291 ± 568 mIU/mL, and a CSF-to-plasma ratio of 0.18 ± 0.07 (mean ± SD) 6 h after injection. Under these treatment conditions, no anti-inflammatory or neuroprotective effect of EPO was observed.

Despite effective antibiotic treatment, neuronal injury is frequent among children and adults with bacterial meningitis resulting in a high rate of death and neurologic sequelae. The hematopoietic cytokine erythropoietin (EPO) provides neuroprotection in models of acute and chronic neurologic diseases. We studied whether recombinant EPO (rEPO) reduces neuronal damage in a rabbit model of Escherichia coli meningitis. Inflammation within the central nervous system (CNS) was monitored by measurement of bacterial load, pleocytosis, protein, and lactate in the cerebrospinal fluid (CSF). Neuronal damage was measured by quantification of the density of apoptotic neurons in the hippocampal dentate gyrus and the concentration of the global neuronal destruction marker neuron-specific enolase (NSE) in CSF. To increase clinical relevance, rEPO was applied as adjunctive therapy from the beginning of antibiotic therapy 12 h after infection. EPO treatment applied as an intravenous injection at a dose of 1000 IU/kg body weight resulted in plasma concentrations of 6993 ± 1406 mIU/mL, CSF concentrations of 1291 ± 568 mIU/mL, and a CSF-to-plasma ratio of 0.18 ± 0.07 (mean ± SD) 6 h after injection. Under these treatment conditions, no anti-inflammatory or neuroprotective effect of EPO was observed.

Using functional magnetic resonance imaging during a verbal memory task, we investigated correlations of signal fluctuations within the hippocampus and ipsilateral frontal as well as temporal areas in temporal lobe epilepsy patients. Declarative memory abilities were additionally examined before and after temporal lobe epilepsy surgery. A significant difference exists in functional connectivity between patients whose mnemonic functions deteriorated and those who remained stable or improved. Univariate analyses showed significantly higher preoperative coupling between the hippocampus and Brodmann area 22 for the group that decreased in verbal learning. We suggest greater coupling to reflect higher functional network integrity. Postoperatively reduced learning ability in patients with higher preoperative coupling underlines the importance of hippocampal interaction with cortical areas for successful memory formation.

Mortality and long-term sequelae rates are high among adults and children with acute bacterial meningitis. Adjunctive treatment with dexamethasone has been shown to reduce systemic complications in bacterial meningitis patients, but corticosteroid treatment may have detrimental effects on hippocampal function. We evaluated the effect of dexamethasone treatment in addition to antibiotic therapy in a rabbit model of Escherichia colimeningitis. A moderate anti-inflammatory effect of dexamethasone could be demonstrated with respect to the inflammatory mediator prostaglandin E2, whereas no significant effect of dexamethasone on tumor necrosis factor-α, cerebrospinal fluid pleocytosis, protein, lactate, indicators of global neuronal damage, or blood gas analysis was found. Dexamethasone, however, increased the rate of apoptotic neurons in the granular layer of the hippocampal dentate gyrus. In view of the proapoptotic effect of adjunctive dexamethasone on hippocampal neuronal cells in animal models of Gram-positive and Gram-negative meningitis, the application of dexamethasone should be considered carefully in those forms of bacterial meningitis for which no evidence-based data of beneficial effect in humans are available, such as neonatal meningitis, bacillary Gram-negative meningitis or nosocomial forms of meningitis (e.g.following neurosurgery).

