bluuebunny/crossref_metadata_2025 huggingface dataset:
The Adverse Long-Term Impact of Renal Impairment in Patients Undergoing Percutaneous Coronary Intervention in the Drug-Eluting Stent Era
Authors: Appleby Clare E. , Ivanov Joan , Lavi Shahar , Mackie Karen , Horlick Eric M. , Ing Douglas , Overgaard Christopher B. , Seidelin Peter H. , von Harsdorf Rüdiger , Džavík Vladimír
Published: July 2009

Background—

An observational study determining the long-term impact of chronic kidney disease (CKD) on patients undergoing percutaneous coronary intervention at a tertiary cardiac referral center. CKD is associated with poor in-hospital outcomes after percutaneous coronary intervention, but its effect beyond 1 year, particularly in the drug-eluting stent (DES) era, has not been reported.

Methods and Results—

Baseline creatinine was available for 11 953 patients entered into a prospective registry (April 2000 to September 2007). Patients were stratified: those with or without at least moderate CKD (creatinine clearance, <60 mL/min). Follow-up data were obtained through linkage to a provincial registry. Kaplan–Meier analysis was performed. Cox multiple-regression analysis identified independent predictors of late mortality and major adverse cardiac events (MACE) and examined the association between DES use and late outcomes in the presence or absence of CKD. CKD was present in 3070 patients (25.7%). In-hospital mortality and MACE were significantly increased in CKD (3.34% versus 0.44%,
P
<0.001 and 5.73% versus 2.2%,
P
<0.001). Survival and MACE-free survival at 7 years were reduced (64.5�1.4% versus 89.4�0.5%,
P
<0.001; 44.0�1.4% versus 63.4�0.8%,
P
<0.001). CKD was an independent predictor of late mortality and MACE (hazard ratio [HR]: 2.18, CI: 1.90 to 2.49,
P
<0.0001; HR: 1.37, CI: 1.25 to 1.49,
P
<0.0001). DES use was associated with a significant reduction in both (HR: 0.71, CI: 0.60 to 0.83,
P
<0.0001; HR: 0.70, CI: 0.63 to 0.78,
P
<0.0001). In patients with CKD, DES use was associated with reduced revascularization (HR: 0.68, CI: 0.53 to 0.88,
P
=0.004) and reduced MACE (HR: 0.81, CI: 0.69 to 0.95,
P
=0.011) but not reduced mortality (HR: 0.85, CI: 0.69 to 1.05,
P
=0.1).

Conclusion—

In a large registry of “all comers” for percutaneous coronary intervention, CKD was an independent predictor of adverse late outcomes. DES use may be associated with improved long-term outcomes in this high-risk cohort, but further prospective studies are required.
A Qualitative Study to Identify Barriers to Local Implementation of Prehospital Termination of Resuscitation Protocols
Authors: Sasson Comilla , Forman Jane , Krass David , Macy Michelle , Kellermann Arthur L. , McNally Bryan F.
Published: July 2009

Background—

Despite the existence of national American Heart Association guidelines and 2 termination-of-resuscitation (TOR) rules for ceasing efforts in refractory out-of-hospital cardiac arrest, many emergency medical services agencies in the United States have adopted their own local protocols. Public policies and local perceptions may serve as barriers or facilitators to implementing national TOR guidelines at the local level.

Methods and Results—

Three focus groups, lasting 90 to 120 minutes, were conducted at the National Association of Emergency Medical Services Physicians meeting in January 2008. Snowball sampling was used to recruit participants. Two reviewers analyzed the data in an iterative process to identify recurrent and unifying themes. We identified 3 distinct groups whose current policies or perceptions may impede efforts to adopt national TOR guidelines: payers who incentivize transport; legislators who create state mandates for transport and allow only narrow use of do-not-resuscitate orders; and communities where cultural norms are perceived to impede termination of resuscitation. Our participants suggested that national organizations, such as the American Heart Association and American College of Emergency Physicians, may serve as potential facilitators in addressing these barriers by taking the lead in asking payers to change reimbursement structures; encouraging legislators to revise laws to reflect the best available medical evidence; and educating the public that rapid transport to the hospital cannot substitute for optimal provision of prehospital care.

