bluuebunny/crossref_metadata_2025 huggingface dataset:
Naloxone Reversal of Morphine- and Morphine-6-Glucuronide-induced Respiratory Depression in Healthy Volunteers
Authors: Olofsen Erik , van Dorp Eveline , Teppema Luc , Aarts Leon , Smith Terry W. , Dahan Albert , Sarton Elise
Published: May 2010

Background

Opioid-induced respiratory depression is antagonized effectively by the competitive opioid receptor antagonist naloxone. However, to fully understand the complex opioid agonist-antagonist interaction, the effects of various naloxone doses on morphine and morphine-6-glucuronide (M6G)-induced respiratory depression were studied in healthy volunteers.

Methods

Twenty-four subjects received 0.15 mg/kg morphine intravenously at t = 0 followed by placebo, 200 or 400 microg naloxone at t = 30 min. Thirty-two subjects received 0.3 mg/kg M6G intravenously at t = 0 followed by placebo, 25, 100, or 400 microg naloxone at t = 55 min. There were a total of 8 subjects per treatment group. Respiration was measured on a breath-to-breath basis at constant end-tidal Pco2. A mechanism-based pharmacokinetic-pharmacodynamic model consisting of a part describing biophase equilibration and a part describing receptor association-dissociation kinetics was used to analyze the data.

Results

Naloxone reversal of M6G-induced respiratory depression developed more slowly than reversal of the respiratory effect of morphine. A simulation study revealed that this was related to the slower receptor association-dissociation kinetics of M6G (koff M6G = 0.0327 +/- 0.00455 min versus morphine 0.138 +/- 0.0148 min; values are typical +/-SE). Duration of naloxone reversal was longer for M6G. This was related to the three- to fourfold greater potency of naloxone as an antagonist against M6G compared with morphine. Increasing the naloxone dose had no effect on the speed of reversal, but it did extend reversal duration.

Conclusions

Naloxone reversal of the opioid effect is dependent on the receptor association-dissociation kinetics of the opioid that needs reversal with respect to the rate of reversal. The pharmacodynamics of naloxone determines reversal magnitude and duration.
Functional Studies of RYR1 Mutations in the Skeletal Muscle Ryanodine Receptor Using Human RYR1 Complementary DNA
Authors: Sato Keisaku , Pollock Neil , Stowell Kathryn M.
Published: May 2010

Background

Malignant hyperthermia is associated with mutations within the gene encoding the skeletal muscle ryanodine receptor, the calcium channel that releases Ca from sarcoplasmic reticulum stores triggering muscle contraction, and other metabolic activities. More than 200 variants have been identified in the ryanodine receptor, but only some of these have been shown to functionally affect the calcium channel. To implement genetic testing for malignant hyperthermia, variants must be shown to alter the function of the channel. A number of different ex vivo methods can be used to demonstrate functionality, as long as cells from human patients can be obtained and cultured from at least two unrelated families. Because malignant hyperthermia is an uncommon disorder and many variants seem to be private, including the newly identified H4833Y mutation, these approaches are limited.

Methods

The authors cloned the human skeletal muscle ryanodine receptor complementary DNA and expressed both normal and mutated forms in HEK-293 cells and carried out functional analysis using ryanodine binding assays in the presence of a specific agonist, 4-chloro-m-cresol, and the antagonist Mg.

Results

Transiently expressed human ryanodine receptor proteins colocalized with an endoplasmic reticulum marker in HEK-293 cells. Ryanodine binding assays confirmed that mutations causing malignant hyperthermia resulted in a hypersensitive channel, while those causing central core disease resulted in a hyposensitive channel.

Conclusions

The functional assays validate recombinant human skeletal muscle ryanodine receptor for analysis of variants and add an additional mutation (H4833Y) to the repertoire of mutations that can be used for the genetic diagnosis of malignant hyperthermia.
Adaptive Support Ventilation Prevents Ventilator-induced Diaphragmatic Dysfunction in Piglet
Authors: Jung Boris , Constantin Jean-Michel , Rossel Nans , Le Goff Charlotte , Sebbane Mustapha , Coisel Yannael , Chanques Gerald , Futier Emmanuel , Hugon Gerald , Capdevila Xavier , Petrof Basil , Matecki Stefan , Jaber Samir
Published: May 2010

Background

Contrary to adaptive support ventilation (ASV), prolonged totally controlled mechanical ventilation (CMV) results in the absence of diaphragm activity and causes ventilator-induced diaphragmatic dysfunction. Because maintaining respiratory muscles at rest is likely a major cause of ventilator-induced diaphragmatic dysfunction, ASV may prevent its occurrence in comparison with CMV. The aim of our study was to compare the effects of ASV with those of CMV on both in vivo and in vitro diaphragmatic properties.

Methods

Two groups of six anesthetized piglets were ventilated during a 72-h period. Piglets in the CMV group (n = 6) were ventilated without spontaneous ventilation, and piglets in the ASV group (n = 6) were ventilated with spontaneous breaths. Transdiaphragmatic pressure was measured after bilateral, supramaximal transjugular stimulation of the two phrenic nerves. A pressure-frequency curve was drawn after stimulation from 20 to 120 Hz of the phrenic nerves. Diaphragm fiber proportions and mean sectional area were evaluated.

Results

After 72 h of ventilation, transdiaphragmatic pressure decreased by 30% of its baseline value in the CMV group, whereas it did not decrease in the ASV group. Although CMV was associated with an atrophy of the diaphragm (evaluated by mean cross-sectional area of both the slow and fast myosin chains), atrophy was not detected in the ASV group.

