bluuebunny/crossref_metadata_2025 huggingface dataset:
Iodixanol Versus Low-Osmolar Contrast Media for Prevention of Contrast Induced Nephropathy
Authors: From Aaron M. , Al Badarin Firas J. , McDonald Furman S. , Bartholmai Brian J. , Cha Stephen S. , Rihal Charanjit S.
Published: July 2010

Background—

Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN.

Methods and Results—

We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents (
P
=0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55;
P
<0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention.

Conclusions—

Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.
Strut Coverage and Vessel Wall Response to a New-Generation Paclitaxel-Eluting Stent With an Ultrathin Biodegradable Abluminal Polymer
Authors: Guagliumi Giulio , Sirbu Vasile , Musumeci Giuseppe , Bezerra Hiram G. , Aprile Alessandro , Kyono Hiroyuki , Fiocca Luigi , Matiashvili Aleksandre , Lortkipanidze Nikoloz , Vassileva Angelina , Popma Jeffrey J. , Allocco Dominic J. , Dawkins Keith D. , Valsecchi Orazio , Costa Marco A.
Published: July 2010

Background—

Polymer-coated drug-eluting stents are effective in preventing restenosis but have been associated with delayed healing and incomplete strut coverage. It is unknown whether paclitaxel-eluting stents (PES) with minimal biodegradable abluminal coating enhances strut coverage while preventing neointimal hyperplasia. Using optical coherence tomography (OCT) as a primary imaging modality, we assessed the proportion of uncovered struts at 6-month follow-up in PES coated with durable versus ultrathin (<1 μm) biodegradable abluminal polymers.

Methods and Results—

In this pilot trial, 60 patients with de novo lesions (≤25 mm) in native coronary vessels were randomly assigned to receive either TAXUS Liberté PES or JACTAX PES, a Liberté stent with polymer deposited abluminally as microdots (JACTAX HD: 9.2 μg each of polymer and paclitaxel per 16-mm stent; JACTAX LD: 5 μg each). OCT follow-up occurred at 6 months with clinical follow-up through 1 year. The primary end point was percent uncovered struts by OCT. An independent core laboratory blinded to stent assignment analyzed images. The 6-month rate of uncovered struts per patient was 5.3±14.7% for TAXUS Liberté, 7.0±12.2% for JACTAX HD, and 4.6±7.3% for JACTAX LD (
P
=0.81); percent malapposed struts was 1.4±4.4%, 0.8±1.9%, and 1.1±2.8%, respectively (
P
=0.86). Strut-level intimal thickness was 0.20±0.10, 0.22±0.15, and 0.24±0.15 mm (
P
=0.64); percent volume obstruction by OCT was 22.2±12.8, 22.5±16.2, and 25.8±15.2 (
P
=0.69). There were no deaths, Q-wave myocardial infarctions, or stent thromboses through 1 year.

Conclusions—

JACTAX PES with an ultrathin microdot biodegradable abluminal polymer did not result in improved strut coverage at 6 months compared with TAXUS Liberté.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00776204.
Relaxation of Selection, Niche Construction, and the Baldwin Effect in Language Evolution
Authors: Yamauchi Hajime , Hashimoto Takashi
Published: July 2010

Deacon has suggested that one of the key factors of language evolution is not characterized by an increase in genetic contribution, often known as the Baldwin effect, but rather by a decrease. This process effectively increases linguistic learning capability by organizing a novel synergy of multiple lower-order functions previously irrelevant to the process of language acquisition. Deacon posits that this transition is not caused by natural selection. Rather, it is due to the relaxation of natural selection. While there are some cases in which relaxation caused by some external factors indeed induces the transition, we do not know what kind of relaxation has worked in language evolution. In this article, a genetic-algorithm-based computer simulation is used to investigate how the niche-constructing aspect of linguistic behavior may trigger the degradation of genetic predisposition related to language learning. The results show that agents initially increase their genetic predisposition for language learning—the Baldwin effect. They create a highly uniform sociolinguistic environment—a linguistic niche construction. This means that later generations constantly receive very similar inputs from adult agents, and subsequently the selective pressure to retain the genetic predisposition is relaxed.
Pacific Islands Families Study: The Association of Infant Health Risk Indicators and Acculturation of Pacific Island Mothers Living in New Zealand
Authors: Borrows Jim , Williams Maynard , Schluter Philip , Paterson Janis , Langitoto Helu S.
Published: July 2010

The Pacific Islands Families study follows a cohort of 1,398 Pacific infants born in Auckland, New Zealand. This article examines associations between maternal acculturation, measured by an abbreviated version of the General Ethnicity Questionnaire, and selected infant and maternal health risk indicators. Findings reveal that those with strong alignment to Pacific culture had significantly better infant and maternal risk factor outcomes than those with weak cultural alignment. In terms of Berry’s classical acculturation model, separators had the best infant and maternal outcomes; integrators had reasonable infant and maternal outcomes, while assimilators and marginalisors appeared to have the poorest infant and maternal outcomes. These findings suggest that retaining strong cultural links for Pacific immigrants is likely to have positive health benefits.
Values and Display Rules for Specific Emotions
Authors: Koopmann-Holm Birgit , Matsumoto David
Published: July 2010

