bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical evaluation of diamine silver fluoride/potassium iodide as a dentine desensitizing agent. A pilot study
Authors: Craig GG , Knight GM , McIntyre JM 
Published: May 2012

AbstractBackground:  The aim of the present study was to compare the efficacy of an experimental diamine silver fluoride/potassium iodide product with an oxalic acid‐based preparation in reducing dentine hypersensitivity.Methods:  The study was conducted as a double‐blind, randomized clinical trial. A total of 19 subjects with dentine hypersensitivity on both sides of their upper arch were selected. The most sensitive tooth in each quadrant was identified and received a cold stimulus. The response was recorded on a visual analogue scale (VAS). The tooth thus selected was treated with one of the treatment agents. One week later the level of dentine sensitivity was assessed. Participants were also asked for their subjective assessment of treatment effects.Results:  The mean difference between VAS at baseline and seven days for teeth treated with diamine silver fluoride/potassium iodide was greater than that for teeth treated with the oxalic acid‐based preparation (p = 0.0134). The subjects’ subjective assessment of changes in dentine hypersensitivity indicated that more obtained relief with the diamine silver fluoride/potassium iodide treatment (p = 0.0129).Conclusions:  It was concluded that an experimental diamine silver fluoride/potassium iodide product has potential as a treatment for dentine hypersensitivity.
Reactivity of nonsteroidal anti-inflammatory drugs with peroxidase: a classification of nonsteroidal anti-inflammatory drugs
Authors: Miura Toshiaki 
Published: May 2012

Abstract

Objectives
To improve understanding of the essential effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on prostaglandin H synthase (PGHS), the reactivity of NSAIDs with peroxidases and the tyrosyl radical derived from myoglobin was examined.

Methods
Horseradish peroxidase and myoglobin were used as models of peroxidase and cyclooxygenase of PGHS, respectively.

Key findings
From the results, a new classification of NSAIDs has been proposed. Class 1 includes the majority of NSAIDs, which reacted with horseradish peroxidase compound I, thus causing a spectral change by PGHS peroxidase and also including diminished electron spin resonance signals of the tyrosyl radical of myoglobin. They reduced compound I of horseradish peroxidase and scavenged the tyrosyl radical. The branched-chain mechanism by which the porphyrin radical is transferred to the tyrosine residue of the protein might be blocked by these NSAIDs. Class 2 includes salicylic acid derivatives that reacted only with the porphyrin radical and not with horseradish peroxidase compound II (oxoferryl species). Class 3 includes aspirin, nimesulide, tolmetin, and arylpropionic acid derivatives, including ibuprofen and the coxibs of celecoxib and rofecoxib, which are not substrates for horseradish peroxidase or PGHS peroxidase.

Conclusions
Understanding the essential mode of action of NSAIDs is particularly important for designing an effective therapeutic strategy against inflammatory diseases.
The Fanconi Anemia Pathway Limits Human Papillomavirus Replication
Authors: Hoskins Elizabeth E. , Morreale Richard J. , Werner Stephen P. , Higginbotham Jennifer M. , Laimins Laimonis A. , Lambert Paul F. , Brown Darron R. , Gillison Maura L. , Nuovo Gerard J. , Witte David P. , Kim Mi-Ok , Davies Stella M. , Mehta Parinda A. , Butsch Kovacic Melinda , Wikenheiser-Brokamp Kathryn A. , Wells Susanne I. 
Published: May 2012

ABSTRACT
High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and cause anogenital and head and neck squamous cell carcinomas (SCCs). The E7 gene is considered the predominant viral oncogene and drives proliferation and genome instability. While the implementation of routine screens has greatly reduced the incidence of cervical cancers which are almost exclusively HPV positive, the proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV oncogene expression and genome load are linked to disease progression, but genetic risk factors that regulate oncogene abundance and/or genome amplification remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome characterized at least in part by extreme susceptibility to SCCs. FA results from mutations in one of 15 genes in the FA pathway, whose protein products assemble in the nucleus and play important roles in DNA damage repair. We report here that loss of FA pathway components FANCA and FANCD2 stimulates E7 protein accumulation in human keratinocytes and causes increased epithelial proliferation and basal cell layer expansion in the HPV-positive epidermis. Additionally, FANCD2 loss stimulates HPV genome amplification in differentiating cells, demonstrating that the intact FA pathway functions to restrict the HPV life cycle. These findings raise the possibility that FA genes suppress HPV infection and disease and suggest possible mechanism(s) for reported associations of HPV with an FA cohort in Brazil and for allelic variation of FA genes with HPV persistence in the general population.
Structural and Biochemical Characterization of the Vaccinia Virus Envelope Protein D8 and Its Recognition by the Antibody LA5
Authors: Matho Michael H. , Maybeno Matt , Benhnia Mohammed Rafii-El-Idrissi , Becker Danielle , Meng Xiangzhi , Xiang Yan , Crotty Shane , Peters Bjoern , Zajonc Dirk M. 
Published: May 2012

