bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety during the monitoring of diabetic patients: trial teaching course on health professionals and diabetics - SEGUDIAB study
Authors: Cabré Juan J , Ripoll Marta , Hernández Josep M , Basora Josep , Bejarano Ferran , Arija Victoria
Published: June 2011

Background

Safety for diabetic patients means providing the most suitable treatment for each type of diabetic in order to improve monitoring and to prevent the adverse effects of drugs and complications arising from the disease. The aim of this study is to analyze the effect of imparting educational interventions to health professionals regarding the safety of patients with Diabetes Mellitus (DM).

Methods

Design: A cluster randomized trial with a control group.

Setting and sample: The study analyzed ten primary healthcare centres (PHC) covering approximately 150,000 inhabitants. Two groups of 5 PHC were selected on the basis of their geographic location (urban, semi-urban and rural), their socio-economic status and the size of their PHC, The interventions and control groups were assigned at random. The study uses computerized patient records to individually assess subjects aged 45 to 75 diagnosed with type 1 and type 2 DM, who met the inclusion conditions and who had the variables of particular interest to the study.

Trial: The educational interventions consisted of a standardized teaching course aimed at doctors and nurses. The course lasted 6 hours and was split into three 2-hour blocks with subsequent monthly refresher courses.

Measurement: For the health professionals, the study used theDiabetes Attitude Scale(DAS-3) to assess their attitudes and motivation when monitoring diabetes. For the patients, the study assessed factors related to their degree of control over the disease at onset, 6, 12 and 24 months.

Main variables: levels of HbA1c.

Analysis: The study analyzed the effect of the educational interventions both on the attitudes and motivations of health professionals and on the degree of control over the diabetes in both groups.

Discussion

Imparting educational interventions to health professionals would improve the monitoring of diabetic patients. The most effective model involves imparting the course to both doctors and nurses. However, these models have not been tested on our Spanish population within the framework of primary healthcare.

Trial registration

ClinicalTrials.gov:NCT01087541
Socio-demographic and lifestyle factors associated with overweight in a representative sample of 11-15 year olds in France: Results from the WHO-Collaborative Health Behaviour in School-aged Children (HBSC) cross-sectional study
Authors: Dupuy Marie , Godeau Emmanuelle , Vignes Céline , Ahluwalia Namanjeet
Published: June 2011

Background

The prevalence of overweight in children and adolescents is high and overweight is associated with poor health outcomes over short- and long-term. Lifestyle factors can interact to influence overweight. Comprehensive studies linking overweight concomitantly with several demographic and potentially-modifiable lifestyle factors and health-risk behaviours are limited in adolescents - an age-group characterized by changes in lifestyle behaviours and high prevalence of overweight. Thus, the objective of the current study was to examine the association of overweight with several socio-demographic and lifestyle variables simultaneously in a representative sample of adolescents.

Methods

A nationally representative sample of 11-15 year-olds (n = 7154) in France participated as part of the WHO-Collaborative Health Behaviour in School-aged Children (HBSC) study. Students reported data on their age, height, weight, socio-demographic variables, lifestyle factors including nutrition practices, physical activity at two levels of intensity (moderate and vigorous), sedentary behaviours, as well as smoking and alcohol consumption patterns using standardized HBSC protocols. Overweight (including obesity) was defined using the IOTF reference. The multivariate association of overweight with several socio-demographic and lifestyle factors was examined with logistic regression models.

Results

The adjusted odds ratios for the association with overweight were: 1.80 (95% CI: 1.37-2.36) for low family affluence; 0.73 (0.60-0.88) for eating breakfast daily; 0.69 (0.56-0.84) for moderate to vigorous physical activity (MVPA); and 0.71 (0.59-0.86) for vigorous physical activity (VPA). Significant interactions between age and gender as well as television (TV) viewing and gender were noted: for boys, overweight was not associated with age or TV viewing; in contrast, for girls overweight correlated negatively with age and positively with TV viewing. Fruit and vegetable intake, computer and video-games use, smoking and alcohol consumption were not associated with overweight.

