bluuebunny/crossref_metadata_2025 huggingface dataset:
Web‐based self‐help for problem drinkers: a pragmatic randomized trial
Authors: Riper Heleen , Kramer Jeannet , Smit Filip , Conijn Barbara , Schippers Gerard , Cuijpers Pim
Published: December 2008

Aims  Self‐help interventions for adult problem drinkers in the general population have proved effective. The question is whether this also holds for self‐help interventions delivered over the internet.

Design  We conducted a pragmatic randomized trial with two parallel groups, using block randomization stratified for gender and with follow‐up at 6 months.

Setting  The intervention and trial were conducted online in the Netherlands in 2003–2004.

Participants  We selected 261 adult problem drinkers from the general population with a weekly alcohol consumption above 210 g of ethanol for men or 140 g for women, or consuming at least 60 g (men) or 40 g (women) at least 1 day a week over the past 3 months. Participants were randomized to either the experimental drinking less (DL) condition or to the control condition (PBA).

Intervention  DL is a web‐based, multi‐component, interactive self‐help intervention for problem drinkers without therapist guidance. The recommended treatment period is 6 weeks. The intervention is based on cognitive–behavioural and self‐control principles. The control group received access to an online psychoeducational brochure on alcohol use (PBA).

Outcome measures  We assessed the following outcome measures at 6‐month follow‐up: (i) the percentage of participants who had reduced their drinking levels to within the normative limits of the Dutch guideline for low‐risk drinking; and (ii) the reduction in mean weekly alcohol consumption.

Findings  At follow‐up, 17.2% of the intervention group participants had reduced their drinking successfully to within the guideline norms; in the control group this was 5.4% [odds ratio (OR) = 3.66; 95% confidence interval (CI) 1.3–10.8; P = 0.006; number needed to treat (NNT) = 8.5]. The intervention subjects decreased their mean weekly alcohol consumption significantly more than control subjects, with a difference of 12.0 standardized units (95% CI 5.9–18.1; P < 0.001; standardized mean difference 0.40).

Conclusions  To our knowledge this is one of the first randomized controlled trials on a web‐based self‐help intervention without therapist guidance for self‐referred problem drinkers among the adult general population. The intervention showed itself to be effective in reducing problem drinking in the community.
Psychiatric comorbidity in young cocaine users: induced versus independent disorders
Authors: Herrero M. Jesús , Domingo‐Salvany Antonia , Torrens Marta , Brugal M. Teresa ,   the ITINERE Investigators
Published: December 2008

Aims  To examine the psychiatric status of young cocaine users using a validated instrument for the evaluation of psychiatric comorbidity, emphasizing the distinction between independent and induced psychiatric conditions.

Design  Cross‐sectional study.

Setting  Barcelona, Spain.

Participants  A cohort of 139 young (18–30 years) adult current regular cocaine users.

Measurements  The Psychiatric Research Interview for Substance and Mental Disorders (PRISM‐IV, which produces diagnoses according to DSM‐IV criteria, including Axis II antisocial and borderline personality disorders).

Findings  Nearly 42.5% of the subjects presented psychiatric comorbidity. The most common Axis I diagnoses were mood disorders (26.6%) and anxiety disorders (13%). Increasing age, having ever received treatment for drug use and freebase cocaine use were associated with substance‐induced disorders diagnoses relative to primary Axis I disorders.

Conclusions  This study has shown a relatively high prevalence of psychiatric comorbidity in cocaine users recruited in non‐clinical settings. Future studies examining potential differential factors associated with primary versus substance‐induced disorders are necessary to optimize the implementation of more suitable approaching programmes for young regular cocaine users.
Randomized controlled trial of the effects of completing the Alcohol Use Disorders Identification Test questionnaire on self‐reported hazardous drinking
Authors: McCambridge Jim , Day Maria
Published: December 2008

Aims  The direct effects of screening on drinking behaviour have not previously been evaluated experimentally. We tested whether screening reduces self‐reported hazardous drinking in comparison with a non‐screened control group.

Design  Two‐arm randomized controlled trial (RCT), with both groups blinded to the true nature of the study.

Setting and participants  A total of 421 university students aged 18–24 years, recruited in five London student unions.

Interventions  Both groups completed a brief pen‐and‐paper general health and socio‐demographic questionnaire, which for the experimental group also included the 10‐item Alcohol Use Disorders Identification Test (AUDIT) screening questionnaire.

Measurements  The primary outcome was the between‐group difference in AUDIT score at 2–3‐month follow‐up. Eight secondary outcomes comprised other aspects of hazardous drinking, including dedicated measures of alcohol consumption, problems and dependence.

Findings  A statistically significant effect size of 0.23 (0.01–0.45) was detected on the designated primary outcome. The marginal nature of the statistical significance of this effect was apparent in additional analyses with covariates. Statistically significant differences were also obtained in three of eight secondary outcomes, and the observed effect sizes were not dissimilar to the known effects of brief interventions.

