bluuebunny/crossref_metadata_2025 huggingface dataset:
Dental phenomics: advancing genotype to phenotype correlations in craniofacial research
Authors: Yong R , Ranjitkar S , Townsend GC , Smith RN , Evans AR , Hughes TE , Lekkas D , Brook AH
Published: February 2014

The field of dental phenomics provides many opportunities to elucidate the roles of genetic, epigenetic and environmental factors in craniofacial development. To date, research findings have helped to clarify the pathogenesis of many conditions, aiding diagnosis and clinical management. This paper provides an overview of dental phenomics research in some commonly encountered oral diseases in everyday clinical practice, as well as research relating to craniofacial growth and development. Clinically, advances in cariology and periodontology have led to better diagnostic capabilities and treatment provision. In the study of growth and development, important information regarding the varying clinical presentation and pathogenesis of many disorders is now apparent through the accurate quantification of phenotypes. Improvements in two‐dimensional (2D) and three‐dimensional (3D) imaging and analytical techniques have allowed for accurate dental phenotyping, and efforts are ongoing to apply thesein vitrotechniques to thein vivosetting. The field of dental phenomics represents an exciting avenue that links research findings to practical application, and collaboration between researcher and clinicians will help advance the field further.
A Family‐Based Robust Multivariate Association Test Using Maximum Statistic
Authors: Hsieh Tsung‐Jen , Chang Shu‐Hui , Tai John Jen
Published: February 2014

For characterizing the genetic mechanisms of complex diseases familial data with multiple correlated quantitative traits are usually collected in genetic studies. To analyze such data, various multivariate tests have been proposed to investigate the association between the underlying disease genes and the multiple traits. Although these multivariate association tests may have better power performance than the univariate association tests, they suffer from loss of testing power when the genetic models of the putative genes are misspecified. To address the problem, in this paper we aim to develop a family‐based robust multivariate association test. We will first establish the optimal multivariate score tests for the recessive, additive, and dominant genetic models. Based on these optimal tests, a maximum‐type robust multivariate association test is then obtained. Simulations are conducted to compare the power of our method with that of other existing multivariate methods. The results show that the robust multivariate test does manifest the robustness in power over all plausible genetic models. A practical data set is applied to demonstrate the applicability of our approach. The results suggest that the robust multivariate test is more powerful than the robust univariate test when dealing with multiple quantitative traits.
Decreased diversity of nasal microbiota and their secreted extracellular vesicles in patients with chronic rhinosinusitis based on a metagenomic analysis
Authors: Choi E.‐B. , Hong S.‐W. , Kim D.‐K. , Jeon S. G. , Kim K.‐R. , Cho S.‐H. , Gho Y. S. , Jee Y.‐K. , Kim Y.‐K.
Published: February 2014

Background

Chronic rhinosinusitis (CRS) is an inflammatory process in the nasal cavity and paranasal sinuses, and bacteria have been considered to be a cause. Indeed, recent evidence indicates that bacteria‐derived extracellular vesicles (EV) appear to be an important causative agent of inflammatory diseases. Here, we aimed to evaluate the diversity of nasal microbiota and their secreted EV in patients with CRS.

Methods

Nasal lavage (NAL) fluid samples were obtained from five patients with CRS with polyposis, three patients with CRS without polyposis, and three non‐CRS controls. After preparation of bacteria and EV from samples using differential centrifugation, genomic DNA was extracted and 16S‐rDNA amplicons were subjected to high‐throughput pyrosequencing on a Roche 454 GS‐FLX platform.

Results

Metagenomics showed that bacteria composition was positively correlated with EV composition. Samples from patients with CRS had greater bacterial abundance and lower diversity, both from bacteria and the EV portion of samples, compared with non‐CRS samples. At each phylogenetic level, Bacteroidetes decreased while Proteobacteria increased in the CRS group at the phylum level. At the genus level, Prevotella spp. decreased in the CRS group, while Staphylococcus spp. increased from both bacteria and EV. Moreover, Staphylococcus aureus and its secreting EV compositions were higher in samples from CRS with polyps compared with CRS without polyps.

Conclusions

These results suggest that patients with CRS have altered nasal microbiota and decreased diversity in bacterial compositions as well as increased S. aureus abundance in those patients with polyps.
Omalizumab therapy is associated with reduced circulating basophil populations in asthmatic children
Authors: Hill D. A. , Siracusa M. C. , Ruymann K. R. , Tait Wojno E. D. , Artis D. , Spergel J. M.
Published: February 2014

