bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of interventions for the prevention of small‐for‐gestational age fetuses and perinatal mortality: a review of systematic reviews
Authors: MORRIS RACHEL K. , OLIVER EMILY A. , MALIN GEMMA , KHAN KHALID S. , MEADS CATHERINE 
Published: October 2012

AbstractPrevious narrative reviews in this area have concluded that there are few interventions that are likely to be beneficial and that further high‐quality research is required. Our objective was to perform a review of systematic reviews of the effectiveness of interventions for the prevention of small‐for‐gestational age (SGA) fetuses and perinatal mortality, to summarize the most up‐to‐date evidence and assess quality. Searches were carried out by using Medline, Embase, Cochrane Library and DARE (inception to September 2011), by hand searching of journal and reference lists and by contact with experts. Systematic reviews of randomized controlled trials were selected. Two reviewers independently selected articles and assessed the methodological and reporting quality. Data were extracted on study characteristics, quality and results. Summary data were presented as relative risks (RRs) and 95% confidence intervals (CIs). There were 834 randomized controlled trials (>668 672 participants), reporting on 45 different interventions. The most effective interventions to prevent the SGA fetus were antiplatelets at <16 weeks in women at risk of pre‐eclampsia (RR 0.47; CI 0.30–0.74) and progesterone therapy for prevention of preterm birth (RR 0.64; CI 0.49–0.83). For the prevention of perinatal mortality in high‐risk women, antiplatelets (RR 0.69; CI 0.53–0.90) and antenatal corticosteroids (RR 0.77; CI 0.67–0.89) were effective interventions. It is concluded that effective interventions are available for reducing the occurrence of SGA fetuses and preventing related perinatal mortality. Some are effective in all women, while others target specific co‐morbidities. There is a need to consider a comprehensive approach to primary prevention that targets SGA along with pre‐eclampsia and preterm birth.
Impact of Clostridium difficile colitis on 5‐year health outcomes in patients with ulcerative colitis
Authors: Murthy S. K. , Steinhart A. H. , Tinmouth J. , Austin P. C. , Daneman N. , Nguyen G. C. 
Published: October 2012

SummaryBackgroundClostridium difficile colitis (CDC) is associated with an increased short‐term mortality risk in hospitalised ulcerative colitis (UC) patients. We sought to determine whether CDC also impacts long‐term risks of adverse health events in this population.AimTo determine whether CDC also impacts long‐term risks of adverse health events in this population.MethodsA population‐based retrospective cohort study was conducted of UC patients hospitalised in Ontario, Canada between 2002 and 2008. Patients with and without CDC were compared on the rates of adverse health events. The primary outcomes were the 5‐year adjusted risks of colectomy and death.ResultsAmong 181 patients with CDC and 1835 patients without CDC, the 5‐year cumulative colectomy rates were 44% and 33% (P = 0.0052) and the 5‐year cumulative mortality rates were 27% and 14% (P < 0.0001) respectively. CDC was associated with a higher adjusted 5‐year risk of mortality [adjusted hazard ratio (aHR) 2.40, 95% CI 1.37–4.20], but not of colectomy (aHR 1.18, 95% CI 0.90–1.54). CDC impacted mortality risk both during index hospitalisation (adjusted odds ratio 8.90, 95% CI 2.80–28.3) as well as over 5 years following hospital discharge among patients who recovered from their acute illness (aHR 2.41, 95% CI 1.37–4.22). Colectomy risk was not influenced by CDC in this cohort.ConclusionClostridium difficile colitis is associated with increased short‐term and long‐term mortality risks among hospitalised ulcerative colitis patients. As colectomy risk is not similarly impacted by Clostridium difficile colitis, factors predictive of death among C. difficile‐infected ulcerative colitis patients require elucidation.
Pharmacokinetics and central nervous system effects of the novel dual NK1/NK3 receptor antagonist GSK1144814 in alcohol‐intoxicated volunteers
Authors: te Beek Erik T. , Hay Justin L. , Bullman Jonathan N. , Burgess Clare , Nahon Kimberly J. , Klaassen Erica S. , Gray Frank A. , van Gerven Joop M. A. 
Published: October 2012