Conclusion

Maintaining diaphragmatic contractile activity by using the ASV mode may protect the diaphragm against the deleterious effect of prolonged CMV, as demonstrated both in vitro and in vivo, in healthy piglets.
Anesthetic Sevoflurane Causes Neurotoxicity Differently in Neonatal Naïve and Alzheimer Disease Transgenic Mice
Authors: Lu Yan , Wu Xu , Dong Yuanlin , Xu Zhipeng , Zhang Yiying , Xie Zhongcong
Published: May 2010

Background

Recent studies have suggested that children undergoing surgery under anesthesia could be at an increased risk for the development of learning disabilities, but whether anesthetics contribute to this learning disability is unclear. Therefore, the authors set out to assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on caspase activation, apoptosis, beta-amyloid protein levels, and neuroinflammation in the brain tissues of neonatal naïve and Alzheimer disease (AD) transgenic mice.

Methods

Six-day-old naïve and AD transgenic (B6.Cg-Tg[amyloid precursor protein swe, PSEN1dE9]85Dbo/J) mice were treated with sevoflurane. The mice were killed at the end of the anesthesia, and the brain tissues were harvested and then subjected to Western blot, immunocytochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction.

Results

Herein, the authors show for the first time that sevoflurane anesthesia induced caspase activation and apoptosis, altered amyloid precursor protein processing, and increased beta-amyloid protein levels in the brain tissues of neonatal mice. Furthermore, sevoflurane anesthesia led to a greater degree of neurotoxicity in the brain tissues of the AD transgenic mice when compared with naïve mice and increased tumor necrosis factor-alpha levels in the brain tissues of only the AD transgenic mice. Finally, inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate attenuated sevoflurane-induced caspase-3 activation and beta-amyloid protein accumulation in vivo.

Conclusion

These results suggest that sevoflurane may induce neurotoxicity in neonatal mice. AD transgenic mice could be more vulnerable to such neurotoxicity. These findings should promote more studies to determine the potential neurotoxicity of anesthesia in animals and humans, especially in children.
Pharmacokinetics of Lidocaine, Bupivacaine, and Levobupivacaine in Plasma and Brain in Awake Rats
Authors: Ikeda Yuko , Oda Yutaka , Nakamura Taketo , Takahashi Ryota , Miyake Wakako , Hase Ichiro , Asada Akira
Published: May 2010

Background

We have compared the pharmacokinetics and brain distribution of lidocaine, racemic bupivacaine (bupivacaine), and levobupivacaine in awake, spontaneously breathing rats.

Methods

Lidocaine (0.5 mg x kg x min), bupivacaine (0.1 mg x kg x min), or levobupivacaine (0.1 mg x kg x min) was continuously administered to rats for 2 h (n = 12, each anesthetic). Blood samples and cerebral dialysate were collected during infusion and for 2 h after termination of infusion. Concentrations of anesthetics in the cerebral extracellular fluid were measured by microdialysis using the retrodialysis calibration method. Tissue-to-plasma partition coefficients calculated from the total (protein-bound and unbound) and unbound concentrations in plasma and brain as well as pharmacokinetic parameters in plasma and cerebral extracellular fluid were compared among the three anesthetics.

Results

There were no differences in plasma total or unbound concentrations between bupivacaine and levobupivacaine. Concentrations of bupivacaine in the cerebral extracellular fluid were significantly higher than levobupivacaine (P < 0.001). Despite no differences in the ratio of total brain concentration to total plasma concentration among the three anesthetics, the ratio of cerebral extracellular fluid concentration to plasma unbound fraction of bupivacaine was significantly higher than lidocaine and levobupivacaine (0.58 +/- 0.09, 0.47 +/- 0.18, and 0.40 +/- 0.09, respectively; P = 0.03 and 0.003, respectively).

Conclusions

Although the ratio of total brain concentration to total plasma concentrations of lidocaine, bupivacaine, and levobupivacaine was similar, concentration ratio of bupivacaine in the cerebral extracellular fluid to plasma unbound fraction was significantly higher than lidocaine and levobupivacaine.
Effect of PSD-95/SAP90 and/or PSD-93/Chapsyn-110 Deficiency on the Minimum Alveolar Anesthetic Concentration of Halothane in Mice
Authors: Tao Feng , Skinner John , Yang Ya , Johns Roger A.
Published: May 2010

Background

The authors have previously shown that the clinically relevant concentrations of inhalational anesthetics dose-dependently inhibit the postsynaptic density protein (PSD)-95, Dlg, and ZO-1 domain-mediated protein interactions between N-methyl-d-aspartate receptors and PSD-95/synaptic-associated protein (SAP) 90 or PSD-93/Chapsyn-110 and that the knockdown of spinal PSD-95/SAP90 significantly reduces the minimum alveolar concentration (MAC) for isoflurane in rats.

Methods

The authors designed antisense oligodeoxynucleotides based on the mouse PSD-95/SAP90 and PSD-93/Chapsyn-110 messenger RNAs that correspond to their PSD-95, Dlg, and ZO-1 domain nucleotides and can specifically knock down the respective proteins. The authors intrathecally injected antisense oligodeoxynucleotides into wild-type and PSD-93/Chapsyn-110 knockout mice to investigate the effect of PSD-95/SAP90 and/or PSD-93/Chapsyn-110 deficiency on halothane anesthesia.