Based on the CAD Triad Hypothesis (Rozin, Lowery, Imada, & Haidt, 1999), the authors hypothesized relationships between specific values and display rules for specific emotions. In particular, the authors proposed that Conservation and Self-Enhancement would be related to the display rule to express contempt, Conservation would be related to the display rule to express disgust, and Openness to Change and Self-Transcendence would be related to the display rules to express anger and sadness. To test this framework and its cross-cultural applicability, the present study examines values and emotional display rules among 106 U.S. Americans and 77 Germans. As predicted, Americans valued Conservation and Self-Enhancement more than did Germans, who valued Openness to Change and Self-Transcendence more than did Americans. These value differences were associated with differences in display rules; Americans endorsed contempt and disgust expressions more than did Germans, who endorsed anger and sadness expressions more than did Americans. Values mediated (“unpackaged”) many of these country differences in display rules. Implications of these findings are discussed.
Culture- and Gender-Specific Implications of Relational and Collective Contexts on Spontaneous Self-Descriptions
Authors: Kashima Emiko S. , Hardie Elizabeth A. , Wakimoto Ryutaro , Kashima Yoshihisa
Published: July 2010

Social contexts that invoke sociality may be more relational in Asian cultures and for women in general but more collective in Anglo-European cultures and for men in general. Study 1 tested this notion by priming Australians and Asians in Australia with four contextual primes: individual, relational (interpersonal), collective (out-group), and control (nonsocial). As predicted, the relational context increased the proportion of social self-descriptions (relational and collective jointly) among Asians and women, whereas the collective context increased it among Australians. Study 2 reexamined the effects of contextual primes by using relational, in-group, and out-group primes with Japanese students in Japan. Japanese women activated their relational self more when primed with the relational context, whereas men activated their collective self more when primed with a collective (in-group or out-group) context. Both culture and gender interact with social context to show configural effects on the self.
Intergenerational Support and Life Satisfaction: A Comparison of Chinese, Indonesian, and German Elderly Mothers
Authors: Schwarz Beate , Albert Isabelle , Trommsdorff Gisela , Gang Zheng  , Shaohua Shi  , Nelwan Peter R.
Published: July 2010

The exchange of support between generations is a fundamental feature of intergenerational relationships. Although most studies have concentrated on the impact of social support on the receiver, effects on subjective well-being of the provider of support have been studied less often. Given cultural differences in the norms and values of intergenerational relationships, the present study compared samples from rural and urban China, Indonesia, and Germany. The results showed that in the different cultural contexts elderly mothers’ well-being was differently related to help that they provided to their adult daughters. The results are discussed from a culture-informed perspective on intergenerational relationships.
MCP-1 Production in Temporomandibular Joint Inflammation
Authors: Ogura N. , Satoh K. , Akutsu M. , Tobe M. , Kuyama K. , Kuboyama N. , Sakamaki H. , Kujiraoka H. , Kondoh T.
Published: July 2010

Synovitis, which is characterized by the infiltration of inflammatory cells, often accompanies progression of temporomandibular joint disorder (TMD) symptoms. Because IL-1β is elevated in synovial fluids obtained from TMDs, we hypothesized that IL-1β-responsive genes in synoviocytes may help identify the putative genes associated with synovitis. Using microarray analysis, we found that monocyte chemoattractant protein-1 (MCP-1) mRNA levels were elevated in IL-1β-stimulated synoviocytes. MCP-1 is a member of the chemokine superfamily. The production of MCP-1 was increased in synoviocytes treated with IL-1β. When IL-1β was injected into the cavities of rat TMJs, inflammatory cells and MCP-1-positive cells were detected in the synovial tissues. Furthermore, MCP-1 levels were higher in synovial fluids from individuals with pain compared with those without pain. Inhibitors of MAP-kinases and NF-κB reduced IL-1β-induced MCP-1 production. These results suggest that MCP-1 stimulated by IL-1β is one of the factors associated with the inflammatory progression of TMDs.
The Role of NELL-1, a Growth Factor Associated with Craniosynostosis, in Promoting Bone Regeneration
Authors: Zhang X. , Zara J. , Siu R.K. , Ting K. , Soo C.
Published: July 2010

Efforts to enhance bone regeneration in orthopedic and dental cases have grown steadily for the past decade, in line with increasingly sophisticated regenerative medicine. To meet the unprecedented demand for novel osteospecific growth factors with fewer adverse effects compared with those of existing adjuncts such as BMPs, our group has identified a craniosynostosis-associated secreted molecule, NELL-1, which is a potent growth factor that is highly specific to the osteochondral lineage, and has demonstrated robust induction of bone in multiple in vivo models from rodents to pre-clinical large animals. NELL-1 is preferentially expressed in osteoblasts under direct transcriptional control of Runx2, and is well-regulated during skeletal development. NELL-1/Nell-1 can promote orthotopic bone regeneration via either intramembranous or endochondral ossification, both within and outside of the craniofacial complex. Unlike BMP-2, Nell-1 cannot initiate ectopic bone formation in muscle, but can induce bone marrow stromal cells (BMSCs) to form bone in a mouse muscle pouch model, exhibiting specificity that BMPs lack. In addition, synergistic osteogenic effects of Nell-1 and BMP combotherapy have been observed, and are likely due to distinct differences in their signaling pathways. NELL-1’s unique role as a novel osteoinductive growth factor makes it an attractive alternative with promise for future clinical applications. [ Note: NELL-1 and NELL-1 indicate the human gene and protein, respectively; Nell-1 and Nell-1 indicate the mouse gene and protein, respectively.]
Preparation of an Al2O3—EVA Co-film and its Thermal Conductivity
Authors: Mingxia Shen  , Jing He  , Yinxin Cui  , Yaoming Zhang
Published: July 2010

