bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral infections of the pubis
Authors: Castronovo C , Lebas E , Nikkels-Tassoudji N , Nikkels A F
Published: February 2012

There are no demographic data published on those with viral infections of the pubis (VIPs). We conducted a two-year prospective study to collect demographic information on patients with VIPs. Data were gathered on age, sex, diagnosis, low (≤10) or high (>10) lesion number, symptoms, how the patient discovered the lesions, localization, lesions beyond the pubis, risk factors, shaving habits, human papillomavirus (HPV) vaccination status and treatment. In a total of 61 patients, molluscum contagiosum (MC) was identified in 71%, condylomata acuminata (CA) in 11%, concomitant MC and CA infections in 11% and herpes simplex virus (HSV) infection in 4.8%. Shaving represented a risk factor for a high lesion number, but not for the extension beyond the pubis. MC, CA and HSV infections affecting the pubis are uncommon and often asymptomatic. As they may represent a hidden source of infection we recommend thorough inspection of the pubis during routine skin examination.
Lichen planus of the external urinary meatus masquerading sexually transmitted disease
Authors: Verma P , Pandhi D
Published: February 2012

Lichen planus is a chronic inflammatory mucocutaneous disorder of the skin including the scalp, the nails, and the oral and genital mucosae. Ocular, oesophageal, bladder, nasal, laryngeal, otic, gastric, and anal involvement has been documented. In this report, we describe a unique case of orogenital lichen planus affecting the external urinary meatus, masquerading as sexually transmitted urethritis and erosive genital disease.
Difficulties experienced in defining the microbial cause of pelvic inflammatory disease
Authors: Taylor-Robinson D , Jensen J S , Svenstrup H , Stacey C M
Published: February 2012

Clinical assessment of women with pelvic pain was a poor indicator of disease seen at laparoscopy. Thus, of 109 women, 22 at laparoscopy had salpingitis, 19 had adhesions without salpingitis, 20 had endometriosis or ovarian pathology and 48 no observable abnormality. In all laparoscopic categories, Ureaplasma spp. and Mycoplasma hominis, but not Mycoplasma genitalium, were at least as common in the cervix/vagina as Chlamydia trachomatis and equally frequent in the endometrium. However , C. trachomatis had the greatest propensity for spread to the Fallopian tubes. Thus, of 28 women who had C. trachomatis organisms in the vagina/cervix, 13 had them in a Fallopian tube (ratio 2.2:1); the ratio was 6:1 for Neisseria gonorrhoeae, 8:1 for M. genitalium, 21:1 for M. hominis and 31:1 for Ureaplasma spp. M. hominis organisms in a large number were detected most often in women with salpingitis. The likelihood of spread of Ureaplasma urealyticum and U. parvum from the lower to the upper genital tract was about the same and they were detected only once each in a tube, which was not inflamed in either case. Multiple bacteria were often detected at a single site, making it difficult to establish the exact cause of disease. However N. gonorrhoeae was considered to be the sole cause of salpingitis in one woman and the primary or equal primary contributor in four others; C. trachomatis was involved in at least 11 women, mostly as the sole cause or as the primary contributor; M. genitalium was considered the cause in one woman and had possible involvement in three others; and M. hominis was a questionable sole cause in one woman and the primary or equal primary contributor in three. Serologically, C. trachomatis was related to adhesions, without salpingitis, more often (63%) than any other micro-organism. M. genitalium may have been implicated in one case. Serologically, a previous C. trachomatis infection was indicated in 40% of women without an observable laparoscopic abnormality. C. trachomatis in the endometrium and tubes of women without any laparoscopic abnormality suggests subclinical disease, endometritis or endosalpingitis. There was evidence for a smaller proportion (19%) of women without an abnormality having been infected previously with M. genitalium. To some extent this is consistent with the infrequency of acute M. genitalium infections in this cohort of women.
Genitourinary medicine clinic policies on domestic violence across England and Wales: a postal questionnaire survey
Authors: Sanmani L , Chapman C
Published: February 2012

Domestic violence (DV) is prevalent in the UK. There are no national recommendations for assessment of DV in genitourinary (GU) medicine clinics. Bournemouth GU medicine clinic has a referral pathway for victims of DV. A postal questionnaire survey was carried out to determine whether GU medicine clinics across England and Wales had local policies in place to assess DV and also to establish their views on routine assessment of DV within GU medicine. The response rate was 53%. Most clinics had access to patient literature. Only 20% of the clinics had a policy in place to assist victims of DV. Although over 50% agreed that routine assessment for DV should happen in GU medicine clinics, only 11% clinics routinely asked about DV.
Knowledge of human papillomavirus and anal cancer among men who have sex with men attending a New York City sexually transmitted diseases clinic
Authors: Sanchez D M , Pathela P , Niccolai L M , Schillinger J A
Published: February 2012