Conclusions  It is unclear to what extent these findings represent the effects of screening alone, a Hawthorne effect in which drinking behaviour has changed in response to monitoring, or whether they indicate reporting bias. These possibilities have important implications both for the dissemination of screening as an intervention in its own right and for behavioural intervention trials methodology.
Neither interleukin‐4 receptor α expression on CD4+ T cells, or macrophages and neutrophils is required for protective immunity to Trichinella spiralis
Authors: Michels Chesney E. , Scales Hannah E. , Saunders Karin A. , McGowan S. , Brombracher Frank , Alexander James , Lawrence Catherine E.
Published: December 2008

The T helper type 2 (Th2) mediated expulsion of the gastrointestinal nematode Trichinella spiralis requires interleukin‐4 receptor α (IL‐4Rα) expression on both bone‐marrow‐derived and non‐bone‐marrow‐derived cells. To more definitively investigate the role of IL‐4/IL‐13 responsiveness in the development of protective immunity to T. spiralis, cell‐specific IL‐4Rα signalling on CD4+ T cells (Lckcre IL‐4Rα−/flox) and macrophages/neutrophils (LysMcre IL‐4Rα−/flox) was analysed on the BALB/c background. Infection of wild‐type and control IL‐4Rα−/flox mice induced a Th2‐type immune response with elevated IL‐4 cytokine production, parasite‐specific immunoglobulin G1 (IgG1), total IgE, intestinal mastocytosis and enteropathy. In contrast, global IL‐4Rα‐deficient BALB/c mice showed reduced worm expulsion, antibody production, intestinal mastocytosis and gut pathology. BALB/c mice generated with cell‐specific deletion of IL‐4Rα on CD4+ T lymphocytes or macrophages/neutrophils, controlled gastrointestinal helminth infection by eliciting a protective immune response comparable to that observed with wild‐type and IL‐4Rα−/flox controls. Together, this shows that the development of host protective Th2 responses accompanied by parasite loss is independent of IL‐4Rα expression on CD4+ T cells and macrophages/neutrophils.
Pulp revascularization of necrotic bilateral bicuspids using a modified novel technique to eliminate potential coronal discolouration: a case report
Authors: Reynolds K. , Johnson J. D. , Cohenca N.
Published: December 2008

Aim  To present a case report in which the pulp of two bilateral mandibular premolars with dens evaginatus were revascularized using a modified novel technique to avoid undesired crown discolouration.

Summary  Recently, regeneration of necrotic pulps has become an alternative conservative treatment option for young permanent teeth with immature roots and is a subject of great interest in the field of endodontics. This novel procedure exploits the full potential of the pulp for dentine deposition and produces a stronger mature root that is better able to withstand the forces than can result in fracture. However, the current protocol has potential clinical and biological complications. Amongst them, crown discolouration, development of resistant bacterial strains and allergic reaction to the intracanal medication. In the case presented, a modified technique to avoid undesired crown discolouration was applied sealing the dentinal tubules of the chamber, thus avoiding any contact between the tri‐antibiotic paste and the dentinal walls.

Key learning points  • Sealing the dentinal tubules of the chamber prevents the undesirable crown discolouration produced by tri‐antibiotic medication whilst maintaining the revascularization potential of the pulp.

• Further research is warranted to seek an alternative infection control protocol capable of preventing possible allergic reactions and development of resistant strains of bacteria, as well as a biological material capable of inducing angiogenesis and allow a more predictable scaffold and tissue regeneration.
Stress distribution of three NiTi rotary files under bending and torsional conditions using a mathematic analysis
Authors: Kim T. O. , Cheung G. S. P. , Lee J. M. , Kim B. M. , Hur B. , Kim H. C.
Published: December 2008

Aim  To compare and evaluate the stress distribution of three NiTi instruments of various cross‐sectional configurations under bending or torsional condition using a finite‐element analysis model.

Methodology  Three NiTi files (ProFile, ProTaper and ProTaper Universal) were scanned using Micro‐CT to produce a three‐dimensional digital model. The behaviour of the instrument under bending or torsional loads was analysed mathematically in software (ABAQUS V6.5‐1), taking into consideration the nonlinear mechanical characteristic of NiTi material.

Results  ProFile showed the greatest flexibility, followed by ProTaper Universal and ProTaper. The highest stress was observed at the surface near the cutting edge and the base of (opposing) flutes during cantilever bending. Concentration of stresses was observed at the bottom of the flutes in ProFile and ProTaper Universal instruments in torsion. The stress was more evenly distributed over the surface of ProTaper initially, which then concentrated at the middle of the convex sides when the amount of angular deflection was increased.

Conclusion  Incorporating a U‐shaped groove in the middle of each side of the convex‐triangular design lowers the flexural rigidity of the origin ProTaper design. Bending leads to the highest surface stress at or near the cutting edge of the instrument. Stress concentration occurs at the bottom of the flute when the instrument is subjected to torsion.
Necrotic pulp tissue dissolution by passive ultrasonic irrigation in simulated accessory canals: impact of canal location and angulation
Authors: Al‐Jadaa A. , Paqué F. , Attin T. , Zehnder M.
Published: December 2008

Aim  To evaluate whether passive ultrasonic irrigation (PUI) of 2.5% NaOCl would dissolve necrotic pulp tissue from simulated accessory root canals (SACs) better than passive placement of the irrigant, when temperature was equilibrated between the two treatments.

Methodology  Transparent root canal models (n = 6) were made from epoxy resin. SACs of 0.2 mm diameter were placed at defined angles and positions in the mid‐canal and apical area. SACs were filled with necrotic bovine pulp tissue. PUI was performed five times for 1 min each with irrigant replenishment after every minute. Main canal temperature was measured after each minute, and a digital photograph was taken. In control experiments, mock treatments were performed with the same set‐up without activation of the file using heated NaOCl to mimic the temperature created by PUI. Experiments were repeated five times. Digital photographs were analysed for the distance of dissolved tissue into the SACs in mm. Overall comparison (sum of dissolved tissue from all five accessory canals) between treatments was performed using paired t‐test. Differences between SAC angulation and position after PUI were investigated using anova/Bonferroni (alpha < 0.05).