Conclusion—

We have identified 3 influential groups who will need to work with national organizations to overcome current policies or prevailing perceptions that may impede implementing national TOR guidelines.
A New Form of Social Withdrawal in Japan: a Review of Hikikomori
Authors: Teo Alan R.
Published: July 2009

The purpose of this article is to provide a clinical review of a unique, emerging form of severe social withdrawal that has been described in Japan. This paper begins with a case vignette, then reviews the case defi nition, epidemiology, psychopathology, differential diagnosis, and treatment and management of the condition. Called hikikomori, it is well known to both the psychiatric community and general public in Japan but it has never been reviewed in the English medical literature. Patients are mostly adolescent and young adult men who become recluses in their parents’ homes for months or years. They withdraw from contact with family, rarely have friends, and do not attend school or hold a job. Never described before the late 1970s, hikikomori has become a silent epidemic with tens, perhaps hundreds, of thousands of cases now estimated in Japan. The differential diagnosis includes anxiety and personality disorders, but current nosology in the Diagnostic and Statistic Manual of Mental Disorders may not adequately capture the concept of hikikomori. Treatment strategies are varied and lack a solid evidence base, but often include milieu, family, and exposure therapy. Much further research, including population-based and prospective studies, needs to be conducted to characterize and provide an evidence base for treatment of this condition.
All-water-blown Integral Skin Foam Prepared by Novel Polypropylene Glycols
Authors: Wada Hiroshi , Fukuda Hiroki
Published: July 2009

Integral skin foam (designated ISF) consisting of core (cellular foam) and solid skin is produced in one operation. Since the recommendation of Montreal Protocol in 1987 to phase out five CFCs, the three major possibilities for producing ISF studied in the past include replacement of CFC with HCFC, HFC, or water. Recently, the use of HCFC-141b for blowing agent was also phased out at the end of 2003, and HFCs have been criticized for their high Global Warming Potential (GWP). However, it is difficult to produce a skin layer using water as the blowing agent because carbon dioxide (CO2), which is generated by an isocyanate—water reaction is unlikely to condense at the mold surface. We have developed a new technology to produce all-water-blown ISF. A novel polypropylene glycol, which contains an extremely small amount of byproducts (monool) and has narrow molecular weight distribution compared with conventional polypropylene glycols was applied to this new system. In case of applying this novel polypropylene glycol in all-water-blown ISF system, it is easy to control the balance between the gelling reaction and blowing reaction of ISF. Therefore, we have been able to obtain a tight skin layer like HFC-blown ISF.
Analysis of the Impact Properties of Structural Foams
Authors: Michaeli Walter , Florez Laura , Obeloer Dominik , Brinkmann Markus
Published: July 2009

Several efforts have been made to predict the mechanical properties of structural foams, mainly under tensile and flexural loading modes. The prediction of the mechanical behavior of foams subjected to impact loads remains, however, an unfulfilled challenge. Several investigations have studied the variation of impact properties of structural foams. Both the studied materials, the testing methods employed and the techniques used for sample preparation, vary broadly. Some studies regarding the relation between density and energy absorption capabilities have been conclusive. The influence of cell size and skin thickness have also been analyzed. So far, results show that the foam structure adds a number of complexities to the limited characterization capabilities of conventional impact methods. This study aims to contribute to the understanding of the failure behavior of structural foams. The influence of three different factors will be addressed: the type of imposed loading, through variations in the test method used; the nature of the studied base material (semicrystalline vs. amorphous), and the influence of the foam morphology.
Even Paranoids Have Enemies
Authors: Kelman Ari
Published: July 2009

This article explores the origin and implications of the rumor that government authorities intentionally destroyed the levee fronting New Orleans's lower 9th Ward during Hurricane Katrina. The author argues that these rumors should not be dismissed as fanciful conspiracy theories, but must instead be placed in the context of New Orleans's environmental history. That history includes numerous episodes in which commercial elites colluded with elected officials to place the city's poor and working classes in harm's way during urban disasters. As a result, the levee rumors during Hurricane Katrina may be understood as a form of resistance, a way in which displaced residents of the lower 9th Ward tried to shape the discourse about the causes and consequences of the hurricane, insisting that, rather than being understood as a so-called natural disaster, it must be understood as a human-constructed catastrophe.
Improving the Quality of Ability Estimates Through Multidimensional Scoring and Incorporation of Ancillary Variables
Authors: de la Torre Jimmy
Published: July 2009

For one reason or another, various sources of information, namely, ancillary variables and correlational structure of the latent abilities, which are usually available in most testing situations, are ignored in ability estimation. A general model that incorporates these sources of information is proposed in this article. The model has a general formulation that allows incorporation of either source or both sources of information in scoring the examinees using various item response models and subsumes the traditional method of expected a posteriori as a special case. Results show that using the different sources of information singly or simultaneously provides better ability estimates (i.e., higher correlation with the true abilities and smaller posterior variance and mean squared error). The optimal condition occurs when several short tests measuring highly correlated abilities that also correlate highly with the covariates are used. Markov chain Monte Carlo parameter estimation algorithms corresponding to the different model formulations are also developed. Simulated and actual data are analyzed to establish the usefulness and feasibility of the proposed models. Several practical considerations in using these models are also discussed.
Postdivorce Family Stability and Changes in Adolescents’ Academic Performance
Authors: Yongmin Sun  , Yuanzhang Li
Published: July 2009