Conclusions

In multivariate model, family affluence, breakfast consumption and moderate to vigorous as well as vigorous physical activity were negatively associated with overweight. These findings extend previous research to a setting where multiple risk and protective factors were simultaneously examined and highlight the importance of multi-faceted approaches promoting physical activity and healthy food choices such as breakfast consumption for overweight prevention in adolescents.
Happiness and health behaviours in Chilean college students: A cross-sectional survey
Authors: Piqueras José A , Kuhne Walter , Vera-Villarroel Pablo , van Straten Annemieke , Cuijpers Pim
Published: June 2011

Background

Happiness has been associated with a range of favourable health outcomes through two pathways: its relationship with favourable biological responses to stress and with healthy lifestyles and prudent health behaviours. There are a substantial number of cross-cultural studies about happiness, but none of them has studied the association of happiness with perceived stress and health behaviours in Latin American samples. Therefore, the aim of this study was to examine the association between general happiness and these variables in a Latin American sample.

Methods

We conducted a survey to examine the status of 3461 students aged between 17 and 24 years old (mean age = 19.89; SD = 1.73) who attended University of Santiago de Chile during 2009. The healthy behaviours indexes assessed were the frequency of daily physical exercise, fruits/vegetables intake, breakfast and lunch intake, smoking, alcohol and other drugs consumption. We also included the assessment of perceived stress and Body Mass Index. All of them were evaluated using a self-report questionnaire.

Results

The univariate and multivariate binary logistic regression analyses showed that being female and younger was related to a higher happiness, as well as that people self-reporting daily physical activity, having lunch and fruits and vegetables each day had a higher likelihood (OR between 1.33 and 1.40) of being classified as "very happy". Those who informed felt stressed in normal circumstances and during tests situations showed a lower likelihood (0.73 and 0.82, respectively) of being considered "very happy". Regarding drug consumption, taking tranquilizers under prescription was negative related to "subjective happiness" (OR = 0.62), whereas smoking was positive associated (OR = 1.20).

Conclusions

The findings of this study mainly support the relationship between happiness and health outcomes through the two pathways previously mentioned. They also underscore the importance of that some healthy behaviours and person's cognitive appraisal of stress are integrated into their lifestyle for college students. Additionally, highlight the importance of taking into account these variables in the design of strategies to promote health education in university setting.
Nurse forecasting in Europe (RN4CAST): Rationale, design and methodology
Authors: Sermeus Walter , Aiken Linda H , Van den Heede Koen , Rafferty Anne Marie , Griffiths Peter , Moreno-Casbas Maria Teresa , Busse Reinhard , Lindqvist Rikard , Scott Anne P , Bruyneel Luk , Brzostek Tomasz , Kinnunen Juha , Schubert Maria , Schoonhoven Lisette , Zikos Dimitrios ,   RN4CAST consortium
Published: June 2011

Background

Current human resources planning models in nursing are unreliable and ineffective as they consider volumes, but ignore effects on quality in patient care. The project RN4CAST aims innovative forecasting methods by addressing not only volumes, but quality of nursing staff as well as quality of patient care.

Methods/Design

A multi-country, multilevel cross-sectional design is used to obtain important unmeasured factors in forecasting models including how features of hospital work environments impact on nurse recruitment, retention and patient outcomes. In each of the 12 participating European countries, at least 30 general acute hospitals were sampled. Data are gathered via four data sources (nurse, patient and organizational surveys and via routinely collected hospital discharge data). All staff nurses of a random selection of medical and surgical units (at least 2 per hospital) were surveyed. The nurse survey has the purpose to measure the experiences of nurses on their job (e.g. job satisfaction, burnout) as well as to allow the creation of aggregated hospital level measures of staffing and working conditions. The patient survey is organized in a sub-sample of countries and hospitals using a one-day census approach to measure the patient experiences with medical and nursing care. In addition to conducting a patient survey, hospital discharge abstract datasets will be used to calculate additional patient outcomes like in-hospital mortality and failure-to-rescue. Via the organizational survey, information about the organizational profile (e.g. bed size, types of technology available, teaching status) is collected to control the analyses for institutional differences.

This information will be linked via common identifiers and the relationships between different aspects of the nursing work environment and patient and nurse outcomes will be studied by using multilevel regression type analyses. These results will be used to simulate the impact of changing different aspects of the nursing work environment on quality of care and satisfaction of the nursing workforce.

Discussion

RN4CAST is one of the largest nurse workforce studies ever conducted in Europe, will add to accuracy of forecasting models and generate new approaches to more effective management of nursing resources in Europe.
Proteomics research on muscle-invasive bladder transitional cell carcinoma
Authors: Niu Hai Tao , Dong Zhen , Jiang Gang , Xu Ting , Liu Yan Qun , Cao Yan Wei , Zhao Jun , Wang Xin Sheng
Published: June 2011

Background

Aimed to facilitate candidate biomarkers selection and improve network-based multi-target therapy, we perform comparative proteomics research on muscle-invasive bladder transitional cell carcinoma. Laser capture microdissection was used to harvest purified muscle-invasive bladder cancer cells and normal urothelial cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature.