Basophils have been implicated in promoting the early development of TH2 cell responses in some murine models of TH2 cytokine‐associated inflammation. However, the specific role of basophils in allergic asthma remains an active area of research. Recent studies in animal models and human subjects suggest that IgE may regulate the homeostasis of human basophil populations. Here, we examine basophil populations in children with severe asthma before and during therapy with the IgE‐directed monoclonal antibody omalizumab. Omalizumab therapy was associated with a significant reduction in circulating basophil numbers, a finding that was concurrent with improved clinical outcomes. The observation that circulating basophils are reduced following omalizumab therapy supports a mechanistic link between IgE levels and circulating basophil populations, and may provide new insights into one mechanism by which omalizumab improves asthma symptoms.
Mobile Simulation Unit: taking simulation to the surgical trainee
Authors: Pena Guilherme , Altree Meryl , Babidge Wendy , Field John , Hewett Peter , Maddern Guy
Published: February 2014

Background

Simulation‐based training has become an increasingly accepted part of surgical training. However, simulators are still not widely available to surgical trainees. Some factors that hinder the widespread implementation of simulation‐based training are the lack of standardized methods and equipment, costs and time constraints. We have developed a Mobile Simulation Unit (MSU) that enables trainees to access modern simulation equipment tailored to the needs of the learner at the trainee's workplace.

Methods

From July 2012 to December 2012, the MSU visited six hospitals in South Australia, four in metropolitan and two in rural areas. Resident Medical Officers, surgical trainees, Fellows and International Medical Graduates were invited to voluntarily utilize a variety of surgical simulators on offer. Participants were asked to complete a survey about the accessibility of simulation equipment at their workplace, environment of the MSU, equipment available and instruction received. Utilization data were collected.

Results

The MSU was available for a total of 303 h over 52 days. Fifty‐five participants were enrolled in the project and each spent on average 118 min utilizing the simulators. The utilization of the total available time was 36%. Participants reported having a poor access to simulation at their workplace and overwhelmingly gave positive feedback regarding their experience in the MSU.

Conclusion

The use of the MSU to provide simulation‐based education in surgery is feasible and practical. The MSU provides consistent simulation training at the surgical trainee's workplace, regardless of geographic location, and it has the potential to increase participation in simulation programmes.
Early oral feeding following laparoscopic colorectal cancer surgery
Authors: Kim Hyung Ook , Lee Sung Ryol , Choi Won Joon , Kim Hungdai
Published: February 2014

Background

Early oral feeding (EOF) following colorectal surgery can accelerate patient recovery and shorten hospital stay. However, some patients are intolerable to postoperative early oral feeding. The aim of this study was to evaluate the tolerability of EOF following laparoscopic colorectal cancer surgery and the effects of intravenous lidocaine.

Methods

The cohort in this randomized, placebo‐controlled trial (ClinicalTrial.gov, NCT01346917) comprised of 77 patients undergoing elective laparoscopic colorectal cancer surgery. For patients randomized to the lidocaine group, a loading dose of 1 mg/kg lidocaine prior to skin incision, and a continuous dose of 1 mg/kg/h lidocaine with 90 mg ketorolac (non‐steroidal anti‐inflammatory drug) (in normal saline, total 240 mL) was administered for 24 h. Patients randomized to the placebo group received a loading dose of 5 mL saline and a continuous dose of 90 mg ketorolac in 240 mL saline. The primary outcome measure was prevalence of postoperative nausea/vomiting and intolerance to EOF.

Results

Altogether, 68 patients completed the study and were analyzed. Postoperative nausea and vomiting were higher in the control group but did not reach statistical significance (P = 0.054). Tolerability of EOF was 96.9% in the lidocaine group and 91.7% in the control group (P = 0.62). There was no difference in postoperative pain, opioid consumption, bowel function recovery or postoperative hospital stay.

Conclusion

Perioperative intravenous lidocaine administered for laparoscopic colorectal cancer surgery might reduce postoperative nausea and vomiting. However, a high tolerability to EOF following colorectal surgery can be achieved by laparoscopic surgery alone without other supportive treatment.
Patients' recollection and understanding of informed consent: a literature review
Authors: Sherlock Anne , Brownie Sonya
Published: February 2014

Objective

To explore patients' recollection and understanding of the proposed medical procedures for which they have consented.

Methods

Six databases were searched from January 1995 to March 2013 for articles using the MeSH terms ‘informed consent’, ‘patients’ and ‘comprehension’, and the free text search term ‘patient understanding’. This search identified 354 articles. Once duplicates (n = 213) were removed, the remaining 141 articles were screened, resulting in 13 high‐quality studies that met the inclusion criteria.

Results

When asked to reflect on the consenting process, between 21% and 86% of patients were able to recall the potential risks and complications of their medical procedure. The degree of understanding of the consenting process decreased with age. Some patients were of the opinion that the primary purpose of the consent procedure was to protect hospitals and doctors.

Patients

Level of education, literacy and language competency, combined with physicians' ability to effectively explain the medical procedure and the inherent risks and complications, were important determinants of patients' capacity to provide fully informed consent. The use of education materials delivered in written form or embedded in an interactive multimedia process led to improvements in patients' understanding of the implications of surgery.