Three waves of panel data from 7,897 adolescents in the National Education Longitudinal Studies have been used to investigate whether a stabilized postdivorce family environment benefits adolescents’ academic performance trajectories. The analyses indicate that compared with peers who grow up in stable postdivorce families, children of divorce who experience additional family transitions during late adolescence make less progress in their math and social studies performance over time. Furthermore, family resource differences before and during late adolescence either partially or completely account for the less positive performance trajectories in two types of divorced families. Finally, daughters in unstable postdivorce families appear to make less academic progress over time than sons. The study illustrates the importance of incorporating both postdivorce family transitions and repeatedly measured child outcomes in the investigation of divorce effects.
Onset of Resin Micro-Cracks in Unidirectional Glass Fiber Laminates with Integrated SHM Sensors: Experimental Results
Authors: Ghezzo Fabrizia , Huang Yi , Nemat-Nasser Sia
Published: July 2009

This article presents the results of experiments conducted in order to identify and locate the failure initiation in glass fiber/epoxy laminates with integrated structural health monitoring sensors (SHM) and electronics. Recent advances in health monitoring technologies have resulted in the development of micro-dimensional devices that can be embedded into composite laminates. Notwithstanding their small size, such inclusions may affect the response of the composite. Damage induced by the peak values of stress concentration around the embedded inclusion is, in fact, one of the main concerns in smart structures technology. To address this specific issue, unidirectional S2 glass fiber/epoxy laminated composites are fabricated with embedded small implants that mimic potential sensors and microprocessors. Quasi-static tensile tests are then performed on those samples while monitoring them by the acoustic emission (AE) technique. Additionally, the microstructure of the material with and without implants is explored. The AE results show that early low-medium amplitude events are detected at the implant location and the micrographic inspections reveal that micro-cracks initiate at the device-composite matrix interface and grow around the implant causing the debond of the external component from the surrounding resin system.
Correlating Low-energy Impact Damage with Changes in Modal Parameters: A Preliminary Study on Composite Beams
Authors: Shahdin Amir , Morlier Joseph , Gourinat Yves
Published: July 2009

This article is an experimental study of the effects of multi-site damage on the vibration response of a composite beam damaged by low-energy impact. The variation of the modal parameters with different levels of impact energy and density of impact is studied. Specimens are impacted symmetrically in order to induce a global rate of damage. A damage detection tool Damage Index is introduced in order to verify the estimation of damping ratios. Design of Experiments is used to establish the sensitivity of both energy of impact and density of damage. The DOE analysis results (using natural frequency only) indicate that impact energy for 2nd, 3rd, and 4th bending modes is the most significant factor contributing to the changes in the modal parameters for this kind of symmetrical dynamic test.
Experimental Investigation on Statistical Moment-based Structural Damage Detection Method
Authors: Xu Y.L. , Zhang J. , Li J.C. , Xia Y.
Published: July 2009

Although vibration-based structural damage detection methods have demonstrated various degrees of success, the damage detection of civil structures still remains as a challenging task. The main obstacles include the insensitivity to local damage and the high sensitivity to measurement noise. A new structural damage detection method based on the statistical moments of dynamic responses of a structure has been recently proposed by the authors, and the numerical study manifested that the proposed method is sensitive to local structural damage but insensitive to measurement noise. The experimental investigation on this method is presented in this article. Three shear building models with and without damage were built and subjected to ground motions generated by a shaking table. The displacement and acceleration responses of each building model at each floor were recorded. The recorded ground motion and building responses as well as identified structural damping ratios were then used to identify damage locations and severities using the statistical moment-based damage detection method. The identified damage locations and severities were compared with the theoretical values. The comparison is found satisfactory, and the method proposed is effective and feasible.
Aggressive Data Reduction for Damage Detection in Structural Health Monitoring
Authors: Park Chiwoo , Jiong Tang  , Yu Ding
Published: July 2009

