bluuebunny/crossref_metadata_2025 huggingface dataset:
Early cerebral infarction as a risk factor for poor outcome after aneurysmal subarachnoid haemorrhage
Authors: Juvela S. , Siironen J.
Published: September 2011

Background and purpose:  After aneurysmal subarachnoid haemorrhage, severity of bleeding, and occurrence of rebleeding and cerebral infarcts are the main factors predicting outcome. We investigated predictive risk factors for both early and late cerebral infarcts, and whether time of appearance of infarct is associated with outcome.

Methods:  Previous diseases as well as clinical, laboratory and radiological variables including serial CT scans were recorded for 173 patients admitted within 48 h after bleeding and with ruptured aneurysm occlusion by open surgery within 60 h. Factors predicting occurrence of cerebral infarct and poor outcome at 3 months according to the Glasgow Outcome Scale were tested using multiple logistic regression.

Results:  Of several potential predictors, poor outcome was independently predicted by patient age, rebleeding, intraventricular haemorrhage, intracerebral haematoma, delayed cerebral ischaemia with fixed symptoms and early new ischaemic lesion on CT scan appearing on the 1st post‐operative morning (P < 0.01 for each factor). After adjustment for confounding factors, occurrence of early infarct (odds ratio 12.5; 95% confidence interval 3.2–48.7; P < 0.01), both early and late infarct (6.6; 1.1–40.4; P < 0.05), and late infarct only (2.4; 0.6–9.1) increased risk for poor outcome. Adjusted independent significant risk factors for early infarction were duration of artery occlusion during surgery (1.4/min; 1.1–1.7, P < 0.01) and admission plasma glucose level (1.3 per mM; 1.0–1.6, P < 0.05) and for late infarction amount of subarachnoid blood (4.5; 1.3–14.9, P < 0.05).

Conclusion:  Early infarction after surgical aneurysm occlusion seems to have different risk factors and worse prognosis than late infarct which is mostly associated with delayed cerebral ischaemia.
Saints as the ‘Living Gospel’: Von Balthasar's Revealers of the Revealer, Rahner's Mediators of the Mediator
Authors: Sullivan Patricia A.
Published: September 2011

The theologies of the saints of Hans Urs Von Balthasar and Karl Rahner are grounded in the theologians' distinct articulations of the relationship between nature and grace, Rahner's shaped by his response to the Nouvelle Théologie and Von Balthasar's influenced by his engagement with Henri De Lubac and Karl Barth. It is a generalization, but one useful for drawing contrasts, that for Rahner the saints are mediators of the Mediator and that for Von Balthasar they are revealers of the Revealer. While the theologies can be reconciled, a richer understanding of the function of saints can emerge by maintaining the contrasts. The symbolic capacity of saints in Rahner's thought and the saints' exemplary abandonment to personal mission in Von Balthasar's thought are each an emphasis valuable in communicating saints' instructional and efficacious presence for others in the ecclesial Body.
Improving homeless persons' utilisation of primary care: lessons to be learned from an outreach programme in The Netherlands
Authors: Elissen Arianne MJ , Van Raak Arno JA , Derckx Emmy WCC , Vrijhoef Hubertus JM
Published: September 2011

Elissen AMJ, Van Raak AJA, Derckx EWCC, Vrijhoef HJM. Improving homeless persons' utilisation of primary care: lessons to be learned from an outreach programme in The Netherlands

Faced with rising homelessness, countries around the world are in need of innovative approaches to caring for those without shelter, who, more often than not, suffer from severe health problems. We conducted a case study of an innovative Dutch Primary Care for the Homeless (PCH) programme to gain insight into clients' demographic characteristics, health problems and service use, and to develop an explanation for its success in increasing the latter. Our analyses are based on a combination of quantitative and qualitative data. The results of the study suggest that the success of the PCH programme can be explained by the providers' pragmatism and will to adapt their mode of care provision to the behavioural patterns and needs of their homeless clients.
A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats
Authors: Li Qian‐Qian , Luo Yi‐Xiao , Sun Cheng‐Yu , Xue Yan‐Xue , Zhu Wei‐Li , Shi Hai‐Shui , Zhai Hai‐Feng , Shi Jie , Lu Lin
Published: September 2011

J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07502.x

Heroin use has seriously threatened public heath in many countries, but the existing therapies continue to have many limitations. Recently, immunotherapy has shown efficacy in some clinical studies, including vaccines against nicotine and cocaine, but no opioid vaccines have been introduced in clinical studies. The development of a novel opioid antigen designed specifically for the prevention of heroin addiction is necessary. A morphine–keyhole limpet hemocyanin conjugate was prepared and administered subcutaneously in rats. Antibody titers in plasma were measured using an enzyme‐linked immunosorbent assay (ELISA). Competitive ELISA was used to assess the selectivity of the antibodies. Dopamine concentrations in the nucleus accumbens in rats after vaccine administration were determined by high‐performance liquid chromatography with electrochemical detection. The effects of the vaccine on the heroin‐primed restatement of self‐administration and locomotor sensitization were evaluated. A novel hapten, 6‐glutarylmorphine, was produced, and the vaccine generated a high antibody titer response. This vaccine displayed specificity for both morphine and heroin, but the anti‐morphine antibodies could not recognize dissimilar therapeutic opioid compounds, such as buprenorphine, methadone, naloxone, naltrexone, codeine, and nalorphine. The morphine antibody significantly decreased morphine‐induced locomotor activity in rats after immunization. Importantly, rats immunized with this vaccine did not exhibit heroin‐primed reinstatement of heroin seeking when antibody levels were sufficiently high. The vaccine reduced dopamine levels in the nucleus accumbens after morphine administration, which is consistent with its behavioral effects. These results suggest that immunization with a novel vaccine is an effective means of inducing a morphine‐specific antibody response that is able to attenuate the behavioral and psychoactive effects of heroin.
Different in vitro and in vivo profiles of substituted 3‐aminopropylphosphinate and 3‐aminopropyl(methyl)phosphinate GABAB receptor agonists as inhibitors of transient lower oesophageal sphincter relaxation
Authors: Lehmann A , Antonsson M , Aurell‐Holmberg A , Blackshaw LA , Brändén L , Elebring T , Jensen J , Kärrberg L , Mattsson JP , Nilsson K , Oja SS , Saransaari P , von Unge S
Published: September 2011