Men who have sex with men (MSM) are at risk for human papillomavirus (HPV) infection and anal cancer (AC) yet little is known regarding MSM knowledge and risk perception for these outcomes. We surveyed 116 MSM attending a sexually transmitted disease clinic and found that over a quarter (27%) did not know HPV is transmitted via anal sex and most (77%) were unaware of the link with AC. Many MSM (60%) perceived risk for HPV; far fewer (35%) perceived risk for AC. In adjusted logistic regression analyses, having friends or acquaintances with HPV or genital warts was associated with knowledge of anal HPV transmission (odds ratio [OR] = 4.3; 95% confidence interval [CI] = 1.4, 13.4) and AC risk-perception (OR = 6.2; 95% CI = 2.3, 16.7); reporting a regular source of care was associated with awareness of a link between HPV and AC (OR = 3.1; 95% CI = 1.1, 9.1); and MSM and women versus MSM, had less perceived risk for HPV (OR = 0.05; CI = 0.01, 0.29). Nearly all expressed hypothetical acceptance of HPV vaccine. In our sample, many MSM were unaware of a link between MSM sexual practices and HPV-related outcomes.
A national audit on the management of pelvic inflammatory disease in UK genitourinary medicine clinics
Authors: Oroz C , Bailey H , Hollows K , Lee J , Mullan H , Theobald N
Published: February 2012

The prompt and effective treatment of pelvic inflammatory disease (PID) may reduce the risk of complications such as infertility, ectopic pregnancy and pelvic pain. We conducted a national audit to investigate the treatment of women diagnosed with PID and associated rates of partner notification in genitourinary (GU) medicine clinics during 2008 and compared our results with the British Association of Sexual Health and HIV (BASHH) 2005 national guideline. Among a total of 1,105,587 female attendees, national data showed 18,421 cases of PID diagnosed in GU medicine clinics, giving an incidence of 167 cases per 10,000 attendences. We audited a national sample of 1132 PID cases for review. Of those, 504 (44.5%) received a recommended treatment regimen and 447 (39%) of named male contacts were treated. Adherence to recommended treatment and partner notification did not reach national standards.
Transcription regulates telomere dynamics in human cancer cells
Authors: Arora Rajika , Brun Catherine M. , Azzalin Claus M.
Published: February 2012

Telomeres are nucleoprotein structures capping the physical ends of linear eukaryotic chromosomes. Although largely heterochromatic, telomeres are transcribed into telomeric repeat-containing RNA (TERRA) molecules by RNA polymerase II. The functions associated with telomere transcription and TERRA remain ill defined. Here we show that the transcriptional activity of human telomeres directly regulates their movement during interphase. We find that chemical inhibition of global transcription dampens telomere motion, while global stimulation promotes it. Likewise, when DNA methyltransferase enzymes are deleted to augment telomere transcription, we observe increased telomere movement. Finally, using a cell line engineered with a unique transcriptionally inducible telomere, we show that transcription of one specific telomere stimulates only its own dynamics without overtly affecting its stability or its length. We reveal a new and unforeseen function for telomere transcription as a regulator of telomere motion, and speculate on the intriguing possibility that transcription-dependent telomere motion sustains the maintenance of functional and dysfunctional telomeres.
RNA binding is more critical to the suppression of silencing function ofCucumber mosaic virus2b protein than nuclear localization
Authors: González Inmaculada , Rakitina Daria , Semashko Maria , Taliansky Michael , Praveen Shelly , Palukaitis Peter , Carr John P. , Kalinina Natalia , Canto Tomás
Published: February 2012

Previously, we found that silencing suppression by the 2b protein and six mutants correlated both with their ability to bind to double-stranded (ds) small RNAs (sRNAs) in vitro and with their nuclear/nucleolar localization. To further discern the contribution to suppression activity of sRNA binding and of nuclear localization, we have characterized the kinetics of in vitro binding to a ds sRNA, a single-stranded (ss) sRNA, and a micro RNA (miRNA) of the native 2b protein and eight mutant variants. We have also added a nuclear export signal (NES) to the 2b protein and assessed how it affected subcellular distribution and suppressor activity. We found that in solution native protein bound ds siRNA, miRNA, and ss sRNA with high affinity, at protein:RNA molar ratios ∼2:1. Of the four mutants that retained suppressor activity, three showed sRNA binding profiles similar to those of the native protein, whereas the remaining one bound ss sRNA at a 2:1 molar ratio, but both ds sRNAs with 1.5–2 times slightly lower affinity. Three of the four mutants lacking suppressor activity failed to bind to any sRNA, whereas the remaining one bound them at far higher ratios. NES-tagged 2b protein became cytoplasmic, but suppression activity in patch assays remained unaffected. These results support binding to sRNAs at molar ratios at or near 2:1 as critical to the suppressor activity of the 2b protein. They also show that cytoplasmically localized 2b protein retained suppressor activity, and that a sustained nuclear localization was not required for this function.
Should I Repeat My 1:2s QC Rejection?
Authors: Parvin Curtis A , Kuchipudi Lakshmi , Yundt-Pacheco John C
Published: February 2012

BACKGROUND

Repeating a QC that is outside 2SD from the mean (1:2s rule) appears to be a common practice. Although this form of repeat sampling is frowned on by many, the comparative power of the approach has not been formally evaluated.

METHODS

We computed power functions mathematically and by computer simulation for 4 different 1:2s repeat-sampling strategies, as well as the 1:2s rule, the 1:3s rule, and 2 common QC multirules.

RESULTS

The false-rejection rates for the repeat-sampling strategies were similarly low to those of the 1:3s QC rule. The error detection rates for the repeat-sampling strategies approached those of the 1:2s QC rule for moderate to large out-of-control error conditions. In most cases, the power of the repeat-sampling strategies was superior to the power of the QC multirules we evaluated. The increase in QC utilization rate ranged from 4% to 13% for the repeat-sampling strategies investigated.