Results

A total of 885/890 proteins commonly appeared in 4 paired samples. 295/337 of the 488/493 proteins that specific expressed in tumor/normal cells own gene ontology (GO) cellular component annotation. Compared with the entire list of the international protein index (IPI), there are 42/45 GO terms exhibited as enriched and 9/5 exhibited as depleted, respectively. Several pathways exhibit significantly changes between cancer and normal cells, mainly including spliceosome, endocytosis, oxidative phosphorylation, etc. Finally, descriptive statistics show that the PI Distribution of candidate biomarkers have certain regularity.

Conclusions

The present study identified the proteome expression profile of muscle-invasive bladder cancer cells and normal urothelial cells, providing information for subcellular pattern research of cancer and offer candidate proteins for biomarker panel and network-based multi-target therapy.
The contribution of aestivating mosquitoes to the persistence of Anopheles gambiae in the Sahel
Authors: Adamou Abdoulaye , Dao Adama , Timbine Seydou , Kassogué Yaya , Yaro Alpha Seydou , Diallo Moussa , Traoré Sékou F , Huestis Diana L , Lehmann Tovi
Published: June 2011

Background

Persistence of African anophelines throughout the long dry season (4-8 months) when no surface waters are available remains one of the enduring mysteries of medical entomology. Recent studies demonstrated that aestivation (summer diapause) is one mechanism that allows the African malaria mosquito, Anopheles gambiae, to persist in the Sahel. However, migration from distant localities - where reproduction continues year-round - might also be involved.

Methods

To assess the contribution of aestivating adults to the buildup of populations in the subsequent wet season, two villages subjected to weekly pyrethrum sprays throughout the dry season were compared with two nearby villages, which were only monitored. If aestivating adults are the main source of the subsequent wet-season population, then the subsequent wet-season density in the treated villages will be lower than in the control villages. Moreover, since virtually only M-form An. gambiae are found during the dry season, the reduction should be specific to the M form, whereas no such difference is predicted for S-form An. gambiae or Anopheles arabiensis. On the other hand, if migrants arriving with the first rain are the main source, no differences between treated and control villages are expected across all members of the An. gambiae complex.

Results

The wet-season density of the M form in treated villages was 30% lower than that in the control (P < 10-4, permutation test), whereas no significant differences were detected in the S form or An. arabiensis.

Conclusions

These results support the hypothesis that the M form persist in the arid Sahel primarily by aestivation, whereas the S form and An. arabiensis rely on migration from distant locations. Implications for malaria control are discussed.
Geometric nonlinear diffusion filter and its application to X-ray imaging
Authors: Michel-González Eric , Cho Min Hyoung , Lee Soo Yeol
Published: June 2011

Background

Denoising with edge preservation is very important in digital x-ray imaging since it may allow us to reduce x-ray dose in human subjects without noticeable degradation of the image quality. In denoising filter design for x-ray imaging, edge preservation as well as noise reduction is of great concern not to lose detailed spatial information for accurate diagnosis. In addition to this, fast computation is also important since digital x-ray images are mostly comprised of large sized matrices.

Methods

We have developed a new denoising filter based on the nonlinear diffusion filter model. Rather than employing four directional gradients around the pixel of interest, we use geometric parameters derived from the local pixel intensity distribution in calculating the diffusion coefficients in the horizontal and vertical directions. We have tested the filter performance, including edge preservation and noise reduction, using low dose digital radiography and micro-CT images.

Results

The proposed denoising filter shows performance similar to those of nonlinear anisotropic diffusion filters (ADFs), one Perona-Malik ADF and the other Weickert's ADF in terms of edge preservation and noise reduction. However, the computation time has been greatly reduced.

Conclusions

We expect the proposed denoising filter can be greatly used for fast noise reduction particularly in low-dose x-ray imaging.
A chalcone-related small molecule that induces methuosis, a novel form of non-apoptotic cell death, in glioblastoma cells
Authors: Overmeyer Jean H , Young Ashley M , Bhanot Haymanti , Maltese William A
Published: June 2011

Background

Methuosis is a unique form of non-apoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell.