AimsAntagonism of both NK1 and NK3 receptors may be an effective strategy in the pharmacotherapy of schizophrenia, drug addiction or depression. GSK1144814 is a novel selective dual NK1/NK3 receptor antagonist. The potential influence of GSK1144814 on the effects of alcohol was investigated.MethodsIn a blinded, randomized, placebo‐controlled, two period crossover study, the pharmacokinetics and central nervous system (CNS) effects of single oral doses of 200 mg GSK1144814 were evaluated in 20 healthy volunteers, using a controlled alcohol infusion paradigm to maintain stable alcohol concentrations with subsequent analysis of eye movements, adaptive tracking, body sway, visual analogue scales, Epworth sleepiness scale and the verbal visual learning test.ResultsFrequent adverse effects were mild somnolence, fatigue and headache. Plasma concentration of GSK1144814 in the presence of alcohol was maximal 1.5 h after dose administration. GSK1144814 did not affect alcohol pharmacokinetics. Co‐administration of GSK1144814 and alcohol impaired saccadic reaction time and peak velocity, adaptive tracking, alertness, sleepiness, word recognition and recognition reaction time compared with administration of alcohol alone, but the size of the interaction was small.ConclusionsAdministration of GSK1144814 in the presence of alcohol was generally well tolerated and not likely to produce clinically relevant additional impairments after alcohol consumption.
Anti‐tumour immunotherapy with Vγ9Vδ2 T lymphocytes: from the bench to the bedside
Authors: Braza Mounia S. , Klein Bernard 
Published: October 2012

SummaryGamma delta (γδ) Τ cells are non‐conventional T lymphocyte effectors that can interact with and eradicate tumour cells. Several data demonstrate that these T cells, which are implicated in the first line of defence against pathogens, have anti‐tumour activity against many cancers and suggest that γδ Τ cell‐mediated immunotherapy is feasible and might induce objective tumour responses. Due to the importance of γδ Τ lymphocytes in the induction and control of immunity, a complete understanding of their biology is crucial for the development of a potent cancer immunotherapy. This review discusses recent advances in γδ Τ basic research and data from clinical trials on the use of γδ Τ cells in the treatment of different cancers. It analyses how this knowledge might be applied to develop new strategies for the clinical manipulation and the potentiation of γδ Τ lymphocyte activity in cancer immunotherapy.
When does anxiety help or hinder cognitive test performance? The role of working memory capacity
Authors: Owens Matthew , Stevenson Jim , Hadwin Julie A. , Norgate Roger 
Published: October 2012

Cognitive interference theories (e.g. attentional control theory, processing efficiency theory) suggest that high levels of trait anxiety predict adverse effects on the performance of cognitive tasks, particularly those that make high demands on cognitive resources. We tested an interaction hypothesis to determine whether a combination of high anxiety and low working memory capacity (WMC) would predict variance in demanding cognitive test scores. Ninety six adolescents (12‐ to 14‐years‐old) participated in the study, which measured self‐report levels of trait anxiety, working memory, and cognitive test performance. As hypothesized, we found that the anxiety‐WMC interaction explained a significant amount of variance in cognitive test performance (ΔR2 .07, p < .01). Trait anxiety was unrelated to cognitive test performance for those adolescents with average WMC scores (β = .13, p > .10). In contrast, trait anxiety was negatively related to test performance in adolescents with low WMC (β = −.35, p < .05) and positively related to test performance in those with high WMC (β = .49, p < .01). The results of this study suggest that WMC moderates the relationship between anxiety and cognitive test performance and may be a determinant factor in explaining some discrepancies found in the literature. Further research is needed to fully understand the mechanisms involved.
Community dental clinics: providers' perspectives
Authors: Wallace Bruce B. , MacEntee Michael I. , Harrison Rosamund , Hole Rachelle , Mitton Craig 
Published: October 2012