Results  Passive ultrasonic irrigation caused a rise in irrigant temperature in the main canal to 53.5 ± 2.7 °C after the fifth minute. PUI dissolved a total of 6.4 ± 2.1 mm, mock treatment controlled for heat: 1.4 ± 0.6 mm (P < 0.05). No significant influence of SAC position or angulation was found.

Conclusions  Passive ultrasonic irrigation promotes positive tissue‐dissolving effects beyond a rise in irrigant temperature.
Pegylated interferon‐alpha2a/ribavirin treatment of recurrent hepatitis C after liver transplantation
Authors: Dinges S. , Morard I. , Heim M. , Dufour J.‐F. , Müllhaupt B. , Giostra E. , Clavien P.‐A. , Mentha G. , Negro F. ,   for the Swiss Association for the Study of the Liver (SASL 17)
Published: December 2008

Abstract: Hepatitis C virus (HCV) infection invariably recurs after liver transplantation (LT), leading to significant morbidity and mortality. Although the combination of pegylated interferon‐alpha (IFN‐α)/ribavirin is the preferred treatment for these patients, the optimal schedule remains undetermined. In an uncontrolled trial, 19 patients with HCV infection recurring after LT received pegylated IFN‐α2a, 180 μg weekly, and ribavirin, 10 mg/kg body weight daily, for 48 weeks. The proportion of patients with undetectable HCV RNA in their serum after 12 weeks of treatment was 53%. Five patients (26%) dropped out of the study due to intolerance (in 2 cases), depression (in 1), or infectious complications (in 2). A sustained virological response (SVR), defined as undetectable serum HCV RNA 24 weeks after the end of treatment, was observed in 9/19 patients (47%). SVR was associated with an early virological response after 12 weeks of therapy (P<0.001) and a treatment duration >80% (P=0.02), but not with baseline HCV RNA level or a cumulative dose of pegylated IFN‐α2a or ribavirin >80% of the scheduled dose. All 4 patients with genotype 2 or 3 reached SVR, as compared with 33% of patients with genotype 1 or 4 (P=0.03). A 48‐week course of pegylated IFN‐α2a/ribavirin therapy is effective in patients with recurrent HCV infection after LT.
Chronic urticaria: the autoimmune paradigm
Authors: Philpott H. , Kette F. , Hissaria P. , Gillis D. , Smith W.
Published: December 2008

Chronic urticaria is a disease consisting of spontaneous pruritic welts, present on all or most days for more than 6 weeks. It is commonly supposed to be allergic in origin, although allergy is not the cause in the majority of cases, and it has therefore been termed ‘chronic idiopathic urticaria’. Recent evidence indicates that at least a subset of patients in whom no extrinsic or internal cause can be identified are in fact autoimmune in origin. This is based mainly on the detection of pathogenic autoantibodies to the high‐affinity immunoglobulin E receptor FcɛR1, which are thought to activate cutaneous mast cells. In this article, we review the evidence that has given rise to this autoimmune ‘paradigm’ and its impact on diagnosis and management.
Cerebral venous thrombosis associated with ulcerative colitis
Authors: De Cruz P. , Lust M. , Trost N. , Wall A. , Gerraty R. , Connell W. R.
Published: December 2008

Thromboembolic complications, such as deep venous thrombosis and pulmonary embolism, are well recognized in patients with inflammatory bowel disease (IBD). We describe three cases of cerebral venous thrombosis complicating ulcerative colitis. Cerebral venous thrombosis is a rare but potentially devastating complication of IBD, and the diagnosis needs to be considered in any patient with IBD presenting with neurological symptoms.
The participation of children with multi‐sensory impairment in person‐centred planning
Authors: Taylor Kim
Published: December 2008

Consultation with pupils with learning disabilities through the use of person‐centred planning methods is becoming increasingly common. However, little research has focused on pupils with multi‐sensory impairment (MSI). Kim Taylor has taught children with special educational needs for over 25 years and holds a post‐graduate diploma in multi‐sensory impairment. In this article, she suggests that the characteristics of MSI affect the capacity of some pupils to participate in person‐centred planning. Kim Taylor presents case studies in which she investigates the impact that the characteristics of MSI have upon adults’abilities to elicit the views of children with MSI about their experiences in the classroom. The article provides an analysis of the factors that maximised the children's involvement and participation and a commentary on the trustworthiness of the outcomes of the consultation processes described. At the end of her article, Kim Taylor commits herself to implementing improved approaches in the classroom and calls upon other practitioners to follow her example.
Enhancement of Identifying Cancer Specialists through the Linkage of Medicare Claims to Additional Sources of Physician Specialty
Authors: Pollack Lori A. , Adamache Walter , Eheman Christie R. , Ryerson A. Blythe , Richardson Lisa C.
Published: December 2008

Objective. To examine the number of cancer specialists identified in three national datasets, the effect of combining these datasets, and the use of refinement rules to classify physicians as cancer specialists.

Data Sources. 1992–2003 linked Surveillance, Epidemiology, and End Results (SEER)‐Medicare data and a cancer‐free comparison population of Medicare beneficiaries, Unique Physician Identification Number (UPIN) Registry, and the American Medical Association (AMA) Masterfile.