Conclusions

This review found that patients' recollection and understanding of the medical procedure, risks and complications is often low, particularly among older individuals. The use of interactive multimedia and written material that are easy‐to‐read and comprehend, and prepared for individual patients has been shown to increase patient awareness, recollection and understanding of the consenting procedure.
Rent, Real Estate, and Flood Mitigation in New Orleans East
Authors: Baxter Vern
Published: February 2014

This paper presents results from a study of environmental harm created in the collision of real estate speculation and the political process that governed extension of the urban frontier of New Orleans into its eastern wetlands. Near term concerns of rent‐seeking real estate capital and the contested politics of urban infrastructure expansion challenged a fragmented state charged with regulatory oversight and protection of investments in land and citizens. The paper engages theoretically the relative inattention of urban political ecology theory to rent as a way to theorize how capital flows through land, and argues for increased attention to the problem of land rent and the multiple scales of political engagement that manage ecological crisis immanent in the metabolism of nature and society under capitalism.
On the Performativity of Pill Pricing: Theory and Reality in the Economics of Global Pharmaceuticalization
Authors: Christophers Brett
Published: February 2014

One often‐highlighted contemporary phenomenon in the pharmaceuticals industry is the use of “tiered pricing”, where essential medicines are sold more cheaply in low‐income than high‐income countries to widen access. With economists having for decades championed the applicability of such pricing to pharmaceuticals, this could be interpreted as a textbook case of “economic performativity”—the economic world increasingly conforming to economic models. In reality, however, tiered pharmaceutical pricing remains rare. Yet this article nonetheless urges retention of the performativity concept, albeit suitably reworked. For, insofar as the industry demonstrates nominal commitment to the model and to the social principles associated with it, it performs valuable political work. Moreover, it does help perform the pharmaceutical economy, by reproducing it in its existing form: repeatedly questioning the model's workability, Western manufacturers are able to continue to avoid putting it widely into practice and, in the process, jeopardizing the profits generated by conventional pricing.
Cerebral perfusion pressure in women with preeclampsia is elevated even after treatment of elevated blood pressure
Authors: Sonneveld Milan J. , Brussé Ingrid A. , Duvekot Johannes J. , Steegers Eric A.P. , Grune Frank , Visser Gerhard H.
Published: February 2014

Cerebral perfusion pressure (CPP) is elevated in preeclampsia, and may predispose to cerebrovascular complications and progression to eclampsia. We estimated zero flow pressure (ZFP) and CPP using simultaneously obtained arterial blood pressure and middle cerebral artery blood flow velocity in 10 women with preeclampsia, all treated with methyldopa with or without nifedipine, and 18 healthy pregnant controls. Mean ± SD ZFP was lower in women with preeclampsia than in controls (16.8 ± 10.9 vs. 31.7 ± 15.0 mmHg, p = 0.01) whereas CPP was considerably higher (82.3 ± 17.7 vs. 55.0 ± 11.7 mmHg, p < 0.001), as was the cerebral flow index (41.9 ± 18.0 vs. 25.6 ± 11.2, p = 0.02). There was a significant correlation between blood pressure and CPP in women with preeclampsia, but not in controls. Women with preeclampsia may have an increased cerebral perfusion due to a reduced ZFP and increased CPP despite treatment with antihypertensive medication. More rigorous antihypertensive therapy, aimed at reducing CPP, could result in a decrease in cerebral complications in women with preeclampsia.
Possible Benefits of Catheters With Lateral Holes in Coronary Thrombus Aspiration: A Computational Study for Different Clot Viscosities and Vacuum Pressures
Authors: Soleimani Sajjad , Dubini Gabriele , Pennati Giancarlo
Published: February 2014

According to a number of clinical studies, coronary aspiration catheters are useful tools to remove a thrombus (blood clot) blocking a coronary artery. However, these thrombectomy devices may fail to remove the blood clot entirely. Few studies have been devoted to a systematic analysis of factors affecting clot aspiration. The geometric characteristics of the aspiration catheter, the physical properties of the thrombus, and the applied vacuum pressure are crucial parameters. In this study, the aspiration of a blood clot blocking a coronary bifurcation is computationally simulated. The clot is modeled as a highly viscous fluid, and a two‐phase (blood and clot) problem is solved. The effects of geometric variations in the tip of the coronary catheter, including lateral hole size and location, are investigated considering different aspiration pressures and clot viscosities. A Bird–Carreau model is adopted for blood viscosity, while a power law model is used to describe the clot rheology. Computational results for blood clot aspiration show that the presence of holes in the lateral part of the tip of the catheter can be beneficial depending on clot viscosity, hole features, and applied aspiration pressure. In general, the holes are beneficial when the clot viscosity is low, while aspiration catheters without any extra lateral holes exhibit better performance for higher clot viscosity. However, when higher aspiration pressures are applied, the catheters tend to behave relatively similarly in removing clots with various viscosities, reducing the role of the clot viscosity.
Review article: HCV genotype 3 – the new treatment challenge
Authors: Ampuero J. , Romero‐Gómez M. , Reddy K. R.
Published: February 2014

Background

Over the past several years, hepatitis C therapy has been pegylated interferon and ribavirin based. Although protease inhibitor‐based therapy has enhanced response rates in genotype 1, the recent advances in therapy have demonstrated a challenge in genotype 3, a highly prevalent infection globally.