While wireless sensors are increasingly adopted in various applications, the need of developing data reduction methods to alleviate data transmission rate issue between the sensors and the data interpretation unit becomes more urgent. This article presents a new data reduction method for sensors used in structural health monitoring application. Our goal is to achieve an effective data reduction capability while maintaining adequate power for damage detection. We propose to establish an explicit measure of damage detection capability for the features in the response signals and use this measure to select the subset of the features that balance between the degree of data reduction and the damage detection capability. We also explore a computationally efficient procedure searching for the best subset of the features. This new method is tested on experimentally obtained Lamb wave signals for beam damage detection. Performance comparisons with respect to the existing methods demonstrate the strength of the proposed method.
Rap signaling is crucial for the competence of IL-7 response and the development of B-lineage cells
Authors: Katayama Yoshinori , Sekai Miho , Hattori Masakazu , Miyoshi Ichiro , Hamazaki Yoko , Minato Nagahiro
Published: July 2009

Rap family GTPases consist of multiple members with substantial functional redundancy. With the use of transgenic mice conditionally expressing a bona fide dominant-negative Rap1 mutant, Rap1A17, capable of inhibiting the activation of all Rap family members in B-lineage cells (mb.1-Rap1A17 Tg), we demonstrate that these mice show a defective generation of pre-B cells in bone marrow, resulting in a significant diminution of peripheral mainstream B cells. The effect is attributed to the impaired survival and expansion of B-lineage progenitors in response to IL-7, despite normal IL-7Rα expression. The pre-B cells from mb.1-Rap1A17 Tg mice showed a significantly reduced expression of c-myc and E2A, and the competence of IL-7 response was restored by the transduction of c-myc, but not by constitutively active (CA) Stat5a, CA PI3K-p100, or bcl-2. The residual follicular B cells with complete Cre-mediated recombination proliferated normally in response to B-cell receptor stimulation and showed efficient germinal center reaction in vivo. These results show that endogenous Rap signaling plays a crucial role selectively in B-lineage cell development by sustaining the competence for IL-7 response, whereas it is dispensable for mature B-cell function.
Transcriptome analysis of the venom gland of the scorpion Scorpiops jendeki: implication for the evolution of the scorpion venom arsenal
Authors: Ma Yibao , Zhao Ruiming , He Yawen , Li Songryong , Liu Jun , Wu Yingliang , Cao Zhijian , Li Wenxin
Published: July 2009

Background

The family Euscorpiidae, which covers Europe, Asia, Africa, and America, is one of the most widely distributed scorpion groups. However, no studies have been conducted on the venom of a Euscorpiidae species yet. In this work, we performed a transcriptomic approach for characterizing the venom components from a Euscorpiidae scorpion, Scorpiops jendeki.

Results

There are ten known types of venom peptides and proteins obtained from Scorpiops jendeki. Great diversity is observed in primary sequences of most highly expressed types. The most highly expressed types are cytolytic peptides and serine proteases. Neurotoxins specific for sodium channels, which are major groups of venom components from Buthidae scorpions, are not detected in this study. In addition to those known types of venom peptides and proteins, we also obtain nine atypical types of venom molecules which haven't been observed in any other scorpion species studied to date.

Conclusion

This work provides the first set of cDNAs from Scorpiops jendeki, and one of the few transcriptomic analyses from a scorpion. This allows the characterization of a large number of venom molecules, belonging to either known or atypical types of scorpion venom peptides and proteins. Besides, our work could provide some clues to the evolution of the scorpion venom arsenal by comparison with venom data from other scorpion lineages.
Identification of a novel nucleolin related protein (NRP) gene expressed during rat spermatogenesis
Authors: Chathoth Keerthi T , Ganesan Gayatri , Rao MRS
Published: July 2009

Background

Nucleolin is a major nucleolar phosphoprotein involved in various steps of ribosome biogenesis in eukaryotic cells. As nucleolin plays a significant role in ribosomal RNA transcription we were interested in examining in detail the expression of nucleolin across different stages of spermatogenesis and correlate with the transcription status of ribosomal DNA in germ cells.

Results

By RT PCR and western blot analysis we found that nucleolin is strongly down regulated in meiotic spermatocytes and haploid germ cells. We have identified a new nucleolin related protein (NRP) gene in the rat genome, which is over expressed in the testis and is up regulated several fold in meiotic spermatocytes and haploid germ cells. The NRP protein lacks the acidic stretches in its N terminal domain, and it is encoded in rat chromosome 15 having a different genomic organization as compared to nucleolin gene present on chromosome 9. We have also found NRP genes encoded in genomes of other mammalian species. We performed run-on transcription assay where we have observed that rDNA is transcribed at much lower level in meiotic spermatocytes and haploid spermatids as compared to diploid cells. By siRNA knock down experiments we could also demonstrate that NRP can support rDNA transcription in the absence of nucleolin.