ABSTRACTSmallpox vaccine is considered a gold standard of vaccines, as it is the only one that has led to the complete eradication of an infectious disease from the human population. B cell responses are critical for the protective immunity induced by the vaccine, yet their targeted epitopes recognized in humans remain poorly described. Here we describe the biochemical and structural characterization of one of the immunodominant vaccinia virus (VACV) antigens, D8, and its binding to the monoclonal antibody LA5, which is capable of neutralizing VACV in the presence of complement. The full-length D8 ectodomain was found to form a tetramer. We determined the crystal structure of the LA5 Fab-monomeric D8 complex at a resolution of 2.1 Å, as well as the unliganded structures of D8 and LA5-Fab at resolutions of 1.42 Å and 1.6 Å, respectively. D8 features a carbonic anhydrase (CAH) fold that has evolved to bind to the glycosaminoglycan (GAG) chondroitin sulfate (CS) on host cells. The central positively charged crevice of D8 was predicted to be the CS binding site by automated docking experiments. Furthermore, sequence alignment of various poxvirus D8 orthologs revealed that this crevice is structurally conserved. The D8 epitope is formed by 23 discontinuous residues that are spread across 80% of the D8 protein sequence. Interestingly, LA5 binds with a high-affinity lock-and-key mechanism above this crevice with an unusually large antibody-antigen interface, burying 2,434 Å2of protein surface.
Development and Validation of the Chinese Version of the Massachusetts General Hospital Acupuncture Sensation Scale: An Exploratory and Methodological Study
Authors: Yu David Tai Wai , Jones Alice Yee Man , Pang Marco Yiu Chung 
Published: May 2012

Background The Massachusetts General Hospital Acupuncture Sensation Scale (MASS) is a tool to measure needle sensations. The aims of the present study were to develop a Chinese version and to assess its psychometric properties. Methods This study was a methodological and exploratory study. The English version of the MASS was translated into Chinese using standardised translation procedures. Content validity was conducted by nine acupuncture experts. The prefinal Chinese version (C-MASS) was then administered to 30 acupuncture-naïve, healthy subjects. Electroacupuncture was performed on the right LI4 and LI11 acupoints for 30 min. A test–retest reliability measurement was administered 1–2 weeks later. Construct validity was examined by comparing results from C-MASS and the Short-Form McGill Pain Questionnaire (SF-MPQ). The construct validity was further assessed by the principle component analysis. Results C-MASS demonstrated a content validity ratio on relevance and importance from −0.04 to 1.00. Convergent validity was demonstrated by its significant association with the sensory dimension of SF-MPQ (γ=0.63, p<0.05). Discriminant validity was demonstrated by its low association with the affective dimension of SF-MPQ (γ=−0.3, p=0.111). A five-factor structure of C-MASS was established by factor analysis. C-MASS demonstrated good internal consistency (Cronbach's α=0.71) and test–retest reliability (intraclass correlation coefficient=0.92). Since the descriptor ‘sharp pain’ was not a valid needle sensation related to deqi, this was removed from C-MASS. We renamed the scale as the Modified MASS-Chinese version (C-MMASS). Conclusions A 12-descriptor C-MMASS was established and shown to be a reliable and valid tool in reporting needle sensations associated with deqi among healthy young Chinese people.
Clinical influences on antibiotic prescribing decisions for lower respiratory tract infection: a nine country qualitative study of variation in care
Authors: Brookes-Howell Lucy , Hood Kerenza , Cooper Lucy , Coenen Samuel , Little Paul , Verheij Theo , Godycki-Cwirko Maciek , Melbye Hasse , Krawczyk Jaroslaw , Borras-Santos Alicia , Jakobsen Kristin , Worby Patricia , Goossens Herman , Butler Christopher C 
Published: May 2012