BACKGROUND AND PURPOSE Gastro‐oesophageal reflux is predominantly caused by transient lower oesophageal sphincter relaxation (TLOSR) and GABAB receptor stimulation inhibits TLOSR. Lesogaberan produces fewer CNS side effects than baclofen, which has been attributed to its affinity for the GABA transporter (GAT), the action of which limits stimulation of central GABAB receptors. To understand the structure–activity relationship for analogues of lesogaberan (3‐aminopropylphosphinic acids), and corresponding 3‐aminopropyl(methyl)phosphinic acids, we have compared representatives of these classes in different in vitro and in vivo models.

EXPERIMENTAL APPROACH The compounds were characterized in terms of GABAB agonism in vitro. Binding to GATs and cellular uptake was done using rat brain membranes and slices respectively. TLOSR was measured in dogs, and CNS side effects were evaluated as hypothermia in mice and rats.

KEY RESULTS 3‐Aminopropylphosphinic acids inhibited TLOSR with a superior therapeutic index compared to 3‐aminopropyl(methyl)phosphinic acids. This difference was most likely due to differential GAT‐mediated uptake into brain cells of the former but not latter. In agreement, 3‐aminopropyl(methyl)phosphinic acids were much more potent in producing hypothermia in rats even when administered i.c.v.

CONCLUSIONS AND IMPLICATIONS An enhanced therapeutic window for 3‐aminopropylphosphinic acids compared with 3‐aminopropyl(methyl)phosphinic acids with respect to inhibition of TLOSR was observed and is probably mechanistically linked to neural cell uptake of the former but not latter group of compounds. These findings offer a platform for discovery of new GABAB receptor agonists for the treatment of reflux disease and other conditions where selective peripheral GABAB receptor agonism may afford therapeutic effects.
Role of 5‐HT1 receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn
Authors: Jeong Hyo‐Jin , Mitchell Vanessa A , Vaughan Christopher W
Published: September 2011

BACKGROUND AND PURPOSE 5‐HT receptor agonists have variable nociceptive effects within the spinal cord. While there is some evidence for 5‐HT1A spinally‐mediated analgesia, the role of other 5‐HT1 receptor subtypes remains unclear. In the present study, we examined the spinal actions of a range of 5‐HT1 agonists, including sumatriptan, on acute pain, plus their effect on afferent‐evoked synaptic transmission onto superficial dorsal horn neurons.

EXPERIMENTAL APPROACH For in vivo experiments, 5‐HT agonists were injected via chronically implanted spinal catheters to examine their effects in acute mechanical and thermal pain assays using a paw pressure analgesymeter and a Hargreave's device. For in vitro experiments, whole‐cell patch‐clamp recordings of primary afferent‐evoked glutamatergic EPSC were made from lamina II neurons in rat lumbar spinal slices.

KEY RESULTS Intrathecal (i.t.) delivery of the 5‐HT1A agonist R ± 8‐OH‐DPAT (30–300 nmol) produced a dose‐dependent thermal, but not mechanical, analgesia. Sumatriptan and the 5‐HT1B, 5‐HT1D, 5‐HT1F agonists CP93129, PNU109291 and LY344864 (100 nmol) had no effect on either acute pain assay. R ± 8‐OH‐DPAT (1 µM) and sumatriptan (3 µM) both reduced the amplitude of the evoked EPSC. In contrast, CP93129, PNU109291 and LY344864 (0.3–3 µM) had no effect on the evoked EPSC. The actions of both R ± 8‐OH‐DPAT and sumatriptan were abolished by the 5‐HT1A antagonist WAY100635 (3 µM).

CONCLUSIONS AND IMPLICATIONS These findings indicate that the 5‐HT1A receptor subtype predominantly mediates the acute antinociceptive and cellular actions of 5‐HT1 ligands within the rat superficial dorsal horn.
Cyclosporin variably and inconsistently reduces infarct size in experimental models of reperfused myocardial infarction: a systematic review and meta‐analysis
Authors: Lim WY , Messow CM , Berry C
Published: September 2011