Conclusion

We have identified a new nucleolin variant over expressed in germ cells in rat and analyzed its domain structure. We attribute that the transcriptional activity of rDNA genes in the late spermatogenesis is due to the presence of this variant NRP. The expression of this variant in the germ cells in the absence of nucleolin, could have additional functions in the mammalian spermatogenesis which needs to be investigated further.
Response of the primary tumor in symptomatic and asymptomatic stage IV colorectal cancer to combined interventional endoscopy and palliative chemotherapy
Authors: Cameron Silke , Hünerbein Diana , Mansuroglu Tümen , Armbrust Thomas , Scharf Jens-Gerd , Schwörer Harald , Füzesi László , Ramadori Giuliano
Published: July 2009

Background

The treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease.

Methods

20 patients [14 men, 6 women, median age 67 (39–82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83%) or asymptomatic (17%) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy.

Results

Response of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3–71) months. No complications due to the primary were observed.

Conclusion

This study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC.
Anti-tumor effect of Liqi, a traditional Chinese medicine prescription, in tumor bearing mice
Authors: Ji Deng-Bo , Ye Jia , Jiang Yi-Min , Qian Bo-Wen
Published: July 2009

Background

Liqi, an herbal preparation used in traditional Chinese medicine, has been used to treat cancer in China for centuries. We investigated the anti-tumor effects of liqi and their mechanisms in mice that had been xenografted with tumors.

Methods

Sarcoma 180 tumor, Lewis lung carcinoma, and SGC-7901 cells were implanted in BALB/c mice, C57BL/6 mice, and BALB/c nude mice, respectively. Liqi was administered to subgroups of these mice. The tumor weight and size were measured. Cell cycle analysis and T lymphocyte subsets were determined by flow cytometry. The activity of NK cells and TNF was tested using cytotoxicity assay on YAC-1 cells and L929 cells, respectively, and the activity of IL-2 was tested with an IL-2-dependent CTLL-2 cell proliferation assay. Platelet aggregation was monitored by measuring electric impedance, and the levels of thromboxane A2 (TXA2) and prostacyclin (PGI2) in blood were measured by125I-TXB2and125I-Keto-PGF1αradioimmunoassay.

Results

The results showed that liqi inhibited tumor growth in tumor-implanted mice and arrested the cell proliferation in the G0/G1 phase and reduced the portion of cells in S and G2/M phase for SGC-7901 cells. Liqi increased the activity of NK cells and TNF-α, stimulated IL-2 production and activity, and regulated T lymphocyte subpopulations. Liqi inhibited the Lewis lung carcinoma metastasis by inhibiting platelet aggregation and normalizing the balance between TXA2and PGI2.

Conclusion

All these findings demonstrated that liqi has an anti-tumor effect in vivo. The mechanism may be related to immune regulation and anticoagulation effects.
An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats
Authors: Salvetti Natalia R , Panzani Carolina G , Gimeno Eduardo J , Neme Leandro G , Alfaro Natalia S , Ortega Hugo H
Published: July 2009

Background

Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence.

Methods

We compared the number of in situ apoptotic cells by TUNEL assay, expression of active caspase-3 and members of Bcl-2 family by immunohistochemistry; and cell proliferation by the expression of the proliferation markers: PCNA and Ki-67.

Results

The proliferation index was low in granulosa of tertiary and cystic follicles of light exposed rats when compared with tertiary follicles of control animals, while in theca interna only cystic follicles presented low proliferation index when compared with tertiary follicles (p < 0.05). The granulosa of cysts exhibited a similar cell DNA fragmentation to early atretic follicles. In the granulosa and theca interna, active caspase-3 shown similar immunostaining levels in tertiary and cystic follicles (p < 0.05). The granulosa cells presented high expression of Bcl-2, Bcl-xL and Bcl-w in the tertiary and cystic follicles with diminishing intensity in the atretic follicles, except with Bcl-w where the intensity was maintained in the atretic follicles (p < 0.05). The expression of Bax was weak in the healthy and cystic follicles. In the theca interna, Bcl-2 expression was the same as the pattern found in the granulosa; no differences were found between tertiary and cystic follicles from both groups for Bcl-xL and Bcl-w. The expression of Bax in this layer was higher in the tertiary follicles of the treated animals (p < 0.05) while the values for cystic follicles were similar to those in the tertiary follicles of controls. The theca externa showed low expression of the pro and anti-apoptotic proteins.