To decrease the working temperature of the photovoltaic (PV) module in a solar PV system, an elastic co-film with excellent mechanical properties and adhesiveness, as well as high thermal conductivity, was fabricated based on the composition of a thermal-conductive alumina and ethylene vinyl acetate (EVA) polymer. The thermal conductivity of co-films with various particle sizes, dosage, surface properties, etc. of alumina was investigated by the laser scattering method. The scanning electron microscopic results showed that the co-film with 80 shares of submicron alumina in EVA polymer had a good interface binding. The thermal-conductive mechanism of the co-film was likewise discussed.
Fast rewarming after deep hypothermic circulatory arrest in rats impairs histologic outcome and increases NFκB expression in the brain
Authors: Gordan M Lucia , Kellermann Kristine , Blobner Manfred , Nollert Georg , Kochs Eberhard F , Jungwirth Bettina
Published: July 2010

Objective: Deep hypothermia is used as a neuroprotectant during cardiac surgery utilizing deep hypothermic circulatory arrest (DHCA), although the ideal rewarming strategy is not known yet. Some of the neuroprotective properties of hypothermia seem to be mediated by Nuclear Factor Kappa B (NFκB) as an important transcription factor. The current study was designed to investigate the effect of the rewarming rate on histologic outcome and cerebral NFκB expression one day following DHCA in rats.

Methods: With IRB approval, 20 rats were cannulated for cardiopulmonary bypass (CPB), cooled to a rectal temperature of 15-18°C, subjected to 45min of DHCA and randomly assigned to either a slow (40 min) or a fast (20 min) rewarming protocol. At 24 hours post DHCA, the number of eosinophilic neurons was analyzed with hematoxylin and eosin (HE) staining, and NFκB expression immunohistochemically. The two experimental groups were compared with untreated control rats.

Results: HE staining showed more eosinophilic neurons in the motor cortex following fast rewarming (60 [15-388]) compared to slow rewarming (15 [10—21]) (p<0.05). Neuronal expression of NFκB was increased in the fast rewarming group in both brain areas, the motor cortex (fast: 258 [135-393]; slow: 165 [80—212]; control: 73 [44-111]) as well as the hippocampus (fast: 243 [209-314]; slow: 202 [187-239]; control: 86 [68-108]) (p<0.05). Hyperthermic episodes were strictly avoided.

Conclusions: Fast rewarming with strict avoidance of hyperthermia after DHCA in rats was accompanied by pronounced histologic damage and accentuated cerebral NFκB expression.
Pandemic 2009 H1N1 Influenza Virus Causes Diffuse Alveolar Damage in Cynomolgus Macaques
Authors: Herfst S. , van den Brand J. M. A. , Schrauwen E. J. A. , de Wit E. , Munster V. J. , van Amerongen G. , Linster M. , Zaaraoui F. , van Ijcken W. F. J. , Rimmelzwaan G. F. , Osterhaus A. D. M. E. , Fouchier R. A. M. , Andeweg A. C. , Kuiken T.
Published: July 2010

The pathogenesis of lower respiratory tract disease from the pandemic 2009 H1N1 (H1N1v) influenza A virus is poorly understood. Therefore, either H1N1v virus or a seasonal human H1N1 influenza A virus was inoculated into cynomolgus macaques as a nonhuman primate model of influenza pneumonia, and virological, pathological, and microarray analyses were performed. Macaques in the H1N1v group had virus-associated diffuse alveolar damage involving both type I and type II alveolar epithelial cells and affecting an average of 16% of the lung area. In comparison, macaques in the seasonal H1N1 group had milder pulmonary lesions. H1N1v virus tended to be reisolated from more locations in the respiratory tract and at higher titers than seasonal H1N1 virus. In contrast, differential expression of messenger RNA transcripts between H1N1v and seasonal H1N1 groups did not show significant differences. The most upregulated genes in H1N1v lung samples with lesions belonged to the innate immune response and proinflammatory pathways and correlated with histopathological results. Our results demonstrate that the H1N1v virus infects alveolar epithelial cells and causes diffuse alveolar damage in a nonhuman primate model. Its higher pathogenicity compared with a seasonal H1N1 virus may be explained in part by higher replication in the lower respiratory tract.
Do Patients With Absence Epilepsy Respond to Ketogenic Diets?
Authors: Groomes Laura B. , Pyzik Paula L. , Turner Zahava , Dorward Jennifer L. , Goode Victoria H. , Kossoff Eric H.
Published: July 2010

Dietary therapies are established as beneficial for symptomatic generalized epilepsies such as Lennox-Gastaut syndrome; however, the outcome for idiopathic generalized epilepsy has never been specifically reported. The efficacy of the ketogenic and modified Atkins diet for childhood and juvenile absence epilepsy was evaluated from both historical literature review and patients treated at Johns Hopkins Hospital. Upon review of 17 published studies in which absence epilepsy was included as a patient subpopulation, approximately 69% of 133 with clear outcomes patients who received the ketogenic diet had a >50% seizure reduction, and 34% of these patients became seizure free. At Johns Hopkins Hospital, the ketogenic diet (n = 8) and modified Atkins diet (n = 13) led to similar outcomes, with 18 (82%) having a >50% seizure reduction, of which 10 (48%) had a >90% seizure reduction and 4 (19%) were seizure free. Neither age at diet onset, number of anticonvulsants used previously, particular diet used, nor gender correlated with success.
Residential Relocation of Amenity Migrants to Florida: “Unpacking” Post-amenity Moves
Authors: Lovegreen Loren D. , Kahana Eva , Kahana Boaz
Published: July 2010