Cyclosporin is an immunosuppressant that has recently been proposed as a treatment to prevent reperfusion injury in acute myocardial infarction (MI). We aimed to determine the overall efficacy of cyclosporin in experimental studies of acute reperfused MI. We conducted a systematic review and stratified meta‐analysis of published studies describing the efficacy of cyclosporin in experimental models of acute reperfused MI. We included all in vivo publications of cyclosporin where infarct size was measured. A literature search identified 29 potential studies of which 20 fulfilled the eligibility criteria. In these studies (involving four species of animals), cyclosporin reduced myocardial infarct size by a standardized mean (95% confidence interval) difference of −1.60 (−2.17, −1.03) compared with controls. Cyclosporin failed to demonstrate a convincing benefit in studies involving pigs. Despite this observation, the overall efficacy of cyclosporin did not differ across species (P= 0.358). The dose of cyclosporin given did not affect final infarct size (P= 0.203). Funnel plots of these data suggested heterogeneity among the studies. Cyclosporin had variable effects on infarct size compared with placebo. Cyclosporin had no effect on myocardial infarct size in swine, raising a question over the potential cardioprotective effects of cyclosporin in man.
Thiocolchicoside suppresses osteoclastogenesis induced by RANKL and cancer cells through inhibition of inflammatory pathways: a new use for an old drug
Authors: Reuter Simone , Gupta Subash C , Phromnoi Kanokkarn , Aggarwal Bharat B
Published: September 2011

BACKGROUND AND PURPOSE Most patients with cancer die not because of the tumour in the primary site, but because it has spread to other sites. Common tumours, such as breast, multiple myeloma, and prostate tumours, frequently metastasize to the bone. To search for an inhibitor of cancer‐induced bone loss, we investigated the effect of thiocolchicoside, a semi‐synthetic colchicoside derived from the plant Gloriosa superba and clinically used as a muscle relaxant, on osteoclastogenesis induced by receptor activator of NF‐κB ligand (RANKL) and tumour cells.

EXPERIMENTAL APPROACH We used RAW 264.7 (murine macrophage) cells, a well‐established system for osteoclastogenesis, and evaluated the effect of thiocolchicoside on RANKL‐induced NF‐κB signalling and osteoclastogenesis as well as on osteoclastogenesis induced by tumour cells.

KEY RESULTS Thiocolchicoside suppressed osteoclastogenesis induced by RANKL, and by breast cancer and multiple myeloma cells. Inhibition of the NF‐κB pathway was responsible for this effect since the colchicoside inhibited RANKL‐induced NF‐κB activation, activation of IκB kinase (IKK) and suppressed inhibitor of NF‐κBα (IκBα) phosphorylation and degradation, an inhibitor of NF‐κB. Furthermore, an inhibitor of the IκBα kinase γ or NF‐κB essential modulator, the regulatory component of the IKK complex, demonstrated that the NF‐κB signalling pathway is mandatory for osteoclastogenesis induced by RANKL.

CONCLUSIONS AND IMPLICATIONS Together, these data suggest that thiocolchicoside significantly suppressed osteoclastogenesis induced by RANKL and tumour cells via the NF‐κB signalling pathway. Thus, thiocolchicoside, a drug that has been used for almost half a century to treat muscle pain, may also be considered as a new treatment for bone loss.

LINKED ARTICLE This article is commented on by Micheau et al., pp. 2124–2126 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01792.x
Liposome‐Encapsulated Hemoglobin Alleviates Hearing Loss After Transient Cochlear Ischemia and Reperfusion in the Gerbil
Authors: Okada Masahiro , Kawaguchi Akira T. , Hakuba Nobuhiro , Takeda Shoichiro , Hyodo Jun , Imai Kiyohiro , Hato Naohito , Gyo Kiyofumi
Published: September 2011

To test liposome‐encapsulated hemoglobin (LEH) in transient cochlear ischemia/reperfusion as a model of sudden deafness, Mongolian gerbils were randomly assigned to receive 2 mL/kg of either low‐affinity LEH (l‐LEH, P50O2 = 40 mm Hg), high‐affinity LEH (h‐LEH, P50O2 = 10 mm Hg), homologous red blood cells (RBCs), or saline (each group n = 6) 30 min before 15‐min occlusion of the bilateral vertebral arteries and reperfusion. Sequential changes in hearing were assessed by auditory brain response 1, 4, and 7 days after ischemia/reperfusion, when the animals were sacrificed for pathological studies. h‐LEH was significantly more protective than l‐LEH in suppressing hearing loss, in contrast to RBC or saline treatment, at 8, 16, and 32 kHz, where hearing loss was most severe (P < 0.05 between any two groups) on the first day after cochlear ischemia/reperfusion. Thereafter, hearing loss improved gradually in all groups, with a significant difference among groups up to 7 days, when morphological studies revealed that the inner hair cells but not the outer hair cells, were significantly lost in the groups in the same order. The results suggest that pretreatment with h‐LEH is significantly more protective than l‐LEH in mitigating hearing loss and underlying pathological damage, in contrast to transfusion or saline infusion 7 days after transient cochlear ischemia/reperfusion.
Alcohol Increases the Permeability of Airway Epithelial Tight Junctions in Beas‐2B and NHBE Cells
Authors: Simet Samantha. M. , Wyatt Todd A. , DeVasure Jane , Yanov Daniel , Allen‐Gipson Diane , Sisson Joseph H.
Published: September 2011

Background:  Tight junctions form a continuous belt‐like structure between cells and act to regulate paracellular signaling. Protein kinase C (PKC) has been shown to regulate tight junction assembly and disassembly and is activated by alcohol. Previous research has shown that alcohol increases the permeability of tight junctions in lung alveolar cells. However, little is known about alcohol’s effect on tight junctions in epithelium of the conducting airways. We hypothesized that long‐term alcohol exposure reduces zonula occluden‐1 (ZO‐1) and claudin‐1 localization at the cell membrane and increases permeability through a PKC‐dependent mechanism.