Conclusion

These results show that the combination of weak proliferation indices and low apoptosis observed in follicular cysts, could explain the cause of the slow growth of cystic follicles and the maintenance of a static condition without degeneration, which leads to their persistence. These alterations may be due to structural and functional modifications that take place in these cells and could be related to hormonal changes in animals with this condition.
Analysis of host- and strain-dependent cell death responses during infectious salmon anemia virus infection in vitro
Authors: Schiøtz Berit L , Bækkevold Espen S , Poulsen Lene C , Mjaaland Siri , Gjøen Tor
Published: July 2009

Background

Infectious salmon anemia virus (ISAV) is an aquatic orthomyxovirus and the causative agent of infectious salmon anemia (ISA), a disease of great importance in the Atlantic salmon farming industry.In vitro, ISAV infection causes cytophatic effect (CPE) in cell lines from Atlantic salmon, leading to rounding and finally detachment of the cells from the substratum. In this study, we investigated the mode of cell death duringin vitroISAV infection in different Atlantic salmon cell lines, using four ISAV strains causing different mortalityin vivo.

Results

The results show that caspase 3/7 activity increased during the course of infection in ASK and SHK-1 cells, infected cells showed increased surface expression of phosphatidylserine and increased PI uptake, compared to mock infected cells; and morphological alterations of the mitochondria were observed. Expression analysis of immune relevant genes revealed no correlation between in vivo mortality and expression, but good correlation in expression of interferon genes.

Conclusion

Results from this study indicate that there is both strain and cell type dependent differences in the virus-host interaction during ISAV infection. This is important to bear in mind when extrapolatingin vitrofindings to thein vivosituation.
Minocycline Treatment Inhibits Microglial Activation and Alters Spinal Levels of Endocannabinoids in a Rat Model of Neuropathic Pain
Authors: Guasti Leonardo , Richardson Denise , Jhaveri Maulik , Eldeeb Khalil , Barrett David , Elphick Maurice R , Alexander Stephen PH , Kendall David , Michael Gregory J , Chapman Victoria
Published: July 2009

Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats ( P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral ( P < 0.001) and contralateral ( P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly ( P < 0.01) decreased levels of 2-AG and significantly ( P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states.
Genetic Variation in the Serotonin Transporter Gene (5-HTTLPR, Rs25531) Influences the Analgesic Response to the Short Acting Opioid Remifentanil in Humans
Authors: Kosek Eva , Jensen Karin B , Lonsdorf Tina B , Schalling Martin , Ingvar Martin
Published: July 2009

Background

There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders.

Results

At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SAand SA/LG) as compared to those with high expression(LA/LA), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression.

Conclusion

This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.
Papillary fibroelastoma of the left atrial wall: a case report
Authors: Bicer Murat , Cikirikcioglu Mustafa , Pektok Erman , Müller Hajo , Dettwiler Sarah , Kalangos Afksendiyos
Published: July 2009

Cardiac papillary fibroelastoma is a rare, benign cardiac tumor. It often arises from valvular endocardium, and non-valvular endocardial location is rare. Although transthoracic echocardiography is usually sufficient for the diagnosis of most cardiac tumors, small tumors such as papillary fibroelastoma may be missed. Transesophageal echocardiography is superior to transthoracic echocardiography in diagnosing these tumors. Despite their benign histology, and independent of their size, they should be resected surgically because of their high potential for embolization.

In this report, we present a case of papillary fibroelastoma located on the left atrial wall, presenting with symptoms of cerebral ischemia. The patient was treated surgically for the prevention of further embolic complications. Pertinent literature is also reviewed for this rare and benign cardiac tumor.
Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity
Authors: Toussirot Éric , Saas Philippe , Deschamps Marina , Pouthier Fabienne , Perrot Lucille , Perruche Sylvain , Chabod Jacqueline , Tiberghien Pierre , Wendling Daniel
Published: July 2009

Introduction

Spondylarthropathies (SpA) are characterized by abnormal immune responses including T cell activation. Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses. A soluble form of CTLA-4 (sCTLA-4), resulting from an alternative splicing, has been identified and was found increased in several autoimmune diseases. Here, we evaluated circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA. Intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL) were also studied.

Methods

Sera from 165 patients with SpA were evaluated for sCTLA-4 measurements. Results were compared with those from 71 patients with rheumatoid arthritis (RA) and 88 healthy subjects. In 32 patients with SpA, 22 patients with RA and 15 healthy controls, we analyzed the intracellular CTLA-4 expression in CD4+ T cells, CD8+ T cells, activated (HLA-DR+Foxp3-) CD4+ T cells, CD4+ regulatory (CD25+Foxp3+) T cells and in CD3 negative cells by flow cytometry. Expression of the full length (coding for membrane CTLA-4) and spliced form (coding for sCTLA-4) of CTLA-4 transcripts in PBL were analyzed by quantitative real-time polymerase chain reaction (QRT-PCR).

