The impact of cognitive reserve on delayed neurocognitive recovery after major non-cardiac surgery: an exploratory substudy

IntroductionDelayed neurocognitive recovery is a common and severe complication after surgery and anesthesia with an adverse impact on daily living, morbidity, and mortality. High cognitive reserve may mitigate the development of delayed neurocognitive recovery, however, supporting data is lacking. We aimed to assess the association between cognitive reserve and delayed neurocognitive recovery in the early postoperative period.MethodsThis is a substudy of two prospective observational studies. Adult patients undergoing elective major non-cardiac surgery, who were fluent in German, were eligible for study participation. Patients with any pre-existing central nervous system disorders were excluded. Cognitive reserve was assessed using the Cognitive Reserve Index questionnaire. Delayed neurocognitive recovery was defined as a decline in cognitive function compared with baseline assessments and was evaluated with a battery of neuropsychological tests on the day of hospital admission and between day three post procedure and before hospital discharge.ResultsA total of 67 patients with a median age of 67 [IQR: (63–73)] years were included in our analysis. We found delayed neurocognitive recovery in 22.4% of patients. There was a significant association between Cognitive Reserve Index questionnaire total score and the occurrence of delayed neurocognitive recovery in the early postoperative period [OR = 0.938, (95% CI, 0.891; 0.988), p = 0.015].ConclusionHigher cognitive reserve in elderly patients undergoing major non-cardiac surgery decreases the risk for subsequent delayed neurocognitive recovery in the early postoperative period

Nerve growth factor inhibits PC12 cell PDE 2 phosphodiesterase activity and increases PDE 2 binding to phosphoproteins

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66241/1/j.1471-4159.2001.00133.x.pd

Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice

<p>Abstract</p> <p>Background</p> <p>In the past, ciliated receptor neurons, basal cells, and supporting cells were considered the principal components of the main olfactory epithelium. Several studies reported the presence of microvillous cells but their function is unknown. A recent report showed cells in the main olfactory epithelium that express the transient receptor potential channel TrpM5 claiming that these cells are chemosensory and that TrpM5 is an intrinsic signaling component of mammalian chemosensory organs. We asked whether the TrpM5-positive cells in the olfactory epithelium are microvillous and whether they belong to a chemosensory system, i.e. are olfactory neurons or trigeminally-innervated solitary chemosensory cells.</p> <p>Results</p> <p>We investigated the main olfactory epithelium of mice at the light and electron microscopic level and describe several subpopulations of microvillous cells. The ultrastructure of the microvillous cells reveals at least three morphologically different types two of which express the TrpM5 channel. None of these cells have an axon that projects to the olfactory bulb. Tests with a large panel of cell markers indicate that the TrpM5-positive cells are not sensory since they express neither neuronal markers nor are contacted by trigeminal nerve fibers.</p> <p>Conclusion</p> <p>We conclude that TrpM5 is not a reliable marker for chemosensory cells. The TrpM5-positive cells of the olfactory epithelium are microvillous and may be chemoresponsive albeit not part of the sensory apparatus. Activity of these microvillous cells may however influence functionality of local elements of the olfactory system.</p

Maternal Behavior is Impaired in Female Mice Lacking Type 3 Adenylyl Cyclase

Although chemosensory signals generated by mouse pups may trigger maternal behavior of females, the mechanism for detection of these signals has not been fully defined. As some odorant receptors are coupled to the type 3 adenylyl cyclase (AC3), we evaluated the role of AC3 for maternal behavior using AC3−/− female mice. Here, we report that maternal behavior is impaired in virgin and postpartum AC3−/− mice. Female AC3−/− mice failed the pup retrieval assay, did not construct well-defined nests, and did not exhibit maternal aggression. Furthermore, AC3−/− females could not detect odorants or pup urine in the odorant habituation test and were unable to detect pups by chemoreception. In contrast to wild-type mice, AC activity in main olfactory epithelium (MOE) preparations from AC3−/− female mice was not stimulated by odorants or pheromones. Moreover, odorants and pheromones did not evoke electro-olfactogram (EOG) responses in the MOE of AC3−/− female mice. We hypothesize that the detection of chemical signals that trigger maternal behavior in female mice depends upon AC3 in the MOE