Methods:  To test this hypothesis, we exposed normal human bronchial epithelial (NHBE) cells, cells from a human bronchial epithelial transformed cell line (Beas‐2B), and Beas‐2B expressing a PKCα dominant negative (DN) to alcohol (20, 50, and 100 mM) for up to 48 hours. Immunofluorescence was used to assess changes in ZO‐1, claudin‐1, claudin‐5, and claudin‐7 localization. Electric cell–substrate impedance sensing was used to measure the permeability of tight junctions between monolayers of NHBE, Beas‐2B, and DN cells.

Results:  Alcohol increased tight junction permeability in a concentration‐dependent manner and decreased ZO‐1, claudin‐1, claudin‐5, and claudin‐7 localization at the cell membrane. To determine a possible signaling mechanism, we measured the activity of PKC isoforms (alpha, delta, epsilon, and zeta). PKCα activity significantly increased in Beas‐2B cells from 1 to 6 hours of 100 mM alcohol exposure, while PKCζ activity significantly decreased at 1 hour and increased at 3 hours. Inhibiting PKCα with Gö‐6976 prevented the alcohol‐induced protein changes in both ZO‐1 and claudin‐1 at the cell membrane. PKCα DN Beas‐2B cells were resistant to alcohol‐induced protein alterations.

Conclusions:  These results suggest that alcohol disrupts ZO‐1, claudin‐1, claudin‐5, and claudin‐7 through the activation of PKCα, leading to an alcohol‐induced “leakiness” in bronchial epithelial cells. Such alcohol‐induced airway‐leak state likely contributes to the impaired airway host defenses associated with acute and chronic alcohol ingestion.
The Drift Toward Problem Behavior During the Transition to Adolescence: The Contributions of Youth Disclosure, Parenting, and Older Siblings
Authors: Low Sabina , Snyder James , Shortt Joann Wu
Published: September 2011

Prospective associations of mothers’ parenting processes, youth disclosure, and youth problem behavior were examined in a longitudinal design following 244 adolescent sibling dyads over a 3‐year period. For both siblings, authoritative parenting was positively associated with youth disclosure and was negatively related to problem behavior, and coercive parenting was negatively associated with youth disclosure and was positively related to problem behavior. When the influence of older sibling problem behavior on younger sibling problem behavior was modeled, younger sibling disclosure accounted for the relationship of maternal parenting processes to problem behavior. Findings indicate the important role of sibling influence in the development of problem behavior, contextualizing the relative roles of maternal parenting and youth disclosure in the transmission of risk.
“You Can Help People”: Adolescents’ Views on Engaging Young People in Longitudinal Research
Authors: Robbins Spring C. Cooper , Rawsthorne Margot , Paxton Karen , Hawke Catherine , Rachel Skinner S. , Steinbeck Katharine
Published: September 2011

We sought to discover adolescents’ thoughts about participation in longitudinal research and identify recruitment and retention strategies that were meaningful to them. We conducted seven focus groups with 10–15‐year‐olds in two large rural centers in New South Wales, Australia, and all focus groups were digitally recorded, transcribed, and analyzed. Adolescents discussed factors salient to their involvement in focus groups, as well as factors that may influence involvement in a longitudinal study. At the outset of the focus groups, adolescents had a positive view of “research,” but were reluctant to engage in research that involved biologic samples. Effective recruitment of adolescents requires an appreciation of motivators, and time and resources to extend potential participants’ understanding.
Optimal Monetary Policy in an Operational Medium‐Sized DSGE Model
Authors: ADOLFSON MALIN , LASÉEN STEFAN , LINDÉ JESPER , SVENSSON LARS E.O.
Published: September 2011

We show how to construct optimal policy projections in Ramses, the Riksbank’s open‐economy medium‐sized dynamic stochastic general equilibrium model for forecasting and policy analysis. Bayesian estimation of the parameters of the model indicates that they are relatively invariant to alternative policy assumptions and supports our view that the model parameters may be regarded as unaffected by the monetary policy specification. We discuss how monetary policy, and in particular the choice of output gap measure, affects the transmission of shocks. Finally, we use the model to assess the recent Great Recession in the world economy and how its impact on the economic development in Sweden depends on the conduct of monetary policy. This provides an illustration on how Rames incoporates large international spillover effects.
Precautionary Saving and Endogenous Labor Supply with and without Intertemporal Expected Utility
Authors: NOCETTI DIEGO , SMITH WILLIAM T.
Published: September 2011

We analyze precautionary saving behavior in a framework with labor and nonlabor income risks, an endogenous supply of labor, and a representation of preferences that disentangles attitudes toward risk, attitudes toward intertemporal substitution, and ordinal preferences for consumption and leisure. This preference structure allows us to disentangle and to describe in an intuitive way the different forces that determine precautionary saving “in the small” and “in the large.”
Thromboembolic Risk Evaluation in Patients with Atrial Fibrillation Using a Modified CHADS2 Scoring System
Authors: CHA MYUNG‐JIN , OH GYU‐CHUL , HAHN SEOKYUNG , CHOI EUE‐KEUN , OH SEIL
Published: September 2011

Thromboembolic Risk Stratification in AF. Background: Antithrombotic recommendations for relatively low risk patients with atrial fibrillation (AF) are not well established. Some patients with CHADS2 score = 0 have a CHA2DS2–VASc score of 2, which indicated warfarin therapy in the latter system. We evaluated the thromboembolic risk in AF patients with a CHADS2 score of 0 or 1.

Methods: A total of 695 patients with AF that were followed for ≥ 12 months (median 65.6 months, range 12–138 months), were analyzed retrospectively. The modified CHADS2 score (MCS) was applied as follows. Each CHADS2 score group was divided into 2 groups, A and B (i.e., MCS 0A vs 0B, and MCS 1A vs 1B) according to the number of nonmajor risk factors (female gender, chronic kidney disease, coronary artery disease, age 65–74 years). Group A had 0 or 1, and group B had 2 or more nonmajor risk factors.