Mortality and long-term sequelae rates are high among adults and children with acute bacterial meningitis. Adjunctive treatment with dexamethasone has been shown to reduce systemic complications in bacterial meningitis patients, but corticosteroid treatment may have detrimental effects on hippocampal function. We evaluated the effect of dexamethasone treatment in addition to antibiotic therapy in a rabbit model of Escherichia coli meningitis. A moderate anti-inflammatory effect of dexamethasone could be demonstrated with respect to the inflammatory mediator prostaglandin E2, whereas no significant effect of dexamethasone on tumor necrosis factor-a, cerebrospinal fluid pleocytosis, protein, lactate, indicators of global neuronal damage, or blood gas analysis was found. Dexamethasone, however, increased the rate of apoptotic neurons in the granular layer of the hippocampal dentate gyrus. In view of the proapoptotic effect of adjunctive dexamethasone on hippocampal neuronal cells in animal models of Gram-positive and Gram-negative meningitis, the application of dexamethasone should be considered carefully in those forms of bacterial meningitis for which no evidence-based data of beneficial effect in humans are available, such as neonatal meningitis, bacillary Gram-negative meningitis or nosocomial forms of meningitis (e.g. following neurosurgery).

Gender-related differences in brain activation patterns and their lateralization associated with cognitive functions have been reported in the field of language, emotion, and working memory. Differences have been hypothesized to be due to different cognitive strategies. The aim of the present study was to test whether lateralization of brain activation in the hippocampi during memory processing differs between the sexes. We acquired functional magnetic resonance imaging data from healthy female and male study participants performing a spatial memory task and quantitatively assessed the lateralization of hippocampal activation in each participant. Hippocampal activation was significantly more left lateralized in women, and more right lateralized in men. Correspondingly, women rated their strategy as being more verbal than men did.

Zusammenfassung Hintergrund und Ziel: Die medikamentöse lokale intraarterielle Fibrinolyse (LIF) ist ein mittlerweile anerkanntes und etabliertes Verfahren. Ungeachtet der Wahl des Fibrinolytikums liegen die Rekanalisationszeiten allerdings bei 1–2 h, so dass zunehmend neue mechanische Techniken erprobt werden, die eine Verkürzung der Rekanalisationszeiten ermöglichen sollen. Durch eine schnellere Rekanalisation kann die Infarktgröße verkleinert werden, was zu einem besseren klinischneurologischen Outcome führt. In der vorliegenden Arbeit werden die Technik der Laserlyse und erste Ergebnisse vorgestellt. Die Patienten wurden im Rahmen der „Safety and Performance Study“ bzw. der Folgestudie („Pivotal Study“) eingeschlossen. Vor der Behandlung wurden NIHSS („National Institute of Health Stroke Scale“) sowie mRS („modified Rankin Scale“) erhoben. Der Grad der Rekanalisation wurde anhand der angiographischen Ergebnisse ermittelt. Die klinischen Verlaufsuntersuchungen erfolgten 24 h, 7 Tage und 30 Tage nach Behandlung. Patienten: 20 Patienten wurden eingeschlossen. 13 Patienten wurden mit Gefäßverschlüssen im vorderen und sieben Patienten mit Verschlüssen im hinteren Stromkreislauf in die Studie aufgenommen. Entsprechend den Vorgaben der Studie wurden zwölf Behandlungen als technisch komplett mit dem EPAR-System und acht Behandlungen als inkomplett eingestuft. In fünf von acht Fällen wurde der Laserkatheter eingeführt, aber keine Laserbehandlung durchgeführt. Ergebnisse: Die Rekanalisationsergebnisse im vertebrobasilären Stromgebiet mit einer 86%igen Rekanalisationsrate bei einer mittleren Laserzeit von 7,6 min (1,3–18,9 min) sind viel versprechend, während die Rekanalisationsrate im vorderen Stromkreislauf lediglich 31% betrug (mittlere Laserzeit von 5,5 min [0–15,6 min]). Schlussfolgerung: Neben dem Nachweis des Studienziels Sicherheit und technische Machbarkeit erwies sich diese neue Methode als effektiv in Bezug auf eine rasche Rekanalisation, so dass sie eine weitere Therapieoption zur Behandlung des akuten Schlaganfalls darstellen könnte.