CONCLUSIONS

The repeat-sampling strategies provide an effective tactic to take advantage of the desirable properties of both the 1:2s and 1:3s QC rules. Additionally, the power of the repeat-sampling strategies compares favorably with the power of 2 common QC multirules. These improvements come with a modest increase in the average number of controls tested.
The Measure of a Magazine: Assessing the Influence of the Christian Century
Authors: Coffman Elesha
Published: February 2012

The Christian Century is generally regarded as the most influential Protestant magazine of the early twentieth century. But what does it mean to call the Century influential? Whom did it influence, and how? This article takes a historical approach, examining the size of the Century's audience, the nature of the magazine's impact on its readers, and the ability of those readers to extend the magazine's impact beyond themselves. The main source for this investigation is a cache of more than 2,100 unpublished letters collected in 1928 to celebrate Charles Clayton Morrison's twentieth anniversary as editor. In subscribers' own words, the letters illustrated the Century's role as a crucial link among readers with similar backgrounds and aspirations, as well as the limits of its reach beyond this cohort. The article argues that the Century was influential, but not because it converted (directly or through its clergy readers) large numbers of American Protestants to its progressive vision for Christianity. Rather, the Century was primarily influential in the process of mainline identification, both in the sense of defining which writers, institutions, and ideas belonged to the emerging mainline tradition and in the sense of offering readers an opportunity to identify with that tradition. A better understanding of the Century's influence during the Morrison era sheds light on the rise of the mainline. Additionally, a better understanding of the kinds of influence magazines do and do not exercise is helpful for anyone who looks to periodicals to provide a barometer of cultural trends.
Elaboração e caracterização de compósitos magnéticos
Authors: Rodrigues Vanessa Isabel do Santos , Pampanelli Andrea Brasco , Roxo Katiane de Oliveira , Korb Matias de Angelis , Veit Hugo Marcelo , Malfatti Célia de Fraga
Published: February 2012

No processo de têmpera por indução, o material é aquecido por um campo magnético gerado por uma corrente alternada de alta frequência, que passa através de uma bobina. Para melhorar a eficiência do processo, são utilizados, junto à bobina, orientadores de fluxo magnético, que são materiais magnéticos moles. Esses orientadores de fluxo são constituídos de componentes ferromagnéticos e um ligante dielétrico. Geralmente é necessário realizar um ajuste dimensional desses concentradores, através de usinagem, gerando perda de matéria-prima e produção de resíduo. Nesse trabalho, foi realizada a elaboração de um compósito de matriz polimérica a partir do resíduo oriundo do processo de ajuste dimensional. Para elaboração desse compósito, o resíduo foi cominuído e misturado com dois tipos diferentes de resinas fenólicas na concentração de 3%. Os compósitos magnéticos obtidos foram caracterizados quanto à morfologia, propriedades mecânicas, magnéticas, elétricas e caracterização ambiental. Os resultados mostraram que os compósitos apresentaram redução das propriedades magnéticas e mecânicas comparativamente ao material original. Mesmo assim o material apresenta potencial para uso como concentrador de fluxo, pois foi observada a redução das perdas magnéticas.
Briefing: Young Coastal Scientists and Engineers Conference 2011
Authors: Brown Jennifer M. , Chesher Tim J. , Beveridge Andrew J. , Shafiai Siti H. , O'Hara Murray Rory B. , Smyth Thomas A. G. , Bricheno Lucy M. , Way Oliver G.
Published: February 2012

The 7th UK Young Coastal Scientists and Engineers Conference welcomed 60 scientists and engineers to come together and discuss coastal research. The conference was hosted by the National Oceanography Centre in Liverpool, 30–31 March 2011. Early career practitioners and researchers presented 42 short papers on a range of topics driven by current issues addressed by UK universities, government agencies and consultancies. Although all presentations had a coastal theme, content varied from small-scale processes to regional-scale monitoring and management, covering topics such as structure impact, sediment transport, morphology, waves, currents, ecology, oxygen, estuarine systems, stratification, modelling, observation, ice, renewables and extreme events. This paper presents the keynote lecture and six abstracts considered to be of particular merit by the panel of judges. The conference continues to travel the UK and will be held at Bangor University in 2012.
Influence of self-compacting concrete on the lateral pressure on formwork
Authors: McCarthy Michael J. , Dhir Ravinda K. , Caliskan Sinan , Ashraf M. Kashif
Published: February 2012

The paper describes a study carried out to examine the effect of self-compacting concrete (SCC) on the lateral pressure on formwork. This comprised two series: (a) control tests, with SCC and comparative concretes (Portland cement (PC) and superplasticised, high-consistence (SP-HC)) cast in 8·0 m columns and walls, and measurements made of concrete and pore water pressures (ten elements) and (b) site tests, with similar properties considered on actual reinforced SCC members during their construction (seven elements). In the control tests, concrete was poured from above to the rising surface at slow (3·0 m/h) and fast (80·0 m/h) rates of rise (with compaction used in the PC and SP-HC concretes only). The results from these indicate that maximum concrete pressures with SCC were slightly lower than those of the comparative concretes at both rates of rise and in columns and walls. Pore water pressures were less than concrete pressures, except with the fast rate of rise for SCC and SP-HC concrete, where the reverse occurred (with the concretes having similar values or SCC slightly higher), which seemed to relate to the concrete properties/pour details and differences in concrete/pore water pressure measurement methods. Maximum pressures for SCC in the control tests were less than hydrostatic and those calculated using the CIRIA report 108 guidance method ( Clear and Harrison, 1985 ). For the site tests, where base-to-top pouring was mainly used (i.e. concrete was passed by way of a hopper at the top of the formwork through a pipe running to its base and kept in place throughout the pour) maximum pressures for SCC were found to exceed hydrostatic in some cases, indicating that this method may give higher pressures. To investigate this further, data from the literature covering SCC pressure measurements on formwork were examined. These showed general agreement with the results of the current study using base-to-top pours and where concrete pumping from below had been adopted, which tended to be at the upper end of the maximum pressure range for SCC. Consideration is given to how SCC may fit within CIRIA 108 for estimating concrete pressure on formwork.
New developments in bridge flutter analysis
Authors: Mannini Claudio , Bartoli Gianni , Borri Claudio
Published: February 2012