Results

Here we describe a novel chalcone-like molecule, 3-(2-m ethyl-1H- i ndol-3-yl)-1-(4-p yridinyl)-2-p ropen-1-one (MIPP) that induces cell death with the hallmarks of methuosis. MIPP causes rapid accumulation of vacuoles derived from macropinosomes, based on time-lapse microscopy and labeling with extracellular fluid phase tracers. Vacuolization can be blocked by the cholesterol-interacting compound, filipin, consistent with the origin of the vacuoles from non-clathrin endocytic compartments. Although the vacuoles rapidly acquire some characteristics of late endosomes (Rab7, LAMP1), they remain distinct from lysosomal and autophagosomal compartments, suggestive of a block at the late endosome/lysosome boundary. MIPP appears to target steps in the endosomal trafficking pathway involving Rab5 and Rab7, as evidenced by changes in the activation states of these GTPases. These effects are specific, as other GTPases (Rac1, Arf6) are unaffected by the compound. Cells treated with MIPP lose viability within 2-3 days, but their nuclei show no evidence of apoptotic changes. Inhibition of caspase activity does not protect the cells, consistent with a non-apoptotic death mechanism. U251 glioblastoma cells selected for temozolomide resistance showed sensitivity to MIPP-induced methuosis that was comparable to the parental cell line.

Conclusions

MIPP might serve as a prototype for new drugs that could be used to induce non-apoptotic death in cancers that have become refractory to agents that work through DNA damage and apoptotic mechanisms.
Undifferentiated connective tissue disease presenting with prevalent interstitial lung disease: Case report and review of literature
Authors: Lunardi Francesca , Balestro Elisabetta , Nordio Beatrice , Cozzi Franco , Polverosi Roberta , Sfriso Paolo , Braccioni Fausto , Calabrese Fiorella
Published: June 2011

Undifferentiated connective tissue diseases (UCTDs) are clinical entities characterised by signs and symptoms suggestive of a systemic autoimmune disease, which do not fulfil the diagnostic criteria for a defined connective tissue disease. Lung involvement can complicate the course and management of the disease, often determining a worse outcome. Respiratory dysfunction as the first clinical manifestation has seldom been reported.

We describe a case of a female patient who developed significant respiratory dysfunction as the principal clinical sign. Video-assisted thoracoscopy was performed and a histological pattern of nonspecific interstitial pneumonia (NSIP) was found. A pathological diagnosis suggested careful follow-up with extensive immunological screening which then detected Raynaud's phenomenon and positivity of antinuclear antibodies. After a multidisciplinary discussion (pneumologist, radiologist, pathologist and rheumatologist) a final diagnosis of NSIP associated with UCTD was made. The diagnosis of UCTD should be considered when NSIP is diagnosed even in cases with evident first clinical manifestations of severe respiratory dysfunction. A multidisciplinary approach in the field of interstitial lung disease with NSIP, also including rheumatologic expertise, is fundamental to achieve a prompt and correct diagnosis.
Adolescents' leisure activities, parental monitoring and cigarette smoking - a cross-sectional study
Authors: Guo Hui , Reeder Anthony I , McGee Rob , Darling Helen
Published: June 2011

Background

Adolescent participation in leisure activities is developmentally beneficial, but certain activities may increase health compromising behaviours, such as tobacco smoking. A limited range of leisure activities has been studied, with little research on out-of-school settings where parental supervision is a potential protective factor. Tobacco smoking is an important, potentially modifiable health determinant, so understanding associations between adolescent leisure activities, parental monitoring, demographic factors and daily smoking may inform preventive strategies. These associations are reported for a New Zealand adolescent sample.

Methods

Randomly selected schools (n = 145) participated in the 2006 Youth In-depth Survey, a national, biennial study of Year 10 students (predominantly 14-15 years). School classes were randomly selected and students completed a self-report questionnaire in class time. Adjustment for clustering at the school level was included in all analyses. Since parental monitoring and demographic variables potentially confound relations between adolescent leisure activities and smoking, variables were screened before multivariable modelling. Given prior indications of demographic differences, gender and ethnic specific regression models were built.

Results and Discussion

Overall, 8.5% of the 3,161 students were daily smokers, including more females (10.5%) than males (6.5%). In gender and ethnic specific multivariate analysis of associations with daily smoking (adjusted for age, school socioeconomic decile rating, leisure activities and ethnicity or gender, respectively), parental monitoring exhibited a consistently protective, dose response effect, although less strongly among Māori. Attending a place of worship and going to the movies were protective for non-Māori, as was watching sports, whereas playing team sport was protective for all, except males. Attending a skate park was a risk factor for females and Māori which demonstrated a strong dose response effect.