Study Design. We compared differences in counts of cancer specialists identified in Medicare claims only with the number obtained by combining data sources and after using rules to refine specialty identification.

Data Extraction. We analyzed physician specialty variables provided on Medicare claims, along with the specialties obtained by linkage of unencrypted UPINs on Medicare claims to the UPIN Registry, the AMA Masterfile, and all sources combined.

Principle Findings. Medicare claims identified the fewest number of cancer specialists (n=11,721) compared with 19,753 who were identified when we combined all three datasets. The percentage increase identified by combining datasets varied by subspecialty (187 percent for surgical oncologists to 50 percent for radiation oncologists). Rules created to refine identification most affected the count of radiation oncologists.

Conclusions. Researchers should consider taking the additional effort and cost to refine classification by using additional data sources based on their study objectives.
Disturbance‐Response Analysis: a Method for Rapid Assessment of the Threat to Species in Disturbed Areas
Authors: MARTORELL CARLOS , PETERS EDWARD M.
Published: December 2008

Abstract:  We developed a method with which to analyze a specie's response to chronic anthropogenic disturbance (CAD). We regressed density of individuals on the intensity of 3 disturbance agents (human activities, raising livestock, and land degradation) along CAD gradients to determine how much CAD is experienced by a species; whether species are ruderal (achieving maximum densities in disturbed sites); whether density declines as a result of CAD; which disturbance agents are responsible for this reduction; and the number of populations that decline as a result of CAD. We tested the method on 9 threatened Mammillaria species (Cactaceae). Seven species were ruderal. In 4 species, actual disturbance surpassed the CAD intensity in which plants achieved their maximum densities; thus, the density of those 4 species appeared to be declining. For 7 species, some populations were threatened by human activities or livestock, whereas others were favored by them. Land degradation negatively affected all species. Our results allowed us to distinguish 4 groups of species that had similar responses and thus may require different forms of management. Our method provided an estimation of the growth rate (λ) of the studied populations that was significantly correlated with λs obtained from demographic studies. The size structures of populations were consistent with the predictions of the analysis, which suggests our results are consistent and reliable. Disturbance–response analysis provides a basis for management in heavily populated areas, where conservation must be achieved along with development activities that cause CAD. The method provides readily interpretable information, which facilitates participative decision making; the data are rapidly generated, which makes it appropriate when results are required promptly or for assessment of large numbers of species; and it provides a comprehensive perception of how threatened species behave in the real world.
Interactions between Ecological Traits and Host Plant Type Explain Distribution Change in Noctuid Moths
Authors: MATTILA NIINA , KOTIAHO JANNE S. , KAITALA VEIJO , KOMONEN ATTE , PÄIVINEN JUSSI
Published: December 2008

Abstract: The ecological traits of species determine how well a species can withstand threats to which it is exposed. If these predisposing traits can be identified, species that are most at risk of decline can be identified and an understanding of the processes behind the declines can be gained. We sought to determine how body size, specificity of larval host plant, overwintering stage, type of host plant, and the interactions of these traits are related to the distribution change in noctuid moths. We used data derived from the literature and analyzed the effects of traits both separately and simultaneously in the same model. When we analyzed the traits separately, it seemed the most important determinants of distribution change were overwintering stage and type of host plant. Nevertheless, ecological traits are often correlated and the independent effect of each trait may not be seen in analyses in which traits are analyzed separately. When we accounted for other correlated traits, the results were substantially different. Only one trait (body size), but 3 interactions, explained distribution change. This finding suggests that distribution change is not determined by 1 or 2 traits; rather, the effect of the traits depends on other interacting traits. Such complexity makes it difficult to understand the processes behind distribution changes and emphasizes the need for basic ecological knowledge of species. With such basic knowledge, a more accurate picture of the factors causing distribution changes and increasing risk of extinction might be attainable.
Developmental tumourigenesis: NCAM as a putative marker for the malignant renal stem/progenitor cell population
Authors: Pode‐Shakked Naomi , Metsuyanim Sally , Rom‐Gross Eithan , Mor Yoram , Fridman Eduard , Goldstein Itamar , Amariglio Ninette , Rechavi Gideon , Keshet Gilmor , Dekel Benjamin
Published: December 2008

During development, renal stem cells reside in the nephrogenic blastema. Wilms’ tumour (WT), a common childhood malignancy, is suggested to arise from the nephrogenic blastema that undergoes partial differentiation and as such is an attractive model to study renal stem cells leading to cancer initiation and maintenance. Previously we have made use of blastema‐enriched WT stem‐like xenografts propagated in vivo to define a ‘WT‐stem’ signature set, which includes cell surface markers convenient for cell isolation (frizzled homolog 2 [Drosophila] – FZD2, FZD7, G‐protein coupled receptor 39, activin receptor type 2B, neural cell adhesion molecule – NCAM). We show by fluorescence‐activated cell sorting analysis of sphere‐forming heterogeneous primary WT cultures that most of these markers and other stem cell surface antigens (haematopoietic, CD133, CD34, c‐Kit; mesenchymal, CD105, CD90, CD44; cancer, CD133, MDR1; hESC, CD24 and putative renal, cadherin 11), are expressed in WT cell sub‐populations in varying levels. Of all markers, NCAM, CD133 and FZD7 were constantly detected in low‐to‐moderate portions likely to contain the stem cell fraction. Sorting according to FZD7 resulted in extensive cell death, while sorted NCAM and CD133 cell fractions were subjected to clonogenicity assays and quantitative RT‐PCR analysis, exclusively demonstrating the NCAM+ fraction as highly clonogenic, overexpressing the WT ‘stemness’ genes and topoisomerase2A (TOP2A), a bad prognostic marker for WT. Moreover, treatment of WT cells with the topoisomerase inhibitors, Etoposide and Irinotecan resulted in down‐regulation of TOP2A along with NCAM and WT1. Thus, we suggest NCAM as a marker for the WT progenitor cell population. These findings provide novel insights into the cellular hierarchy of WT, having possible implications for future therapeutic options.
Dexamethasone inhibits lipopolysaccharide‐induced hydrogen sulphide biosynthesis in intact cells and in an animal model of endotoxic shock
Authors: Li Ling , Whiteman Matthew , Moore Philip K.
Published: December 2008