The first part of this paper is devoted to an approximate approach to flutter, which is attained through simplification of the flutter equations. The critical wind speed and the flutter frequency can be calculated with the proposed formulas by employing only three flutter derivatives instead of the usual eight coefficients. This approach may be seen as an easy engineering tool for a better tailoring of bridge structures at early design stages. In addition, the simplicity of the equations allows better understanding of the mechanism of flutter instability and the role played by structural parameters such as damping. In particular, an explanation is provided for soft- and hard-type flutter. The second part of the paper outlines a model to take into account the uncertainty in the measurement of self-excited forces in a flutter analysis. Ad hoc wind tunnel tests allowed determination of the statistical properties of the measured flutter derivatives. These coefficients are treated as independent normally distributed random variables, and Monte Carlo simulations are performed in order to determine the probability distribution function of the critical wind speed. The paper concludes with an example of application of the proposed probabilistic flutter assessment method.
Inactivation of Ascaris eggs in water using sequential solar driven photo-Fenton and free chlorine
Authors: Bandala Erick R. , González Liliana , Sanchez-Salas Jose Luis , Castillo Jordana H.
Published: February 2012

Sequential helminth egg inactivation using a solar driven advanced oxidation process (AOP) followed by chlorine was achieved. The photo-assisted Fenton process was tested alone under different H2O2 and/or Fe(II) concentrations to assess its ability to inactivate Ascaris suum eggs. The effect of free chlorine alone was also tested. The lowest egg inactivation results were found using Fe(II) or H2O2 separately (5 and 140 mmol L−1, respectively) in dark conditions, which showed about 28% inactivation of helminth eggs. By combining Fe(II) and H2O2 at the same concentrations described earlier, 55% of helminth egg inactivation was achieved. By increasing the reagent's concentration two-fold, 83% egg inactivation was achieved after 120 min of reaction time. Process efficiency was enhanced by solar excitation. Using solar disinfection only, the A. suum eggs inactivation reached was the lowest observed (58% egg inactivation after 120 min (120 kJ L−1)), compared with tests using the photo-Fenton process. The use of the photo-Fenton reaction enhanced the process up to over 99% of egg inactivation after 120 kJ L−1 when the highest Fe(II) and H2O2 concentration was tested. Practically no effect on the helminth eggs was observed with free chlorine alone after 550 mg min L−1 was used. Egg inactivation in the range of 25–30% was obtained for sequential processes (AOP then chlorine) using about 150 mg min L−1.
Effect of environmental parameters on the inactivation of the waterborne pathogen Campylobacter in a Mediterranean river
Authors: Rodríguez S. , Araujo R.
Published: February 2012

Campylobacter is a major waterborne pathogen that can be found in rivers of the Mediterranean area. Characteristics of these rivers change throughout the seasons due to variations in environmental parameters. As these variations may affect water survival of Campylobacter, we analyzed it in the Llobregat River using three approaches whose complexity increase progressively: (i) river water microcosms in the laboratory subjected to varying temperatures; (ii) insitu experiments carried out in the river, in which bacteria were exposed to varying levels of environmental parameters; and (iii) monitoring of thermotolerant Campylobacter in the river over two years. Campylobacter was quantified using the most probable number (MPN) method. The results showed that an increase in water temperature accelerates Campylobacter inactivation, measured as the loss of culturability. Insitu experiments revealed that inactivation rates were also affected by sunlight, but not by pH, oxygen concentration or water conductivity. These observations are supported by the seasonality detected in Llobregat River. Campylobacter inactivation was fastest in spring and summer, when temperature and solar radiation were at their highest. The results highlight the importance of considering the inactivation rates in natural conditions to improve the monitoring of this pathogen and thus evaluate properly the health risk associated to water.
Total and infectious Cryptosporidium oocyst and total Giardia cyst concentrations from distinct agricultural and urban contamination sources in Eastern Canada
Authors: Lalancette Cindy , Généreux Mylène , Mailly Jacinthe , Servais Pierre , Côté Caroline , Michaud Aubert , Di Giovanni George D. , Prévost Michèle
Published: February 2012

Cryptosporidium and Giardia (oo)cyst concentrations are frequently used for assessing drinking water safety. The widely used USEPA Method 1623 provides total counts of (oo)cysts, but may not be accurate for human health risk characterization, since it does not provide infectivity information. The total counts and infectious fraction of Cryptosporidium oocysts and the total counts of Giardia cysts were assessed in major fecal pollution sources. Fresh calf and cow feces, their manure, and the discharge point were sampled in a small rural sub-watershed (n = 20, 21, 10, 10). Median concentrations for total (oo)cysts were higher in calves (333 oocysts g−1; 111 cysts g−1) than in cows (52 oocysts g−1; 7 cysts g−1). Infectious oocysts were found in 17 (7%) of the samples and none were found in manure or at the discharge point. Urban sources were sampled in the influent and effluent (n = 19, 18) of two wastewater treatment plants. Peak concentrations were 533 oocysts L−1 and 9,010 cysts L−1 for influents and 89 oocysts L−1 and 472 cysts L−1 for effluents. Infectious oocyst fractions varied from below the detection limit to 7–22% in the effluent and influent respectively. These infectious fractions are significantly lower than those currently used for quantitative microbial risk assessment estimates.
Phenotypic stress response of Pseudomonas aeruginosa following culture in water microcosms
Authors: Cheriaa Jihane , Rouabhia Mahmoud , Maatallah Makaoui , Bakhrouf Amina
Published: February 2012