Conclusions

There were significant differences in the risk of daily smoking across leisure activities by gender and ethnicity. This reinforces the need to be alert for, and respond to, gender and ethnic differences in the pattern of risk and protective factors. However, given the consistently protective, dose response effect of parental monitoring, our findings confirm that assisting oversight of adolescent leisure activities may be a key component in public health policy and prevention programmes.
DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
Authors: Wang Zhiquan , Zhang Yu , Zhang Shi , Guo Qianqian , Tan Yuyan , Wang Xinyi , Xiong Ran , Ding Jianqing , Chen Shengdi
Published: June 2011

Background

Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD.

Results

We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis.

Conclusion

Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD).
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice
Authors: Lasagna-Reeves Cristian A , Castillo-Carranza Diana L , Sengupta Urmi , Clos Audra L , Jackson George R , Kayed Rakez
Published: June 2011

Background

The correlation between neurofibrillary tangles of tau and disease progression in the brains of Alzheimer's disease (AD) patients remains an area of contention. Innovative data are emerging from biochemical, cell-based and transgenic mouse studies that suggest that tau oligomers, a pre-filament form of tau, may be the most toxic and pathologically significant tau aggregate.

Results

Here we report that oligomers of recombinant full-length human tau protein are neurotoxic in vivo after subcortical stereotaxic injection into mice. Tau oligomers impaired memory consolidation, whereas tau fibrils and monomers did not. Additionally, tau oligomers induced synaptic dysfunction by reducing the levels of synaptic vesicle-associated proteins synaptophysin and septin-11. Tau oligomers produced mitochondrial dysfunction by decreasing the levels of NADH-ubiquinone oxidoreductase (electron transport chain complex I), and activated caspase-9, which is related to the apoptotic mitochondrial pathway.

Conclusions

This study identifies tau oligomers as an acutely toxic tau species in vivo, and suggests that tau oligomers induce neurodegeneration by affecting mitochondrial and synaptic function, both of which are early hallmarks in AD and other tauopathies. These results open new avenues for neuroprotective intervention strategies of tauopathies by targeting tau oligomers.
Cell functional enviromics: Unravelling the function of environmental factors
Authors: Teixeira Ana P , Dias João ML , Carinhas Nuno , Sousa Marcos , Clemente João J , Cunha António E , von Stosch Moritz , Alves Paula M , Carrondo Manuel JT , Oliveira Rui
Published: June 2011

Background

While functional genomics, focused on gene functions and gene-gene interactions, has become a very active field of research in molecular biology, equivalent methodologies embracing the environment and gene-environment interactions are relatively less developed. Understanding the function of environmental factors is, however, of paramount importance given the complex, interactive nature of environmental and genetic factors across multiple time scales.

Results

Here, we propose a systems biology framework, where the function of environmental factors is set at its core. We set forth a "reverse" functional analysis approach, whereby cellular functions are reconstructed from the analysis of dynamic envirome data. Our results show these data sets can be mapped to less than 20 core cellular functions in a typical mammalian cell culture, while explaining over 90% of flux data variance. A functional enviromics map can be created, which provides a template for manipulating the environmental factors to induce a desired phenotypic trait.

Conclusion

Our results support the feasibility of cellular function reconstruction guided by the analysis and manipulation of dynamic envirome data.
CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas
Authors: Veeravagu Anand , Jiang Bowen , Patil Chirag G , Lee Marco , Soltys Scott G , Gibbs Iris C , Chang Steven D
Published: June 2011

Objective

Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas.

Methods

In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively.

Results

Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%.

Conclusions

CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.
Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury
Authors: Chou Yu-Hsiang , Huang Tao-Min , Wu Vin-Cent , Wang Cheng-Yi , Shiao Chih-Chung , Lai Chun-Fu , Tsai Hung-Bin , Chao Chia-Ter , Young Guang-Huar , Wang Wei-Jei , Kao Tze-Wah , Lin Shuei-Liong , Han Yin-Yi , Chou Anne , Lin Tzu-Hsin , Yang Ya-Wen , Chen Yung-Ming , Tsai Pi-Ru , Lin Yu-Feng , Huang Jenq-Wen , Chiang Wen-Chih , Chou Nai-Kuan , Ko Wen-Je , Wu Kwan-Dun , Tsai Tun-Jun ,   the NSARF Study Group
Published: June 2011

Introduction

Sepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients.

