Predicting Cannabis Abuse Screening Test (CAST) Scores: A Recursive Partitioning Analysis Using Survey Data from Czech Republic,Italy, the Netherlands and Sweden

Introduction

Cannabis is Europe''s most commonly used illicit drug. Some users do not develop dependence or other problems, whereas others do. Many factors are associated with the occurrence of cannabis-related disorders. This makes it difficult to identify key risk factors and markers to profile at-risk cannabis users using traditional hypothesis-driven approaches. Therefore, the use of a data-mining technique called binary recursive partitioning is demonstrated in this study by creating a classification tree to profile at-risk users.

Methods

59 variables on cannabis use and drug market experiences were extracted from an internet-based survey dataset collected in four European countries (Czech Republic, Italy, Netherlands and Sweden), n = 2617. These 59 potential predictors of problematic cannabis use were used to partition individual respondents into subgroups with low and high risk of having a cannabis use disorder, based on their responses on the Cannabis Abuse Screening Test. Both a generic model for the four countries combined and four country-specific models were constructed.

Results

Of the 59 variables included in the first analysis step, only three variables were required to construct a generic partitioning model to classify high risk cannabis users with 65–73% accuracy. Based on the generic model for the four countries combined, the highest risk for cannabis use disorder is seen in participants reporting a cannabis use on more than 200 days in the last 12 months. In comparison to the generic model, the country-specific models led to modest, non-significant improvements in classification accuracy, with an exception for Italy (p = 0.01).

Conclusion

Using recursive partitioning, it is feasible to construct classification trees based on only a few variables with acceptable performance to classify cannabis users into groups with low or high risk of meeting criteria for cannabis use disorder. The number of cannabis use days in the last 12 months is the most relevant variable. The identified variables may be considered for use in future screeners for cannabis use disorders.     

Weakened Resilience in Parenting Self-Efficacy in Pregnant Women Who Were Abused in Childhood: An Experimental Test

This study tested experimentally whether the combination of a history of childhood abuse and confrontation with difficult infant temperament is associated with negative changes in parenting self-efficacy. First-time pregnant women (N = 243) participated in the Adult Attachment Interview, which was used to assess the occurrence of abuse by parents in childhood and unresolved representations, and completed a task asking them to respond to infant cries. Sixty of the 243 participants (25%) experienced childhood abuse, mostly physical or sexual. The task simulated infant temperamental difficulty by manipulating soothing success in order to reflect an easy-to-soothe (80% soothing success) and a difficult-to-soothe infant (20% soothing success). Both after baseline and after each of the two stimulus series women assessed their parenting self-efficacy. Women who reported childhood abuse did not differ from women who reported no childhood abuse in parenting self-efficacy at baseline or in response to the easy-to-soothe infant (relative to baseline), but decreased more in parenting self-efficacy following the difficult-to-soothe infant. Effects did not vary according to resolution of trauma. These findings suggest that in response to infant temperamental difficulty, women who experienced childhood abuse may more easily lose confidence in their parenting abilities, which underlines the importance of preparing at-risk women for the possible challenges that come along with parenthood.     

Toward a controllable headspace composition—Growth,development, and headspace of a micropropagatedPrunus rootstock in different containers

The body and closure device of a tissue culture container are of paramount importance in the determination of the headspace composition, and influence plant growth and development. In fact, the container determines gas exchange with the environment quantitatively and qualitatively. When exchange occurred via permeability, we demonstrated that a properly controlled container atmosphere (CA) cannot be obtained because accumulation and/or depletion of gases occur; modified atmosphere (MA) is then a better term. Our experiments also gave information about a) gas exchange mechanisms and b) the influence of headspace composition on plant growth and development. These are prerequisites for the understanding and final control of the headspace composition. Three containers, differing in their gas exchange mechanism, were evaluated. This paper also considered that even under “controlled” culture conditions (container, environment, explant weight, etc.) variations from container to container are registered, probably due to the explant itself.     