Aim

To provide a comprehensive summary of the literature evaluating the unique characteristics and evolving therapies in genotype 3.

Methods

A structured search in PubMed, the Cochrane Library and EMBASE was performed using defined key words, including only full text papers and abstracts in English.

Results

HCV genotype 3 is more prevalent in Asia and among intra‐venous drug users. Furthermore, it interferes with lipid and glucose metabolism, and the natural history involves a more rapid progression of liver disease and a higher incidence of hepatocellular carcinoma (HCC). New therapies with protease inhibitors have focused on genotype 1 largely and have demonstrated enhanced responses, but have limited activity against genotype 3. Thus far, in clinical trials, NS5B and NS5A inhibitors have performed more poorly in genotype 3, while a cyclophilin inhibitor, alisporivir, has shown promise.

Conclusions

As treatments for HCV have evolved, genotype 3 has become the most difficult to treat. Furthermore, genotype 3 has special characteristics, such as insulin resistance and alterations in lipid metabolism, which may partly explain the lower treatment responses. A great deal of emphasis on advancing therapy is needed in this population that appears to have a more rapid progression of liver disease and a higher incidence of HCC.
Latitudinal variation of morphological characteristics in the swallowtail Sericinus montelus Gray, 1798 (Lepidoptera: Papilionidae)
Authors: Zheng Xia‐Lin , Yang Qiu‐Sheng , Hu Yu‐Wei , Lei Chao‐Liang , Wang Xiao‐Ping
Published: February 2014

Patterns of latitudinal variation in the phenotype or genotype of an organism may provide evidence for natural selection. In this study, we investigated seven populations of swallowtail Sericinus montelus Gray, 1798 (Lepidoptera: Papilionidae), a non‐migratory species, to explore the latitudinal variation of morphological characteristics in adults. The results showed that body size and the development of dark pigmentation on wings in this species responded strongly to latitude. The body size of both male and female adult of S. montelus was negatively correlated with latitude. These findings provided solid evidence to support the converse Bergmann's rule. We considered that the observed variation in morphological characteristics was most likely mediated by the seasonal length and thermoperiod to adapt to different latitudinal environment (e.g. shortened developmental time of immature stages for smaller body size at higher latitude). Moreover, the tendency towards progressively darker colour patterns (only in adult males) at increasingly low latitudes was consistent with Gloger's rule. We suggested that the observed colour variation was most likely associated with thermoregulation. Slight variation in the morphology of the W‐shaped stripe on the forewing of adult females was also found, and we presumed that the functions of sexual preferences, mimicry and thermoregulation might be involved.
Mechanisms and assessment of statin‐related muscular adverse effects
Authors: Moßhammer Dirk , Schaeffeler Elke , Schwab Matthias , Mörike Klaus
Published: February 2014

Statin‐associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life‐threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin‐related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450‐mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.
Structure–Activity Relationship of Terpenes with Anti‐Inflammatory Profile – A Systematic Review
Authors: de Santana Souza Marilia Trindade , Almeida Jackson Roberto Guedes da Silva , de Souza Araujo Adriano Antunes , Duarte Marcelo Cavalcante , Gelain Daniel Pens , Moreira José Cláudio Fonseca , dos Santos Marcio Roberto Viana , Quintans‐Júnior Lucindo José
Published: February 2014

Inflammation is a complex biological response that in spite of having available treatments, their side effects limit their usefulness. Because of this, natural products have been the subject of incessant studies, among which the class of terpenes stands out. They have been the source of study for the development of anti‐inflammatory drugs, once their chemical diversity is well suited to provide skeleton for future anti‐inflammatory drugs. This systematic review reports the studies present in the literature that evaluate the anti‐inflammatory activity of terpenes suffering any change in their structures, assessing whether these changes also brought changes in their effects. The search terms anti‐inflammatory agents, terpenes, and structure–activity relationship were used to retrieve English language articles in SCOPUS, PUBMED and EMBASE published between January 2002 and August 2013. Twenty‐seven papers were found concerning the structural modification of terpenes with the evaluation of anti‐inflammatory activity. The data reviewed here suggest that modified terpenes are an interesting tool for the development of new anti‐inflammatory drugs.
Haptoglobin, alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania
Authors: Cox Sharon E. , Makani Julie , Soka Deogratias , L'Esperence Veline S. , Kija Edward , Dominguez‐Salas Paula , Newton Charles R. J. , Birch Anthony A. , Prentice Andrew M. , Kirkham Fenella J.
Published: February 2014

Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co‐inheritance in SCA of alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co‐inheritance of these polymorphisms on CBFv in 601 stroke‐free Tanzanian SCA patients aged <24 years. Homozygosity for alpha‐thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild‐type (β‐coefficient −16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha‐thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35–0·8] & RRR = 0·43 [95% CI:0·23–0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17–0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co‐inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha‐thalassaemia in reducing risk of abnormal CBFv.
Serotonin (5‐HT)2A/2C receptor agonist (2,5‐dimethoxy‐4‐idophenyl)‐2‐aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat
Authors: Tu Hongjian , Cao Nailong , Gu Baojun , Si Jiemin , Chen Zhong , Andersson Karl‐Erik
Published: February 2014

Objectives

To examine the effects of the serotonin (5‐HT)2A/2C receptor agonist (2,5‐dimethoxy‐4‐idophenyl)‐2‐aminopropane hydrochloride (DOI) on micturition in rats with diabetes mellitus (DM).

Methods

Female Sprague–Dawley rats (n = 16) were divided into two groups: rats with Type 1 DM and age‐matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram (CMG) studies were performed 8 weeks post‐injection in all rats under urethane anaesthesia. The selective 5‐HT2A antagonist ketanserin was administered after each DOI dose–response curve was plotted. All drugs were administered i.v.

Results

Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post‐void residual urine volume (PVR), and a markedly lower voiding efficiency. In DM rats, DOI (0.01–0.3 mg/kg) induced significant dose‐dependent increases in micturition volume and reductions in PVR, resulting in greater voiding efficiency. CMG measurements showed a dose‐dependent increase in high‐frequency oscillation (HFO) activity, evidenced by an increased duration of HFOs per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI‐induced changes.

Conclusions

The HFOs observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5‐HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies.
Penile prosthesis insertion in patients with refractory ischaemic priapism: early vs delayed implantation
Authors: Zacharakis Evangelos , Garaffa Gulio , Raheem Amr A. , Christopher Andrew N. , Muneer Asif , Ralph David J.
Published: February 2014

Objective

To compare the long‐term results of early and delayed insertion of a penile prosthesis (PP) in men with refractory ischaemic priapism (IP).

Patients and Methods

Early insertion of a PP was carried out in 68 men with IP within a median of 7 days from the onset of priapism, while 27 had delayed insertion after a median of 5 months. The results for sexual ability, satisfaction and subjective penile shortening were assessed by questioning at follow‐up visits.

Results

In the early group, a malleable and an inflatable PP were implanted in 64 and four patients, respectively. After a median follow‐up of 17 months, six patients needed revision surgery due to infection and curvature. Patient's satisfaction rate and ability to have sexual intercourse was 96%. In the delayed group, a malleable PP was inserted in 12 patients and an inflatable in the remaining 15. In all, 80% of the patients required a second corporotomy and downsized cylinders due to dense fibrosis. After a median follow‐up of 21 months, seven patients required revision surgery due to infection, erosion and mechanical failure. In all, 25 patients were able to engage in sexual intercourse but the satisfaction rate was only 60% mainly due to significant penile shortening.

Conclusions

Early PP implantation should be the preferred option in patients with IP, as the procedure is technically easier, has less complication rates and allows greater preservation of penile length.
The RAZOR (randomized open vs robotic cystectomy) trial: study design and trial update
Authors: Smith Norm D. , Castle Erik P. , Gonzalgo Mark L. , Svatek Robert S. , Weizer Alon Z. , Montgomery Jeffrey S. , Pruthi Raj S. , Woods Michael E. , Tollefson Matthew K. , Konety Badrinath R. , Shabsigh Ahmad , Krupski Tracey , Barocas Daniel A. , Dash Atreya , Quek Marcus L. , Kibel Adam S. , Parekh Dipen J.
Published: February 2014

The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot‐assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health‐related quality of life (HRQL) measures with a primary endpoint of 2‐year progression‐free survival (PFS). RAZOR is a multi‐institutional, randomized, non‐inferior, phase III trial that will enrol at least 320 patients with T1–T4, N0–N1, M0 bladder cancer with ≈160 patients in both the RARC and ORC arms at 15 participating institutions. Data will be collected prospectively at each institution for cancer outcomes, complications of surgery and HRQL measures, and then submitted to trial data management services Cancer Research and Biostatistics (CRAB) for final analyses. To date, 306 patients have been randomized and accrual to the RAZOR trial is expected to conclude in 2014. In this study, we report the RAZOR trial experimental design, objectives, data safety, and monitoring, and accrual update. The RAZOR trial is a landmark study in urological oncology, randomizing T1–T4, N0–N1, M0 patients with bladder cancer to ORC vs RARC, PLND and urinary diversion. RAZOR is a multi‐institutional, non‐inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2‐year PFS. Full data from the RAZOR trial are not expected until 2016–2017.
Inconsistencies in the roles of family‐ and paid‐ carers in monitoring health issues in people with learning disabilities: some implications for the integration of health and social care
Authors: Willis Diane S.
Published: February 2014

Accessible summary

This paper looks at the views of paid‐ and family‐carers about discussing health matters with people with learning disabilities.