Results

High levels of sCTLA-4 were found in the SpA group compared to the RA group and healthy controls (P < 0.0001). Soluble CTLA-4 serum levels strongly correlated with clinical index of disease activity BASDAI (r = 0.42, P < 0.0001) and C-reactive protein (CRP) levels (r = 0.17, P = 0.037). In contrast to RA patients, SpA patients did not exhibit changes in intracellular CTLA-4 expression in the different PBL subsets tested. Finally, the SpA group showed a preferential expression of the spliced CTLA-4 mRNA (P = 0.0014) in PBL.

Conclusions

SpA patients exhibit high levels of circulating sCTLA-4 that may result from an alternative splicing of CTLA-4 transcripts. This may influence immune activation and regulation in SpA.
Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study
Authors: Bøyesen Pernille , Hoff Mari , Ødegård Sigrid , Haugeberg Glenn , Syversen Silje W , Gaarder Per I , Okkenhaug Cecilie , Kvien Tore K
Published: July 2009

Introduction

Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration.

Methods

163 patients with RA of short disease duration (2.4 years) were included and followed longitudinally. Antibodies to cyclic citrullinated protein (anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed from baseline blood-samples. Hand BMD was measured by digital X-ray radiogrammetry (DXR) based on hand and wrist radiographs obtained at baseline and 1, 2 and 5-year follow-up.

Results

During the study period, DXR-BMD decreased by median (inter quartile range) 1.7% (4.1 to 0.4), 2.8% (5.3 to 0.9) and 5.6% (11.7 to 2.3) after 1, 2 and 5 years, respectively. Elevated baseline anti-CCP, RF, ESR and CRP levels were in univariate linear regression analyses consistently associated with DXR-BMD change at all time-points. Anti-CCP and ESR were independently associated with hand DXR-BMD in multivariate linear regression analyses. Elevated anti-CCP levels were consistent and independent predictors of loss in cortical hand bone during the study period, with the odds ratios (95% confidence interval) 2.2 (1.0 to 4.5), 2.6 (1.1 to 6.2) and 4.9 (1.4 to 16.7) for the 1, 2, and 5-year follow-up periods, respectively.

Conclusions

Anti-CCP and ESR were found to be independent predictors of early localised BMD loss. This finding adds to the understanding of anti-CCP and ESR as important predictors of bone involvement in RA.
Serum Interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study
Authors: Liu Kathleen D , Altmann Christopher , Smits Gerard , Krawczeski Catherine D , Edelstein Charles L , Devarajan Prasad , Faubel Sarah
Published: July 2009

Introduction

Acute kidney injury (AKI) is associated with high mortality rates. New biomarkers that can identify subjects with early AKI (before the increase in serum creatinine) are needed to facilitate appropriate treatment. The purpose of this study was to test the role of serum cytokines as biomarkers for AKI and prolonged mechanical ventilation.

Methods

This was a case-control study of children undergoing cardiac surgery. AKI was defined as a 50% increase in serum creatinine from baseline within 3 days. Levels of serum interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, IL-17, interferon (IFN)-γ, tumor necrosis factor-α (TNF-α), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using a bead-based multiplex cytokine kit in conjunction with flow-based protein detection and the Luminex LabMAP multiplex system in 18 cases and 21 controls. Levels of IL-6 and IL-8 were confirmed with single-analyte ELISA; IL-18 was also measured with single-analyte ELISA.

Results

IL-6 levels at 2 and 12 hours after cardiopulmonary bypass (CPB) and IL-8 levels at 2, 12 and 24 hours were associated with the development of AKI using the Wilcoxon rank-sum test and after adjustment for age, gender, race, and prior cardiac surgery in multivariate logistic regression analysis. In patients with AKI, IL-6 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation (defined as mechanical ventilation for more than 24 hours postoperatively) by receiver operator curve (ROC) analysis, with an area under the ROC curve of 0.95. IL-8 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation in all patients. Serum IL-18 levels were not different between those with and without AKI.

Conclusions

Serum IL-6 and IL-8 values identify AKI early in patients undergoing CPB surgery. Furthermore, among patients with AKI, high IL-6 levels are associated with prolonged mechanical ventilation, suggesting that circulating cytokines in patients with AKI may have deleterious effects on other organs, including the lungs.
Rural–urban migration and depression in ageing family members
left behind
Authors: Abas Melanie A. , Punpuing Sureeporn , Jirapramukpitak Tawanchai , Guest Philip , Tangchonlatip Kanchana , Leese Morven , Prince Martin
Published: July 2009

Background

It has been suggested that rural–urban migration will have adverse
consequences for older parents left behind.