Vertical distribution and feeding pattern of Euphausiacea (Crustacea) in the eastern Banda Sea (Indonesia) during the SE and NW monsoons

The vertical distribution of Euphausiacea (Crustacea) in theeastern Banda Sea (Indonesia) during the SE and NW monsoon seasonswas studied. In August 1984 and February/ March 1985, stratifiedday and night sampling was carried out between 0 and 500 m atfour stations. A total of 31 species was found, of which mostwere present in both monsoon seasons. Species with a high presencein samples and performing diurnal vertical migration in bothmonsoon seasons were Euphausia diomedeae, Euphausia pseudogibba,Thysanopoda monacantha, Thysanopoda iricus-pidaia and Nematoscelismicrops. Species with a high presence in samples showing nodiurnal vertical migration in both monsoon seasons were Euphausiasimilis, Nematobrachion boopis. Nematoscelis tenella, Stylocheironmaximum and Thysanopoda orientalis. The density of Euphausiaceaat the sampled stations was higher, but more heterogeneous,in the nutrient-enriched SE monsoon period than in the relativelynutrient-poor NW monsoon season, when densities were lower andmore similar. The vertical distributions and diurnal verticalmigration of species did not show a unanimous and strong responseto seasonal hydrographic differences. The day–night depthdistribution pattern of the Euphausiacea population in the upper500 m is largely the same in both seasons, with comparable migrationranges. Some species showed a somewhat upward shifted depthdistribution in the nutrient-enriched period. For mesopelagicand bathypelagic species especially, food resources were thenfavourable in the upper layers, as indicated by rare recordsof Thysanopoda crisiata. Analyses of stomach contents snowedmainly a nocturnal feeding pattern for the diurnal verticalmigrating species and a continuous feeding pattern for the non-migratingspecies.     

Developmental changes in rat brain monoamine metabolism and β-adrenoceptor subtypes after chronic prenatal exposure to propranolol

The aim of this study was to investigate whether a chronic prenatal β-blockade can alter the maturation of the noradrenergic system in the rat brain. Pregnant female and adult male rats were treated for 10 days with the β-antagonist propranolol dissolved in the drinking water (40–50 mg/kg/day). Direct and long-term effects on β-adrenoceptors and monoamine metabolism in various rat brain regions were determined.

After the prenatal treatment the propranolol level in the foetal brain was 0.9 μg/g, while in the adult brain 2.0 μg/g was present. The foetal β1-receptors were significantly up-regulated by propranolol (200%), whereas the β2-receptor number remained unaltered. On postnatal days 4 and 21 the number of both β-subtypes was the same as that of controls. Noradrenaline, its metabolite 3-methoxy-4-hydroxyphenylglycol and their ratio were unaltered directly after the prenatal treatment. In the PN 21 offspring, however, the metabolite level had increased in the frontal cortex (+17%) and hippocampus (+32%), and the ratio in the hippocampus (37%) and medulla pons (+34%). Prenatal treatment also induced a significant increase of the 5-hydroxyindolacetic acid·5-hydroxytryptamine ratio (+15%) in the medulla pons at GD 21. No direct or lasting effects were found on dopamine metabolism. Propranolol treatment of adult rats gave no direct changes in monoamine metabolism.

We concluded that chronic prenatal propranolol exposure (a) reversibly up-regulates foetal β1-adrenoceptors, and (b) increases the NA activity in the brain in later life.     

The ferredoxin-NADP+ oxidoreductase-binding protein is not the 17-kDa component of the cytochrome b/f complex

The complex between ferredoxin-NADP+ oxidoreductase and its proposed membrane-binding protein (Vallejos, R. H., Ceccarelli, E., and Chan, R. (1984) J. Biol. Chem. 259, 8048-8051) was isolated from spinach thylakoids and compared with isolated cytochrome b/f complex containing associated ferredoxin NADP+ oxidoreductase (Clark, R. D., and Hind, G. (1983) J. Biol. Chem. 258, 10348-10354). There was no immunological cross-reactivity between the 17.5-kDa binding protein and an antiserum raised against the 17-kDa polypeptide of the cytochrome complex. Association of ferredoxin-NADP+ oxidoreductase with the binding protein or with the thylakoid membrane gave an allotopic shift in the pH profile of diaphorase activity, as compared to the free enzyme. This effect was not seen in enzyme associated with the cytochrome b/f complex. Identification of the 17.5-kDa binding protein as the 17-kDa component of the cytochrome b/f complex is ruled out by these results.     