The purpose of the present study was to explore the potential behavioural changes of Pseudomonas aeruginosa following growth in different aquatic environmental conditions. To achieve this, P. aeruginosa was cultured in various water microcosms for 12 months under fixed (pH, nutrients and temperature) factors. P. aeruginosa responses to these conditions were investigated using colony morphotype, biochemical and enzymatic characterisation, pyocin typing, serotyping, sensitivity to different classes of antibiotics and molecular identification. Results show that starvation in water microcosms lead to unusual phenotypes. Of interest is that the pyocin changed from 24/n in the wild type to 83/a following culture in the water microcosms, and the serotype changed from O6 in the wild type to O1 in microcosm-cultured P. aeruginosa. Furthermore, the starvation period in various aquatic microcosms enhanced the resistance of P. aeruginosa against beta-lactam antibiotics. Compared to the other aquatic environments, the seawater microcosm produced the greatest amount of variations in P. aeruginosa. Overall, data demonstrated a high adaptability of P. aeruginosa to environmental changes. This may explain the unusual antibiotic-resistant phenotypes belonging to P. aeruginosa species, and their capacity for spreading that leads to human infections.
Improving Ethics Education in Accounting: Lessons from Medicine and Law
Authors: Liu Chunhui , Yao Lee J , Hu Nan
Published: February 2012

The purpose of this paper is to offer accounting educators additional perspectives for ethics education by considering teaching approaches from medicine and law. It takes the form of literature review and argument. The paper finds that ethics education in accounting shows deficiencies in terms of code-bound content, less systematic formal training, less informal hands-on training, and less usage of partnering in comparison to ethics education in medicine and law, thereby producing students with higher moral cognitive capabilities. Based on these findings, the authors provide some recommendations for improvement.

Data Availability:  Data used in this study are available from the first author upon request.
Cholecystokinin Plays a Novel Protective Role in Diabetic Kidney Through Anti-inflammatory Actions on Macrophage
Authors: Miyamoto Satoshi , Shikata Kenichi , Miyasaka Kyoko , Okada Shinichi , Sasaki Motofumi , Kodera Ryo , Hirota Daisho , Kajitani Nobuo , Takatsuka Tetsuharu , Kataoka Hitomi Usui , Nishishita Shingo , Sato Chikage , Funakoshi Akihiro , Nishimori Hisakazu , Uchida Haruhito Adam , Ogawa Daisuke , Makino Hirofumi
Published: February 2012

Inflammatory process is involved in the pathogenesis of diabetic nephropathy. In this article, we show that cholecystokinin (CCK) is expressed in the kidney and exerts renoprotective effects through its anti-inflammatory actions. DNA microarray showed that CCK was upregulated in the kidney of diabetic wild-type (WT) mice but not in diabetic intracellular adhesion molecule-1 knockout mice. We induced diabetes in CCK-1 receptor (CCK-1R) and CCK-2R double-knockout (CCK-1R−/−,-2R−/−) mice, and furthermore, we performed a bone marrow transplantation study using CCK-1R−/− mice to determine the role of CCK-1R on macrophages in the diabetic kidney. Diabetic CCK-1R−/−,-2R−/− mice revealed enhanced albuminuria and inflammation in the kidney compared with diabetic WT mice. In addition, diabetic WT mice with CCK-1R−/− bone marrow–derived cells developed more albuminuria than diabetic CCK-1R−/− mice with WT bone marrow–derived cells. Administration of sulfated cholecystokinin octapeptide (CCK-8S) ameliorated albuminuria, podocyte loss, expression of proinflammatory genes, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore, CCK-8S inhibited both expression of tumor necrosis factor-α and chemotaxis in cultured THP-1 cells. These results suggest that CCK suppresses the activation of macrophage and expression of proinflammatory genes in diabetic kidney. Our findings may provide a novel strategy of therapy for the early stage of diabetic nephropathy.
Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes
Authors: Liu Ming , Lara-Lemus Roberto , Shan Shu-ou , Wright Jordan , Haataja Leena , Barbetti Fabrizio , Guo Huan , Larkin Dennis , Arvan Peter
Published: February 2012

Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an improper site, producing two subpopulations of molecules. Both show impaired oxidative folding and are retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER exit of coexpressed wild-type proinsulin, accounting for its dominant-negative behavior. Upon increased expression of ER–oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative folding of wild-type proinsulin improves, accelerating its ER export and increasing wild-type insulin production. We conclude that the efficiency of SP cleavage is linked to the oxidation of (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of the mutant as well as that of coexpressed wild-type proinsulin. Improving oxidative folding of wild-type proinsulin may provide a feasible way to rescue insulin production in patients with MIDY.
Increasing Circulating IGFBP1 Levels Improves Insulin Sensitivity, Promotes Nitric Oxide Production, Lowers Blood Pressure, and Protects Against Atherosclerosis
Authors: Rajwani Adil , Ezzat Vivienne , Smith Jessica , Yuldasheva Nadira Y. , Duncan Edward R. , Gage Matthew , Cubbon Richard M. , Kahn Matthew B. , Imrie Helen , Abbas Afroze , Viswambharan Hema , Aziz Amir , Sukumar Piruthivi , Vidal-Puig Antonio , Sethi Jaswinder K. , Xuan Shouhong , Shah Ajay M. , Grant Peter J. , Porter Karen E. , Kearney Mark T. , Wheatcroft Stephen B.
Published: February 2012