Results

Both PSD-95/SAP90 and PSD-93/Chapsyn-110 antisense oligodeoxynucleotides caused a dose-dependent and significant reduction in the MAC of halothane in wild-type mice. The intrathecal injection of PSD-95/SAP90 antisense oligodeoxynucleotide at different doses (25 and 50 microg) reduced halothane MAC by 40 and 55%, respectively, and intrathecal injection of PSD-93/Chapsyn-110 antisense oligodeoxynucleotide at different doses (12 and 24 microg) reduced halothane MAC by 25 and 53%, respectively. The PSD-95/SAP90 antisense oligodeoxynucleotide showed similar effect on halothane MAC in wild-type and PSD-93/Chapsyn-110 knockout mice, suggesting that the combination of PSD-95/SAP90 knockdown with PSD-93/Chapsyn-110 deletion did not have an additive effect on halothane anesthesia.

Conclusions

The current results indicate that PSD-95/SAP90 and PSD-93/Chapsyn-110 are involved in the molecular mechanisms of halothane anesthesia and that the functional role of PSD-95/SAP90 in halothane anesthesia is not enhanced after PSD-93/Chapsyn-110 deletion.
Evolution of a genomic regulatory domain: The role of gene co-option and gene duplication in the Enhancer of split complex
Authors: Duncan Elizabeth J. , Dearden Peter K.
Published: May 2010

The Drosophila Enhancer of split complex [E(spl)-C] is a remarkable complex of genes many of which are effectors or modulators of Notch signaling. The complex contains different classes of genes including four bearded genes and seven basic helix-loop-helix (bHLH) genes. We examined the evolution of this unusual complex by identifying bearded and bHLH genes in the genome sequences of Arthropods. We find that a four-gene E(spl)-C, containing three bHLH genes and one bearded gene, is an ancient component of the genomes of Crustacea and Insects. The complex is well conserved in insects but is highly modified in Drosophila, where two of the ancestral genes of the complex are missing, and the remaining two have been duplicated multiple times. Through examining the expression of E(spl)-C genes in honeybees, aphids, and Drosophila, we determined that the complex ancestrally had a role in Notch signaling. The expression patterns of genes found inserted into the complex in some insects, or that of ancestral E(spl)-C genes that have moved out of the complex, imply that the E(spl)-C is a genomic domain regulated as a whole by Notch signaling. We hypothesize that the E(spl)-C is a Notch-regulated genomic domain conserved in Arthropod genomes for around 420 million years. We discuss the consequence of this conserved domain for the recruitment of novel genes into the Notch signaling cascade.
A Prominent Role of the Flagellin Receptor FLAGELLIN-SENSING2 in Mediating Stomatal Response to Pseudomonas syringae pv tomato DC3000 in Arabidopsis
Authors: Zeng Weiqing , He Sheng Yang
Published: May 2010

The FLAGELLIN-SENSING2 (FLS2) receptor kinase recognizes bacterial flagellin and initiates a battery of downstream defense responses to reduce bacterial invasion through stomata in the epidermis and bacterial multiplication in the apoplast of infected plants. Recent studies have shown that during Pseudomonas syringae pv tomato (Pst) DC3000 infection of Arabidopsis (Arabidopsis thaliana), FLS2-mediated immunity is actively suppressed by effector proteins (such as AvrPto and AvrPtoB) secreted through the bacterial type III secretion system (T3SS). We provide evidence here that T3SS effector-based suppression does not appear to be sufficient to overcome FLS2-based immunity during Pst DC3000 infection, but that the phytotoxin coronatine (COR) produced by Pst DC3000 also plays a critical role. COR-deficient mutants of Pst DC3000 are severely reduced in virulence when inoculated onto the leaf surface of wild-type Columbia-0 plants, but this defect was rescued almost fully in fls2 mutant plants. Although bacteria are thought to carry multiple microbe-associated molecular patterns, stomata of fls2 plants are completely unresponsive to COR-deficient mutant Pst DC3000 bacteria. The responses of fls2 plants were similar to those of the Arabidopsis G-protein alpha subunit1-3 mutant, which is defective in abscisic acid-regulated stomatal closure, but were distinct from those of the Arabidopsis non-expressor of PR genes1 mutant, which is defective in salicylic acid-dependent stomatal closure and apoplast defense. Epistasis analyses show that salicylic acid signaling acts upstream of abscisic acid signaling in bacterium-triggered stomatal closure. Taken together, these results suggest a particularly important role of FLS2-mediated resistance to COR-deficient mutant Pst DC3000 bacteria, and nonredundant roles of COR and T3SS effector proteins in the suppression of FLS2-mediated resistance in the Arabidopsis-Pst DC3000 interaction.
The Acidic A-Domain of Arabidopsis Toc159 Occurs as a Hyperphosphorylated Protein
Authors: Agne Birgit , Andrès Charles , Montandon Cyril , Christ Bastien , Ertan Anouk , Jung Friederike , Infanger Sibylle , Bischof Sylvain , Baginsky Sacha , Kessler Felix
Published: May 2010

The translocon at the outer membrane of the chloroplast assists the import of a large class of preproteins with amino-terminal transit sequences. The preprotein receptors Toc159 and Toc33 in Arabidopsis (Arabidopsis thaliana) are specific for the accumulation of abundant photosynthetic proteins. The receptors are homologous GTPases known to be regulated by phosphorylation within their GTP-binding domains. In addition to the central GTP-binding domain, Toc159 has an acidic N-terminal domain (A-domain) and a C-terminal membrane-anchoring domain (M-domain). The A-domain of Toc159 is dispensable for its in vivo activity in Arabidopsis and prone to degradation in pea (Pisum sativum). Therefore, it has been suggested to have a regulatory function. Here, we show that in Arabidopsis, the A-domain is not simply degraded but that it accumulates as a soluble, phosphorylated protein separated from Toc159. However, the physiological relevance of this process is unclear. The data show that the A-domain of Toc159 as well as those of its homologs Toc132 and Toc120 are targets of a casein kinase 2-like activity.
GM1 / GD1b / GA1 synthase expression results in the reduced cancer phenotypes with modulation of composition and raft‐localization of gangliosides in a melanoma cell line
Authors: Dong Yu , Ikeda Kazutaka , Hamamura Kazunori , Zhang Qing , Kondo Yuji , Matsumoto Yasuyuki , Ohmi Yuhsuke , Yamauchi Yoshio , Furukawa Keiko , Taguchi Ryo , Furukawa Koichi
Published: May 2010