Cytoplasmic free calcium, myosin light chain phosphorylation, and force in phasic and tonic smooth muscle

The time course of [Ca2+]i, tension, and myosin light chain phosphorylation were determined during prolonged depolarization with high K+ in intact tonic (rabbit pulmonary artery) and phasic (longitudinal layer of guinea pig ileum) smooth muscles. [Ca2+]i was monitored with the 340 nm/380 nm signal ratio of the fluorescent indicator fura-2. The fluorescence ratio had a similar time course in both muscle types during depolarization with 109 mM [K+]o; after a transient peak, there was a decline to 70% of its peak value in tonic smooth muscle, and to 60% in phasic smooth muscle. Tension, however, continued to increase in the pulmonary artery, while in the ileum it declined in parallel with the [Ca2+]i. On changing [K+]o from 109 to 20 mM, tension and [Ca2+]i either remained unchanged or declined in parallel in the pulmonary artery. Phosphorylation of the 20-kD myosin light chain, measured during stimulation of muscle strips with 109 mM [K+]o in another set of experiments, increased from 3% to a peak of 50% in the intact pulmonary artery, and then declined to a steady state value of 23%. In the intact ileum, a very rapid, early transient phosphorylation (up to 50%) at 2-3 s was seen. This transient declined by 30 s to a value that was close to the resting level (7%), while tension remained at 55% of its peak force. A quick release during maintained stimulation induced no detectable change in the [Ca2+]i in either type of smooth muscle. We discuss the possibility that the slowly rising tonic tension in pulmonary artery could be due to cooperativity between phosphorylated and nonphosphorylated crossbridges.     

KREMEN1 Is a Host Entry Receptor for a Major Group of Enteroviruses

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Tyrosine phosphorylation of Munc18‐1 inhibits synaptic transmission by preventing SNARE assembly

Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18‐1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho‐proteomics abolished the stimulatory effect of Munc18‐1 on SNARE complex formation (“SNARE‐templating”) and membrane fusion in vitro. Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18‐1‐null neurons expressing Munc18‐1_Y473D. Synaptic transmission was temporarily restored by high‐frequency stimulation, as well as by a Munc18‐1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming. On the other hand, expression of non‐phosphorylatable Munc18‐1 supported normal synaptic transmission. We propose that SFK‐dependent Munc18‐1 phosphorylation may constitute a potent, previously unknown mechanism to shut down synaptic transmission, via direct occlusion of a Synaptobrevin/VAMP2 binding groove and subsequent hindrance of conformational changes in domain 3a responsible for vesicle priming. This would strongly interfere with the essential post‐docking SNARE‐templating role of Munc18‐1, resulting in a largely abolished pool of releasable synaptic vesicles.     

Rhodopsin(s) in eubacteria

While the biochemical basis of photosynthesis by bacteriochlorophyll-based reaction centres in purple phototrophic Eubacteria and retinal-based bacteriorhodopsin in the Archaebacterium Halobacterium salinarium has been elucidated in great detail, much less is known about photosensory signal transduction; this is especially the case for Eubacteria. Recent findings on two different photosensory proteins in two different Eubacteria, which both show clear resemblances to the rhodopsins, will be presented. The photoactive yellow protein (PYP) from the purple phototrophic organism Ectothiorhodospira halophila probably functions as the photoreceptor for a new type of negative phototaxis response and has been studied in some detail with respect to its structural and photochemical characteristics. On basis of crystallographic an photochemical data it has been proposed that PYP contains retinal as a chromophore. However, we have unambiguously demonstrated that the PYP chromophore is different from retinal, in spite of the fact that PYP's photochemical properties show striking similarities with the rhodopsins. The cyanobacterium Calothrix sp. displays complementary chromatic adaptation, a process in which the pigment composition of the phycobilisomes is adjusted to the spectral characteristics of the incident light. In orange light the blueish chromophore phycocyanin is present, in green light the reddish phycoerythrin is synthesized. On the basis of the action spectrum of this adaptation process, we hypothesized that a rhodopsin is the photosensor in this process. In line with this, we found that nicotine, an inhibitor of the biosynthesis of beta-carotene (which is the precursor of retinal), abolishes chromatic adaptation. Direct proof of the involvement of a photosensory rhodopsin was obtained in experiments in which the chromatic adaptation response was restored by the addition of retinal to the cultures. The two photosensory proteins mentioned above represent the first examples of eubacterial photoreceptors that can be studied at a molecular level. Our current knowledge on these two proteins and their status as retinal proteins will be reviewed.