Objectives: This study aimed to unpack characteristics of interstate and intrastate moves undertaken by elderly amenity migrants. The authors examined these moves in the context of Litwak and Longino’s life-course typology of migration. Method: In an 11-year longitudinal study, the authors examined the first move made by respondents out of a large Florida retirement community where no services were offered. Data from premove and postmove in-person interviews were used. Results: This article found five distinct post-amenity move types, reflecting different degrees of dependency: (a) serial amenity moves, (b) positioning moves, (c) informal assistance moves, (d) formal assistance moves, and (e) dependency moves. Discussion: Findings of this study not only support Litwak and Longino’s migration typology but also elaborate and extend it. Only some older adults (20.4%) make counterstream assistance moves. Additional move types reflect new options for late-life migration to enhance person— environment fit.
Nationwide population-based epidemiologic study of systemic lupus erythematosus in Taiwan
Authors: Chiu Y-M. , Lai C-H.
Published: July 2010

The purpose of the study was to investigate the epidemiology and medical costs of systemic lupus erythematosus (SLE) in Taiwan. Cases of SLE were identified from the National Health Insurance Research Database with corresponding International Classification of Diseases, Ninth Revision (ICD-9) code 710.0 from January 2000 to December 2007. Age and sex-specific incidences were estimated by dividing the incidence number by population data obtained from the Department of Statistics, Ministry of the Interior. During the study period, 22,182 cases were identified. The average annual incidence rate was 8.1 per 100,000. The incidence was especially high in women of 20—54 years. The female:male incidence ratio increased with age to a peak in the age group of 40—44, and then declined. The prevalence increased steadily during the study period from 42.2/100,000 in 2000 to 67.4/100,000 in 2007, while the incidence decreased steadily from 9.9/100,000/year in 2001 to 6.8/100,000/year in 2007. The average cost was US$71.5 for each outpatient service and US$1922.3 for each hospitalization. This is the first epidemiologic study of both pediatric and adult SLE in Taiwan. The incidence and prevalence were higher than in most reports on Whites. The sex ratio was similar to that of Whites, with a marked female predominance, especially during reproductive age. There was a probable lower survival rate for male patients.
Prolactin’s role in the pathogenesis of the antiphospholipid syndrome
Authors: Praprotnik S. , Agmon-Levin N. , Porat-Katz BS , Blank M. , Meroni PL , Cervera R. , Miesbach W. , Stojanovich L. , Szyper-Kravitz M. , Rozman B. , Tomsic M. , Shoenfeld Y.
Published: July 2010

Increased levels of serum prolactin have been reported in patients with various autoimmune diseases and have been associated with lupus disease activity. Currently, there is a lack of data regarding hyperprolactinaemia in patients with the antiphospholipid syndrome. Hence, this study was carried out in order to evaluate the prevalence and clinical significance of hyperprolactinaemia in antiphospholipid syndrome. A total of 172 European patients with antiphospholipid syndrome and 100 geographically and sex-matched healthy controls were included in the study; none had obvious causes of hyperprolactinaemia. All patients underwent clinical assessment for disease manifestations, in addition to laboratory assessment for serum prolactin, antiphospholipid antibodies and some other biomarkers of autoimmune diseases. The tests were performed utilizing the LIAISON® Analyzer (DiaSorin, Sallugia Italy). Hyperprolactinaemia was detected in 21/172 patients with antiphospholipid syndrome and 0/100 controls (p < 0.001). This significant difference was present in both genders and was obvious even after subgrouping the patients into primary and secondary antiphospholipid syndrome. When clinical features were compared, hyperprolactinaemia was associated with reproductive failure, including early and late pregnancy loss (p < 0.05), as well as intrauterine growth retardation (p < 0.05). Hyperprolactinaemia was negatively related to arthralgias, venous thrombosis, pulmonary microthrombosis, pulmonary hypertension in both primary antiphospholipid syndrome and antiphospholipid syndrome secondary to other diseases, and to neurological manifestations in primary antiphospholipid syndrome (p<0.05). The data indirectly imply that prolactin may play a role in the pathogenesis of antiphospholipid syndrome, especially antiphospholipid syndrome-related reproductive failure.
Novel diagnostic and clinical aspects of anti-PCNA antibodies detected by novel detection methods
Authors: Mahler M. , Silverman ED , Fritzler MJ
Published: July 2010