Neurochemical findings in Wistar rats during acute and protracted opioid withdrawal

In der vorliegenden Arbeit sollte untersucht werden, ob die achtwöchige orale Einnahme des Opioides Etonitazen durch Wistar-Ratten neben kurzfristigen Veränderungen zu protrahierten Adaptationen neurochemischer Strukturen der Signaltransduktion führen kann. Zugleich wurde gefragt, ob sich innerhalb dieses Zeitraumes ein freiwilliger Konsum des Opioides unterscheidbar von einem erzwungenen (forcierten) Konsummuster abbilden würde. Einem Teil der in Einzelhaltung lebenden Tiere wurde die Wahl zwischen Etonitazenlösung und Wasser ermöglicht. Eine zweite Gruppe bekam ausschließlich Etonitazenlösung zur Deckung des Flüssigkeitsbedarfs. Die neurochemischen Untersuchungen wurden nach zweitägigem bzw. sechswöchigem Entzug durchgeführt. Bei der Untersuchung des mu-Opioidrezeptors (MOR) wurden keine Veränderungen der maximalen Bindungsdichte oder Rezeptoraffinität gemessen. Die max. Bindungsdichte der MOR-gekoppelten Gi/o-Proteine war im akuten Entzug in beiden konsumierenden Gruppen erhöht, während die intrinsische Fähigkeit des MOR-Agonisten DAMGO zur G-Proteinaktivierung in der forciert behandelten Gruppe im gleichen Zeitraum verstärkt war. Insgesamt war die Entkoppelung der Gi/o-Proteine vom MOR im akuten Entzug erschwert. Die Ergebnisse deuten auf eine vor allem dosisabhängige Erhöhung des G-Proteinpools und Verstärkung der G-Proteinaktivierbarkeit im akuten Entzug hin. Im akuten Entzug zeigten sich eine erhöhte Dichte des Dopamin D1/5-Rezeptors und eine Verstärkung der hochaffinen Bindungsstelle innerhalb der forciert behandelten Gruppe im "limbischen Vorderhirn" (inkl. Nucleus accumbens). Dem gegenüber war die Bindungsdichte nach sechswöchiger Abstinenz erniedrigt und die hochaffine Bindungsstelle abgeschwächt. Die gemessene Erhöhung bzw. Erniedrigung der max. D1/5-Bindungsdichte und die Verstärkung bzw. Abschwächung der hochaffinen Bindungsstelle könnten als Gegenregulation zu einer vermuteten verminderten basalen Dopaminausschüttung im akuten bzw. einer sensitisierten Dopaminausschüttung im protrahierten Entzug aufgefasst werden. Die Stimulierbarkeit der Adenylatzyklase (AC) über Aktivierung des Dopamin D1/5-Rezeptors war gleichzeitig im "limbischen Vorderhirn" im akuten Entzug und nach sechswöchiger Abstinenz in allen substanzerfahrenen Gruppen erniedrigt. Aus den Messungen ergab sich eine funktionelle Entkoppelung von D1/5-Rezeptor und stimulatorischen G-Proteinen. Die pharmakologische Potenz von GTPgammaS zur Inhibition der AC war im "limbischen Vorderhirn" im akuten Entzug und nach sechswöchiger Abstinenz in allen substanzerfahrenen Gruppen signifikant verstärkt. Die signifikant erniedrigten EC50-Werte wurden als persistierende Sensitisierung des inhibitorischen G-Proteinwegs interpretiert. Die persistierende funktionelle Entkoppelung von D1/5-Rezeptor und stimulatorischen G-Proteinen während gleichzeitiger Sensitisierung des inhibitorischen u.a. D2-rezeptorgekoppelten G-Proteinwegs wurde als persistierende Dysbalance gewertet, die in einem Hirnareal auftrat, dass mit den verstärkenden und verhaltensmodulierenden Wirkungen der Opioide verknüpft ist. Möglicherweise sind diese Langzeitfolgen einer oralen Etonitazenselbsteinnahme mit Adaptationen des motivierten Verhaltens verbunden. Insgesamt ließen sich keine gesonderten Effekte des freiwilligen Konsummusters auf neurochemische Adaptationen nachweisen. Es wird hier in erster Linie von dosisabhängigen Veränderungen im Rahmen eines intermittierenden Verabreichungsschemas ausgegangen. Grundsätzlich sind neben aktiven adaptiven Vorgängen neurodegenerative Prozesse durch Agonisteneinwirkung oder Entzug als Ursache für persistierende neurochemische Veränderungen nicht auszuschließen.Rats orally self-administered the selective mu-opioid receptor (MOR) agonist etonitazene for 8 weeks (forced and free choice conditions yielding high and low dose intake). The animals were sacrificed after 2 days respectively after 6 weeks of drug deprivation. Neurochemical studies were performed to reveal possible changes of cortical and mesolimbic signaltransmission; main hypothesis expected changes of MOR-binding, G-protein coupling, Dopamine D1/5-receptor-binding and activity of adenylylcyclase (AC). The total MOR-receptor-binding or receptor-affinity in 3[H]-DAMGO binding studies were not changed by etonitazene pretreatment in either drug consuming group compared do drug-naive controls. Total binding of MOR-coupled Gi/o-proteins in 35[S]GTPgammaS-binding studies and the intrinsic capability of DAMGO to activate G-proteins were increased after 2 days of drug deprivation only in both drug consuming groups. The results were seen as a dose-related increase of the G-protein-pool and increase in potential G-protein-activity. SCH23390-binding-studies in limbic forebrain (including nucleus accumbens) revealed a higher dopamine D1/5-receptor binding density and strengthening of high-affinity-binding after two days of drug deprivation among the group of forced drug consumption. After six weeks of abstinence dopamine D1/5-receptor binding density and high-affinity-binding were decreased among the group of forced drug consumption. Free choice consumption did not display any significant changes of D1/5-receptor binding density respectively high-affinity-binding. Results were interpreted as a counter regulation versus a presumed deprived basal dopamine release during acute withdrawal and a sensitized dopamine release during prolonged abstinence. Stimulation of AC via activation of dopamine D1/5-receptors was reduced in all drug consuming groups after 2 days and six weeks of withdrawal in limbic forebrain. Studies revealed a functional decoupling of D1/5-receptors from Gs-proteins. EC50-values of GTPgammaS to inhibit AC were significantly reduced in all drug consuming groups after 2 days and six weeks of withdrawal in limbic forebrain. The decreased EC50-values were seen as persisting sensitization of inhibitory G-proteins. The lasting functional decoupling of D1/5-receptors from Gs-proteins and at the same time persisting sensitization of inhibitory (also D2-receptor coupled) G-proteins were interpreted as an imbalance of dopamine receptor related signal transmission in a brain area linked to reinforcing and behavioral effects of opioides. The described changes after orally etonitazene consumption might be related to adaptations of motivated behavior. Overall no separate effects of free choice consumption were revealed. Findings were interpreted primarily as dose related adaptations after intermittend drug intake. Besides adaptive effects changes due to neurodegeneration caused by the agonist or by withdrawal seem to be possible