Low concentrations of insulin-like growth factor (IGF) binding protein-1 (IGFBP1) are associated with insulin resistance, diabetes, and cardiovascular disease. We investigated whether increasing IGFBP1 levels can prevent the development of these disorders. Metabolic and vascular phenotype were examined in response to human IGFBP1 overexpression in mice with diet-induced obesity, mice heterozygous for deletion of insulin receptors (IR+/−), and ApoE−/− mice. Direct effects of human (h)IGFBP1 on nitric oxide (NO) generation and cellular signaling were studied in isolated vessels and in human endothelial cells. IGFBP1 circulating levels were markedly suppressed in dietary-induced obese mice. Overexpression of hIGFBP1 in obese mice reduced blood pressure, improved insulin sensitivity, and increased insulin-stimulated NO generation. In nonobese IR+/− mice, overexpression of hIGFBP1 reduced blood pressure and improved insulin-stimulated NO generation. hIGFBP1 induced vasodilatation independently of IGF and increased endothelial NO synthase (eNOS) activity in arterial segments ex vivo, while in endothelial cells, hIGFBP1 increased eNOS Ser1177 phosphorylation via phosphatidylinositol 3-kinase signaling. Finally, in ApoE−/− mice, overexpression of hIGFBP1 reduced atherosclerosis. These favorable effects of hIGFBP1 on insulin sensitivity, blood pressure, NO production, and atherosclerosis suggest that increasing IGFBP1 concentration may be a novel approach to prevent cardiovascular disease in the setting of insulin resistance and diabetes.
Glucagon-Like Peptide 1 Recruits Microvasculature and Increases Glucose Use in Muscle via a Nitric Oxide–Dependent Mechanism
Authors: Chai Weidong , Dong Zhenhua , Wang Nasui , Wang Wenhui , Tao Lijian , Cao Wenhong , Liu Zhenqi
Published: February 2012

Glucagon-like peptide 1 (GLP-1) increases tissue glucose uptake and causes vasodilation independent of insulin. We examined the effect of GLP-1 on muscle microvasculature and glucose uptake. After confirming that GLP-1 potently stimulates nitric oxide (NO) synthase (NOS) phosphorylation in endothelial cells, overnight-fasted adult male rats received continuous GLP-1 infusion (30 pmol/kg/min) for 2 h plus or minus NOS inhibition. Muscle microvascular blood volume (MBV), microvascular blood flow velocity (MFV), and microvascular blood flow (MBF) were determined. Additional rats received GLP-1 or saline for 30 min and muscle insulin clearance/uptake was determined. GLP-1 infusion acutely increased muscle MBV (P < 0.04) within 30 min without altering MFV or femoral blood flow. This effect persisted throughout the 120-min infusion period, leading to a greater than twofold increase in muscle MBF (P < 0.02). These changes were paralleled with increases in plasma NO levels, muscle interstitial oxygen saturation, hind leg glucose extraction, and muscle insulin clearance/uptake. NOS inhibition blocked GLP-1–mediated increases in muscle MBV, glucose disposal, NO production, and muscle insulin clearance/uptake. In conclusion, GLP-1 acutely recruits microvasculature and increases basal glucose uptake in muscle via a NO-dependent mechanism. Thus, GLP-1 may afford potential to improve muscle insulin action by expanding microvascular endothelial surface area.
Candesartan Cilexetil Improves Angiotensin II Type 2 Receptor–Mediated Neurite Outgrowth via the PI3K-Akt Pathway in Fructose-Induced Insulin-Resistant Rats
Authors: Hashikawa-Hobara Narumi , Hashikawa Naoya , Inoue Yusuke , Sanda Hitomi , Zamami Yoshito , Takatori Shingo , Kawasaki Hiromu
Published: February 2012

We have shown previously that stimulation of the angiotensin II type 2 receptor (AT2R) results in nerve facilitation. In this study, we determined the capacity of candesartan to correct expression patterns characteristic of neuropathy and AT2R-mediated neurite outgrowth in the fructose-induced insulin-resistant rat, which is one of the human hyperinsulinemia models. Wistar rats received a 15% (w/v) fructose solution in their drinking water for 4 weeks (fructose-drinking rats [FDRs]), with or without candesartan (5 mg/kg/day). We evaluated physiological and behavioral parameters and performed immunohistochemical studies. We found that the FDR developed insulin resistance and downregulated both AT2R neuronal function and phosphorylated Akt expression in dorsal root ganglia (DRG) neurons. Candesartan improved neurite outgrowth in the FDR, which was associated with the restoration of AT2R and phosphorylated Akt expression. Furthermore, downregulation of phosphoinositide 3-kinase (PI3K) inhibited AT2R-mediated neurite outgrowth in control DRG cells. PI3K activation increased AT2R-mediated neurite outgrowth and phosphorylated Akt expression in FDR DRG cells. These results suggest that the decrease of AT2R-mediated neurite outgrowth in FDRs is likely to be the result of decreased PI3K-dependent Akt activation. Candesartan improved AT2R neuronal function and Akt phosphorylation, which were associated with sensory nerve defects and insulin sensitivity in the FDR.
Complement Activation and Prognosis in Patients With Type 2 Diabetes and Myocardial Infarction
Authors: Mellbin Linda G. , Bjerre Mette , Thiel Steffen , Hansen Troels K.
Published: February 2012