Results: In patients with CHADS2 score = 1, there were 13 thromboembolic events (0.65%/year) in 343 MCS 1A patients, and 12 thromboembolic events (1.90%/year) in 108 MCS 1B patients. Thromboembolic risk was significantly higher in the MCS 1B compared to the MCS 1A patients (P = 0.006). In 244 patients with CHADS2 score = 0, the thromboembolic risk of MCS 0B was similar to that of MCS 0A (P = 0.095), and 26 patients had a CHA2DS2–VASc score of 2.

Conclusion: Patients with MCS 1B had a higher thromboembolic risk than patients with MCS 1A. Antithrombotic strategies for patients with a CHA2DS2–VASc score of 2 but a CHADS2 score of 0 need further investigation. J Cardiovasc Electrophysiol, Vol. 23, pp. 155‐162, February 2012)
A Latent Variable Approach to Study Gene–Environment Interactions in the Presence of Multiple Correlated Exposures
Authors: Sánchez Brisa N. , Kang Shan , Mukherjee Bhramar
Published: September 2011

Summary Many existing cohort studies initially designed to investigate disease risk as a function of environmental exposures have collected genomic data in recent years with the objective of testing for gene–environment interaction (G × E) effects. In environmental epidemiology, interest in G × E arises primarily after a significant effect of the environmental exposure has been documented. Cohort studies often collect rich exposure data; as a result, assessing G × E effects in the presence of multiple exposure markers further increases the burden of multiple testing, an issue already present in both genetic and environment health studies. Latent variable (LV) models have been used in environmental epidemiology to reduce dimensionality of the exposure data, gain power by reducing multiplicity issues via condensing exposure data, and avoid collinearity problems due to presence of multiple correlated exposures. We extend the LV framework to characterize gene–environment interaction in presence of multiple correlated exposures and genotype categories. Further, similar to what has been done in case–control G × E studies, we use the assumption of gene–environment (G‐E) independence to boost the power of tests for interaction. The consequences of making this assumption, or the issue of how to explicitly model G‐E association has not been previously investigated in LV models. We postulate a hierarchy of assumptions about the LV model regarding the different forms of G‐E dependence and show that making such assumptions may influence inferential results on the G, E, and G × E parameters. We implement a class of shrinkage estimators to data adaptively trade‐off between the most restrictive to most flexible form of G‐E dependence assumption and note that such class of compromise estimators can serve as a benchmark of model adequacy in LV models. We demonstrate the methods with an example from the Early Life Exposures in Mexico City to Neuro‐Toxicants Study of lead exposure, iron metabolism genes, and birth weight.
Exogenous Thrombin Delivery Promotes Collateral Capillary Arterialization and Tissue Reperfusion in the Murine Spinotrapezius Muscle Ischemia Model
Authors: BRUCE ANTHONY C. , PEIRCE SHAYN M.
Published: September 2011

Please cite this paper as: Bruce AC and Peirce SM. Exogenous Thrombin Delivery Promotes Collateral Capillary Arterialization and Tissue Reperfusion in the Murine Spinotrapezius Muscle Ischemia Model. Microcirculation 19: 143–154, 2012.

Objective:  We examined the effects of exogenously delivered thrombin on cell recruitment in skeletal muscle and the formation of new collateral arterioles in the microvasculature in response to ligation‐induced ischemia.

Methods:  Thrombin or vehicle was locally applied to both ligated and nonoperated Balb/c spinotrapezius muscles, which were harvested after three or seven days, imaged using confocal microscopy, and analyzed.

Results:  Thrombin treatment resulted in accelerated arterialization of collateral capillaries and accelerated tissue reperfusion in ischemic muscles. Uninjured muscle treated with thrombin displayed increased vascular cell adhesion molecule 1 expression on arteriole and venule endothelium, increased expression of smooth muscle α‐actin on capillary‐sized vessels, increased infiltration by CD11b+ leukocytes, and mast cell infiltration and degranulation.

Conclusions:  Exogenous delivery of thrombin enhances microvascular collateral development in response to ischemic insult, and accelerates tissue reperfusion. Elicited responses from multiple cell types probably contribute to these effects.
Morphology and Phylogeny of a New Urostylid Ciliate, Monocoronella carnea n. g., n. sp. (Ciliophora, Hypotricha) from Daya Bay, Southern China
Authors: CHEN XUMIAO , DONG JUN , LIN XIAOFENG , AL‐RASHEID KHALED A. S.
Published: September 2011

ABSTRACT. The morphology, infraciliature and small subunit ribosomal RNA gene‐based phylogeny of an urostylid ciliate, Monocoronella carnea n. g., n. sp., found in coastal areas off Daya Bay, Southern China, were investigated. The new genus Monocoronella n. g. is recognized by the following features: having conspicuous frontal cirri forming a long and single corona; buccal and frontoterminal cirri present; single marginal row on each side; adoral zone, midventral complex and transverse cirri in Pseudokeronopsis mode. The type species M. carnea n. sp. is diagnosed by the combination of marine habitat and brown‐reddish color of the cortical granules. Phylogenetic analyses for the new taxon indicate that Monocoronella n. g. is most closely related to Bergeriella, and is located within the core Urostylida clade. A misidentification in previous literature was recognized and a new species, Monocoronella dragescoi n. sp. [Basionym: Holosticha (Keronopsis) monilata (Kahl 1928) sensu Dragesco (1970) et sensu Dragesco and Dragesco‐Kernéis (1986), non sensu Kahl (1928)], was suggested.
Effects of Evaluation of Societal Conditions and Work–Family Conflict on Social Cynicism and Distress: A Longitudinal Analysis1
Authors: LI FULI , LEUNG KWOK
Published: September 2011