Autoantibodies targeting the proliferating cell nuclear antigen have been considered as a specific biomarker for systemic lupus erythematosus, and were historically identified by indirect immunofluorescence and then confirmed by other more specific immunoassays. Our objective was to investigate the anti-PCNA immune response in various disease conditions. Unselected sera referred to a clinical diagnostic laboratory and other sera from various diseases cohorts and controls were tested for anti-PCNA antibodies by enzyme-linked immunosorbent assay (ELISA), line immunoassay (LIA) and an addressable laser bead assay (ALBIA) using full-length human proliferating cell nuclear antigen. Two out of 2500 sequential, unselected sera (0.07%) referred to a diagnostic laboratory for autoantibody analysis showed a proliferating cell nuclear antigen-like staining pattern. Good agreement was found between ELISA, ALBIA and LIA. At cut-off values resulting in 100% specificity, 52.5% (ELISA), 42.5% (ALBIA) and 35% (LIA) of samples with a proliferating cell nuclear antigen-like indirect immunofluorescence staining pattern were positive. In the indirect immunofluorescence proliferating cell nuclear antigen immunoblot (IB)-positive group, anti-PCNA antibodies were frequently accompanied by anti-Ro52, and in the indirect immunofluorescence PCNA-negative but LIA PCNA-positive group by various other autoantibodies. The prevalence of anti-PCNA antibodies was highest in Sjögren’s syndrome (5.0%). In conclusion, the proliferating cell nuclear antigen-like staining pattern was rarely found (0.07%) in sequential, unselected sera. Further, indirect immunofluorescence is not an accurate screening method to identify anti-PCNA antibodies as their presence may be masked by other autoantibodies. The specific association of anti-PCNA antibodies with systemic lupus erythematosus was not confirmed in our study. Lupus (2010) 19, 1527—1533.
Predictive Model for Postoperative Delirium in Cardiac Surgical Patients
Authors: Afonso Anoushka , Scurlock Corey , Reich David , Raikhelkar Jayashree , Hossain Sabera , Bodian Carol , Krol Marina , Flynn Brigid
Published: July 2010

Delirium is a common complication following cardiac surgery, and the predictors of delirium remain unclear. The authors performed a prospective observational analysis to develop a predictive model for postoperative delirium using demographic and procedural parameters. A total of 112 adult postoperative cardiac surgical patients were evaluated twice daily for delirium using the Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Model for the ICU (CAM-ICU). The incidence of delirium was 34% (n = 38). Increased age (odds ratio [OR] = 2.5; 95% confidence interval [CI] = 1.6-3.9; P < .0001, per 10 years) and increased duration of surgery (OR = 1.3; 95% CI = 1.1-1.5; P = .0002, per 30 minutes) were independently associated with postoperative delirium. Gender, BMI, diabetes mellitus, preoperative ejection fraction, surgery type, length of cardiopulmonary bypass, intraoperative blood component administration, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and Charlson Comorbidity Index, were not independently associated with postoperative delirium.
Persistent microalbuminuria after treatment with renin-angiotensin axis blockers: causes and results of treatment intensification
Authors: Robles NR , Velasco J. , Espinosa J. , Mena C. , Angulo E. , MICREX Group Investigators
Published: July 2010

Aims: The first phase of this study aimed to determine the causes of persistent microalbuminuria after treatment with renin—angiotensin axis (RAA) blocking drugs. In a second phase we tried to determine if strict control of blood pressure and intensive RAA blockade could induce remission or reduction of microalbuminuria in clinical (primary care) practice.

Patients and methods: The study included both diabetic patients and non-diabetic hypertensive patients treated with RAA drugs in the presence of microalbuminuria. 211 patients were recruited (mean age 66.6±11.3 years, 111 men, 117 were diabetic). In the first phase treatment was optimized at standard doses. In the second phase treatment was increased during a three months period to reach a blood pressure (BP) < 130/80 mmHg by adding other antihypertensive treatment and to obtain maximal RAA blockade using long-acting drugs, increased dosage, or adding further medication at night.

Results: Initial mean BP was 141±16/81±11 mmHg. BP control was unsatisfactory (control of systolic blood pressure [SBP] 19.3%; diastolic blood pressure [DBP] 37.6%). Dosage of RAA blocking drugs was inadequate in 21% of patients. Only 27.4% of patients were taking antihypertensive drugs at night. 30.1% of patients took once daily short acting drugs. During the studymean SBP was reduced to 137±13 mmHg (p < .001) and DBP decreased to 79±10 mmHg (p < .001). Control of SBP improved to 24.5% and DBP control went to 44.4%. Mean microalbuminuria decreased from 64.4±47.0 mg/day to 50.1±53.0 mg/day (p < .001) and the prevalence of microalbuminuria was reduced to 59.1%.

Conclusions: Persistent microalbuminuria was associated with poor blood pressure control and inadequate drug dosage. Low frequency of administration of drugs at night and inappropriate once-daily pills intake were frequent. Strict control of blood pressure and intensive RAA blockade significantly reduced the prevalence of microalbuminuria.
Single-Port Laparoscopy for the Drainage of Abdominal Infected Fluid Collections in Children, With the TriPort System: Initial Experience of 2 Cases
Authors: Agrawal Sanjay , Slovick Anna , Soon Yuen
Published: July 2010