OBJECTIVE

The activation of the complement system may be involved in the pathology of myocardial infarction (MI) and type 2 diabetes. To explore their potential as prognostic markers, we characterized two factors in the complement cascade, the end product sC5b-9 and the mannose-binding lectin–associated Ser protease-2 (MASP-2), in type 2 diabetic patients with suspected MI.

RESEARCH DESIGN AND METHODS

Plasma sC5b-9 and MASP-2 were determined in patients with MI and type 2 diabetes (n = 397; median age 70; male 68%). The adjudicated end points were cardiovascular events (CVEs), including cardiovascular mortality and nonfatal MI or stroke.

RESULTS

The median sC5b-9 was 134 μg/L (interquartile range [IQR] 101–190 μg/L) and the median MASP-2 was 333 μg/L (IQR 235–463 μg/L), with no significant correlation between them. Women had higher sC5b-9 than men (median 152 vs. 130 μg/L; P = 0.02). Both sC5b-9 and MASP-2 were correlated to age and creatinine clearance, while MASP-2 was also correlated to BMI. During a median follow-up of 2.4 years, CVEs occurred in 141 patients (36%). Both sC5b-9 (hazard ratio 1.37 [95% CI 1.13–1.65]; P < 0.01) and MASP-2 (0.68 [0.51–0.92]; P = 0.01) predicted CVEs in unadjusted analyses. After multiple adjustments, the predictive capacity remained for sC5b-9 (1.30 [1.02–1.66]; P = 0.04) but not for MASP-2.

CONCLUSIONS

In type 2 diabetic patients with MI, high levels of sC5b-9 predict future CVE. This indicates that the complement system may play a significant role in the pathology of the subsequent myocardial damage and that the pathways leading to complement activation warrant further exploration as potential therapeutic targets to improve the prognosis for these patients.
Metabolic Consequences of Hepatic Steatosis in Overweight and Obese Adolescents
Authors: Wicklow Brandy A. , Wittmeier Kristy D.M. , MacIntosh Andrea C. , Sellers Elizabeth A.C. , Ryner Lawrence , Serrai Hacene , Dean Heather J. , McGavock Jonathan M.
Published: February 2012

OBJECTIVE

To test the hypothesis that hepatic steatosis is associated with risk factors for type 2 diabetes in overweight and obese youth, mediated by cardiorespiratory fitness.

RESEARCH DESIGN AND METHODS

This was a cross-sectional study comparing insulin sensitivity between 30 overweight and obese adolescents with hepatic steatosis, 68 overweight and obese adolescents without hepatic steatosis, and 11 healthy weight adolescents without hepatic steatosis. Cardiorespiratory fitness was determined by a graded maximal exercise test on a cycle ergometer. Secondary outcomes included presence of metabolic syndrome and glucose response to a 75-g oral glucose challenge.

RESULTS

The presence of hepatic steatosis was associated with 55% lower insulin sensitivity (P = 0.02) and a twofold greater prevalence of metabolic syndrome (P = 0.001). Differences in insulin sensitivity (3.5 vs. 4.5 mU ⋅ kg−1 ⋅ min−1, P = 0.03), prevalence of metabolic syndrome (48 vs. 20%, P = 0.03), and glucose area under the curve (816 vs. 710, P = 0.04) remained between groups after matching for age, sex, and visceral fat. The association between hepatic steatosis and insulin sensitivity (β = −0.24, t = −2.29, P < 0.025), metabolic syndrome (β = −0.54, t = −5.8, P < 0.001), and glucose area under the curve (β = 0.33, t = 3.3, P < 0.001) was independent of visceral and whole-body adiposity. Cardiorespiratory fitness was not associated with hepatic steatosis, insulin sensitivity, or presence of metabolic syndrome.

CONCLUSIONS

Hepatic steatosis is associated with type 2 diabetes risk factors independent of cardiorespiratory fitness, whole-body adiposity, and visceral fat mass.
The Accuracy Benefit of Multiple Amperometric Glucose Sensors in People With Type 1 Diabetes
Authors: Castle Jessica R. , Pitts Amy , Hanavan Kathryn , Muhly Rhonda , El Youssef Joseph , Hughes-Karvetski Colleen , Kovatchev Boris , Ward W. Kenneth
Published: February 2012

OBJECTIVE

To improve glucose sensor accuracy in subjects with type 1 diabetes by using multiple sensors and to assess whether the benefit of redundancy is affected by intersensor distance.

RESEARCH DESIGN AND METHODS

Nineteen adults with type 1 diabetes wore four Dexcom SEVEN PLUS subcutaneous glucose sensors during two 9-h studies. One pair of sensors was worn on each side of the abdomen, with each sensor pair placed at a predetermined distance apart and 20 cm away from the opposite pair. Arterialized venous blood glucose levels were measured every 15 min, and sensor glucose values were recorded every 5 min. Sensors were calibrated once at the beginning of the study.