ObjectivesThere is variation in antibiotic prescribing for lower respiratory tract infections (LRTI) in primary care that does not benefit patients. This study aims to investigate clinicians' accounts of clinical influences on antibiotic prescribing decisions for LRTI to better understand variation and identify opportunities for improvement.DesignMulti country qualitative interview study. Semi-structured interviews using open-ended questions and a patient scenario. Data were subjected to five-stage analytic framework approach (familiarisation, developing a thematic framework from the interview questions and emerging themes, indexing, charting and mapping to search for interpretations), with interviewers commenting on preliminary reports.SettingPrimary care.Participants80 primary care clinicians randomly selected from primary care research networks based in nine European cities.ResultsClinicians reported four main individual clinical factors that guided their antibiotic prescribing decision: auscultation, fever, discoloured sputum and breathlessness. These were considered alongside a general impression of the patient derived from building a picture of the illness course, using intuition and familiarity with the patient. Comorbidity and older age were considered main risk factors for poor outcomes. Clinical factors were similar across networks, apart from C reactive protein near patient testing in Tromsø. Clinicians developed ways to handle diagnostic and management uncertainty through their own clinical routines.ConclusionsClinicians emphasised the importance of auscultation, fever, discoloured sputum and breathlessness, general impression of the illness course, familiarity with the patient, comorbidity, and age in informing their antibiotic prescribing decisions for LRTI. As some of these factors may be overemphasised given the evolving evidence base, greater standardisation of assessment and integration of findings may help reduce unhelpful variation in management. Non-clinical influences will also need to be addressed.
A new user cohort study comparing the safety of long-acting inhaled bronchodilators in COPD
Authors: Jara Michele , Wentworth Charles , Lanes Stephan 
Published: May 2012

ObjectiveTo investigate a possible increased risk observed in tiotropium clinical trials of stroke and other adverse events.DesignNew users of long-acting anticholinergic therapy (tiotropium HandiHaler®) were compared with new users of long-acting β-agonist (LABA) monotherapy, and propensity scores were used to control confounding.SettingUK healthcare system general practitioner electronic medical record database.Participants10 840 patients newly prescribed tiotropium (n=4767) or LABA (n=6073), at least 40 years old, and not having asthma as their only respiratory illness.Primary and secondary outcome measuresIncidence rates of total stroke, myocardial infarction, angina and other adverse events.ResultsTiotropium was associated with increased rates of stroke (HR=1.49, 95% CI 0.91 to 2.45), angina (HR=1.38, 95% CI 0.88 to 2.16) and myocardial infarction (HR=1.26, 95% CI 0.72 to 2.21). Groups had similar rates of chronic obstructive pulmonary disease exacerbation (HR=0.95, 95% CI 0.80 to 1.12) and pneumonia (HR=0.96, 95% CI 0.58 to 1.58). Tiotropium was associated with a lower rate of total mortality (HR=0.70, 95% CI 0.56 to 0.89) and asthma exacerbations (HR=0.46, 95% CI 0.36 to 0.57) than users of LABA.ConclusionSmall increased risks of serious ischaemic cardiovascular events have been reported with inhaled anticholinergic medication from randomised and nonrandomized studies of ipratropium, tiotropium HandiHaler® and tiotropium Respimat®. Additional research is needed to understand the full extent of cardiovascular effects of inhaled anticholinergic medications and the patients who may be most susceptible.
Keeping children safe at home: protocol for three matched case–control studies of modifiable risk factors for falls
Authors: Kendrick Denise , Maula Asiya , Stewart Jane , Clacy Rose , Coffey Frank , Cooper Nicola , Coupland Carol , Hayes Mike , McColl Elaine , Reading Richard , Sutton Alex , M L Towner Elizabeth , Craig Watson Michael ,   on behalf of the Keeping Children Safe Study Group
Published: May 2012

BackgroundChildhood falls result in considerable morbidity, mortality and health service use. Despite this, little evidence exists on protective factors or effective falls prevention interventions in young children.ObjectivesTo estimate ORs for three types of medically attended fall injuries in young children in relation to safety equipment, safety behaviours and hazard reduction and explore differential effects by child and family factors and injury severity.DesignThree multicentre case–control studies in UK hospitals with validation of parental reported exposures using home observations. Cases are aged 0–4 years with a medically attended fall injury occurring at home, matched on age and sex with community controls. Children attending hospital for other types of injury will serve as unmatched hospital controls. Matched analyses will use conditional logistic regression to adjust for potential confounding variables. Unmatched analyses will use unconditional logistic regression, adjusted for age, sex, deprivation and distance from hospital in addition to other confounders. Each study requires 496 cases and 1984 controls to detect an OR of 0.7, with 80% power, 5% significance level, a correlation between cases and controls of 0.1 and a range of exposure prevalences.Main outcome measuresFalls on stairs, on one level and from furniture.DiscussionAs the largest in the field to date, these case control studies will adjust for potential confounders, validate measures of exposure and investigate modifiable risk factors for specific falls injury mechanisms. Findings should enhance the evidence base for falls prevention for young children.
Prasugrel is effective and safe for neurointerventional procedures
Authors: Stetler William R , Chaudhary Neeraj , Thompson Byron Gregory , Gemmete Joseph J , Maher Cormac O , Pandey Aditya S 
Published: May 2012

BackgroundClopidogrel bisulfate and aspirin are routinely administered as dual antiplatelet agents for many neurointerventional procedures, especially for intravascular stent placement. Many patients are non-responsive to clopidogrel, either secondary to drug interactions or from variations of cytochrome P450 enzymes. Prasugrel (brand name Effient, Eli Lilly and Company, Indianapolis, IN, USA) is a new antiplatelet agent that has been utilized extensively in patients undergoing cardiovascular procedures but its safety and efficacy during neurointerventional procedures have not been evaluated.ObjectiveTo examine whether prasugrel is a safe and effective alternative to clopidogrel for neurointerventional procedures, especially in those patients who are either non-responders or allergic to clopidogrel.MethodsThe medical records of all patients undergoing neurointerventional procedures at our institution who received prasugrel between January 2009 and July 2011 were retrospectively reviewed. A systematic chart review was performed and the following data were recorded: demographics, aneurysm location, endovascular techniques, peri- and post-procedural complications, hemorrhagic complications, clinical outcome and angiographic outcome.Results16 patients undergoing neurointerventional procedures received prasugrel over a 2 year interval. All patients who had follow-up studies of P2Y12 inhibition had immediate therapeutic response to prasugrel. There were no complications related to ischemic or intracranial hemorrhage.ConclusionPrasugrel is a viable alternative to clopidogrel for patients undergoing neurointerventional procedures who are non-responders to clopidogrel. Further study is needed to evaluate the safety, efficacy and cost-effectiveness of prasugrel compared with clopidogrel for patients undergoing neurointerventional procedures.
P126 Improving the management of antenatal women with positive syphilis serology within a genitourinary medicine service
Authors: Patel S , Aroney R , Bird M , Rice P , Hay P 
Published: May 2012

BackgroundCongenital syphilis (STS) can be prevented through antenatal screening and treatment. The true incidence of congenital STS is unknown; ∼10 cases/yr have been reported to the HPA by GUM clinics (probably reflects 30%–50% of cases). An audit at our centre (∼5000 deliveries/yr) in 2004, highlighted suboptimal management of pregnant women with positive STS serology.MethodsA pathway has subsequently been developed and we report our findings since June 2004. Antenatal screening results are reviewed by a multidisciplinary team (MDT: virology, GU, antenatal, paediatric) experienced in the management of syphilis. Our GU team manages all pregnant women with positive serology who undergo full evaluation (incl. an STI check), further tests or treatment as necessary and follow-up of the neonate.Results123 referrals (108 pregnant women with positive STS serology) were received by the GU department from June 2004 to December 2009. Of these referrals, 36% (44) had STS (1 primary, 1 secondary, 6 early latent, 36 late latent), 37% (46) were previously treated, and 27% (33) were biological false positives. Those with untreated STS—median age 30 (IQR 26–35); ethnicity: 45% (20) black African, 23% (10) black Caribbean, 18% (8) white other, 9% (4) Asian, 2% (1) black British, 2% (1) white British. All women attended the GU clinic for treatment and follow-up; with one exception who remained untreated (late latent STS) and was repatriated prior to delivery to Uganda in 2004. GU screens identified Chlamydia (3), TV (2), warts (2), herpes (1), BV (6), thrush (5) and hepatitis B (4) in those with untreated STS.DiscussionOur innovative MDT approach where each positive antenatal STS result is managed by our GU team has resulted in prompt treatment of untreated cases, identification of untreated STIs, and no reported cases of congenital STS. Our effective robust pathway includes standardised communication with all relevant teams and we encourage its use nationally.
P136 Sexual health services have a key role in the diagnosis and initial assessment of hepatitis C
Authors: Donson H , Rogstad K E , Campbell L , Raza M , Cope A 
Published: May 2012

BackgroundHepatitis C is a major cause of liver disease, cirrhosis and liver cancer but is increasingly amenable to treatment. Sexual health services often have unique access to test patients within risk groups.AimTo assess the role of sexual health services in diagnosis and initial assessment of Hepatitis C (HCV).MethodPatients diagnosed with HCV at a large inner city sexual health service from 1 July 2009 to 30 June 2011 were identified along with a control group of negative patients.Results4430 HCV tests were performed on 3395 patients. 53 (1.56%) were HCV antibody positive of which 26 (49%) were PCR positive with a detectable viral load. Where genotyping was performed the majority were 3A (50%), 1A (22%) or 1B (22%). The most common reasons for testing were intravenous drug use (64%), men who have sex with men (15%) and sexual intercourse with a known IVDU (9%). 27 patients were referred to HCV services of which only 18 (67%) attended. The main reasons documented for testing within the control group were related to the patient's country of origin (32%), country of origin of a sexual partner (24%) or for men who have sex with men (19%). 34 countries were given as potential sources of increased risk, however only nine patients or sexual partners of patients originated from the three countries of highest HCV prevalence.ConclusionSexual health services provide a unique opportunity for HCV screening in those who may otherwise not be tested. Standardisation is required to clarify who constitutes high risk particularly related to country of origin of patient or sexual partner. Initial assessment of patients diagnosed with HCV in genitourinary medicine clinics may lead to more efficient and cost effective patient care.
P145 Audit of the use of microscopy in heterosexual male patients diagnosed with non-specific urethritis and chlamydial urethritis
Authors: Cucinella A , Priestley C J F 
Published: May 2012

BackgroundIn 2006 BASHH guidelines for STI testing stated that there is no need to do a urethral smear in asymptomatic men. However there are concerns that this could result in delayed treatment of Chlamydia, or failure to diagnose an STI (eg,Mycoplasma genitalium).Aims(1) To ascertain the female pathology associated with NGU. (2) To ascertain the number of women with significant pathology, (Chlamydia or PID) who attended only as a result of partner notification by a man with asymptomatic NGU. (3) To quantify the number of asymptomatic men who would have delayed treatment for chlamydia without immediate microscopy.MethodsNote review of heterosexual males and their female contacts with NSU (100) and Chlamydia (50).Results74% of 100 men treated for NSU were asymptomatic. Of these, 38 attended as a contact of infection and would have been treated anyway without microscopy. Of the remaining 36, 3 female partners had uncomplicated chlamydia and 3 PID but had not sought help for pelvic pain prior to their attendance in GUM. Overall, 70% of partners of men with NSU had significant pathology: Diagnoses in female partners of men with NSU Non-specific PID 35 Chlamydial PID 4 Uncomplicated Chlamydia 6 Non-specific cervicitis 9 Epidemiological treatment 46 of 50 men treated for Chlamydia 42% were asymptomatic. 28 (56%) had evidence of urethritis and a further 11 (22%) without pus on microscopy had noticeable threads in their urine. 47 attended prior to or with their partner, and 15 (30%) were treated at their initial visit due to immediate microscopy. These patients would have had to have been recalled for treatment.ConclusionsIn our cohort, 70% of female partners of men with NSU had significant pathology. 6/36 (17%) might not have been treated had they not attended as a contact of NSU. Microscopy can result in earlier treatment of asymptomatic men with Chlamydia due to immediate diagnosis of NGU, and may still be of value in GUM clinics.