AbstractObjectivesNot‐for‐profit community dental clinics attempt to address the inequities of oral health care for disadvantaged communities, but there is little information about how they operate. The objective of this article is to explain from the perspective of senior staff how five community dental clinics in British Columbia, Canada, provide services.MethodsThe mixed‐methods case study included the five not‐for‐profit dental clinics with full‐time staff who provided a wide range of dental services. We conducted open‐ended interviews to saturation with eight senior administrative staff selected purposefully because of their comprehensive knowledge of the development and operation of the clinics and supplemented their information with a year's aggregated data on patients, treatments, and operating costs.ResultsThe interview participants described the benefits of integrating dentistry with other health and social services usually within community health centres, although they doubted the sustainability of the clinics without reliable financial support from public funds. Aggregated data showed that 75% of the patients had either publically funded or no coverage for dental services, while the others had employer‐sponsored dental insurance. Financial subsidies from regional health authorities allowed two of the clinics to treat only patients who are economically vulnerable and provide all services at reduced costs. Clinics without government subsidies used the fees paid by some patients to subsidize treatment for others who could not afford treatment.ConclusionsNot‐for‐profit dental clinics provide dental services beyond pain relief for underserved communities. Dental services are integrated with other health and community services and located in accessible locations. However, all of the participants expressed concerns about the sustainability of the clinics without reliable public revenues.
Protection against allergic airway inflammation during the chronic and acute phases of Trichinella spiralis infection
Authors: Aranzamendi C. , de Bruin A. , Kuiper R. , Boog C. J. P. , van Eden W. , Rutten V. , Pinelli E. 
Published: October 2012

SummaryBackgroundModulation of the host immune response by helminths has been reported to be essential for parasite survival and also to benefit the host by suppressing inflammatory diseases such as allergies. We have previously shown that excretory‐secretory products of Trichinella spiralis muscle larvae have immunomodulatory properties and induce in vitro the expansion of CD4+CD25+FOXP3+ Treg cells in a TGF‐β‐dependent manner.ObjectiveWe aimed at determining the effect of the acute (intestinal) and the chronic (muscle) phase of T. spiralis infection on experimental allergic airway inflammation (EAAI) to Ovalbumin (OVA) and the involvement of Treg cells.MethodsThe chronic phase was established before OVA‐sensitization/challenge and the acute phase at two‐time points, before and after OVA‐sensitization. Mice were infected with 400 T. spiralis larvae and after euthanasia different pathological features of EAAI were measured. Adoptive transfer of CD4+ T cells from Trichinella infected mice to OVA sensitized/challenged recipients was also performed.ResultsWe found that the chronic as well as the acute phase of Trichinella infection suppress EAAI as indicated by reduction in airway inflammation, OVA‐specific IgE levels in sera, Th2‐cytokine production and eosinophils in bronchoalveolar lavage. This protective effect was found to be stronger during the chronic phase and to be associated with increased numbers of splenic CD4+CD25+FOXP3+ Treg cells with suppressive activity. Adoptive transfer of splenic CD4+ T cells from chronically infected mice with elevated numbers of Treg cells resulted in partial protection against EAAI.Conclusions and Clinical RelevanceThese results demonstrate that the protective effect of T. spiralis on EAAI increases as infection progresses from the acute to the chronic phase. Here, Treg cells may play an essential role in the suppression of EAAI. Elucidating the mechanisms and molecular helminth structures responsible for this regulatory process is relevant to develop alternative tools for preventing or treating allergic asthma.
Quality not quantity for transglutaminase antibody 2: the performance of an endomysial and tissue transglutaminase test in screening coeliac disease remains stable over time
Authors: Swallow K , Wild G , Sargur R , Sanders D S , Aziz I , Hopper A D , Egner W 
Published: October 2012