Single-port or single-incision laparoscopic surgery has been reported for a number of surgical procedures, including cholecystectomy, appendicectomy, and urological procedures. Single-port thoracoscopic procedures for evacuation of empyema have been described. However, to the authors’ knowledge, there has been no report of single-port laparoscopic drainage of abdominal infected fluid collections, especially in children, in the relevant world literature. The authors report the first use of single-port laparoscopy with the TriPort system for drainage of abdominal infected fluid collections in children using the previous open appendicectomy wound. This approach was successfully completed in 2 consecutive children without conversion to open surgery. The operative duration was less than 30 minutes in each case. Both patients had no intraoperative or postoperative complications on follow-up at 8 weeks. Single-port laparoscopy with the TriPort system is safe and technically feasible for the management of pelvic collection and/or abscesses. Also, this technique is useful in multiloculated collections and allows for a washout of the peritoneal cavity at the same time, which is not the case for image-guided drainage. In addition, it also allows checking for the blowout of the appendicectomy stump as the cause for the collection. Finally, it has the advantage of reduced wound morbidity and better cosmesis.
The Cost of Achalasia: Quantifying the Effect of Symptomatic Disease on Patient Cost Burden, Treatment Time, and Work Productivity
Authors: Nenshi Rahima , Takata Julie , Stegienko Stacey , Jacob Binu , Kortan Paul , Deitel Wayne , Laporte Audrey , Darling Gail , Urbach David R.
Published: July 2010

Introduction. Although the incidence of achalasia is low, the burden of suffering is high because it is a chronic incurable disease that predominantly affects young persons. This article aims to describe the impact of achalasia on health-related quality of life, patient cost burden, time dedicated to treatment, and work productivity. Methods. Consecutive patients enrolled in a clinical trial comparing laparoscopic myotomy with pneumatic dilatation from 4 sites across Canada (whose clinical and manometric diagnosis was confirmed) were studied using standardized patient-reported outcomes instruments, including the Achalasia Severity Questionnaire (ASQ), the Medical Outcomes Study 36-item Short Form Questionnaire (SF-36), and the Gastrointestinal Disease—Specific Quality of Life (GIQLI) questionnaire. The authors also measured health care utilization. Results. Questionnaires were completed by 54 patients (median age = 53.5 years; range = 25-78 years; 50.0% male). Patients had been experiencing symptoms for a mean of 4.5 years (standard deviation = 6.1), and 42.6% were on medication for symptom relief. Among them, 74.1% reported that their disease limited their lifestyle. Patients spent an average of CAD$30.70 a month on medication; 37.0% reported that their disease interfered with their work, and patients missed an average of 10.2 days per 6 months. Patients also spent an average of CAD$24.30 on transportation to and from each clinical appointment. Conclusion. Achalasia substantially limits the lifestyle of patients with the disease. It also implies a financial burden of care for patients and leads to decreased work productivity.
Analysis of concrete internal deterioration due to frost action
Authors: Wardeh George , Mohamed Mohamed AS , Ghorbel Elhem
Published: July 2010

This study concerns the frost durability of an ordinary concrete without air-entraining agents. The water—cement ratio and the quantity of cement were chosen within the limitations imposed by the French standard. Physical and mechanical characteristics evolutions during freezing—thawing cycles have been followed. The obtained results show that the reduction in the mechanical resistance and the elastic modulus is accompanied by an increase in the intrinsic permeability. The damage is characterized by a scalar parameter, Df, due to frost action with which the resistance reduction as well as the permeability evolution may be described as a function of crack development.

The pore liquid phase pressure, generated during ice formation, was also calculated by an inverse poroelastic analysis based on strains recorded during freezing—thawing cycles. A negative pore pressure of 25 MPa at a temperature of -15° C resulting in an effective stress representing 25% of the compressive strength was found.
The ADAMTS13 metalloprotease domain: roles of subsites in enzyme activity and specificity
Authors: de Groot Rens , Lane David A. , Crawley James T. B.
Published: July 2010

ADAMTS13 modulates von Willebrand factor (VWF) platelet-tethering function by proteolysis of the Tyr1605-Met1606 bond in the VWF A2 domain. To examine the role of the metalloprotease domain of ADAMTS13 in scissile bond specificity, we identified 3 variable regions (VR1, -2, and -3) in the ADAMTS family metalloprotease domain that flank the active site, which might be important for specificity. Eight composite sequence swaps (to residues in ADAMTS1 or ADAMTS2) and 18 single-point mutants were generated in these VRs and expressed. Swapping VR1 (E184-R193) of ADAMTS13 with that of ADAMTS1 or ADAMTS2 abolished/severely impaired ADAMTS13 function. Kinetic analysis of VR1 point mutants using VWF115 as a short substrate revealed reduced proteolytic function (kcat/Km reduced by 2- to 10-fold) as a result of D187A, R190A, and R193A substitutions. Analysis of VR2 (F216-V220) revealed a minor importance of this region. Mutants of VR3 (G236-A261) proteolysed wild-type VWF115 normally. However, using either short or full-length VWF substrates containing the P1′ M1606A mutation, we identified residues within VR3 (D252-P256) that influence P1′ amino acid specificity, we hypothesize, by shaping the S1′ pocket. It is concluded that 2 subsites, D187-R193 and D252-P256, in the metalloprotease domain play an important role in cleavage efficiency and site specificity.
A prospective study of Epstein-Barr virus antibodies and risk of non-Hodgkin lymphoma
Authors: Bertrand Kimberly A. , Birmann Brenda M. , Chang Ellen T. , Spiegelman Donna , Aster Jon C. , Zhang Shumin M. , Laden Francine
Published: July 2010