Aims

To describe correlates of outmigration and to estimate any association
between outmigration of children and depression in rural-dwelling older
parents.

Method

Population-based survey of 1147 parents aged 60 and over in rural
Thailand. We randomly oversampled parents living without children. We
defined an outmigrant child as living outside their parent's district,
and measured depression as a continuous outcome with a Thai version of
the EURO–D.

Results

Outmigration of all children, compared with outmigration of some or no
children, was independently associated with less depression in parents.
This association remained after taking account of social support, parent
characteristics, health and wealth. Parents with all children outmigrated
received more economic remittances and they perceived support to be as
good as that of those with children close by.

Conclusions

Outmigration of children was not associated with greater depression in
older parents and, after taking account of a range of possible
covariables, was actually associated with less parental depression. This
could be explained by pre-existing advantages in families sending more
migrants and by the economic benefits of migration.
Randomised evaluation of assertive community treatment: 3-year outcomes
Authors: Killaspy Helen , Kingett Stella , Bebbington Paul , Blizard Robert , Johnson Sonia , Nolan Fiona , Pilling Stephen , King Michael
Published: July 2009

The only randomised controlled trial to test high-fidelity assertive community treatment (ACT) in the UK (the Randomised Evaluation of Assertive Community Treatment (REACT) study) found no advantage over usual care from community mental health teams in reducing the need for inpatient care and in other clinical outcomes, but participants found ACT more acceptable and engaged better with it. One possible reason for the lack of efficacy of ACT might be the short period of follow-up (18 months in the REACT study). This paper reports on participants' service contact, in-patient service use and adverse events 36 months after randomisation.
End of the road for treatment-as-usual studies?
Authors: Burns Tom
Published: July 2009

Using treatment as usual (TAU) in trials has obscured the repeated finding that assertive outreach has never reduced hospitalisation when compared with treatment by multidisciplinary teams (community mental health teams, CMHTs). Its use has delayed recognising that CMHTs are the more cost-effective, evidence-based approach. The term should be abandoned and trials should compare two equally well-defined services.
Expanding the Spectrum of Mutations in GH1 and GHRHR: Genetic Screening in a Large Cohort of Patients with Congenital Isolated Growth Hormone Deficiency
Authors: Alatzoglou Kyriaki S. , Turton James P. , Kelberman Daniel , Clayton Peter E. , Mehta Ameeta , Buchanan Charles , Aylwin Simon , Crowne Elisabeth C. , Christesen Henrik T. , Hertel Niels T. , Trainer Peter J. , Savage Martin O. , Raza Jamal , Banerjee Kausik , Sinha Sunil K. , Ten Svetlana , Mushtaq Talat , Brauner Raja , Cheetham Timothy D. , Hindmarsh Peter C. , Mullis Primus E. , Dattani Mehul T.
Published: July 2009

Context: It is estimated that 3–30% of cases with isolated GH deficiency (IGHD) have a genetic etiology, with a number of mutations being reported in GH1 and GHRHR. The aim of our study was to genetically characterize a cohort of patients with congenital IGHD and analyze their characteristics.

Patients and Methods: A total of 224 patients (190 pedigrees) with IGHD and a eutopic posterior pituitary were screened for mutations in GH1 and GHRHR. To explore the possibility of an association of GH1 abnormalities with multiple pituitary hormone deficiencies, we have screened 62 patients with either multiple pituitary hormone deficiencies (42 pedigrees), or IGHD with an ectopic posterior pituitary (21 pedigrees).

Results: Mutations in GH1 and GHRHR were identified in 41 patients from 21 pedigrees (11.1%), with a higher prevalence in familial cases (38.6%). These included previously described and novel mutations in GH1 (C182X, G120V, R178H, IVS3+4nt, a>t) and GHRHR (W273S, R94L, R162W). Autosomal dominant, type II IGHD was the commonest form (52.4%), followed by type IB (42.8%) and type IA (4.8%). Patients with type II IGHD had highly variable phenotypes. There was no difference in the endocrinology or magnetic resonance imaging appearance between patients with and without mutations, although those with mutations presented with more significant growth failure (height, −4.7 ± 1.6 SDS vs. −3.4 ± 1.7 SDS) (P = 0.001). There was no apparent difference between patients with mutations in GH1 and GHRHR.

Conclusions: IGHD patients with severe growth failure and a positive family history should be screened for genetic mutations; the evolving endocrinopathy observed in some of these patients suggests the need for long-term follow-up.

Results suggest screening for mutations in GH1 and GHRHR in patients of certain ethnic backgrounds with severe growth failure and a positive family history.