Summary
National Institute of Clinical Excellence (NICE) and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidance for the diagnosis of coeliac disease has been published. However, there is some controversy regarding the advice on the use of stratifying levels of immunoglobulin (IgA) tissue transglutaminase antibody (TG2) test positivity in the absence of test standardization and the vagueness of the indication to test equivocal samples. Using repeat service audit, we demonstrate that a combination of TG2 followed by IgA endomysial antibodies (EMA) is the best strategy for all degrees of mucosal abnormality using our test combination. Reliance upon immunoassay titre is not as effective, and cannot be applied consistently across populations in the absence of assay standardization. Guidelines advocating the use of tests should involve experts in laboratory diagnostics and external quality assurance to ensure that errors of generalization do not occur and that test performance is achievable in routine diagnostic use.
Immune mechanisms and the impact of the disrupted lung microbiome in chronic bacterial lung infection and bronchiectasis
Authors: Boyton R J , Reynolds C J , Quigley K J , Altmann D M 
Published: October 2012

Summary
Recent studies analysing immunogenetics and immune mechanisms controlling susceptibility to chronic bacterial infection in bronchiectasis implicate dysregulated immunity in conjunction with chronic bacterial infection. Bronchiectasis is a structural pathological end-point with many causes and disease associations. In about half of cases it is termed idiopathic, because it is of unknown aetiology. Bronchiectasis is proposed to result from a ‘vicious cycle’ of chronic bacterial infection and dysregulated inflammation. Paradoxically, both immune deficiency and excess immunity, either in the form of autoimmunity or excessive inflammatory activation, can predispose to disease. It appears to be a part of the spectrum of inflammatory, autoimmune and atopic conditions that have increased in prevalence through the 20th century, attributed variously to the hygiene hypothesis or the ‘missing microbiota’. Immunogenetic studies showing a strong association with human leucocyte antigen (HLA)-Cw*03 and HLA-C group 1 homozygosity and combinational analysis of HLA-C and killer immunoglobulin-like receptors (KIR) genes suggests a shift towards activation of natural killer (NK) cells leading to lung damage. The association with HLA-DR1, DQ5 implicates a role for CD4 T cells, possibly operating through influence on susceptibility to specific pathogens. We hypothesize that disruption of the lung microbial ecosystem, by infection, inflammation and/or antibiotic therapy, creates a disturbed, simplified, microbial community (‘disrupted microbiota’) with downstream consequences for immune function. These events, acting with excessive NK cell activation, create a highly inflammatory lung environment that, in turn, permits the further establishment and maintenance of chronic infection dominated by microbial pathogens. This review discusses the implication of these concepts for the development of therapeutic interventions.
Efficacy and safety of long‐term, continuous subcutaneous octreotide infusion for patients with different subtypes of KATP‐channel hyperinsulinism
Authors: Yorifuji Tohru , Kawakita Rie , Hosokawa Yuki , Fujimaru Rika , Matsubara Kousaku , Aizu Katsuya , Suzuki Shigeru , Nagasaka Hironori , Nishibori Hironori , Masue Michiya 
Published: October 2012

SummaryObjectiveTo evaluate the efficacy of long‐term, continuous, subcutaneous octreotide infusion for congenital hyperinsulinism caused by mutations in the KATP‐channel genes, KCNJ11 and ABCC8.PatientsFifteen Japanese patients with diazoxide‐unresponsive, KATP‐channel hyperinsulinism.MethodsMolecular diagnoses were made by sequencing and multiple ligation‐dependent probe amplification analysis. In patients with paternally inherited, monoallelic mutations, 18F‐DOPA PET scans were performed to determine the location of the lesion. The patients were treated with continuous, subcutaneous octreotide infusion at a dosage of up to 25 μg/kg/day, using an insulin pump to maintain blood glucose levels higher than 3·33 mmol/l. Additional treatments (IV glucose, glucagon or enteral feeding) were administered as needed. The efficacy of the treatment was assessed in patients who received octreotide for 4 months to 5·9 years.ResultsThree patients had biallelic mutations, and 12 had monoallelic, paternally inherited mutations. Four patients with monoallelic mutations showed diffuse 18F‐DOPA uptake, whereas seven patients showed focal uptake. Octreotide was effective in all the patients. The patients with biallelic mutations required a higher dosage (17–25 μg/kg/day), and two patients required additional treatments. By contrast, the patients with monoallelic mutations required a lower dosage (0·5–21 μg/kg/day) irrespective of the PET results and mostly without additional treatments. Treatment was discontinued in three patients at 2·5, 3·3 and 5·9 years of age, without psychomotor delay. Except for growth deceleration at a higher dosage, no significant adverse effects were noted.ConclusionsLong‐term, continuous, subcutaneous octreotide infusion is a feasible alternative to surgery especially for patients with monoallelic KATP‐channel mutations.
The effects of caloric restriction on Fetuin‐A and cardiovascular risk factors in rats and humans: a randomized controlled trial
Authors: Choi Kyung Mook , Han Kyung Ah , Ahn Hee Jung , Lee So Young , Hwang Soon Young , Kim Baek‐Hui , Hong Ho Cheol , Choi Hae Yoon , Yang Sae Jeong , Yoo Hye Jin , Baik Sei Hyun , Choi Dong Seop , Min Kyung Wan 
Published: October 2012