Vol. 7 No. 2, Spring 2016; Muddy Waters: Why Polluted Groundwater Infiltrating Navigable Waters Should Not Be Excluded From National Pollutant Discharge Elimination System Permitting

The debate over whether the Clean Water Act has jurisdiction over migratory groundwater in the same way that it does over navigable waters of the United States (regarding effluent standards) has left a wide split among courts attempting to interpret and apply the policy, goals, and language of the law. The problem lies in the difference between applying the law given its objectives and goals, or in a strict fashion using simply the language in the text of the Clean Water Act, while supplementing support from legislative and case law history. First in this Note, background information is provided regarding the history of the Clean Water Act , National Pollutant Discharge Elimination System (NPDES) permits and the U.S. Environmental Protection Agency regulation, navigable waters of the United States, and the relation of migratory groundwater to this process. What follows is a discussion of methods, rules, and rationales courts and legal authorities have used and provided when holding and not holding that pollutants to migratory groundwater which reach navigable waters of the United States should be regulated through NPDES permitting. Finally, there is a review as to the reason why the Clean Water Act does have jurisdiction over pollutants to migratory groundwater which reach navigable waters and a recommendation that such regulation should occur via NPDES permits

Manipulative versus symbolic treatments for teaching selected logic concepts to grade seven students

Bibliography: p. 38-40