RESULTS

The use of four sensors significantly reduced very large errors compared with one sensor (0.4 vs. 2.6% of errors ≥50% from reference glucose, P < 0.001) and also improved overall accuracy (mean absolute relative difference, 11.6 vs. 14.8%, P < 0.001). Using only two sensors also significantly improved very large errors and accuracy. Intersensor distance did not affect the function of sensor pairs.

CONCLUSIONS

Sensor accuracy is significantly improved with the use of multiple sensors compared with the use of a single sensor. The benefit of redundancy is present even when sensors are positioned very closely together (7 mm). These findings are relevant to the design of an artificial pancreas device.
Validation of Diabetic Retinopathy and Maculopathy Diagnoses Recorded in a U.K. Primary Care Database
Authors: Martín-Merino Elisa , Fortuny Joan , Rivero Elena , García-Rodríguez Luis Alberto
Published: February 2012

OBJECTIVE

To describe the validity of recorded diabetic retinopathy (DR) and diabetic maculopathy (DMP) diagnoses, including edema (DMO) in The Health Improvement Network (THIN) database.

RESEARCH DESIGN AND METHODS

In two independent computer searches, we detected 20,838 patients with diabetes aged 1–84 years with a first DR computer Read entry in 2000–2008 and 4,064 with a first DMP entry. A two-step strategy was used to validate both outcomes as follows: 1) review of patient profiles including free-text comments from primary care practitioners (PCPs) (containing referral information and test results) of a random sample of 500 DR and all DMP computer-detected patients. We classified them in probable, possible, and noncase according to the diagnosis plausibility based on the manual review of the computerized information; and 2) review of questionnaires sent by PCPs and medical records in a random sample (N = 200 for each outcome including 36 diabetic macular edema [DMO]). Gold standard was PCPs’ confirmation.

RESULTS

After profiles review, we categorized 418 as probable/possible DR. In addition, 3,676 DMP were categorized as probable/possible (including 711 DMO). After review of information sent by PCPs, confirmation rates were 87.3 and 87.2%, respectively (90.3% for DMO). When we applied them to the whole sample of computer-detected patients, the weighted confirmation rate was 78.0% for DR and 78.8% for DMP (86.2% for DMO).

CONCLUSIONS

Read codes for DR, DM, and DMO are moderately accurate in identifying incident case subjects of these ophthalmologic complications. The validity improved when incorporating PCPs’ text comments to the patient’s profile. THIN database proved to be a valuable resource to study ophthalmological diabetes complications.
Increased Toll-Like Receptor Activity in Patients With Metabolic Syndrome
Authors: Jialal Ishwarlal , Huet Beverley A. , Kaur Harmeet , Chien Alexander , Devaraj Sridevi
Published: February 2012

OBJECTIVE

The metabolic syndrome (MetS) is highly prevalent and confers an increased risk for diabetes and cardiovascular disease (CVD). While MetS is a proinflammatory state, there is a paucity of data on cellular inflammation in MetS. Toll-like receptors (TLRs) are classical pattern recognition receptors of the innate immune response.

RESEARCH DESIGN AND METHODS

The aim of this study was to examine monocyte TLR2 and TLR4 in MetS patients without diabetes or CVD and control subjects since both of the receptors have been implicated in atherosclerosis and insulin resistance. Fasting blood was obtained for TLR expression and activity.

RESULTS

Circulating levels of high-sensitivity C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and soluble tumor necrosis factor receptor 1 (sTNFR1) were significantly increased in MetS versus control subjects following adjustment for waist circumference. There was a significant increase in both TLR2 and TLR4 surface expression and mRNA on monocytes after adjustment for waist circumference. In addition to increased nuclear factor-κB nuclear binding, there was significantly increased release of IL-1β, IL-6, and IL-8 in MetS versus control subjects following priming of the monocytes with lipopolysaccharides. While both plasma free fatty acids and endotoxin were increased in MetS, they correlated significantly with TLR4 only.

CONCLUSIONS

In conclusion, we make the novel observation that both TLR2 and TLR4 expression and activity are increased in the monocytes of patients with MetS and could contribute to increased risk for diabetes and CVD.
The role of rivers and streams in the migration of alien plants into the Polish Carpathians
Authors: Zając Adam , Tokarska-Guzik Barbara , Zając Maria
Published: February 2012

The role of rivers and streams in the migration of alien plants into the Polish Carpathians

The Carpathians are among the regions of Poland that are generally less susceptible to invasive alien plants. The factor limiting the spread of the species of this group is, above all, the mountain climate. Even species originating from other mountain regions, e.g. the Himalayan Impatiens glandulifera, have their localities only at low elevations, in the Carpathian foothills. In most cases, alien plant species migrate into the Carpathians from the lowlands. The river valleys provide the migration corridors used by alien species in the course of their progress into new territories of the upper mountain localities. The situation along some mountain rivers, where invasive alien species dominate the native vegetation, is dramatic. Their spread is facilitated not only by easy diaspore transport but also by some anthropogenic factors, such as, river engineering and the transformation of riparian habitats and progressing devastation. Currently, we can observe some invasive alien plants "in statu nascendi", developing a new, secondary range in the Carpathians (e.g. Chaerophyllum aureum) or at the foothills, along the Wisła (Vistula) and San river valleys (e.g. Eragrostis albensis). For some species, cities were the destination for the first stage of future migration, e.g. Acer negundo. In the Carpathians, where many national parks and nature reserves are located, the continuous monitoring of the spread of invasive alien plants should be one of the principal activities of botanists.