SummaryObjectivesThe liver‐secreted protein fetuin‐A is associated with insulin resistance, metabolic syndrome, type 2 diabetes and atherosclerosis. We examined the effect of caloric restriction (CR) on fetuin‐A levels and concomitant changes in hepatic steatosis and cardiovascular risk factors in rats and humans.Design and SubjectsWe performed a randomized, controlled clinical trial to examine circulating fetuin‐A levels and cardiovascular risk parameters including visceral fat area (VFA), atherogenic lipid profile, inflammatory markers, adipokines levels and brachial artery endothelial function in 76 overweight women with type 2 diabetes before and after 12 weeks of CR. In addition, the effects of CR on hepatic steatosis and fetuin‐A mRNA expression were evaluated in Otuska Long Evans Tokushima Fatty (OLETF) rats, an animal model of obesity and type 2 diabetes.ResultsCirculating fetuin‐A levels were significantly decreased after 12 weeks of CR and were accompanied by improvements in VFA, blood pressure, glucose, lipid profiles and liver function. The CR group also showed a significant decrease in apolipoprotein B, leptin and insulin resistance compared to those in the control group, although endothelial function was not different. Multiple regression analysis showed that the changes in fetuin‐A levels were independently associated with CR and changes in hsCRP and adiponectin (R2 = 0·156). Moreover, CR significantly reduced hepatic steatosis and fetuin‐A expression, as well as weight, glucose, total cholesterol and triglyceride levels, in OLETF rats.ConclusionCaloric restriction significantly reduced the hepatic expression of fetuin‐A and its circulating levels and improved several cardiovascular risk factors in obese rats and humans with type 2 diabetes.
Implant Stability and Bone Remodeling after 3 and 13 Days of Implantation with an Initial Static Strain
Authors: Halldin Anders , Jimbo Ryo , Johansson Carina B. , Wennerberg Ann , Jacobsson Magnus , Albrektsson Tomas , Hansson Stig 
Published: October 2012

AbstractObjectiveBone is constantly exposed to dynamic and static loads, which induce both dynamic and static bone strains. Although numerous studies exist on the effect of dynamic strain on implant stability and bone remodeling, the effect of static strain needs further investigation. Therefore, the effect of two different static bone strain levels on implant stability and bone remodeling at two different implantation times was investigated in a rabbit model.MethodsTwo different test implants with a diametrical expansion of 0.15 mm (group A) and 0.05 mm (group B) creating initial static bone strains of 0.045 and 0.015, respectively. The implants were inserted in the proximal tibial metaphysis of 24 rabbits to observe the biological response at implant removal. Both groups were compared to control implants (group C), with no diametrical increase. The insertion torque (ITQ) was measured to represent the initial stability and the removal torque (RTQ) was measured to analyze the effect that static strain had on implant stability and bone remodeling after 3 and 13 days of implantation time.ResultsThe ITQ and the RTQ values for test implants were significantly higher for both implantation times compared to control implants. A selection of histology samples was prepared to measure bone to implant contact (BIC). There was a tendency that the BIC values for test implants were higher compared to control implants.ConclusionThese findings suggest that increased static bone strain creates higher implant stability at the time of insertion, and this increased stability is maintained throughout the observed period.