Gangliosides are expressed in neuroectoderm‐derived tumors, and seemed to play roles in the regulation of cancer properties. To examine the behavior and roles of individual gangliosides, GM1/GD1b/GA1 synthase cDNA was introduced into the melanoma cell line SK‐MEL‐37, and changes in tumor phenotypes were analyzed. The transfectant cells showed neo‐expression of GD1b, GT1b, and GM1, and reduced expression of GM3, GM2, GD2, and GD3. Function analyses revealed that the transfectant cells had definite reduction in cell growth and invasion. Tyrosine‐phosphorylation levels of proteins such as p130Cas and paxillin were also reduced in the transfectants. These results suggested that the expression of GM1/GD1b/GA1 synthase resulted in the suppression of tumor properties. In the analyses of the floating patterns of gangliosides using fractions from sucrose density gradient ultracentrifugation of TritonX‐100 extracts, the majority of gangliosides were found in glycolipid‐enriched microdomain (GEM)/raft fractions, while GD3, GD1b, and GT1b in the transfectant cells tended to disperse to non‐GEM/raft fractions. Furthermore, GD3, GD1b, and GT1b in non‐GEM/raft dominantly had unsaturated fatty acids, while those in GEM/rafts contained more saturated forms than in non‐GEM/rafts. This might be a mechanism for the decreased tumor properties in the transfectants of GM1/GD1b/GA1 synthase cDNA. (Cancer Sci 2010)
Smoking cessation in severe mental illness: what works?
Authors: Banham Lindsay , Gilbody Simon
Published: May 2010

Aims  The physical health of people with severe mental illness (SMI) is poor. Smoking‐related illnesses are a major contributor to excess mortality and morbidity. An up‐to‐date review of the evidence for smoking cessation interventions in SMI is needed to inform clinical guidelines.

Methods  We searched bibliographic databases for relevant studies and independently extracted data. Included studies were randomized controlled trials (RCTs) of smoking cessation or reduction conducted in adult smokers with SMI. Interventions were compared to usual care or placebo. The primary outcome was smoking cessation and secondary outcomes were smoking reduction, change in weight, change in psychiatric symptoms and adverse events.

Results  We included eight RCTs of pharmacological and/or psychological interventions. Most cessation interventions showed moderate positive results, some reaching statistical significance. One study compared behavioural support and nicotine replacement therapy (NRT) to usual care and showed a risk ratio (RR) of 2.74 (95% CI 1.10–6.81) for short‐term smoking cessation, which was not significant at longer follow‐up. We pooled five trials that effectively compared bupropion to placebo giving an RR of 2.77 (95% CI 1.48–5.16), which was comparable to Hughes et al.'s 2009 figures for general population data; RR = 1.69 (95% CI 1.53–1.85). Smoking reduction data were too heterogeneous for meta‐analysis, but results were generally positive. Trials suggest few adverse events. All trials recorded psychiatric symptoms and the most significant changes favoured the intervention groups over the control groups.

Conclusions  Treating tobacco dependence is effective in patients with SMI. Treatments that work in the general population work for those with severe mental illness and appear approximately equally effective. Treating tobacco dependence in patients with stable psychiatric conditions does not worsen mental state.
Factors that affect the diagnostic accuracy of liver fibrosis measurement by Fibroscan in patients with chronic hepatitis B
Authors: Kim S. U. , Seo Y. S. , Cheong J. Y. , Kim M. Y. , Kim J. K. , Um S. H. , Cho S. W. , Paik S. K. , Lee K. S. , Han K.‐H. , Ahn S. H.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 498–505

Background  Interquartile range/median value (IQR/M) of liver stiffness measurement (LSM) is a factor in chronic hepatitis C (CHC) leading to over estimation of fibrosis by Fibroscan.

Aim  To investigate factors that affect the accuracy of LSM in chronic hepatitis B (CHB).

Methods  One hundred and ninety‐nine patients were enrolled. Only procedures yielding ≥10 valid measurements were considered reliable. Liver fibrosis was evaluated using the Batts and Ludwig system. Liver biopsy (LB) specimens <15 mm were considered ineligible.

Results  The mean age (142 men and 57 women) was 40.1 years. A significant discordance (discordance of at least two stages between LB and LSM) was identified in 38 (19.1%) and 47 (23.6%) patients respectively, according to Marcellin et al. and Chan et al.’s cutoff values. In multivariate analyses, BMI and fibrosis stage (F0–2 vs. F3–4) were identified as independent predictors for significant discordance (P = 0.040; hazard ratio [HR], 1.126; 95% confidence interval [CI], 1.005–1.261 and P = 0.036; HR, 0.450; 95% CI, 0.213–0.949 respectively) with Marcellin et al.’s cutoffs, whereas fibrosis stage was the only independent predictor (P = 0.004; HR, 0.300; 95% CI, 0.131–0.685) with Chan’s cutoffs.