Zusammenfassung Die Bestimmung der zerebralen Sprachrepräsentation ist wesentlicher Bestandteil der prächirurgischen Diagnostik vor Operationen in potentiell sprachrelevanten Regionen, insbesondere vor elektiven epilepsiechirurgischen Eingriffen. Die etablierten Verfahren Wada-Test und kortikale Stimulation sind invasiv und belastend. Seit ca. 10 Jahren steht die funktionelle Magnetresonanztomographie (fMRT) als nichtinvasive Alternative zur Verfügung. Obwohl in zahlreichen Untersuchungen eine gute Übereinstimmung der Ergebnisse von fMRT und Wada-Test gezeigt werden konnte, gibt es keine allgemein akzeptierten Empfehlungen, in welchen Fällen auf einen Wada-Test verzichtet werden kann. In der vorliegenden Zusammenstellung untersuchten die Autoren, wie sich das diagnostische Procedere seit der klinischen Einführung der Sprach-fMRT an ihrer Institution verändert hat. Seit 1999 wurden in Freiburg 208 Sprach-fMRTs bei 198 Patienten durchgeführt. Im gleichen Zeitraum reduzierte sich der relative Anteil der Patienten der Sektion Prächirurgische Epilepsiediagnostik, bei denen ein Wada-Test durchgeführt wurde, um ca. 50%. Der Anteil der Sprach-fMRTs, der vorwiegend aufgrund mangelhafter Kooperationsfähigkeit der Patienten nicht verwertbar war, lag in den vergangenen 2 Jahren < 10%. Nach Ansicht der Autoren besteht lediglich noch in den Fällen eine zwingende Indikation für einen Wada-Test, in denen keine Sprach-fMRT durchführbar ist oder die fMRT therapeutisch entscheidende Fragen nicht beantworten kann.

ABSTRACTProduction and release of the pneumococcal virulence factors pneumolysin and lipoteichoic and teichoic acid in 75 clinical isolates were investigated. No difference was found between strains causing systemic infection or localized respiratory infection and isolates from asymptomatic carriers. This suggests that the presence of pneumolysin and lipoteichoic and teichoic acid is a necessary but not a sufficient condition for pneumococcal infection and development of invasive disease.

ABSTRACTNecrotic and apoptotic neuronal cell death can be found in pneumococcal meningitis. We investigated the role of Bcl-2 as an antiapoptotic gene product in pneumococcal meningitis using Bcl-2 knockout (Bcl-2−/−) mice. By using a model of pneumococcal meningitis induced by intracerebral infection, Bcl-2-deficient mice and control littermates were assessed by clinical score and a tight rope test at 0, 12, 24, 32, and 36 h after infection. Then mice were sacrificed, the bacterial titers in blood, spleen, and cerebellar homogenates were determined, and the brain and spleen were evaluated histologically. The Bcl-2-deficient mice developed more severe clinical illness, and there were significant differences in the clinical score at 24, 32, and 36 h and in the tight rope test at 12 and 32 h. The bacterial titers in the blood were greater in Bcl-2-deficient mice than in the controls (7.46 ± 1.93 log CFU/ml versus 5.16 ± 0.96 log CFU/ml [mean ± standard deviation]; P< 0.01). Neuronal damage was most prominent in the hippocampal formation, but there were no significant differences between groups. In situ tailing revealed only a few apoptotic neurons in the brain. In the spleen, however, there were significantly more apoptotic leukocytes in Bcl-2-deficient mice than in controls (5,148 ± 3,406 leukocytes/mm2versus 1,070 ± 395 leukocytes/mm2; P< 0.005). Bcl-2 appears to counteract sepsis-induced apoptosis of splenic lymphocytes, thereby enhancing clearance of bacteria from the blood.

ABSTRACTPneumolysin, a virulence factor of Streptococcus pneumoniaewith cytotoxic and proinflammatory activities, occurs at concentrations from 0.85 to 180 ng/ml in cerebrospinal fluid (CSF) of meningitis patients. In pneumococcal cultures and in a rabbit meningitis model, the concentrations of pneumolysin in supernatant and CSF were lower after addition of nonbacteriolytic bactericidal antibiotics (rifampin and clindamycin) than after incubation with ceftriaxone.