Dexamethasone (1 mg/kg, i.p.) administered either 1 hr before or 1 hr after E. coli lipopolysaccharide (LPS, 4 mg/kg, i.p.) in conscious rats inhibited the subsequent (4 hrs) rise in plasma cytokine (interleukin [IL]‐1β, tumour necrosis factor [TNF]‐α), nitrate/nitrite (NO×), soluble intercellular adhesion molecule‐1 (sICAM‐1) concentration and lung/liver myeloperoxidase activity indicative of an anti‐inflammatory effect. Dexamethasone also reduced the LPS‐evoked rise in plasma hydrogen sulphide (H2S) concentration, liver H2S synthesizing activity and expression of cystathionine γ lyase (CSE) and inducible nitric oxide synthase (iNOS). Mifepristone (RU‐486) inhibited these effects. Dexamethasone (1–10 μM) reduced the LPS‐evoked release of IL‐1β, TNF‐α and L‐selectin, decreased expression of CSE and iNOS and diminished nuclear factor κB (NF‐κB)‐DNA binding in isolated rat neutrophils. In contrast, NaHS (100 μM) increased L‐selectin release from rat neutrophils. Dexamethasone also reduced LPS‐induced up‐regulation of CSE in foetal liver cells. 6‐amino‐4‐(4‐phenoxyphenylethylamino) quinazoline (QNZ, 10 nM), a selective inhibitor of transcription via the NF‐κB pathway, abolished LPS‐induced up‐regulation of CSE expression. We propose that inhibition of CSE expression and reduction in formation of the pro‐inflammatory component of H2S activity contributes to the anti‐inflammatory effect of dexamethasone in endotoxic shock. Whether H2S plays a part in the anti‐inflammatory effect of this steroid in other forms of inflammation such as arthritis or asthma warrants further study.
Haemopexin affects iron distribution and ferritin expression in mouse brain
Authors: Morello Noemi , Tonoli Elisabetta , Logrand Federica , Fiorito Veronica , Fagoonee Sharmila , Turco Emilia , Silengo Lorenzo , Vercelli Alessandro , Altruda Fiorella , Tolosano Emanuela
Published: December 2008

Haemopexin (Hx) is an acute phase plasma glycoprotein, mainly produced by the liver and released into plasma where it binds heme with high affinity and delivers it to the liver. This system provides protection against free heme‐mediated oxidative stress, limits access by pathogens to heme and contributes to iron homeostasis by recycling heme iron. Hx protein has been found in the sciatic nerve, skeletal muscle, retina, brain and cerebrospinal fluid (CSF). Recently, a comparative proteomic analysis has shown an increase of Hx in CSF from patients with Alzheimer’s disease, thus suggesting its involvement in heme detoxification in brain. Here, we report that Hx is synthesised in brain by the ventricular ependymal cells. To verify whether Hx is involved in heme scavenging in brain, and consequently, in the control of iron level, iron deposits and ferritin expression were analysed in cerebral regions known for iron accumulation. We show a twofold increase in the number of iron‐loaded oligodendrocytes in the basal ganglia and thalamus of Hx‐null mice compared to wild‐type controls. Interestingly, there was no increase in H‐ and L‐ferritin expression in these regions. This condition is common to several human neurological disorders such as Alzheimer’s disease and Parkinson’s disease in which iron loading is not associated with an adequate increase in ferritin expression. However, a strong reduction in the number of ferritin‐positive cells was observed in the cerebral cortex of Hx‐null animals. Consistent with increased iron deposits and inadequate ferritin expression, malondialdehyde level and Cu–Zn superoxide dismutase‐1 expression were higher in the brain of Hx‐null mice than in that of wild‐type controls. These data demonstrate that Hx plays an important role in controlling iron distribution within brain, thus suggesting its involvement in iron‐related neurodegenerative diseases.
Measuring and monitoring apoptosis and drug toxicity in HIV patients by ligation‐mediated polymerase chain reaction
Authors: Hooker David J. , Gorry Paul R. , Ellett Anne M. , Wesselingh Steven L. , Cherry Catherine L.
Published: December 2008