Conclusions  Success rate and IQR/M were not predictive factors of the accuracy for diagnosing liver fibrosis by Fibroscan in CHB. Fibrosis stage (F0‐2) was the only factor to predict significant discordance between LB and LSM.
Effect‐site concentration of propofol for reduction of remifentanil‐induced cough
Authors: Kim J. Y. , Lee S. Y. , Kim D. H. , Park S. K. , Min S. K.
Published: May 2010

This study examined the effectiveness of different propofol infusion target concentrations on cough suppression, during a target‐controlled remifentanil infusion. Four hundred patients were randomly assigned to receive propofol target effect‐site concentrations of 0, 3.0, 4.5, or 6.0 μg.ml−1. When the propofol effect‐site concentration reached the target, remifentanil was administered at a target effect‐site concentration of 4.0 ng.ml−1. Episodes of cough were recorded over a 2‐min period after remifentanil commencement, and graded as mild (1–2), moderate (3–4), or severe (5 or more). The overall incidence of cough was significantly decreased in by propofol 6.0 μg.ml−1 compared with 0 or 3.0 μg.ml−1 propofol (p < 0.001). The incidence of severe cough was significantly lower with propofol 6.0 μg.ml−1 compared with 3.0 μg.ml−1 (p = 0.03). A propofol target effect‐site concentration of 6.0 μg.ml−1 effectively suppressed remifentanil‐induced cough when remifentanil was administrated at a target effect‐site concentration of 4.0 ng.ml−1.
Trans‐Atlantic, trans‐Pacific and trans‐Indian Ocean dispersal in the small Gondwanan Laurales family Hernandiaceae
Authors: Michalak Ingo , Zhang Li‐Bing , Renner Susanne S.
Published: May 2010

Aim  To investigate the historical biogeography of the pantropical flowering plant family Hernandiaceae (Laurales), which today comprises 62 species in five genera.

Location  Hernandiaceae occur in Africa (9 species), Madagascar (4), the Neotropics (25), Australia (3), southern China, Indochina, Malesia, and on numerous Pacific Islands (32). These numbers include two widespread species, Hernandia nymphaeifolia, which ranges from East Africa to the Ogasawara Islands and New Caledonia, and Gyrocarpus americanus, thought to have a pantropical range.

Methods  We sampled 37 species from all genera, the widespread ones with multiple accessions, for a chloroplast DNA matrix of 2210 aligned nucleotides, and used maximum likelihood to infer species relationships. Divergence time estimation relied on an uncorrelated‐rates relaxed molecular clock calibrated with outgroup fossils of Lauraceae and Monimiaceae.

Results  The deepest split in the family is between a predominantly African–Madagascan–Malesian lineage comprising Hazomalania, Hernandia and Illigera, and an African–Neotropical lineage comprising Gyrocarpus and Sparattanthelium; this split may be 122 (110–134) Myr old. The stem lineages of the five genera date back at least to the Palaeocene, but six splits associated with transoceanic range disjunctions date only to the Oligocene and Miocene, implying long‐distance dispersal. It is inferred that Hernandia beninensis reached the West African islands of São Tomé and Bioko from the West Indies or the Guianas; Hernandia dispersed across the Pacific; and Illigera madagascariensis reached Madagascar from across the Indian Ocean.

Main conclusions  The disjunct ranges and divergence times of sister clades in the Hernandiaceae are partly congruent with the break‐up of West Gondwana, but mostly with later transoceanic dispersal. An exceptional ability to establish following prolonged oceanic dispersal may be largely responsible for the evolutionary persistence of this small clade.
Biogeography of the Monimiaceae (Laurales): a role for East Gondwana and long‐distance dispersal, but not West Gondwana
Authors: Renner Susanne S. , Strijk Joeri S. , Strasberg Dominique , Thébaud Christophe
Published: May 2010

Aim  The biogeography of the tropical plant family Monimiaceae has long been thought to reflect the break‐up of West and East Gondwana, followed by limited transoceanic dispersal.

Location  Southern Hemisphere, with fossils in East and West Gondwana.

Methods  We use phylogenetic analysis of DNA sequences from 67 of the c. 200 species, representing 26 of the 28 genera of Monimiaceae, and a Bayesian relaxed clock model with fossil prior constraints to estimate species relationships and divergence times. Likelihood optimization is used to infer switches between biogeographical regions on the highest likelihood tree.

Results  Peumus from Chile, Monimia from the Mascarenes and Palmeria from eastern Australia/New Guinea form a clade that is sister to all other Monimiaceae. The next‐deepest split is between the Sri Lankan Hortonia and the remaining genera. The African Monimiaceae, Xymalos monospora, then forms the sister clade to a polytomy of five clades: (I) Mollinedia and allies from South America; (II) Tambourissa and allies from Madagascar and the Mascarenes; (III) Hedycarya, Kibariopsis and Leviera from New Zealand, New Caledonia and Australia; (IV) Wilkiea, Kibara, Kairoa; and (V) Steganthera and allies, all from tropical Australasia.

Main conclusions  Tree topology, fossils, inferred divergence times and ances‐tral area reconstruction fit with the break‐up of East Gondwana having left a still discernible signature consisting of sister clades in Chile and Australia. There is no support for previous hypotheses that the break‐up of West Gondwana (Africa/South America) explains disjunctions in the Monimiaceae. The South American Mollinedia clade is only 28–16 Myr old, and appears to have arrived via trans‐Pacific dispersal from Australasia. The clade apparently spread in southern South America prior to the Andean orogeny, fitting with its first‐diverging lineage (Hennecartia) having a southern‐temperate range. The crown ages of the other major clades (II–V) range from 20 to 29 Ma, implying over‐water dispersal between Australia, New Caledonia, New Zealand, and across the Indian Ocean to Madagascar and the Mascarenes. The endemic genus Monimia on the Mascarenes provides an interesting example of an island lineage being much older than the islands on which it presently occurs.
Alexithymia and eating behaviour in severely obese patients
Authors: Noli G. , Cornicelli M. , Marinari G. M. , Carlini F. , Scopinaro N. , Adami G. F.
Published: May 2010

Background:  Alexithymia is the inability to express feelings with words and comprises a psychological construct frequently found in obese individuals. In eating disordered patients who show a tendency to lose control over food intake, personality traits with alexithymic characteristics have been demonstrated. The present cross‐sectional study investigated the relationships between alexithymia and eating behaviour in severely obese patients.