The author found that the roles of paid‐ and family‐carers in monitoring health were not clearly defined.

Explaining health problems and different medical tests to people with learning disabilities proved difficult.

Nevertheless, carers possessed good skills in helping people with learning disabilities understand more about their health.

Changes in the living circumstances of people with learning disabilities have seen responsibility for their health become the provenance of paid‐and family‐carers. Thirteen semi‐structured interviews were conducted with three family‐carers and ten paid‐carers. Findings revealed that the role of these carers was undefined, leading to difficulty in deciphering who was responsible for the health care of the people they supported, with some paid‐carers claiming that health was outwith their remit. The difficulty of monitoring health problems of people with learning disabilities was noted, and carers disclosed skills and techniques that they used to explain health messages to individuals. If the health needs of people with learning disabilities are to be met, then a more consistent approach to health care within the community setting is needed, especially in terms of the remit of paid‐and family‐carers and with the integration of health and social services.
Safe and social: what does it mean anyway??
Authors: Tinney Grainne , Forde Jenny , Hone Loraine , Flanagan Lisa , Smith Martine
Published: February 2014

Accessible summary

People with intellectual disabilities can find it hard to understand what behaviours are ok in what situations and with what people. These rules change all the time, and so it is important to be able to work out how to behave for each new situation.

If people with intellectual disability behave inappropriately, they may be judged as rude. They may put themselves at risk and be unsafe if they do not understand what information is ok to share with others and how to say no if someone is behaving inappropriately with them.

This paper describes a training programme that was developed to help people with intellectual disabilities to work out if a behaviour is ok or not ok. The programme also shows that it is important to think about the person we are with and the place we are in so we can work out if a behaviour is ok or not.

This paper outlines a programme Safe and Social that has been implemented with adults with intellectual disability across multiple contexts in a service based in Ireland. The emphasis within the programme is on providing service users and staff with a framework and the necessary language to discuss social behaviours and boundaries, moving away from an emphasis on rules and regulations. The programme draws on visual supports of three nested circles, red indicating ‘not ok’, green indicating ‘ok’ and a central circle that is used to set the topic of discussion. Over a series of seven modules, adults with intellectual disabilities and their support staff are encouraged to collaboratively problem solve some of the behaviours and understandings that can undermine social acceptability and compromise personal safety. Based on positive outcomes over a five‐year period, we highlight the need for further research to explore the effectiveness of the programme.
Computer‐Aided Discovery of Trypanosoma brucei RNA‐Editing Terminal Uridylyl Transferase 2 Inhibitors
Authors: Demir Özlem , Labaied Mehdi , Merritt Chris , Stuart Ken , Amaro Rommie E.
Published: February 2014

Human African trypanosomiasis (HAT) is a major health problem in sub‐Saharan Africa caused by Trypanosoma brucei infection. Current HAT drugs are difficult to administer and not effective against all parasite species at different stages of the disease which indicates an unmet pharmaceutical need. TbRET2 is an indispensable enzyme for the parasite and is targeted here using a computational approach that combines molecular dynamics simulations and virtual screening. The compounds prioritized are then tested in T. brucei via Alamar blue cell viability assays. This work identified 20 drug‐like compounds which are candidates for further testing in the drug discovery process.
Children's Attractiveness, Gender, and Race Biases: A Comparison of Their Strength and Generality
Authors: Rennels Jennifer L. , Langlois Judith H.
Published: February 2014

Although research suggests that facial attractiveness biases significantly affect social development and interactions, these biases are understudied in the developmental literature and are overlooked when designing interventions relative to gender and race. The authors, therefore, compared how much bias 3‐ to 11‐year‐olds (N = 102) displayed in the three domains. They also examined whether bias and flexibility (understanding that different social groups can possess similar attributes) were related across domains. Children's attractiveness biases, particularly for girl targets, were as strong as or stronger than gender or race biases. Flexibility, but not bias, was related across domains. Developmental scientists and policy makers should increase efforts toward understanding development of attractiveness biases and determine which methods of teaching flexibility are most successful at reducing bias across domains.
Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti-neutrophil cytoplasmic antibodies
Authors: Ohlsson S M , Ohlsson S , Söderberg D , Gunnarsson L , Pettersson Å , Segelmark M , Hellmark T
Published: February 2014

Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in ANCA-associated vasculitis (AAV) by stimulating polymorphonuclear leucocytes (PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this study was to investigate if PMNs from AAV patients are stimulated more readily by ANCA compared with PMNs from healthy controls (HCs). Differences in ANCA characteristics that can account for different stimulation potential were also studied. PMNs from five AAV patients and five HCs were stimulated with 10 different immunoglobulins (Ig)Gs, purified from PR3–ANCA-positive patients, and ROS production, degranulation and neutrophil extracellular trap (NET) formation was measured. ANCA levels, affinity and clinical data of the AAV donors were recorded. The results show that PMNs from AAV patients produce more intracellular ROS (P = 0·019), but degranulate to a similar extent as PMNs from HCs. ROS production correlated with NET formation. Factors that may influence the ability of ANCA to activate PMNs include affinity and specificity for N-terminal epitopes. In conclusion, our results indicate that PMNs from AAV patients in remission behave quite similarly to HC PMNs, with the exception of a greater intracellular ROS production. This could contribute to more extensive NET formation and thus an increased exposure of the ANCA autoantigens to the immune system.
Serum autoantibodies directed against transglutaminase-2 have a low avidity compared with alloantibodies against gliadin in coeliac disease
Authors: Gelderman K A , Drop A C A D , Trouw L A , Bontkes H J , Bouma G , van Hoogstraten I M W , von Blomberg B M E
Published: February 2014

Coeliac disease is characterized by intolerance to gliadin and related gluten components present in wheat, barley and rye. Coeliac disease patients harbour antibodies directed against alloantigens such as gliadin, but also against the autoantigen transglutaminase-2 (TG2). The type and quality of antibody responses provides insight into the underlying immune activation processes. Therefore, in this study we have analysed the avidity of the antibody response directed against the autoantigen TG2 and compared this with antibody responses against the alloantigens gliadin and Escherichia coli. We observed that the immunoglobulin (Ig)A autoantibody response directed against TG2 is of low avidity compared with the IgA response against the alloantigens gliadin and E. coli in the same patients; the same was true for IgG, both in IgA-deficient and in -sufficient coeliac patients. The observed avidities appear not to be related to disease stage, antibody levels, age or duration of exposure to gluten. In conclusion, in coeliac disease there is a clear difference in avidity of the antibody responses directed against the auto- and alloantigens, indicating different regulation or site of initiation of these responses.
Peri‐Implant Response and Microflora in Organ Transplant Patients 1 Year after Prosthetic Loading: A Prospective Controlled Study
Authors: Montebugnoli Lucio , Venturi Mattia , Cervellati Fabio , Servidio Dora , Vocale Caterina , Pagan Flavia , Landini Maria Paola , Magnani Gaia , Sambri Vittorio
Published: February 2014

Background

A recent study conducted in humans demonstrated for the first time that bone loss in the immediate period after implant insertion before loading did not significantly differ in organ transplant recipients with respect to normal subjects.

Purpose

The purpose of this study is to evaluate bone and periodontal response and peri‐implant microflora in a group of organ‐transplanted patients 1 year after prosthetic loading.

Materials and Methods

The study population included 13 consecutive organ‐transplanted (11 hearts, two livers) patients and 13 normal (healthy) control subjects who received 29 and 28 submerged dental implants, respectively. Crestal bone level, peri‐implant probing depth (PIPD), and bleeding on probing were evaluated at prosthetic loading and after 1 year. Samples for microbiological testing were taken from the subgingival microbiota of each implant 1 year after loading and analyzed with polymerase chain reaction. All samples were examined for the presence of five microorganisms: Treponema denticola, Porphyromonas gingivalis, Prevotella intermedia, Tannarella forsythensis, and Actinobacillus actinomycetemcomitans.

Results

A mean bone loss of 0.17 ± 0.10 and 0.20 ± 0.10 mm at 1 year was observed in the group of transplant recipients and in controls, respectively (N.S.). Similar results were obtained considering PIPD changes at 1 year (respectively 0.06 ± 0.71 mm in transplants vs 0.11 ± 0.74 mm in controls). Detection frequencies of pathogens were not statistically different between normal and transplanted patients.

Conclusions

The present pilot study seems to indicate that bone and periodontal response and microbiological status around submerged dental implants in immunocompromised organ‐transplanted patients do not differ 1 year after loading from those observed in control patients and that this particular population of patients may be successfully rehabilitated with dental implants.
Osteoconductive Potential of Mesoporous Titania Implant Surfaces Loaded with Magnesium: An Experimental Study in the Rabbit
Authors: Galli Silvia , Naito Yoshihito , Karlsson Johan , He Wenxiao , Andersson Martin , Wennerberg Ann , Jimbo Ryo
Published: February 2014

Background

Mesoporous coatings enable incorporation of functional substances and sustainedly release them at the implant site. One bioactive substance that can be incorporated in mesoporous is magnesium, which is strongly involved in bone metabolism and in osteoblast interaction.