Severe immunosuppression is an established risk factor for non-Hodgkin lymphoma (NHL), but an association with subclinical immune dysfunction is unclear. We conducted a case-control study nested in the Physicians' Health Study and the Nurses' Health Study cohorts to determine whether patterns of antibody response to Epstein-Barr virus (EBV) were associated with NHL risk. We measured antibody titers against viral capsid antigen, early antigen, and Epstein-Barr nuclear antigen (EBNA-1 and EBNA-2) in blood samples collected before diagnosis from 340 cases and 662 matched controls. Using conditional logistic regression, we estimated rate ratios (RRs) and 95% confidence intervals (CIs) for elevated versus normal titers and the ratio of anti–EBNA-1 to anti–EBNA-2 titers (≤ 1.0 vs > 1.0). We found no association between EBV serostatus, elevated titers, or an EBNA-1/EBNA-2 ratio ≤ 1.0 and NHL risk overall. For chronic lymphocytic leukemia/small lymphocytic lymphoma, suggestive associations were noted for elevated anti–EBNA-2 (RR, 1.74; 95% CI, 0.99-3.05), anti–viral capsid antigen (RR, 1.58; 95% CI, 0.79-3.14), and EBNA-1/EBNA-2 ratio ≤ 1.0 (RR, 1.52; 95% CI, 0.91-2.55). There was no evidence of heterogeneity by subtype. Overall, we found no evidence that EBV antibody profile predicts NHL risk in immunocompetent persons, with the possible exception of chronic lymphocytic leukemia/small lymphocytic lymphoma.
Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy
Authors: Chen Pingguo , Li Conglei , Lang Sean , Zhu Guangheng , Reheman Adili , Spring Christopher M. , Freedman John , Ni Heyu
Published: July 2010

Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder in which maternal antibodies cross the placenta and destroy fetal/neonatal platelets. It has been demonstrated that the neonatal Fc receptor (FcRn) regulates immunoglobulin G (IgG) homeostasis and plays an important role in transplacental IgG transport. However, the role of FcRn in the pathogenesis and therapy of FNIT has not been studied. Here, we developed an animal model of FNIT using combined β3 integrin–deficient and FcRn-deficient (β3−/−FcRn−/−) mice. We found that β3−/−FcRn−/− mice are immunoresponsive to β3+/+FcRn−/− platelets. The generated antibodies were β3 integrin specific and were maintained at levels that efficiently induced thrombocytopenia in adult β3+/+FcRn−/− mice. FNIT was observed when immunized β3−/−FcRn+/+ females were bred with β3+/+FcRn+/+ males, while no FNIT occurred in β3−/−FcRn−/− females bred with β3+/+FcRn−/− males, suggesting that FcRn is indispensable for the induction of FNIT. We further demonstrated that fetal FcRn was responsible for the transplacental transport of various IgG isotypes. We found that anti-FcRn antibody and intravenous IgG prevented FNIT, and that intravenous IgG ameliorated FNIT through both FcRn-dependent and -independent pathways. Our data suggest that targeting FcRn may be a potential therapy for human FNIT as well as other maternal pathogenic antibody-mediated diseases.
Epigenetic silencing of BIM in glucocorticoid poor-responsive pediatric acute lymphoblastic leukemia, and its reversal by histone deacetylase inhibition
Authors: Bachmann Petra S. , Piazza Rocco G. , Janes Mary E. , Wong Nicholas C. , Davies Carwyn , Mogavero Angela , Bhadri Vivek A. , Szymanska Barbara , Geninson Greta , Magistroni Vera , Cazzaniga Giovanni , Biondi Andrea , Miranda-Saavedra Diego , Göttgens Berthold , Saffery Richard , Craig Jeffrey M. , Marshall Glenn M. , Gambacorti-Passerini Carlo , Pimanda John E. , Lock Richard B.
Published: July 2010

Glucocorticoids play a critical role in the therapy of lymphoid malignancies, including pediatric acute lymphoblastic leukemia (ALL), although the mechanisms underlying cellular resistance remain unclear. We report glucocorticoid resistance attributable to epigenetic silencing of the BIM gene in pediatric ALL biopsies and xenografts established in immune-deficient mice from direct patient explants as well as a therapeutic approach to reverse resistance in vivo. Glucocorticoid resistance in ALL xenografts was consistently associated with failure to up-regulate BIM expression after dexamethasone exposure despite confirmation of a functional glucocorticoid receptor. Although a comprehensive assessment of BIM CpG island methylation revealed no consistent changes, glucocorticoid resistance in xenografts and patient biopsies significantly correlated with decreased histone H3 acetylation. Moreover, the histone deacetylase inhibitor vorinostat relieved BIM repression and exerted synergistic antileukemic efficacy with dexamethasone in vitro and in vivo. These findings provide a novel therapeutic strategy to reverse glucocorticoid resistance and improve outcome for high-risk pediatric ALL.
Mechanisms of haplotype divergence at the RGA08 nucleotide-binding leucine-rich repeat gene locus in wild banana (Musa balbisiana)
Authors: Baurens Franc-Christophe , Bocs Stéphanie , Rouard Mathieu , Matsumoto Takashi , Miller Robert NG , Rodier-Goud Marguerite , MBéguié-A-MBéguié Didier , Yahiaoui Nabila
Published: July 2010

Background

Comparative sequence analysis of complex loci such as resistance gene analog clusters allows estimating the degree of sequence conservation and mechanisms of divergence at the intraspecies level. In banana (Musa sp.), two diploid wild species Musa acuminata (A genome) and Musa balbisiana (B genome) contribute to the polyploid genome of many cultivars. The M. balbisiana species is associated with vigour and tolerance to pests and disease and little is known on the genome structure and haplotype diversity within this species. Here, we compare two genomic sequences of 253 and 223 kb corresponding to two haplotypes of the RGA08 resistance gene analog locus in M. balbisiana "Pisang Klutuk Wulung" (PKW).