Methods:  This study analysed 150 obese patients undergoing bariatric surgery and 132 subjects at more than 1 year after biliopancreatic diversion (BPD), when body weight has steadily normalised and any preoccupation with weight, food and diet has been completely abandoned. Obese and operated subjects completed the Toronto Alexithymia Scale (TAS), and eating behaviour was assessed via a semi‐structured interview exploring binge eating disorder (BED), night eating and emotional eating, as well as by utilisation of the Three Factor Eating Questionnaire (TFEQ).

Results:  Although alexithymic patients showed deranged eating behaviour, as evaluated by the TFEQ scores, the frequency of BED, night eating and emotional eating was similar in alexithymic (TAS > 60) and non‐alexithymic patients. However, the prevalence of alexithymia was similar in obese and BPD subjects, whereas, in the operated subjects, TFEQ scores were lower (P < 0.005) than those in obese patients.

Conclusions:  These data suggest that, in severely obese patients, alexithymia does not influence eating behaviour; in severely obese patients, the tendency to lose control over food intake apparently represents a psychological construct that is substantially independent from alexithymia.
Humour appreciation and comprehension in children with intellectual disability
Authors: Degabriele James , Walsh Irene P.
Published: May 2010

Background  Data on typically developing children show that humour development starts from an early age. Studies investigating humour in children with intellectual disability (ID) are few and have generally focused on identifying differences between this population and other groups of children. This study focuses on children with ID as a heterogeneous group and seeks to answer the following questions: (1) what kinds of humour do children with ID appreciate most in a video cartoon? (2) How does the mode of presentation of jokes influence humour comprehension?

Method  This study examines humour appreciation and comprehension in school‐aged children (n = 9; chronological age: 7–11 years) with mild/moderate ID. Specific tools were developed to explore each aspect. Participants rated short scenes from a video cartoon to show their appreciation for different kinds of humour. A set of video‐recorded jokes, with different modes of presentation, were used in the comprehension task.

Results  The greatest appreciation was expressed for physical and visual humour. Non‐specific scenes (i.e. scenes with no particularly funny elements) were also rated highly. Jokes presented with gesture were understood more than jokes told without supports. These differences in comprehension, arising from supported/unsupported jokes, were statistically significant within the group studied.

Conclusions  The context of humour (e.g. being part of a video cartoon) is important in determining what children with ID find funny. The significant difference in comprehension brought about by a change in mode of presentation (i.e. supported/unsupported joke telling) suggests that humour comprehension can be facilitated.
Isolation and characterization of a pigeonpea cyclophilin (CcCYP) gene, and its over‐expression in Arabidopsis confers multiple abiotic stress tolerance
Authors: SEKHAR KAMBAKAM , PRIYANKA BHYRI , REDDY VUDEM DASHAVANTHA , RAO KHAREEDU VENKATESWARA
Published: May 2010

A full‐length cDNA clone of pigeonpea (Cajanus cajan L.) encoding cyclophilin (CcCYP) has been isolated from the cDNA library of plants subjected to drought stress. Amino acid sequence of CcCYP disclosed similarity with that of single‐domain cytosolic cyclophilins of various organisms. Expression profile of CcCYP in pigeonpea plants is strongly induced by different abiotic stresses, indicating its stress‐responsive nature. Compared to the control plants, the transgenic Arabidopsis lines expressing CcCYP exhibited high‐level tolerance against major abiotic stresses, viz., drought, salinity and extreme temperatures as evidenced by increased plant survival, biomass, chlorophyll content and profuse root growth. The CcCYP transgenics, compared to the controls, revealed enhanced peptidyl‐propyl cis‐trans isomerase (PPIase) activity under stressed conditions, owing to transcriptional activation of stress‐related genes besides intrinsic chaperonic activity of the cyclophilin. The transgenic plants subjected to salt stress exhibited higher Na+ ion accumulation in roots as compared to shoots, while a reverse trend was observed in the salt‐stressed control plants, implicating the involvement of CcCYP in the maintenance of ion homeostasis. Expression pattern of CcCYP:GFP fusion protein confirmed the localization of CcCYP predominantly in the nucleus as revealed by intense green fluorescence. The overall results amply demonstrate the implicit role of CcCYP in conferring multiple abiotic stress tolerance at whole‐plant level.
PRECLINICAL STUDY: FULL ARTICLE: Altered architecture and functional consequences of the mesolimbic dopamine system in cannabis dependence
Authors: Spiga Saturnino , Lintas Alessandra , Migliore Michele , Diana Marco
Published: May 2010