Apoptosis has a critical role in normal physiology while its dysregulation has causal links with certain pathologies. A biochemical hallmark of apoptosis, internucleosomal genomic DNA fragmentation, is detectable by ligation‐mediated polymerase chain reaction (LM‐PCR). Here we converted LM‐PCR into a new apoptosis quantifier by dividing trace quantities of 600 bp apoptotic amplicons into those of a single copy house‐keeping gene, generating the LM‐PCR ‘value’. Dynamic range was ∼17‐fold correlating with a ∼200‐fold difference in degree of apoptotic fragmentation. Inter‐ and intra‐gel reliability were both excellent, supporting LM‐PCR's utility with large sample sets. Validation experiments comprising cell exposure to staurosporine over time revealed LM‐PCR is as sensitive as caspase‐3/ELISA and more sensitive than terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling/flourescence‐activated cell sorting (TUNEL/FACS) for distinguishing low degrees of apoptosis (the spectrum most relevant in vivo). The LM‐PCR profile mirrored that of caspase‐3/ELISA but not TUNEL/FACS. We then applied this molecular tool to clinical investigation. Increased apoptosis is implicated in lipoatrophy (subcutaneous fat wasting), a serious, persistent toxicity of some nucleoside analogue reverse transcriptase inhibitors (NRTIs) used in anti‐HIV highly active antiretroviral therapy (HAART). We demonstrated in 105 peripheral blood mononuclear cell samples that elevated LM‐PCR values are seen during therapy with stavudine (d4T), a particularly toxic NRTI (P< 0.0001 versus no HAART, unpaired t‐test). Elevated values were also independently associated with clinical evidence of lipoatrophy (P= 0.007, multiple logistic regression modelling) but not with patient age, CD4 T‐cell count nor HIV viral load (P> 0.8 for each). Together these data demonstrate that LM‐PCR is a robust and reliable quantifier of apoptosis with potential for basic science and clinical investigation.
Network position of hosts in food webs and their parasite diversity
Authors: Chen Hsuan‐Wien , Liu Wei‐Chung , Davis Andrew J. , Jordán Ferenc , Hwang Ming‐Jing , Shao Kwan‐Tsao
Published: December 2008

Parasites are ubiquitous in ecological communities but it is only recently that they have been routinely included in food web studies. Using recently published data and the tool of network analysis, we elucidate features associated with the pattern of parasitism in ecological communities. First we show here that parasitism is non‐random in food webs. Second we demonstrate that parasite diversity, the number of parasite species harboured by a host species, is related to the network position of a host species. Specifically, a host species with high parasite diversity tends to have a wide diet range, occupy a network position close to many prey species, or occupy a network position that can better accumulate resources from species at lower trophic levels. Lastly our results also suggest that a host species with higher vulnerability to predators, being at a network position close to many predatory species, or being involved in many different food chains, tends to be important in parasite transmission.
Hidden patterns of colony size variation in seabirds: a logarithmic point of view
Authors: Jovani Roger , Mavor Roddy , Oro Daniel
Published: December 2008

Explaining the huge variability present in bird colony sizes within and between species is intimately related to the understanding of the proximate and ultimate reasons for bird coloniality. However, natural patterns of colony size frequency distributions (CSFDs) remain poorly known. It is widely believed that colonial birds have similar long‐tailed (highly right‐skewed) CSFDs and that species mainly differ in their maximum colony sizes (in the length of the ‘tail’ of their CSFDs). We used data from the Seabird 2000 project (20 species; 19 978 colonies; 3 779 919 nests), the largest and most detailed dataset currently available, to analyse the CSFDs of seabird breeding in Britain and Ireland. Log‐transformations of colony sizes revealed that the often reported long‐tailed CSFDs in common histograms were hiding contrasting patterns, mainly log‐normal but also power law CSFDs. The different statistical characteristics of CSFDs did not co‐occur at random within species and were in fact highly correlated (e.g. a large geometric mean correlated with a large coefficient of variation). A PCA with these characteristics revealed a smoothed transition between species’ CSFD. Therefore, (a) a logarithmic analysis will allow different aspects of what is currently only referred to as ‘colony size variation’ to be quantified; (b) we challenge the current idea that all species show similar long‐tailed CSFDs; (c) we offer a new (unified) view of colony size variation and discuss how these new patterns confirm, challenge and may advance theoretical and applied research into bird coloniality.
Effect of acute postural variation on diabetic macular oedema
Authors: Vinten Martin , La Cour Morten , Lund‐Andersen Henrik , Larsen Michael
Published: December 2008

Purpose:  This study aimed to study the pathophysiology of diabetic macular oedema (DMO) by analysis of concomitant changes in macular volume (MV), mean arterial blood pressure (MABP), intraocular pressure (IOP), and retinal artery and vein diameters in response to acute postural changes in patients with DMO and healthy subjects.

Methods:  Thirteen patients with DMO (13 eyes) and five healthy subjects (five eyes) were examined after resting in a chair for 15 mins using optical coherence tomography to measure MV and fundus photography to assess retinal vessel diameters. The patients then lay down for 60 mins, during which they were examined repeatedly before they were reseated and examined again. Intraocular pressure was measured using pulse‐air tonometry, arterial blood pressure by sphygomanometry and fluid columns using rulers and a spirit level.

Results:  In healthy subjects, retinal artery (p = 0.02) and vein (p = 0.001) diameters decreased when subjects lay down, whereas MV remained stable. In patients with DMO, no orthostatic variation in retinal vessel diameters could be demonstrated, whereas MV had increased by 2.4 ± 0.6% (mean ± standard error of the mean; p = 0.006) 50 mins after assuming a recumbent position. In both healthy subjects and DMO patients, MABP decreased and IOP increased in a recumbent position, with no significant difference between the groups.