Purpose

The aim of this experimental study was to evaluate the effect of incorporation of magnesium into mesoporous coatings of oral implants on early stages of osseointegration.

Material and Methods

Titanium implants were coated with thin films of mesoporous TiO2 having pore diameters of 6 nm and were loaded with magnesium. The implant surfaces were extensively characterized by means of interferometry, atomic force microscopy, scanning electron microscopy, and energy‐dispersive spectroscopy and then placed in the tibiae of 10 rabbits. After 3 weeks of healing, osseointegration was evaluated by means of removal torque testing and histology and histomorphometry.

Results

Histological and biomechanical analyses revealed no side effects and successful osseointegration of the implants. The biomechanical evaluation evidenced a significant effect of magnesium doping on strengthening the implant‐bone interface.

Conclusions

A local release of magnesium from the implant surfaces enhances implant retention at the early stage of healing (3 weeks after implantation), which is highly desirable for early loading of the implant.
Early Osseointegration Events on Neoss® ProActive and Bimodal Implants: A Comparison of Different Surfaces in an Animal Model
Authors: Grossi‐Oliveira Gustavo Augusto , Antunes Antonio Azoubel , Elias Carlos Nelson , Wennerberg Ann , Sennerby Lars , Salata Luiz Antonio
Published: February 2014

Background

Cell interactions, adherence, and osseointegration at the bone‐implant interface can be directly influenced by the surface properties of the titanium implant.

Purpose

To characterize osseointegration of Neoss® implants with conventional (control group) and hydrophilic (test group) surface treatments.

Materials and Methods

Six Labrador dogs received Neoss implants with conventional and hydrophilic surfaces. The bone‐implant interfaces were evaluated 1 and 4 weeks after implantation, and osseointegration was evaluated using histological, histomorphometric, fluorescence, and resonance frequency analyses. The surfaces were also subjected to topographic and hydrophilicity analyses.

Results

The topographic analyses revealed increased surface roughness in the test group compared with the control group (surface area roughness 0.42 and 0.78 μm, respectively, for control and test group surfaces; p ≤ .05). The wettability values were higher in the test group (contact angles 67.2° and 27.2° for the control and test group surfaces, respectively; p ≤ .05). Implants in the test group also exhibited better stability, more bone‐implant contact, and increased bone area compared with implants in the control group.

Conclusion

Neoss implants in the test group improved bone formation in the early stages of osseointegration compared with implants in the control group.
Efficacy of standard (SLA) and modified sandblasted and acid‐etched (SLActive) dental implants in promoting immediate and/or early occlusal loading protocols: a systematic review of prospective studies
Authors: Chambrone Leandro , Shibli Jamil Awad , Mercúrio Carlos Eduardo , Cardoso Bruna , Preshaw Philip M.
Published: February 2014

Objective

To assess the survival percentage, clinical and radiographic outcomes of sandblasted and acid‐etched (SLA) dental implants and its modified surface (SLActive) in protocols involving immediate and early occlusal loading.

Methods

MEDLINE,EMBASEand the Cochrane Oral Health Group's Trials RegisterCENTRALwere searched in duplicate up to, and including, June 2013 to include randomised controlled trials (RCTs) and prospective observational studies of at least 6‐month duration published in all languages. Studies limited to patients treated withSLAand/orSLActive implants involving a treatment protocol describing immediate and early loading of these implants were eligible for inclusion. Data on clinical and/or radiographic outcomes following implant placement were considered for inclusion.

Results

Of the 447 potentially eligible publications identified by the search strategy, sevenRCTs comprising a total of 853 implants (8% titanium plasma‐sprayed, 41.5%SLAand 50.5%SLActive) and 12 prospective observational studies including 1394SLAand 145SLActive implants were included in this review. According to the Cochrane Collaboration's tool for assessing risk of bias, one of the studies was considered to be at a low risk of bias, whereas the remaining studies were considered to be at an unclear risk. Regarding the observational studies, all of them presented a medium methodological quality based on the ModifiedNewcastle–Ottawa scale. There were no significant differences reported in the studies in relation to implant loss or clinical parameters between the immediate/early loading and delayed loading protocols. Overall, 95% ofSLAand 97% ofSLActive implants still survive at the end of follow‐up.

Conclusions

Despite of the positive findings achieved by the included studies, fewRCTs were available for analysis forSLActive implants. Study heterogeneity, scarcity of data and the lack of pooled estimates represent a limitation between studies' comparisons and should be considered when interpreting the present findings.