Cannabinoid withdrawal produces a hypofunction of mesencephalic dopamine neurons that impinge upon medium spiny neurons (MSN) of the forebrain. After chronic treatment with two structurally different cannabinoid agonists, Δ9‐tetrahydrocannabinol and CP55 940 (CP) rats were withdrawn spontaneously and pharmacologically with the CB1 antagonist SR141716A (SR). In these two conditions, evaluation of tyrosine hydroxylase (TH)‐positive neurons revealed significant morphometrical reductions in the ventrotegmental area but not substantia nigra pars compacta of withdrawn rats. Similarly, confocal analysis of Golgi–Cox‐stained sections of the nucleus accumbens revealed a decrease in the shell, but not the core, of the spines' density of withdrawn rats. Administration of the CB1 antagonist SR to control rats, provoked structural abnormalities reminiscent of those observed in withdrawal conditions and support the regulatory role of cannabinoids in neurogenesis, axonal growth and synaptogenesis by acting as eu‐proliferative signals through the CB1 receptors. Further, these measures were incorporated into a realistic computational model that predicts a strong reduction in the excitability of morphologically altered MSN, yielding a significant reduction in action potential output. These pieces of evidence support the tenet that withdrawal from addictive compounds alters functioning of the mesolimbic system and provide direct morphological evidence for functional abnormalities associated with cannabinoid dependence at the level of dopaminergic neurons and their postsynaptic counterpart and are coherent with recent hypothesis underscoring a hypodopaminergic state as a distinctive feature of the ‘addicted brain’.
CLINICAL STUDY: BRIEF REPORT: Ecstasy (MDMA)‐addicted subjects show increased serum levels of brain‐derived neurotrophic factor, independently from a rise of drug‐induced psychotic symptoms
Authors: Angelucci Francesco , Ricci Valerio , Martinotti Giovanni , Palladino Ilaria , Spalletta Gianfranco , Caltagirone Carlo , Bria Pietro
Published: May 2010

The recreational drug ‘ecstasy’[3,4‐methylenedioxymethamphetamine (MDMA)] exerts a potent action on central serotonergic and dopaminergic neurons. These neurons utilize neurotrophins for their survival and function. In order to explore MDMA effects on neurotrophins, we measured by enzyme‐linked immunosorbent assay the serum levels of brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in ‘ecstasy‐addicted’, ‘ecstasy‐addicted with signs of psychosis’ and ‘healthy’ subjects. We found that BDNF serum levels were significantly increased in both groups of ‘ecstasy‐addicted’ as compared with ‘healthy subjects’, supporting the hypothesis that BDNF is involved in MDMA action.
PRECLINICAL STUDY: FULL ARTICLE: Effects of fatty acid amide hydrolase inhibition on neuronal responses to nicotine, cocaine and morphine in the nucleus accumbens shell and ventral tegmental area: involvement of PPAR‐α nuclear receptors
Authors: Luchicchi Antonio , Lecca Salvatore , Carta Stefano , Pillolla Giuliano , Muntoni Anna L. , Yasar Sevil , Goldberg Steven R. , Pistis Marco
Published: May 2010

The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme that degrades the endogenous cannabinoid N‐acylethanolamine (NAE) anandamide and the endogenous non‐cannabinoid NAEs oleoylethanolamide and palmitoylethanolamide, blocks nicotine‐induced excitation of ventral tegmental area (VTA) dopamine (DA) neurons and DA release in the shell of the nucleus accumbens (ShNAc), as well as nicotine‐induced drug self‐administration, conditioned place preference and relapse in rats. Here, we studied whether effects of FAAH inhibition on nicotine‐induced changes in activity of VTA DA neurons were specific for nicotine or extended to two drugs of abuse acting through different mechanisms, cocaine and morphine. We also evaluated whether FAAH inhibition affects nicotine‐, cocaine‐ or morphine‐induced actions in the ShNAc. Experiments involved single‐unit electrophysiological recordings from DA neurons in the VTA and medium spiny neurons in the ShNAc in anesthetized rats. We found that URB597 blocked effects of nicotine and cocaine in the ShNAc through activation of both surface cannabinoid CB1‐receptors and alpha‐type peroxisome proliferator‐activated nuclear receptor. URB597 did not alter the effects of either cocaine or morphine on VTA DA neurons. These results show that the blockade of nicotine‐induced excitation of VTA DA neurons, which we previously described, is selective for nicotine and indicate novel mechanisms recruited to regulate the effects of addicting drugs within the ShNAc of the brain reward system.
Identifying a targeted population at high risk for infections after liver transplantation in the MELD era
Authors: Sun Hsin‐Yun , Cacciarelli Thomas V. , Singh Nina
Published: May 2010

Sun H‐Y, Cacciarelli TV, Singh N. Identifying a targeted population at high risk for infections after liver transplantation in the MELD era. Clin Transplant 2011: 25: 420–425. © 2010 John Wiley & Sons A/S.

Abstract:  Impact of model for end‐stage liver disease (MELD) scoring system on post‐transplant infections and associated risk factors are unknown. Infections <90 d post‐transplant were assessed in 277 consecutive liver transplant recipients from 1999 to 2008. “High‐risk” factors for infections were pre‐defined as MELD score >30, ICU stay >48 h prior to transplant, intraoperative transfusion ≥15 units, retransplantation, post‐transplant dialysis, or reoperation. Of the 240 recipients in the MELD era (2002–2008), 48.5% had any high‐risk factor. The OR for infection was 1.69, 2.00, 18.00, and 4.50 in recipients with any 1, 2, 3, and ≥4 high‐risk factors, respectively (χ2 for trend, p < 0.001). In logistic regression model, recipient age (OR 1.12, p < 0.05) and any high‐risk factor (OR 2.42, p < 0.05) were associated with infections. Compared with 37 pre‐MELD recipients, the overall infections and mortality at 12 months did not differ in the two eras. In Cox regression model, recipient age (OR 1.09, p < 0.05) and any high‐risk factor (OR 2.42, p < 0.05) remained associated with infections. The overall frequency of infections did not increase in the MELD era. Pre‐defined risk factors accurately predicted the risk of infections in these patients.
Impact of oral care prior to HSCT on the severity and clinical outcomes of oral mucositis
Authors: da Silva Santos Paulo Sérgio , Coracin Fábio Luiz , Barros José Carlos de Almeida , Dulley Frederico Luiz , Nunes Fábio Daumas , Magalhães Marina Gallottini
Published: May 2010

da Silva Santos PS, Coracin FL, Barros JCA, Dulley FL, Nunes FD, Magalhães MG. Impact of oral care prior to HSCT on the severity and clinical outcomes of oral mucositis.  Clin Transplant 2011: 25: 325–328. © 2010 John Wiley & Sons A/S.