Conclusions: The increase in MV that occurs in DMO when changing from a seated to a recumbent position is associated with a failure of retinal artery contraction, a response seen in healthy subjects that appears to counter‐regulate the increase in ocular perfusion pressure caused by assuming a recumbent position.
Conjunctival impression cytology and tear‐film changes in patients with familial Mediterranean fever
Authors: Karalezli Aylin , Borazan Mehmet , Yilmaz Sema , Kiyici Halil , Akova Yonca Aydin
Published: December 2008

Purpose:  To evaluate the ocular surface changes and tear‐film functions in patients with familial Mediterranean fever (FMF).

Methods:  This prospective case–control clinical study examined 35 patients with FMF (group 1) and 35 controls (group 2). All patients underwent a full ophthalmological examination. Ocular surface changes were evaluated by determining cell content of surface conjunctival epithelium using conjunctival impression cytology and tear‐film functions using Schirmer‐I, break‐up time (BUT), corneal fluorescein and Rose Bengal tests. Subjective ocular complaints were scored with a four‐point scale. Between‐group results were compared.

Results:  In group 1, impression cytology revealed grade 0 changes in 15 eyes, grade 1 changes in 11 eyes and grade 2 changes in nine eyes in group 1; in group 2, it revealed grade 0 changes in 27 eyes, grade 1 changes in five eyes and grade 2 changes in three eyes (p = 0.013). Mean goblet cell density was 765 ± 45 cells/mm2 in group 1 and 1730 ± 100 cells/mm2 in group 2 (P < 0.001). Mean results on the Schirmer‐I test results were 17.36 ± 3.18 mm in group 1 and 19.60 ± 4.17 mm in group 2 (p = 0.364). Mean BUT was 8.20 ± 1.60 seconds in group 1 and 9.93 ± 2.33 seconds in group 2 (p = 0.001). Mean corneal fluorescein and Rose Bengal staining scores were 3.26 ± 1.67 and 0.96 ± 0.71 in group 1 and 1.37 ± 0.34 and 0.40 ± 0.49 in group 2 (p = 0.037, p = 0.005). The presence of subjective ocular complaints was more frequent in group 1 than in group 2.

Conclusion:  Despite normal tear production, the ocular surface and tear‐film functions of FMF patients differ from those of healthy individuals. These changes may be related to the chronic inflammatory nature of FMF.
Computational Modeling of LDL and Albumin Transport in an In Vivo CT Image-Based Human Right Coronary Artery
Authors: Sun Nanfeng , Torii Ryo , Wood Nigel B. , Hughes Alun D. , Thom Simon A. M. , Xu X. Yun
Published: December 2008

Low wall shear stress (WSS) is implicated in endothelial dysfunction and atherogenesis. The accumulation of macromolecules is also considered as an important factor contributing to the development of atherosclerosis. In the present study, a fluid-wall single-layered model incorporated with shear-dependent transport parameters was used to investigate albumin and low-density lipoprotein (LDL) transport in an in vivo computed tomographic image-based human right coronary artery (RCA). In the fluid-wall model, the bulk blood flow was modeled by the Navier–Stokes equations, Darcy’s law was employed to model the transmural flow in the arterial wall, mass balance of albumin and LDL was governed by the convection-diffusion mechanism with an additional reaction term in the wall, and the Kedem–Katchalsky equations were applied at the endothelium as the interface condition between the lumen and wall. Shear-dependent models for hydraulic conductivity and albumin permeability were derived from experimental data in literature to investigate the influence of WSS on macromolecular accumulation in the arterial wall. A previously developed so-called lumen-free time-averaged scheme was used to approximate macromolecular transport under pulsatile flow conditions. LDL and albumin accumulations in the subendothelial layer were found to be colocalized with low WSS. Two distinct mechanisms responsible for the localized accumulation were identified: one was insufficient efflux from the subendothelial layer to outer wall layers caused by a weaker transmural flow; the other was excessive influx to the subendothelial layer from the lumen caused by a higher permeability of the endothelium. The comparison between steady flow and pulsatile flow results showed that the dynamic behavior of the pulsatile flow could induce a wider and more diffuse macromolecular accumulation pattern through the nonlinear shear-dependent transport properties. Therefore, it is vital to consider blood pulsatility when modeling the shear-dependent macromolecular transport in large arteries. In the present study, LDL and albumin accumulations were observed in the low WSS regions of a human RCA using a fluid-wall mass transport model. It was also found that steady flow simulation could overestimate the magnitude and underestimate the area of accumulations. The association between low WSS and accumulation of macromolecules leading to atherosclerosis may be mediated through effects on transport properties and mass transport and is also influenced by flow pulsatility.
An Adjustable Triple-Bifurcation Unit Model for Air-Particle Flow Simulations in Human Tracheobronchial Airways
Authors: Kleinstreuer C. , Zhang Z.
Published: December 2008

A new methodology for a swift and accurate computer simulation of large segments of the human lung airways is presented. Focusing on a representative tracheobronchial (TB) region, i.e., G0–G15, nano- and micron particle transports have been simulated for Qin=30l∕min, employing an experimentally validated computer model. The TB tree was geometrically decomposed into triple-bifurcation units with kinematically adjusted multilevel outlet/inlet conditions. Deposition patterns and maximum concentrations differ greatly between nanoparticles (1⩽dp⩽150nm) and micron particles (1⩽dp⩽10μm), which may relate uniquely to health impacts. In comparison with semi-analytical particle deposition results, it is shown that such simple “lung models” cannot predict local deposition values but can match computer simulation results for the entire TB region within 2.5–26%. The present study revealed that turbulent air-particle flow may propagate to G5 for the assumed inhalation flow rate. Geometry and upstream effects are more pronounced for micron particle deposition than for nanoparticle deposition.
The Circadian Clock in
Arabidopsis
Roots Is a Simplified Slave Version of the Clock in Shoots
Authors: James Allan B. , Monreal José A. , Nimmo Gillian A. , Kelly Ciarán L. , Herzyk Pawel , Jenkins Gareth I. , Nimmo Hugh G.
Published: December 2008