Social cynicism, a general belief about the malevolent nature of people and social institutions, shows a negative influence on many attitudes and behaviors, but little is known about the factors that give rise to this belief syndrome. We hypothesized and confirmed the role of low evaluation of societal conditions as an antecedent of social cynicism in a longitudinal study in 3 Chinese cities. Consistent with the person specificity argument, we found that low evaluation of societal conditions exerted little influence on distress, a self‐relevant outcome variable. Instead, work–family conflict, which reflects one's personal experiences, was found to be a significant antecedent of distress, but it exerted little influence on social cynicism, a worldview. Implications of the findings are discussed.
Characterization of recombinant Streptococcus mitis‐derived human platelet aggregation factor
Authors: OHKUNI HISASHI , NAGAMUNE HIDEAKI , OZAKI NANA , TABATA ATSUSHI , TODOME YUKO , WATANABE YUKINO , TAKAHASHI HIDEMI , OHKURA KAZUTO , KOURAI HIROKI , OHTSUKA HIROKI , FISCHETTI VINCENT A. , ZABRISKIE JOHN B.
Published: September 2011

Ohkuni H, Nagamune H, Ozaki N, Tabata A, Todome Y, Watanabe Y, Takahashi H, Ohkura K, Kourai H, Ohtsuka H, Fischetti VA, Zabriskie JB. Characterization of recombinant Streptococcus mitis‐derived human platelet aggregation factor. APMIS 2012; 120: 56–71.

We previously purified Streptococcus mitis‐derived human platelet aggregation factor (Sm‐hPAF) from the culture supernatant of S. mitis strain Nm‐65, isolated from the tooth surface of a patient with Kawasaki disease. Here we produced recombinant Sm‐hPAF protein (rSm‐hPAF) in Escherichia coli, to determine whether rSm‐hPAF conserves its platelet aggregation activity. rSm‐hPAF precursor (665 amino acids) shows up to 36–56% identity with the family of cholesterol‐dependent cytolysins (CDCs), and rSm‐hPAF displayed potent hemolytic activity toward mammalian erythrocytes, including human erythrocytes with platelet aggregation activity. The 162‐amino acid amino‐terminal domain of rSm‐hPAF was found in no other CDCs except lectinolysin; this domain is homologous to a portion of pneumococcal fucolectin‐related protein. Interestingly, suilysin (SLY) and pneumolysin (PLY) of CDCs also exhibit substantial human platelet aggregation activity, similar to rSm‐hPAF, and the platelet aggregation by rSm‐hPAF, SLY, and PLY was morphologically confirmed using light and electron microscopy.
Successful treatment of psoriasis vulgaris with targeted narrow‐band ultraviolet B therapy using a new flat‐type fluorescent lamp
Authors: Nishida Emi , Furuhashi Takuya , Kato Hiroshi , Kaneko Natsumi , Shintani Yoichi , Morita Akimichi
Published: September 2011

Narrow‐band ultraviolet B (NB‐UVB) therapy is widely used for refractory skin diseases. Targeted phototherapy is now being used to reduce the number of sessions and to avoid exposing normal skin. We developed a targeted NB‐UVB therapy using a flat‐type lamp emitting a wavelength similar to that of the TL‐01 fluorescent lamp. Six Japanese patients with psoriasis were recruited and treated with the flat‐type NB‐UVB device with an initial dose of 70% of the minimal erythema dose, with a 20% increase at each subsequent session. The plaque severity score was determined. All lesions of the tested patients were responsive to NB‐UVB therapy using the flat‐type lamp. The mean percent reduction of the lesion was 58.3 ± 17.7%. The mean cumulative dose was 20.8 ± 10.8 J/cm2. No side effects were observed during treatment. The flat‐type targeted NB‐UVB device is compact and convenient, and highly effective for the treatment of limited psoriasis lesions.
MICAL‐L1 is a Tubular Endosomal Membrane Hub that Connects Rab35 and Arf6 With Rab8a
Authors: Rahajeng Juliati , Panapakkam Giridharan Sai Srinivas , Cai Bishuang , Naslavsky Naava , Caplan Steve
Published: September 2011

Endocytosis is a conserved process across species in which cell surface receptors and lipids are internalized from the plasma membrane. Once internalized, receptors can either be degraded or be recycled back to the plasma membrane. A variety of small GTP‐binding proteins regulate receptor recycling. Despite our familiarity with many of the key regulatory proteins involved in this process, our understanding of the mode by which these proteins co‐operate and the sequential manner in which they function remains limited. In this study, we identify two GTP‐binding proteins as interaction partners of the endocytic regulatory protein molecule interacting with casl‐like protein 1 (MICAL)‐L1. First, we demonstrate that Rab35 is a MICAL‐L1‐binding partner in vivo. Over‐expression of active Rab35 impairs the recruitment of MICAL‐L1 to tubular recycling endosomes, whereas Rab35 depletion promotes enhanced MICAL‐L1 localization to these structures. Moreover, we demonstrate that Arf6 forms a complex with MICAL‐L1 and plays a role in its recruitment to tubular endosomes. Overall, our data suggest a model in which Rab35 is a critical upstream regulator of MICAL‐L1 and Arf6, while both MICAL‐L1 and Arf6 regulate Rab8a function.
Active and passive MDMA (‘ecstasy’) intake induces differential transcriptional changes in the mouse brain
Authors: Fernàndez‐Castillo N. , Orejarena M. J. , Ribasés M. , Blanco E. , Casas M. , Robledo P. , Maldonado R. , Cormand B.
Published: September 2011