In three patients with acute occlusion of the basilar artery intra-arterial fibrinolysis resulted in only partial recanalization and revealed severe stenosis as the underlying cause. Application of micro-stents without previous dilatation resulted in vessel re-opening. Two patients had an excellent clinical outcome. One patient died 10 days after the stroke due to brainstem infarction. Emergency primary stent application may improve the outcome in acute basilar artery occlusion, if intra-arterial thrombolysis fails to re-establish a sufficient flow.

The reliability of frontal and temporal fMRI activations for the determination of hemisphere language dominance was evaluated in comparison with intracarotid amytal testing (IAT). Twenty-two patients were studied by IAT (bilateral in 13, unilateral in 9 patients) and fMRI using a paradigm requiring semantic decisions. Global and regional (frontal and temporoparietal) lateralisation indices (LI) were calculated from the number of activated (r>0.4) voxels in both hemispheres. Frontolateral activations associated with the language task were seen in all patients, temporoparietal activations in 20 of 22. Regional LI corresponded better with IAT results than global LI. Frontolateral LI were consistent with IAT in all patients with bilateral IAT (including three patients with right dominant and one patient with bilateral language representation) and were not conflicting in any of the patients with unilateral IAT. Temporoparietal LI were discordant with IAT in two patients with atypical language representation. In the determination of hemisphere dominance for language, regional analysis of fMRI activation is superior to global analysis. In cases with clear-cut fMRI lateralisation, i.e. consistent lateralised activation of frontal and temporoparietal language zones, IAT may be unnecessary. FMRI should be performed prior to IAT in all patients going to be operated in brain regions potentially involved in language.

We present the first measurements of the excited-state relaxation dynamics of a bimetallic class III mixed-valence molecule. The 800 nm absorption of [Ru2TIEDCl4]⁺ (TIED = tetraiminoethylenedimacrocycle) relaxes in 250 and 1000 fs to at least two different intermediate states that can be followed with transient absorption spectroscopy. These states decay in 1.3 and 11.5 ps, and the absorption of the 1.3 ps intermediate displays a large amplitude, very low frequency, highly damped vibrational coherence that completely modulates the absorption. The coherence frequency is 20 ± 5 cm^-1, and the dephasing times range from 360 to 730 fs over the wavelength range of the absorption band. The occurrence of a low-frequency coherence at room temperature, the nearly 100% modulation amplitude, and the phase properties as a function of wavelength are consistent with a nonradiative rate modulation rather than the typical impulsive mechanism that creates a coherent Franck−Condon modulation of the absorption. A nonradiative rate modulation can occur from a vibronic coupling mechanism that is created by breakdown of the Born−Oppenheimer approximation. This type of electronic state coupling likely occurs via nontotally symmetric vibrations, and this is the first time domain measure of a vibronic coupling frequency for inorganic complexes. The resonance Raman activity of the ground-state absorption is consistent with very small mode displacements for the optically connected ground and excited states, as expected for a class III molecule. Since similar nonradiative rates are measured for both the optically excited-state and intermediate-state decays, they both require similar energy gaps in the range of 5000−7000 cm^-1. With these energy gaps, we infer that vibronic coupling matrix elements from 4500 to 11 200 cm^-1 can explain the observed nonradiative decay time of 250 fs. These experiments show that class III molecules, and probably many other inorganic complexes, can have fast nonradiative decay channels from vibronic coupling when electronic states are available at lower energies. Therefore, applications with such molecules require careful molecular design to compete with or reduce rates of return to the ground state.

Functional activation associated with a motor task (fist movements) was studied in three patients with band heterotopias by fMRI. In two patients, additional visual fMRI studies were performed using a flickering checkerboard stimulus. In all patients activation of the outer cortex and of the inner neuronal band could be found during performance of the motor task. Visual stimulation elicited a normal activation pattern without activation of the ectopic neuronal layer in one patient; in another patient activation extended toward the ventricular wall, i.e., along the route of embryonic neuronal migration. The potential participation of ectopic neuronal tissue in physiologic cerebral functions is of clinical impact in patients with neuronal heterotopias suffering from medically intractable seizures prior to epilepsy surgery.

Abstract: Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis.