bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Case Reports of Neuroinvasive West Nile Virus Infection in the Critical Care Unit
Authors: Flores Anticona Edgardo M. , Zainah Hadeel , Ouellette Daniel R. , Johnson Laura E.
Published: August 2012

We describe the clinical course of two cases of neuroinvasive West Nile Virus (WNV) infection in the critical care unit. The first case is a 70-year-old man who presented during summer with mental status changes. Cerebrospinal fluid (CSF) analysis revealed pleocytosis with lymphocyte predominance. WNV serology was positive in the CSF. His condition worsened with development of left-sided weakness and deterioration of mental status requiring intensive care. The patient gradually improved and was discharged with residual left-sided weakness and near-complete improvement in his mental status. The second case is an 81-year-old man who presented with mental status changes, fever, lower extremity weakness, and difficulty in walking. CSF analysis showed pleocytosis with neutrophil predominance. WNV serology was also positive in CSF. During the hospital stay his mentation worsened, eventually requiring intubation for airway protection and critical care support. The patient gradually improved and was discharged with residual upper and lower extremity paresis. Neuroinvasive WNV infection can lead to significant morbidity, especially in the elderly. These cases should be suspected in patients with antecedent outdoor activities during summer. It is important for critical care providers to be aware of and maintain a high clinical suspicion of this disease process.
The Impact of Interferon Lambda 3 Gene Polymorphism on Natural Course and Treatment of Hepatitis C
Authors: Bellanti F. , Vendemiale G. , Altomare E. , Serviddio G.
Published: August 2012

Host genetic factors may predict the outcome and treatment response in hepatitis C virus (HCV) infection. Very recently, three landmark genome-wide association studies identified single nucleotide polymorphisms near the interleukin 28B (IL28B) region which were more frequent in responders to treatment. IL28B encodes interferon (IFN)λ3, a type III IFN involved in host antiviral immunity. Favourable variants of the two most widely studied IL28B polymorphisms, rs12979860 and rs8099917, are strong pretreatment predictors of early viral clearance and sustained viral response in patients with genotype 1 HCV infection. Further investigations have implicated IL28B in the development of chronic HCV infection versus spontaneous resolution of acute infection and suggest that IL28B may be a key factor involved in host immunity against HCV. This paper presents an overview about the biological activity and clinical applications of IL28B, summarizing the available data on its impact on HCV infection. Moreover, the potential usefulness of IFNλin the treatment and natural history of this disease is also discussed.
Effectiveness of Context-Aware Character Input Method for Mobile Phone Based on Artificial Neural Network
Authors: Matsuhara Masafumi , Suzuki Satoshi
Published: August 2012

Opportunities and needs are increasing to input Japanese sentences on mobile phones since performance of mobile phones is improving. Applications like E-mail, Web search, and so on are widely used on mobile phones now. We need to input Japanese sentences using only 12 keys on mobile phones. We have proposed a method to input Japanese sentences on mobile phones quickly and easily. We call this method number-Kanjitranslation method. The number string inputted by a user is translated intoKanji-Kanamixed sentence in our proposed method. Number string toKanastring is a one-to-many mapping. Therefore, it is difficult to translate a number string into the correct sentence intended by the user. The proposed context-aware mapping method is able to disambiguate a number string by artificial neural network (ANN). The system is able to translate number segments into the intended words because the system becomes aware of the correspondence of number segments with Japanese words through learning by ANN. The system does not need a dictionary. We also show the effectiveness of our proposed method for practical use by the result of the evaluation experiment in Twitter data.
Bicuspid Aortic Valve and Thoracic Aortic Aneurysm: Three Patient Populations, Two Disease Phenotypes, and One Shared Genotype
Authors: Hinton Robert B.
Published: August 2012

Bicuspid aortic valve (BAV) and thoracic aortic aneurysm (TAA) are two discrete cardiovascular phenotypes characterized by latent progressive disease states. There is a clear association between BAV and TAA; however the nature and extent of this relationship is unclear. There are both distinct and overlapping developmental pathways that have been established to contribute to the formation of the aortic valve and the aortic root, and the mature anatomy of these different tissue types is intimately intertwined. Likewise, human genetics studies have established apparently separate and common contributions to these clinical phenotypes, suggesting complex inheritance and a shared genetic basis and translating 3 patient populations, namely, BAV, TAA, or both, into a common but diverse etiology. A better understanding of the BAV-TAA association will provide an opportunity to leverage molecular information to modify clinical care through more sophisticated diagnostic testing, improved counseling, and ultimately new pharmacologic therapies.
Necrolytic Migratory Erythema as the First Manifestation of Glucagonoma
Authors: Afsharfard Abolfazl , Atqiaee Khashayar , Lotfollahzadeh Saran , Alborzi Majid , Derakhshanfar Amir
Published: August 2012

Necrolytic migratory erythma (NME) as a rare skin disorder that can affected Perineum, distal extremities, lower abdomen and face are the most commonly affected sites.It can be as a part of Glucagonoma syndrome that is defined as an association of glucagonoma with NME, hyperglucagonemia, glucose intolerance, anemia and weight loss. Here, Authors describe a woman admitted to the dermatology ward with NME which was later found to be associated with glucagonoma and multiple hepatic lesions.
Early Adolescents and Substance Use
Authors: Pavarin Raimondo Maria , Consonni Dario
Published: August 2012

1300 students (54.3% girls) 13–16 years old were interviewed in the urban area of Bologna during 2010. Random effect multiple logistic regression models were used. Results show a reciprocal relationship between alcohol use, tobacco, and cannabis. Most users were offered cannabis, began using at 14 years of age, and do not believe using is very dangerous. They live with only one parent, have more than 50 euros of spending money per month, and abuse alcohol, abuse that increases relative to the intensity of cigarette smoking. Legal/illegal dichotomy seems to overturn, where alcohol becomes a “drug” and the use of tobacco, similar to other drugs, is motivated as a solution to reduce anxiety, combat boredom, relax, and to ease loneliness.
Synthesis, Characterization, and Antimicrobial Activity of Methyl‐2‐aminopyridine‐4‐carboxylate Derivatives
Authors: Nagashree S. , Mallu P. , Mallesha L. , Bindya S.
Published: August 2012

A series of methyl‐2‐aminopyridine‐4‐carboxylate derivatives, 3a–f, were synthesized in order to determine their in vitro antimicrobial activity. The chemical structures of the synthesized compounds were confirmed by elemental analyses, FT‐IR, and 1H NMR spectral studies. Among the synthesized compounds, 3c and 3d showed good antimicrobial activity compared to other compounds in the series.
Antihyperlipidemic Potential of Polyphenol and Glycoside Rich Nerium oleander Flower against Triton WR‐1339‐Induced Hyperlipidemia in Experimental Sprague Dawley Rats
Authors: Gayathri V. , Ananthi S. , Vasanthi Hannah R.
Published: August 2012

Nerium oleander Linn. (NO), an evergreen cardiac glycoside‐rich shrub is used as folklore medicine in China to treat many diseases. It exhibits a wide spectrum of bioactivities but there were not much scientific reports on the bioactivity of N. oleander flowers. In the present study, we have evaluated the toxicity profile of the 50% hydroethanolic extracts of Nerium oleander flowers (ENO) using in vitro brine shrimp lethality assay and MTT cytotoxicity assay and in vivo acute toxicity test as per the OECD guidelines. The antihyperlipidemic activity of the ENO was also studied using Triton WR‐1339‐induced hyperlipemic rats and compared with standard Atorvastatin. In vitro brine shrimp, MTT cytotoxic assay, and in vivo acute toxicity assays showed a wide safety margin which has been evidenced through its lethal concentration (LC50: 795.46 μg/mL) and growth inhibition (GI50: 993.60 μg/ml) values. Plasma lipids and lipoproteins were significantly elevated by the intraperitoneal injection of Triton WR 1339 in hyperlipidemic rats at 6th and 24th hour. ENO pretreatment showed a significant ameliorative action on elevated lipids and lipoproteins in a dose‐dependent manner when compared to standard. Altogether, the results prove that Nerium oleander flowers are not toxic at the tested doses and exhibit antilipimic activity.
Functionalization of Carboxylated Multi‐Wall Nanotubes with Derivatives of N1‐(11H‐Indeno[1,2‐b]quinoxalin‐11‐ylidene)benzene‐1,4‐diamine
Authors: Azizian Javad , Zomorodbakhsh Shahab , Entezari Mahdieh , Anaraki-Ardakani Hossein
Published: August 2012

Quinoxaline derivatives are compounds with pharmaceutical applications. In this study, derivatives of N1‐(11H‐indeno[1,2‐b]quinoxalin‐11‐ylidene)benzene‐1,4‐diamine were synthesized and attached to carboxylated multi‐wall nanotubes (MWNT–COOH). Functionalized carbon nanotubes were characterized by scanning electron microscopy (SEM) to study the shape of structures, transmission electron microscopy (TEM), fast Fourier transform infrared (FT‐IR), Raman spectroscopy, and elemental analysis.
Role for MicroRNA-21 in Atrial Profibrillatory Fibrotic Remodeling Associated With Experimental Postinfarction Heart Failure
Authors: Cardin Sophie , Guasch Eduard , Luo Xiaobin , Naud Patrice , Le Quang Khaï , Shi YanFen , Tardif Jean-Claude , Comtois Philippe , Nattel Stanley
Published: August 2012

Background—

Atrial tissue fibrosis is often an important component of the atrial fibrillation (AF) substrate. Small noncoding microRNAs are important mediators in many cardiac remodeling paradigms. MicroRNA-21 (miR-21) has been suggested to be important in ventricular fibrotic remodeling by downregulating Sprouty-1, a protein that suppresses fibroblast proliferation. The present study examined the potential role of miR-21 in the atrial AF substrate resulting from experimental heart failure after myocardial infarction (MI).

Methods and Results—

Large MIs (based on echocardiographic left ventricular wall motion score index) were created by left anterior descending coronary artery ligation in rats. Changes induced by MI versus sham controls were first characterized with echocardiography, histology, biochemistry, and in vivo electrophysiology. Additional MI rats were then randomized to receive anti–miR-21 (KD21) or scrambled control sequence (Scr21) injections into the left atrial myocardium. Progressive left ventricular enlargement, hypocontractility, left atrial dilation, fibrosis, refractoriness prolongation, and AF promotion occurred in MI rats versus sham controls. Atrial tissues of MI rats showed upregulation of miR-21, along with dysregulation of the target genes Sprouty-1, collagen-1, and collagen-3. KD21 treatment reduced atrial miR-21 expression levels in MI rats to values in sham rats, decreased AF duration from 417 (69–1595; median [Q1–Q3]) seconds to 3 (2–16) seconds (8 weeks after MI;
P
<0.05), and reduced atrial fibrous tissue content from 14.4±1.8% (mean±SEM) to 4.9±1.2% (8 weeks after MI;
P
<0.05) versus Scr21 controls.

Conclusions—

MI-induced heart failure leads to AF-promoting atrial remodeling in rats. Atrial miR-21 knockdown suppresses atrial fibrosis and AF promotion, implicating miR-21 as an important signaling molecule for the AF substrate and pointing to miR-21 as a potential target for molecular interventions designed to prevent AF.
Circulation
Editors' Picks
Authors:   The Editors
Published: August 2012

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the most read manuscripts published on the topic of congenital heart disease within the last year.
Impact of Different ENSO Regimes on Southwest Pacific Tropical Cyclones
Authors: Chand Savin S. , L. McBride John , Tory Kevin J. , Wheeler Matthew C. , Walsh Kevin J. E.
Published: August 2012

The influence of different types of ENSO on tropical cyclone (TC) interannual variability in the central southwest Pacific region (5°–25°S, 170°E–170°W) is investigated. Using empirical orthogonal function analysis and an agglomerative hierarchical clustering of early tropical cyclone season Pacific sea surface temperature, years are classified into four separate regimes (i.e., canonical El Niño, canonical La Niña, positive-neutral, and negative-neutral) for the period between 1970 and 2009. These regimes are found to have a large impact on TC genesis over the central southwest Pacific region. Both the canonical El Niño and the positive-neutral years have increased numbers of cyclones, with an average of 4.3 yr−1 for positive-neutral and 4 yr−1 for canonical El Niño. In contrast, during a La Niña and negative-neutral events, substantially fewer TCs (averages of ~2.2 and 2.4 yr−1, respectively) are observed in the central southwest Pacific. The enhancement of TC numbers in both canonical El Niño and positive-neutral years is associated with the extension of favorable low-level cyclonic relative vorticity, and low vertical wind shear eastward across the date line. Relative humidity and SST are also very conducive for genesis in this region during canonical El Niño and positive-neutral events. The patterns are quite different, however, with the favorable conditions concentrated in the date line region for the positive-neutral, as compared with conditions farther eastward for the canonical El Niño regime. A significant result of the study is the demonstration that ENSO-neutral events can be objectively clustered into two separate regimes, each with very different impacts on TC genesis.
Sensitivity of Western Boundary Transport at the Mean North Equatorial Current Bifurcation Latitude to Wind Forcing
Authors: Zhang Xuebin , Cornuelle Bruce , Roemmich Dean
Published: August 2012

The bifurcation of the North Equatorial Current (NEC) plays an important role in the heat and water mass exchanges between the tropical and subtropical gyres in the Pacific Ocean. The variability of western boundary transport (WBT) east of the Philippine coast at the mean NEC bifurcation latitude (12°N) is examined here. A tropical Pacific regional model is set up based on the Massachusetts Institute of Technology general circulation model and its adjoint, which calculates the sensitivities of a defined meridional transport to atmospheric forcing fields and ocean state going backward in time. The adjoint-derived sensitivity of the WBT at the mean NEC bifurcation latitude to surface wind stress is dominated by curl-like patterns that are located farther eastward and southward with increasing time lag. The temporal evolution of the adjoint sensitivity of the WBT to wind stress resembles wind-forced Rossby wave dynamics but propagating with speeds determined by the background stratification and current, suggesting that wind-forced Rossby waves are the underlying mechanism. Interannual-to-decadal variations of the WBT can be hindcast well by multiplying the adjoint sensitivity and the time-lagged wind stress over the whole model domain and summing over time lags. The analysis agrees with previous findings that surface wind stress (especially zonal wind stress in the western subtropical Pacific) largely determines the WBT east of the Philippines, and with a time lag based on Rossby wave propagation. This adjoint sensitivity study quantifies the contribution of wind stress at all latitudes and longitudes and provides a novel perspective to understand the relationship between the WBT and wind forcing over the Pacific Ocean.
‘No matter how, Jogendranath had to be defeated’: The Scheduled Castes Federation and the making of partition in Bengal, 1945–1947
Authors: Sen Dwaipayan
Published: August 2012

This article offers an explanation for the defeat of Jogendranath Mandal and the Scheduled Castes Federation in the context of partition-era Bengal. Departing from analyses of Scheduled Caste integration, it explores the Federation’s efforts at creating an independent political platform through a strategic alliance with the Muslim League. To this end, it traces Mandal’s and the Federation’s trajectory through the following key moments: the anti-Poona Pact day and Day of Direct Action, the 1946 election, Dr B.R. Ambedkar’s election to the Constituent Assembly, the Calcutta and East Bengal riots, Mandal’s nomination to the Interim Government and the agitation against Partition. In so doing, it tries to show how the Federation’s defeat in Bengal was at least in part a consequence of the Congress’ efforts to engineer its marginalisation, as well as the Congress’ and Hindu Mahasabha’s agitation for the Partition of that province. The Hindu majoritarian impulse that led to the Partition in Bengal thus crippled the Federation’s struggle for Dalit political autonomy.
Relationship Power, Control, and Dating Violence Among Latina Girls
Authors: Lopez Vera , Chesney-Lind Meda , Foley Julia
Published: August 2012

We drew on the theory of gender and power and grounded theory methodology to explore how 18 Latina girls conceptualized power and control within their heterosexual dating relationships. Our findings indicate that boys/men used a number of strategies to control girls, including: regulating appearances and behaviors; cheating and threatening to cheat; and physical and sexual violence. Girls used a variety of strategies to resist these attempts to control them, including: lying, flirting, and cheating; reactive violence; breaking up; and maintaining emotional distance. Girls attempted to subvert boys’ attempts to control them; however, these attempts were not always successful given the constraints of gender that adolescent females must negotiate.
Intersectionality, subjectivity, collectivity and the union: a study of the ‘locked-out’ hotel workers in Toronto
Authors: Soni-Sinha Urvashi
Published: August 2012

The study uses narrative analysis to understand the workers discursive constructions of their classed, gendered and racialized subjective identities and their investments into the collectivity of the union in the context of the lock-out. It goes beyond the Marxian analysis and uses poststructural feminist analysis to understand how the intersectional subjective identities are constituted and their interrelationship to the investments in and constitution of collectivities in the context of industrial action. The study is based on participant observation and interviews of hotel workers in the food and beverage section of a hotel in Toronto, who were locked-out in 2007, and of other workers on the picket line supporting the locked-out workers. These workers are members of UNITE HERE-Local 75 (Now HERE-Local 75), who had been in the process of renewal of their contracts at the time. I would argue that the intersectional subjectivities of the hotel workers and their investments in the collectivity of the union are fluid and relate to their pursuit of material and/or symbolic security through search for an identity as a unionized, active worker or an identity which is secure irrespective of the union.
Stage-Specific Gender Differences in Cognitive and Neuropsychiatric Manifestations of Vascular Dementia
Authors: Xing Yi , Wei Cuibai , Chu Changbiao , Zhou Aihong , Li Fang , Wu Liyong , Song Haiqing , Zuo Xiumei , Wang Fen , Qin Wei , Li Dan , Tang Yi , Jia Xiang-Fei , Jia Jianping
Published: August 2012

Studies on gender differences in the clinical manifestations of vascular dementia (VaD) are still lacking. In the present study, gender comparisons of cognitive and neuropsychiatric profiles were conducted separately for mild and moderate-to-severe VaD in a total of 467 patients with VaD. There were no significant gender differences in cognitive manifestations, except that females performed better on immediate verbal recall than males in mild stage. Women were more likely to exhibit delusions (15.5% vs 7.4%), hallucinations (9.5% vs 3.4%), and depression (43.1% vs 27.3%) in mild stage. The predominance of male patients was observed in apathy at moderate-to-severe stage (50.5% vs 34.8%). To conclude, gender differences existed in neuropsychiatric symptoms of VaD and were especially pronounced in mild stage. Delusions, hallucinations, and depression were more prevalent in females in mild VaD, with the male predominance only in apathy in the later stage.
Small interfering RNA-producing loci in the ancient parasitic eukaryote Trypanosoma brucei
Authors: Tschudi Christian , Shi Huafang , Franklin Joseph B , Ullu Elisabetta
Published: August 2012

Background

At the core of the RNA interference (RNAi) pathway in Trypanosoma brucei is a single Argonaute protein, Tb AGO1, with an established role in controlling retroposon and repeat transcripts. Recent evidence from higher eukaryotes suggests that a variety of genomic sequences with the potential to produce double-stranded RNA are sources for small interfering RNAs (siRNAs).

Results

To test whether such endogenous siRNAs are present in T. brucei and to probe the individual role of the two Dicer-like enzymes, we affinity purified Tb AGO1 from wild-type procyclic trypanosomes, as well as from cells deficient in the cytoplasmic (Tb DCL1) or nuclear (Tb DCL2) Dicer, and subjected the bound RNAs to Illumina high-throughput sequencing. In wild-type cells the majority of reads originated from two classes of retroposons. We also considerably expanded the repertoire of trypanosome siRNAs to encompass a family of 147-bp satellite-like repeats, many of the regions where RNA polymerase II transcription converges, large inverted repeats and two pseudogenes. Production of these newly described siRNAs is strictly dependent on the nuclear DCL2. Notably, our data indicate that putative centromeric regions, excluding the CIR147 repeats, are not a significant source for endogenous siRNAs.

Conclusions

Our data suggest that endogenous RNAi targets may be as evolutionarily old as the mechanism itself.
Leptospira spp. strain identification by MALDI TOF MS is an equivalent tool to 16S rRNA gene sequencing and multi locus sequence typing (MLST)
Authors: Rettinger Anna , Krupka Inke , Grünwald Karola , Dyachenko Viktor , Fingerle Volker , Konrad Regina , Raschel Heribert , Busch Ulrich , Sing Andreas , Straubinger Reinhard K , Huber Ingrid
Published: August 2012

Background

In this study mass spectrometry was used for evaluating extracted leptospiral protein samples and results were compared with molecular typing methods. For this, an extraction protocol for Leptospira spp. was independently established in two separate laboratories. Reference spectra were created with 28 leptospiral strains, including pathogenic, non-pathogenic and intermediate strains. This set of spectra was then evaluated on the basis of measurements with well-defined, cultured leptospiral strains and with 16 field isolates of veterinary or human origin. To verify discriminating peaks for the applied pathogenic strains, statistical analysis of the protein spectra was performed using the software tool ClinProTools. In addition, a dendrogram of the reference spectra was compared with phylogenetic trees of the 16S rRNA gene sequences and multi locus sequence typing (MLST) analysis.

Results

Defined and reproducible protein spectra using MALDI-TOF MS were obtained for all leptospiral strains. Evaluation of the newly-built reference spectra database allowed reproducible identification at the species level for the defined leptospiral strains and the field isolates. Statistical analysis of three pathogenic genomospecies revealed peak differences at the species level and for certain serovars analyzed in this study. Specific peak patterns were reproducibly detected for the serovars Tarassovi, Saxkoebing, Pomona, Copenhageni, Australis, Icterohaemorrhagiae and Grippotyphosa. Analysis of the dendrograms of the MLST data, the 16S rRNA sequencing, and the MALDI-TOF MS reference spectra showed comparable clustering.

Conclusions

MALDI-TOF MS analysis is a fast and reliable method for species identification, although Leptospira organisms need to be produced in a time-consuming culture process. All leptospiral strains were identified, at least at the species level, using our described extraction protocol. Statistical analysis of the three genomospecies L. borgpetersenii, L. interrogans and L. kirschneri revealed distinctive, reproducible differentiating peaks for seven leptospiral strains which represent seven serovars. Results obtained by MALDI-TOF MS were confirmed by MLST and 16S rRNA gene sequencing.
Cross-cultural adaptation and validation of a Bengali version of the modified fibromyalgia impact questionnaire
Authors: Muquith Mohammed A , Islam Md Nazrul , Haq Syed A , ten Klooster Peter M , Rasker Johannes J , Yunus Muhammad B
Published: August 2012

Background

Currently, no validated instruments are available to measure the health status of Bangladeshi patients with fibromyalgia (FM). The aims of this study were to cross-culturally adapt the modified Fibromyalgia Impact Questionnaire (FIQ) into Bengali (B-FIQ) and to test its validity and reliability in Bangladeshi patients with FM.

Methods

The FIQ was translated following cross-cultural adaptation guidelines and pretested in 30 female patients with FM. Next, the adapted B-FIQ was physician-administered to 102 consecutive female FM patients together with the Health Assessment Questionnaire (HAQ), selected subscales of the SF-36, and visual analog scales for current clinical symptoms. A tender point count (TPC) was performed by an experienced rheumatologist. Forty randomly selected patients completed the B-FIQ again after 7 days. Two control groups of 50 healthy people and 50 rheumatoid arthritis (RA) patients also completed the B-FIQ.

Results

For the final B-FIQ, five physical function sub-items were replaced with culturally appropriate equivalents. Internal consistency was adequate for both the 11-item physical function subscale (α = 0.73) and the total scale (α = 0.83). With exception of the physical function subscale, expected correlations were generally observed between the B-FIQ items and selected subscales of the SF-36, HAQ, clinical symptoms, and TPC. The B-FIQ was able to discriminate between FM patients and healthy controls and between FM patients and RA patients. Test-retest reliability was adequate for the physical function subscale (r = 0.86) and individual items (r = 0.73-0.86), except anxiety (r = 0.27) and morning tiredness (r = 0.64).

Conclusion

This study supports the reliability and validity of the B-FIQ as a measure of functional disability and health status in Bangladeshi women with FM.
Rheumatoid arthritis and the incidence of influenza and influenza-related complications: a retrospective cohort study
Authors: Blumentals William A , Arreglado Anna , Napalkov Pavel , Toovey Stephen
Published: August 2012

Background

Patients with rheumatoid arthritis (RA) are known to be at increased risk of infection, particularly if they are taking drugs with immunomodulatory effects. There is a need for more information on the risk of influenza in patients with RA.

Methods

A retrospective cohort study was carried out using data gathered from a large US commercial health insurance database (Thomson Reuters Medstat MarketScan) from 1 January 2000 to 31 December 2007. Patients were ≥18 years of age, with at least two RA claims diagnoses. The database was scanned for incidence of seasonal influenza and its complications on or up to 30 days after an influenza diagnosis in RA patients and matched controls. Other factors accounted for included medical conditions, use of disease-modifying anti-rheumatic drugs (DMARDs), use of biological agents, influenza vaccination and high- or low-dose corticosteroids. Incidence rate ratios (IRRs) were calculated for influenza and its complications in patients with RA.

Results

46,030 patients with RA and a matching number of controls had a median age of 57 years. The incidence of influenza was higher in RA patients than in controls (409.33 vs 306.12 cases per 100,000 patient-years), and there was a 2.75-fold increase in incidence of complications in RA. Presence or absence of DMARDs or biologics had no significant effect. The adjusted IRR of influenza was statistically significant in patients aged 60–69 years, and especially among men. A significantly increased rate of influenza complications was observed in women and in both genders combined (but not in men only) when all age groups were combined. In general, the risk of influenza complications was similar in RA patients not receiving DMARDs or biologics to that in all RA patients. Pneumonia rates were significantly higher in women with RA. Rates of stroke/myocardial infarction (MI) were higher in men, although statistical significance was borderline.

Conclusions

RA is associated with increased incidence of seasonal influenza and its complications. Gender- and age-specific subgroup data indicate that women generally have a greater rate of complications than men, but that men primarily have an increased rate of stroke and MI complications. Concomitant DMARD or biological use appears not to significantly affect the rate of influenza or its complications.
Harpalycin 2 inhibits the enzymatic and platelet aggregation activities of PrTX-III, a D49 phospholipase A2 from Bothrops pirajai venom
Authors: Ximenes Rafael M , Alves Renata S , Pereira Ticiana P , Araújo Renata M , Silveira Edilberto R , Rabello Marcelo M , Hernandes Marcelo Z , Soares Veronica C G , Bristot Daniel , Pires Camila L , Toyama Daniela O , Gaeta Henrique H , Monteiro Helena S A , Toyama Marcos H
Published: August 2012

Background

Harpalycin 2 (HP-2) is an isoflavone isolated from the leaves of Harpalyce brasiliana Benth., a snakeroot found in northeast region of Brazil and used in folk medicine to treat snakebite. Its leaves are said to be anti-inflammatory. Secretory phospholipases A2 are important toxins found in snake venom and are structurally related to those found in inflammatory conditions in mammals, as in arthritis and atherosclerosis, and for this reason can be valuable tools for searching new anti-phospholipase A2 drugs.

Methods

HP-2 and piratoxin-III (PrTX-III) were purified through chromatographic techniques. The effect of HP-2 in the enzymatic activity of PrTX-III was carried out using 4-nitro-3-octanoyloxy-benzoic acid as the substrate. PrTX-III induced platelet aggregation was inhibited by HP-2 when compared to aristolochic acid and p-bromophenacyl bromide (p-BPB). In an attempt to elucidate how HP-2 interacts with PrTX-III, mass spectrometry, circular dichroism and intrinsic fluorescence analysis were performed. Docking scores of the ligands (HP-2, aristolochic acid and p-BPB) using PrTX-III as target were also calculated.

Results

HP-2 inhibited the enzymatic activity of PrTX-III (IC50 11.34 ± 0.28 μg/mL) although it did not form a stable chemical complex in the active site, since mass spectrometry measurements showed no difference between native (13,837.34 Da) and HP-2 treated PrTX-III (13,856.12 Da). A structural analysis of PrTX-III after treatment with HP-2 showed a decrease in dimerization and a slight protein unfolding. In the platelet aggregation assay, HP-2 previously incubated with PrTX-III inhibited the aggregation when compared with untreated protein. PrTX-III chemical treated with aristolochic acid and p-BPB, two standard PLA2 inhibitors, showed low inhibitory effects when compared with the HP-2 treatment. Docking scores corroborated these results, showing higher affinity of HP-2 for the PrTX-III target (PDB code: 1GMZ) than aristolochic acid and p-BPB. HP-2 previous incubated with the platelets inhibits the aggregation induced by untreated PrTX-III as well as arachidonic acid.

Conclusion

HP-2 changes the structure of PrTX-III, inhibiting the enzymatic activity of this enzyme. In addition, PrTX-III platelet aggregant activity was inhibited by treatment with HP-2, p-BPB and aristolochic acid, and these results were corroborated by docking scores.
Characterization of CDKN2A(p16) methylation and impact in colorectal cancer: systematic analysis using pyrosequencing
Authors: Bihl Michel P , Foerster Anja , Lugli Alessandro , Zlobec Inti
Published: August 2012

Background

The aim of this study is to analyse CDKN2A methylation using pyrosequencing on a large cohort of colorectal cancers and corresponding non-neoplastic tissues. In a second step, the effect of methylation on clinical outcome is addressed.

Methods

Primary colorectal cancers and matched non-neoplastic tissues from 432 patients underwent CDKN2A methylation analysis by pyrosequencing (PyroMarkQ96). Methylation was then related to clinical outcome, microsatellite instability (MSI), and BRAF and KRAS mutation. Different amplification conditions (35 to 50 PCR cycles) using a range of 0-100% methylated DNA were tested.

Results

Background methylation was at most 10% with ≥35 PCR cycles. Correlation of observed and expected values was high, even at low methylation levels (0.02%, 0.6%, 2%). Accuracy of detection was optimal with 45 PCR cycles. Methylation in normal mucosa ranged from 0 to >90% in some cases. Based on the maximum value of 10% background, positivity was defined as a ≥20% difference in methylation between tumor and normal tissue, which occurred in 87 cases. CDKN2A methylation positivity was associated with MSI (p = 0.025), BRAF mutation (p < 0.0001), higher tumor grade (p < 0.0001), mucinous histology (p = 0.0209) but not with KRAS mutation. CDKN2A methylation had an independent adverse effect (p = 0.0058) on prognosis.

Conclusion

The non-negligible CDKN2A methylation of normal colorectal mucosa may confound the assessment of tumor-specific hypermethylation, suggesting that corresponding non-neoplastic tissue should be used as a control. CDKN2A methylation is robustly detected by pyrosequencing, even at low levels, suggesting that this unfavorable prognostic biomarker warrants investigation in prospective studies.
Aerobic capacity and disease activity in children, adolescents and young adults with juvenile idiopathic arthritis (JIA)
Authors: van Pelt Philomien A , Takken Tim , van Brussel Marco , de Witte Inge , Kruize Aike A , Wulffraat Nico M
Published: August 2012

Background

As patients with juvenile idiopathic arthritis (JIA) progress into adulthood, long-term outcome is determined by disease activity, physical and psychosocial development. Decreased aerobic capacity may play a critical role in health-related outcomes in JIA, since it has been linked with cardiovascular morbidity and mortality in late adulthood. The objectives of the current study are to examine the aerobic capacity and its relation to parameters of disease activity in children, adolescents and young adults with JIA.

Methods

Sixty-three patients with JIA (aged 10–27 years) were cross sectional studied regarding their aerobic capacity and correlations were made to demographic, disease-related variables, and medication utilization. in a cross-sectional study group of 63 patients of all subtypes. Patients were divided in three age groups, 10–13 years; 14–17 years and 18–27 years.

Results

Reduced aerobic capacity is found in clinical remission as well as active disease in all subtypes and all age groups. Aerobic capacity is more impaired in active disease shown by DAS 28, JADAS 27, ESR and serum thrombocyte counts. Lower haemoglobin has a negative impact. Long-term used medication including methotrexate and corticosteroids didn’t influence outcome. There is no association with current sports participation.

Conclusion

Reduced aerobic capacity is present in children and adolescents with JIA, both in active disease and in patients with remission. Measures of aerobic capacity may serve as important outcome measure in JIA.
Surgical challenge: endoscopic repair of cerebrospinal fluid leak
Authors: Martín-Martín Carlos , Martínez-Capoccioni Gabriel , Serramito-García Ramón , Espinosa-Restrepo Federico
Published: August 2012

Background

Cerebrospinal fluid leaks (CSF) result from an abnormal communication between the subarachnoid space and the extracranial space. Approximately 90% of CSF leak at the anterior skull base manifests as rhinorrhea and can become life-threatening condition. Endoscopic sinus surgery (ESS) has become a common otolaryngologist procedure. The aim of this article is to consider our experience and to evaluate the outcomes in patients who underwent a purely endoscopic repair of CSF leaks of the anterior skull base.

Findings

Retrospective chart review was performed of all patients surgically treated for CSF leaks presenting to the Section of Nasal and Sinus Disorders at the Service of ENT–Head and Neck Surgery, University Hospital Complex of Santiago de Compostela (CHUS), between 2004 and 2010. A total of 30 patients who underwent repair CSF leak by ESS. The success rate was 93.4% at the first attempt; only two patients (6.6%) required a second surgical procedure, and none of it was necessary to use a craniotomy for closure. Follow-up periods ranged from 4 months to 6 years.

Conclusion

Identifying the size, site, and etiology of the CSF leak remains the most important factor in the surgical success. It is generally accepted that the ESS have made procedures minimally invasive, and CSF leak is now one of its well-established indications with low morbidity and high success rate, with one restriction for fistulas of the posterior wall of the frontal sinus should be repaired in conjunction with open techniques.
Stable expression of promyelocytic leukaemia (PML) protein in telomerase positive MCF7 cells results in alternative lengthening of telomeres phenotype
Authors: Yong Jacklyn W Y , Yeo Xiujun , Khan Md Matiullah , Lee Martin B , Prakash Hande M
Published: August 2012

Background

Cancer cells can employ telomerase or the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. Cancer cells that use the ALT pathway exhibit distinct phenotypes such as heterogeneous telomeres and specialised Promyelocytic leukaemia (PML) nuclear foci called APBs. In our study, we used wild-type PML and a PML mutant, in which the coiled-coil domain is deleted (PML C/C-), to investigate how these proteins can affect telomere maintenance pathways in cancer cells that use either the telomerase or ALT pathway.

Results

Stable over-expression of both types of PML does not affect the telomere maintenance in the ALT cells. We report novel observations in PML over-expressed telomerase-positive MCF7 cells: 1) APBs are detected in telomerase-positive MCF7 cells following over-expression of wild-type PML and 2) rapid telomere elongation is observed in MCF7 cells that stably express either wild-type PML or PML C/C-. We also show that the telomerase activity in MCF7 cells can be affected depending on the type of PML protein over-expressed.

Conclusion

Our data suggests that APBs might not be essential for the ALT pathway as MCF7 cells that do not contain APBs exhibit long telomeres. We propose that wild-type PML can either definitively dominate over telomerase or enhance the activity of telomerase, and PML C/C- can allow for the co-existence of both telomerase and ALT pathways. Our findings add another dimension in the study of telomere maintenance as the expression of PML alone (wild-type or otherwise) is able to change the dynamics of the telomerase pathway.
The Decline of Scientific Research Among Surgeons: A Plea to Swim Against the Tide
Authors: Jackler Robert K
Published: August 2012

During my training, a professor advised that a surgeon needs three things:'good hands, a strong back and a mind uncluttered by unnecessary medical details.' in reality, modern surgery is a highly intellectual craft populated by bright and creative people. At least, they start out that way.
Emergency Surgery Handover: Are We Breaching the Data Protection Act?
Authors: Evans C , Kamocka A , Akbari K , Davis A , Soin B
Published: August 2012

An incident involving the discovery of a computed tomography report in the hospital canteen, identifying the patient's name, age and current location, prompted us to review our emergency surgical data protection practice. This highlighted a lack of training, awareness and implementation of data protection policy. All employees working in the NHS are bound by a legal duty of confidence to protect personal information they may come into contact with during the course of their work. They are responsible for any records they create or use during their duties.
A Guide to Pursuing a Higher Degree in Surgery
Authors: Ansell J , Beamish AJ , Warren N , Donnelly P , Torkington J
Published: August 2012

In 2011 the royal College of Surgeons produced a document entitled FromTheory toTheatre: Overcoming Barriers to Innovation in Surgery that states:'Delivering high quality research is the responsibility of anyone involved in any aspect of surgery.' It highlights that in 2008–2009 surgical research received just 1.5% of the £1.53 billion total governmental spend on medical research. From this came a call for a review of public funding of translational research in surgery and academic departments of surgery in delivering this research. The overall outcome was the creation of 15 recommendations.
The Impact of an Independent Sector Treatment Centre on Basic Surgical Training
Authors: Vaughan-Shaw PG , Chiverton SG , Rew DA , Nichols PH
Published: August 2012

The reorganisation of postgraduate medical training in the UK as a result of Calman reforms, the New Deal and the implementation of the European workingTime regulations (EwTr) has led to a substantial reduction in working hours and a fall in operative experience for surgical trainees. The move of large volumes of minor and intermediate NHS surgical caseload into independently run hospitals and specialist centres (of which the Southampton NHS Treatment Centre, an independent sector treatment centre (ISTC) is a well-established example) has also radically altered the basic surgical training environment. The Southampton ISTC is run on contract by Care UK and is medically staffed by a mix of full-time Care UK employees from the UK and abroad as well as by visiting consultants from University Hospital Southampton NHS foundationTrust (UHSFT).
Post-EWTR: Is the UK Still a Centre of Excellence for Surgical Training?
Authors: Khan MEA , Jordan AD , Strange T , Vig S
Published: August 2012

Surgical training in the UK has undergone a radical transformation over the past few years. The limitation of working hours imposed by the European workingTime regulations (EWTR) and a shorter path to consultancy through Modernising Medical Careers has resulted in a shortening of training hours between qualification and completion of specialist training. Some estimate total training hours have reduced by 50%, from 30,000 in the old system to just 15,000 currently. Quite reasonably, there is concern that the current generation of surgical trainees will be less skilled and less competent than their predecessors.
Emergency action required
Authors: Williams Norman
Published: August 2012

As i enter the second year of my presidency i am aware of a variety of pressing matters that we need to get to grips with as soon as possible. There is none more vital than the provision of emergency general surgery. we know from several reports that all is not well, with a disturbing variation in mortality rate across the country that needs to be addressed. As i have said previously, this situation cannot be laid solely at the door of the surgical profession. Trusts must prioritise patients with these needs and ensure there is sufficient provision of imaging facilities (both interventional and diagnostic), theatre availability, high-dependency unit and intensive care unit beds, senior anaesthetic provision, etc. There needs to be an acceptance that emergency work should have the same priority as elective work.
Use of research-based information by school practitioners and determinants of use: a review of empirical research
Authors: Dagenais Christian , Lysenko Larysa , C. Abrami Philip , M. Bernard Robert , Ramde Jean , Janosz Michel
Published: August 2012

The trend towards using research knowledge to improve policies and practices is on the rise. However, despite considerable effort and notable progress in recent years, it seems that school practitioners continue to make little use of research and it is not clear what conditions would facilitate or obstruct this use. This review focuses exclusively on the available empirical1 research about (a) the use of research by school practitioners and (b) the determinants of use, and identifies future directions for research.
What makes a frame persuasive? Lessons from social identity theory
Authors: Mols Frank
Published: August 2012

We know from the issue-framing literature that politicians ‘frame’ issues strategically to influence public perceptions and preferences. We also know that there are different framing techniques. What remains poorly understood, though, is what makes a frame persuasive. The proposition put forward in this debate paper is that social psychological research into leadership and persuasion can shed light on this question. Social Identity theorists have shown that influential leaders are crafty ‘identity entrepreneurs’, whose social influence derives, not from their ability to frame issues, but from their ability to redefine the collective self-understanding. Just how potent this framing technique is becomes visible when examining the way in which radical opposition leaders call the electorate to arms. As will be shown with the help of two examples, by persuading the electorate of an imminent threat to the collective ‘us’, radical opposition leaders are able to gain considerable control not only over whether an ‘issue’ becomes regarded as a problem requiring a policy-solution, but also over whose evidence/knowledge counts.
Experiences of knowledge brokering for evidence-informed public health policy and practice: three years of the Scottish Collaboration for Public Health Research and Policy
Authors: Frost Helen , Geddes Rosemary , Haw Sally , A. Jackson Caroline , Jepson Ruth , D. Mooney John , Frank John
Published: August 2012

Despite a burgeoning literature on, and widespread interest in, knowledge translation and exchange in public health, few articles provide an account of the actual experiences of knowledge brokerage organisations. The Scottish Collaboration for Public Health Research and Policy (SCPHRP) was formed in 2008 to: identify public health interventions that equitably address major health priorities; foster collaboration between public health stakeholders; and build capacity for collaborative intervention research. We describe the model used by SCPHRP and lessons learnt over three years. Intermediate evaluation of the SCPHRP model provides early indications of success in terms of achieving the organisation's aims.
Bad evidence: the curious case of the government-commissioned review of elective home education in England and how parents exposed its weaknesses
Authors: Stafford Bruce
Published: August 2012

Governments in the United Kingdom have been contracting out policy reviews to individuals. One such review, of elective home education in England, reveals serious shortcomings to this practice. This paper explores the shortcomings – methodological and presentational – with the review, and highlights the fact that there was no governmental mechanism or code against which a commissioned review can be held accountable. Although a select committee held an inquiry, it was home educators using the Freedom of Information Act 2000 and social media who identified weaknesses in the review. The review's recommendations were not implemented, but this was only because a general election was called.