The circadian oscillator in eukaryotes consists of several interlocking feedback loops through which the expression of clock genes is controlled. It is generally assumed that all plant cells contain essentially identical and cell-autonomous multiloop clocks. Here, we show that the circadian clock in the roots of mature
Arabidopsis
plants differs markedly from that in the shoots and that the root clock is synchronized by a photosynthesis-related signal from the shoot. Two of the feedback loops of the plant circadian clock are disengaged in roots, because two key clock components, the transcription factors CCA1 and LHY, are able to inhibit gene expression in shoots but not in roots. Thus, the plant clock is organ-specific but not organ-autonomous.
CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA
Authors: Marraffini Luciano A. , Sontheimer Erik J.
Published: December 2008

Horizontal gene transfer (HGT) in bacteria and archaea occurs through phage transduction, transformation, or conjugation, and the latter is particularly important for the spread of antibiotic resistance. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci confer sequence-directed immunity against phages. A clinical isolate of
Staphylococcus epidermidis
harbors a CRISPR spacer that matches the
nickase
gene present in nearly all staphylococcal conjugative plasmids. Here we show that CRISPR interference prevents conjugation and plasmid transformation in
S. epidermidis
. Insertion of a self-splicing intron into
nickase
blocks interference despite the reconstitution of the target sequence in the spliced mRNA, which indicates that the interference machinery targets DNA directly. We conclude that CRISPR loci counteract multiple routes of HGT and can limit the spread of antibiotic resistance in pathogenic bacteria.
Age-Specific Cluster of Cases of Serotype 1
Streptococcus pneumoniae
Carriage in Remote Indigenous Communities in Australia
Authors: Smith-Vaughan H. , Marsh R. , Mackenzie G. , Fisher J. , Morris P. S. , Hare K. , McCallum G. , Binks M. , Murphy D. , Lum G. , Cook H. , Krause V. , Jacups S. , Leach A. J.
Published: December 2008

Seven-valent pneumococcal conjugate vaccination commenced in 2001 for Australian indigenous infants. Pneumococcal carriage surveillance detected substantial replacement with nonvaccine serotypes and a cluster of serotype 1 carriage. Our aim was to review
Streptococcus pneumoniae
serotype 1 carriage and invasive pneumococcal disease (IPD) data for this population and to analyze serotype 1 isolates. Carriage data were collected between 1992 and 2004 in the Darwin region, one of the five regions in the Northern Territory. Carriage data were also collected in 2003 and 2005 from four regions in the Northern Territory. Twenty-six cases of serotype 1 IPD were reported from 1994 to 2007 in the Northern Territory. Forty-four isolates were analyzed by BOX typing and 11 by multilocus sequence typing. In the Darwin region, 26 children were reported carrying serotype 1 (ST227) in 2002 but not during later surveillance. Scattered cases of serotype 1 carriage were noted in two other regions. Cocolonization of serotype 1 with other pneumococcal serotypes was common (34% serotype 1-positive swabs). In conclusion, pneumococcal carriage studies detected intermittent serotype 1 carriage and an ST227 cluster in children in indigenous communities in the Northern Territory of Australia. There was no apparent increase in serotype 1 IPD during this time. The rate of serotype 1 cocolonization with other pneumococcal serotypes suggests that carriage of this serotype may be underestimated.
Generation of Immune Responses against Hepatitis C Virus by Dendritic Cells Containing NS5 Protein-Coated Microparticles
Authors: Gehring Stephan , Gregory Stephen H. , Wintermeyer Philip , Aloman Costica , Wands Jack R.
Published: December 2008

Dendritic cells (DCs) internalize and process antigens as well as activate cellular immune responses. The aim of this study was to determine the capacity of DCs that contain antigen-coated magnetic beads to induce immunity against the nonstructural hepatitis C virus (HCV) antigen 5 (NS5). Splenocytes derived from Fms-like tyrosine kinase receptor 3 (Flt3) ligand-pretreated BALB/c mice were incubated with magnetic beads coated with HCV NS5, lipopolysaccharide (LPS), and/or anti-CD40; purified; and used for immunization. Cellular immunity was measured using cytotoxic T-lymphocyte (CTL) and T-cell proliferation assays, intracellular cytokine staining, and a syngeneic tumor challenge using NS5-expressing SP2/0 myeloma cells in vivo. Splenocytes isolated from animals vaccinated with DCs containing beads coated with NS5, LPS, and anti-CD40 secreted elevated levels of interleukin-2 (IL-2) and gamma interferon in the presence of NS5. The numbers of CD4+, IL-2-producing cells were increased >5-fold in the group immunized with DCs containing beads coated with NS5, LPS, and anti-CD40, paralleled by an enhanced splenocyte proliferative response. Immunization promoted antigen-specific CTL activity threefold compared to the level for control mice and significantly reduced the growth of NS5-expressing tumor cells in vivo. Thus, strategies that employ NS5-coated beads induce cellular immune responses in mice, which correlate well with the natural immune responses that occur in individuals who resolve HCV.