Results

Sequence comparison revealed two regions of contrasting features. The first is a highly colinear gene-rich region where the two haplotypes diverge only by single nucleotide polymorphisms and two repetitive element insertions. The second corresponds to a large cluster of RGA08 genes, with 13 and 18 predicted RGA genes and pseudogenes spread over 131 and 152 kb respectively on each haplotype. The RGA08 cluster is enriched in repetitive element insertions, in duplicated non-coding intergenic sequences including low complexity regions and shows structural variations between haplotypes. Although some allelic relationships are retained, a large diversity of RGA08 genes occurs in this single M. balbisiana genotype, with several RGA08 paralogs specific to each haplotype. The RGA08 gene family has evolved by mechanisms of unequal recombination, intragenic sequence exchange and diversifying selection. An unequal recombination event taking place between duplicated non-coding intergenic sequences resulted in a different RGA08 gene content between haplotypes pointing out the role of such duplicated regions in the evolution of RGA clusters. Based on the synonymous substitution rate in coding sequences, we estimated a 1 million year divergence time for these M. balbisiana haplotypes.

Conclusions

A large RGA08 gene cluster identified in wild banana corresponds to a highly variable genomic region between haplotypes surrounded by conserved flanking regions. High level of sequence identity (70 to 99%) of the genic and intergenic regions suggests a recent and rapid evolution of this cluster in M. balbisiana.
Toll-Like Receptor (TLR) and Nucleosome-binding Oligomerization Domain (NOD) gene polymorphisms and endometrial cancer risk
Authors: Ashton Katie A , Proietto Anthony , Otton Geoffrey , Symonds Ian , McEvoy Mark , Attia John , Scott Rodney J
Published: July 2010

Background

Endometrial cancer is the most common gynaecological malignancy in women of developed countries. Many risk factors implicated in endometrial cancer trigger inflammatory events; therefore, alterations in immune response may predispose an individual to disease. Toll-like receptors (TLRs) and nucleosome-binding oligomerization domain (NOD) genes are integral to the recognition of pathogens and are highly polymorphic. For these reasons, the aim of the study was to assess the frequency of polymorphic variants in TLR and NOD genes in an Australian endometrial cancer population.

Methods

Ten polymorphisms were genotyped in 191 endometrial cancer cases and 291 controls using real-time PCR: NOD1 (rs2075822, rs2907749, rs2907748), NOD2 (rs5743260, rs2066844, rs2066845), TLR2 (rs5743708), TLR4 (rs4986790) and TLR9 (rs5743836, rs187084).

Results

Haplotype analysis revealed that the combination of the variant alleles of the two TLR9 polymorphisms, rs5743836 and rs187084, were protective for endometrial cancer risk: OR 0.11, 95% CI (0.03-0.44), p = 0.002. This result remained highly significant after adjustment for endometrial cancer risk factors and Bonferroni correction for multiple testing. There were no other associations observed for the other polymorphisms in TLR2, TLR4, NOD1 and NOD2.

Conclusions

The variant 'C' allele of rs5743836 causes greater TLR9 transcriptional activity compared to the 'T' allele, therefore, higher TLR9 activity may be related to efficient removal of microbial pathogens within the endometrium. Clearly, the association of these TLR9 polymorphisms and endometrial cancer risk must be further examined in an independent population. The results point towards the importance of examining immune response in endometrial tumourigenesis to understand new pathways that may be implicated in disease.
Gamma knife radiosurgery for movement disorders: a concise review of the literature
Authors: Elaimy Ameer L , Arthurs Benjamin J , Lamoreaux Wayne T , Demakas John J , Mackay Alexander R , Fairbanks Robert K , Greeley David R , Cooke Barton S , Lee Christopher M
Published: July 2010

Medication is the predominant method for the management of patients with movement disorders. However, there is a fraction of patients who experience limited relief from pharmaceuticals or experience bothersome side-effects of the drugs. Deep brain stimulation (DBS) and surgical lesioning of the thalamus and basal ganglia are respected neurosurgical procedures, with valued success rates and a very low incidence of complications. Despite these positive outcomes, DBS and surgical lesioning procedures are contraindicated for some patients. Stereotactic radiosurgery with the Gamma Knife (GK) has been used as a lesioning technique for patients seeking a non-invasive treatment alternative and for medication-intolerable patients, who are unable to undergo DBS or lesioning due to comorbid medical conditions. Tremors of various etiologies are treated using GK thalamotomy, which targets the ventralis intermedius nucleus. GK thalamotomy produces favorable outcomes when treating tremors, with success rates ranging from 80-100%. In contrast, GK pallidotomy targets the internal globus pallidus, and is used in treating bradykinesia, rigidity, and dyskinesia. Although radiosurgery has proven beneficial for tremors, radiosurgical pallidotomy for bradykinesia, rigidity, and dyskinesia remains questionable, with mixed success rates in the literature that ranges from 0-87%. We suggest that GK thalamotomy be offered along with other neurosurgical approaches as a feasible treatment option to patients who prefer the non-invasive nature of radiosurgery and to those who are unqualified candidates for the neurosurgical alternatives. Also, we advise that patients with bradykinesia, rigidity, and dyskinesia be educated about the variability in the literature pertaining to GK pallidotomy before proceeding with treatment.