3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a recreational drug widely used by adolescents and young adults. Although its rewarding effects are well established, there is controversy on its addictive potential. We aimed to compare the consequences of active and passive MDMA administration on gene expression in the mouse brain since all previous studies were based on passive MDMA administration. We used a yoked‐control operant intravenous self‐administration paradigm combined with microarray technology. Transcriptomic profiles of ventral striatum, frontal cortex, dorsal raphe nucleus and hippocampus were analysed in mice divided in contingent MDMA, yoked MDMA and yoked saline groups, and several changes were validated by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The comparison of contingent MDMA and yoked MDMA vs. yoked saline mice allowed the identification of differential expression in several genes, most of them with immunological and inflammatory functions, but others being involved in neuroadaptation. In the comparison of contingent MDMA vs. yoked MDMA administration, hippocampus and the dorsal raphe nucleus showed statistically significant changes. The altered expression of several genes involved in neuroadaptative changes and synapse function, which may be related to learning self‐administration behaviour, could be validated in these two brain structures. In conclusion, our study shows a strong effect of MDMA administration on the expression of immunological and inflammatory genes in all the four brain regions studied. In addition, experiments on MDMA self‐administration suggest that the dorsal raphe nucleus and hippocampus may be involved in active MDMA‐seeking behaviour, and show specific alterations on gene expression that support the addictive potential of this drug.
Bacteremia in feverish children presenting to the emergency department: a retrospective study and literature review
Authors: Bressan Silvia , Berlese Paola , Mion Teresa , Masiero Susanna , Cavallaro Antonietta , Da Dalt Liviana
Published: September 2011

Aim:  To evaluate the incidence of bacteremia, and the isolated pathogens, in well‐appearing children with fever without source (FWS) presenting to the pediatric emergency department (PED), after pneumococcal conjucate vaccine ‐ 7 valent (PCV‐7) widespread introduction in the Veneto region of north‐eastern Italy, and to review the main literature contributions on the subject.

Methods:  Blood cultures performed at the PED of Padova from 1 June 2006 to 31 January 2009 in febrile children aged 1–36 months were retrospectively retrieved. Medical records of previously healthy well‐appearing children with FWS were identified and reviewed.

Results:  The study finally included 392 patients. Bacteremia rate was 0.34% (95% CI 0–1) in the age group 3–36 months and 2% (95% CI 0–4.7) in infants 1–3 months. No Streptococcus pneumoniae was isolated. The literature review identified 10 relevant studies carried out in the USA and Spain showing an overall bacteremia rate <1% for feverish children aged 3–36 months, with values <0.5% in settings with high PCV‐7 coverage.

Conclusion:  Overall bacteremia rate is currently <0.5% in well‐appearing children aged 3–36 months with FWS attending the PED in areas with PCV‐7 widespread vaccination and is sufficiently low to preclude laboratory testing in favour of close follow‐up. Further research is needed to evaluate a more conservative approach in infants 2–3 months of age.
Calcium‐permeable channels in plant cells
Authors: Jammes Fabien , Hu Heng‐Cheng , Villiers Florent , Bouten Roxane , Kwak June M.
Published: September 2011

Calcium signal transduction is a central mechanism by which plants sense and respond to endogenous and environmental stimuli. Cytosolic Ca2+elevation is achieved via two cellular pathways, Ca2+influx through Ca2+channels in the plasma membrane and Ca2+release from intracellular Ca2+stores. Because of the significance of Ca2+channels in cellular signaling, interaction with the environment and developmental processes in plants, a great deal of effort has been invested in recent years with regard to these important membrane proteins. Because of limited space, in this review we focus on recent findings giving insight into both the molecular identity and physiological function of channels that have been suggested to be responsible for the elevation in cytosolic Ca2+level, including cyclic nucleotide gated channels, glutamate receptor homologs, two‐pore channels and mechanosensitive Ca2+‐permeable channels. We provide an overview of the regulation of these Ca2+channels and their physiological roles and discuss remaining questions.
Privatizing Waterworks: Learning from the French Experience*
Authors: Hanke Steve H. , Walters Stephen J.K.
Published: September 2011

In this pair of articles, the first of which was published almost 25 years ago, two distinguished economists make and then revisit the case for privatizing the water supply. While agreeing with the general assessment that waterworks are “natural monopolies,” the authors show that privatization of such enterprises need not lead to the standard monopoly outcomes of above‐competitive prices, reduced output, or inferior service.

As evidence, the authors cite the French experiment with water privatization that began in 1782 with the Perrier brothers' 15‐year contract to provide water for Parisians. Today, an estimated 80% of the French water supply is managed by private firms. And, as the French experience demonstrates, the benefits of large‐scale, single‐firm operations can be obtained at competitive prices by means of a system of franchise bidding in which ownership and/or management rights are awarded to the firm that offers the public the best terms—along with a credible commitment to make good on them.
The Role of Finance and Private Investment in Developing Sustainable Cities
Authors: Macomber John
Published: September 2011

Three trends will drive urban investment, development, and entrepreneurship in the next two decades. The first is urbanization; over the next twenty years, the number of people living in cities will double. Second, shared resources like clean water, clean air, energy, and places to put solid waste are already scarce, and urbanization will only exacerbate shortages. Third, almost no local or national government can mobilize both the capital and the political consensus to make investments in the infrastructure that will lead to more effective use of these resources.