Abstract:  Patients who undergo hematopoietic stem cell transplantation (HSCT) frequently experience gastrointestinal toxicity as a result of their preparative regimen. The most frequent manifestation is oral mucositis (OM) and diarrhea. We studied the effects of oral care prior to HSCT on the severity of OM. Seventy patients suffering from hematologic malignancies who had undergone HSCT were divided into two groups (35 patients – Study Group [SG] and 35 – Control Group [CG]), and the severity of OM was evaluated by two calibrated dentists, using the WHO scale. The patients from the SG received oral care prior to HSCT and those from CG did not receive any dental care. The results showed no differences (p = 0.20) in the incidence or severity of OM among the groups. However, patients from the SG presented a shorter time elapsed (p < 0.001) when compared with the CG (median: 10 vs. 20 d). Our results show the importance of simple, inexpensive preventive intervention to control the time elapsed of OM, which reduces morbidity and, as a consequence, the cost of the treatment.
Acquired prior knowledge modulates audiovisual integration
Authors: Van Wanrooij Marc M. , Bremen Peter , John Van Opstal A.
Published: May 2010

Orienting responses to audiovisual events in the environment can benefit markedly by the integration of visual and auditory spatial information. However, logically, audiovisual integration would only be considered successful for stimuli that are spatially and temporally aligned, as these would be emitted by a single object in space–time. As humans do not have prior knowledge about whether novel auditory and visual events do indeed emanate from the same object, such information needs to be extracted from a variety of sources. For example, expectation about alignment or misalignment could modulate the strength of multisensory integration. If evidence from previous trials would repeatedly favour aligned audiovisual inputs, the internal state might also assume alignment for the next trial, and hence react to a new audiovisual event as if it were aligned. To test for such a strategy, subjects oriented a head‐fixed pointer as fast as possible to a visual flash that was consistently paired, though not always spatially aligned, with a co‐occurring broadband sound. We varied the probability of audiovisual alignment between experiments. Reaction times were consistently lower in blocks containing only aligned audiovisual stimuli than in blocks also containing pseudorandomly presented spatially disparate stimuli. Results demonstrate dynamic updating of the subject’s prior expectation of audiovisual congruency. We discuss a model of prior probability estimation to explain the results.
Neuromagnetic oscillations to emotional faces and prosody
Authors: Chen Yu‐Han , Edgar J. Christopher , Holroyd Tom , Dammers Jürgen , Thönneßen Heike , Roberts Timothy P.L. , Mathiak Klaus
Published: May 2010

Higher association cortices as well as unisensory areas can support multisensory integration [D. Senkowskiet al.(2008)Trends Neurosci., 31, 401–409]. The present study investigated whether audiovisual integration of emotional information emerges early at unisensory or later at higher association cortices. Emotional stimuli were presented in three blocks: audiovisual (AV), auditory (A) and visual (V). Eighteen participants performed a delayed emotional recognition task (happy, angry or neutral prosody and/or facial expression) while whole‐brain magnetoencephalography (MEG) data were obtained. Time–frequency evoked and total power analyses were performed on the sensor data, and source localization of the frequencies of interest performed via a synthetic aperture magnetometry beamformer. To examine crossmodal integration between bimodal and unimodal conditions, two contrasts were specified: AV > A and AV > V. In the AV > A contrast, early effects were observed on both the temporal and the occipital evoked responses. However, at the source level, early alpha suppression was limited to the occipital sources without changes in temporal cortices. In the AV > V contrast, sensor and source findings revealed increased alpha suppression only in temporal cortices, with no changes in visual cortex. Thus, no crossmodal effect in unisensory areas emerged. Instead, increased frontal alpha activity in both the AV > A and AV > V contrasts supports the view that affective information from face and prosody converges at higher association cortices.
Defining overweight and obesity in pre‐school children: IOTF reference or WHO standard?
Authors: Monasta L. , Lobstein T. , Cole T. J. , Vignerová J. , Cattaneo A.
Published: May 2010

Two international datasets are used to define overweight and obesity in pre‐school children: the International Obesity Task Force (IOTF) reference and the WHO standard. This study compares the performance of the two datasets in defining overweight and obesity in 24–60 months old children. This was done by plotting the IOTF cut‐offs against WHO curves and by comparing the prevalence of overweight and obesity, as defined by the IOTF reference and by the WHO standard, using 2001 data from the Czech Republic. The IOTF cut‐off for overweight in 24–60 months old children goes from 1.7 to 1.1 z‐scores on the WHO chart, and for obesity it shifts with age from 2.7 to 2.2 z‐scores. As a consequence, at 5 years of age the prevalence of overweight in Czech girls is 3.4% using the WHO and 15.3% using the IOTF definition. These discrepancies are due to the choice of cut‐offs and to the different criteria used to select the sample for the IOTF reference and the WHO standard. Research is urgently needed to identify, for the WHO standard, BMI cut‐offs associated with an increased risk of overweight and obesity, and associated health outcomes later in life.