This article argues that there is a largely unrecognized opportunity for the private sector to engage in selective investments that can help cities limit the effects of these trends. Investors and entrepreneurs can make money in ways that achieve more productive use of these scarce “public goods;” and by so doing, they can make cities more economically competitive as well as more livable. In making his argument, the author provides a tour of three “new” Asian cities, two of which are held up as models for future development.
Variations in the Gender Composition of Immigrant Populations: How They Matter
Authors: Donato Katharine M. , Alexander Joseph T. , Gabaccia Donna R. , Leinonen Johanna
Published: September 2011

This paper estimates and interprets empirical shifts in the gender composition of immigrants to add to scholarship about the gendering of international migrations over time. We map shifts in gender ratios using micro-level data that permit us to create age-standardized estimates among adult foreign born stock living in the United States since 1850 and in 26 other nations worldwide since 1960. We examine regional and national variations in these shifts, and ask whether and how the gendered composition of foreigners from diverse origins in the United States – the nation that has received the largest populations of migrants for over a century – differs from other nations that receive large numbers of immigrants. We also examine recent variations in gender ratios among immigrants living in six regional destination countries. Results show substantial variation in the gender composition of foreign-born populations, and they offer a starting point for examining causes and consequences in future research.
Optimal Photosensitizers for Photodynamic Therapy of Infections Should Kill Bacteria but Spare Neutrophils
Authors: Tanaka Masamitsu , Kinoshita Manabu , Yoshihara Yasuo , Shinomiya Nariyoshi , Seki Shuhji , Nemoto Koichi , Hirayama Takahiro , Dai Tianhong , Huang Liyi , Hamblin Michael R. , Morimoto Yuji
Published: September 2011

Photodynamic therapy (PDT) for localized microbial infections exerts its therapeutic effect both by direct bacterial killing and also by the bactericidal effects of host neutrophils stimulated by PDT. Therefore, PDT‐induced damage to neutrophils must be minimized, while direct photoinactivation of bacteria is maintained to maximize the therapeutic efficacy of antimicrobial PDT in vivo. However, there has been no study in which the cytocidal effect of PDT on neutrophils was investigated. In this study, the cytocidal effects of PDT on neutrophils were evaluated using different antimicrobial photosensitizers to find suitable candidate photosensitizers for antimicrobial PDT. PDT on murine peripheral‐blood neutrophils was performed in vitro using each photosensitizer at a concentration that exerted a maximum bactericidal effect on methicillin‐resistant Staphylococcus aureus, and morphological alteration and viability of neutrophils were studied. Most neutrophils were viable (>80%) after PDT using toluidine blue‐O (TB) or methylene blue (MB), while neutrophils showed morphological change and their viabilities were decreased (<70%) after PDT using other photosensitizers (erythrosine B, rose bengal, crystal violet, Photofrin, new methylene blue and Laserphyrin). These results suggest that PDT using TB or MB can preserve host neutrophils while exerting a significant therapeutic effect on in vivo localized microbial infection.
Iniquity, Terror and Survival: Welsh Gothic, 1789‐18041
Authors: EDWARDS ELIZABETH
Published: September 2011

Literary critics have recently begun to draw attention to ‘national Gothic’, outlining the importance of themes of conflict and defeated and victorious histories in this form of the Gothic. The contested and unsettled history of Wales provides the perfect conditions for a national Gothic, yet little work has yet been done towards the notion of a specifically Welsh Gothic in the period following the French revolution. This article explores four variations on the theme of writing Gothic in revolution‐era Wales: a tourist Gothic, a Jacobin Gothic, a loyalist Gothic and a post‐colonial Gothic. It shows how writers of this period used the conflicts and iniquities of the Welsh past equally to illustrate Wales's incorporation within a larger united Britain and to figure its otherness, its familiar difference, relative to its historical enemy – England.
Crataegus grossidentata sp. nov. (Rosaceae–Pyreae), a new hawthorn from northern Iran
Authors: Sharifnia Fariba , Ib Christensen Knud , Seyedipour Nasim , Salimpour Fahimeh , Mehregan Iraj
Published: September 2011

Crataegus grossidentata Sharifnia & K. I. Chr., found in northern Iran, is described and illustrated as a species new to science. Its ecology, distribution and taxonomic relationships are discussed. A key to C. grossidentata and other one‐styled taxa of Crataegus occurring in Iran is provided.
Well‐being, Reasonableness, and the Natural Environment
Authors: Kaplan Rachel , Kaplan Stephen
Published: September 2011

This Special Section features a number of perspectives on the vital role played by natural environments. The three empirical papers, using different approaches and measures, representing diverse populations in different countries, and different kinds of natural settings, all provide evidence for the importance of nature to human well‐being. This paper presents the Reasonable Person Model (RPM) as a framework for understanding how the environment can help bring out the best in people. Demographic and regional variations notwithstanding, people are empowered by opportunities to make a difference and be respected, they are concerned with being effective, and their efforts are guided by their mental models. Having nature nearby, even if modest in scale, can be particularly beneficial in offsetting some of the consequences of depleted attentional resources which readily undermine reasonable behavior. We focus on some important distinctions between psychological restoration (and its relationship to the effectiveness domain of RPM) and environmental preference (and its connection to RPM's model building domain). Today's all too pervasive unreasonableness is costly in terms of personal and social well‐being. Understanding the vital capacity of the natural environment can make a substantial difference in bringing out the best in people.