Methods

Patient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT.

Results

Among the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patient's propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05).

Conclusions

Use of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified.
Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy
Authors: Seyler Lucie , Cotton Frédéric , Taccone Fabio Silvio , De Backer Daniel , Macours Pascale , Vincent Jean-Louis , Jacobs Frédérique
Published: June 2011

Introduction

Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics. Continuous renal replacement therapy (CRRT), which is commonly used in septic patients, may further contribute to pharmacokinetic changes. Current recommendations for antibiotic doses during CRRT combine data obtained from heterogeneous patient populations in which different CRRT devices and techniques have been used. We studied whether these recommendations met optimal pharmacokinetic criteria for broad-spectrum antibiotic levels in septic shock patients undergoing CRRT.

Methods

This open, prospective study enrolled consecutive patients treated with CRRT and receiving either meropenem (MEM), piperacillin-tazobactam (TZP), cefepime (FEP) or ceftazidime (CAZ). Serum concentrations of these antibiotics were determined by high-performance liquid chromatography from samples taken before (t = 0) and 1, 2, 5, and 6 or 12 hours (depending on the β-lactam regimen) after the administration of each antibiotic. Series of measurements were separated into those taken during the early phase (< 48 hours from the first dose) of therapy and those taken later (> 48 hours).

Results

A total of 69 series of serum samples were obtained in 53 patients (MEM, n = 17; TZP, n = 16; FEP, n = 8; CAZ, n = 12). Serum concentrations remained above four times the minimal inhibitory concentration for Pseudomonas spp. for the recommended time in 81% of patients treated with MEM, in 71% with TZP, in 53% with CAZ and in 0% with FEP. Accumulation after 48 hours of treatment was significant only for MEM.

Conclusions

In septic patients receiving CRRT, recommended doses of β-lactams for Pseudomonas aeruginosa are adequate for MEM but not for TZP, FEP and CAZ; for these latter drugs, higher doses and/or extended infusions should be used to optimise serum concentrations.
Role of Glycated Hemoglobin in the Prediction of Future Risk of T2DM
Authors: Abdul-Ghani Muhammad A. , Abdul-Ghani Tamam , Müller Gabriele , Bergmann Antje , Fischer Sabine , Bornstein Stefan , DeFronzo Ralph A. , Schwarz Peter
Published: June 2011

Aim:

The aim of this study was to assess the predictive power of glycated hemoglobin (HbA1c) for future type 2 diabetes risk.

Research Design and Methods:

Six hundred eighty-seven subjects who were free of type 2 diabetes mellitus (T2DM) participated in the study. Each subject received a 75-g oral glucose tolerance test at baseline and 624 received a repeat oral glucose tolerance test after 3.5 ± 0.1 yr of follow-up. Anthropometric measurements, lipid profile, and HbA1c were measured during the baseline visit. Logistic multivariate models were created with T2DM status at follow-up as the dependent variable and other parameters as the independent variables. The receiver-operating characteristic (ROC) was used to assess the predictive discrimination of the various models.

Results:

HbA1c was a significant predictor of future T2DM risk (area under the ROC curve = 0.73, P < 0.0001). A HbA1c cut point of 5.65% had the maximal sum of sensitivity and specificity. Although the area under the ROC curve of HbA1c was smaller than the area under the ROC curve of both the 1-h plasma glucose concentration and a multivariate logistic model (including anthropometric parameters, lipid profile, and fasting plasma glucose), the addition of HbA1c to both the 1-h plasma glucose and the multivariate logistic model significantly increased their predictive power.

Conclusion:

Although HbA1c alone is a weaker predictor of future T2DM risk compared with the 1-h plasma glucose, it provides additive information about future T2DM risk when added to previously published prediction models.
Ectodysplasin and Wnt pathways are required for salivary gland branching morphogenesis
Authors: Häärä Otso , Fujimori Sayumi , Schmidt-Ullrich Ruth , Hartmann Christine , Thesleff Irma , Mikkola Marja L.
Published: June 2011

The developing submandibular salivary gland (SMG) is a well-studied model for tissue interactions and branching morphogenesis. Its development shares similar features with other ectodermal appendages such as hair and tooth. The ectodysplasin (Eda) pathway is essential for the formation and function of several ectodermal organs. Mutations in the signaling components of the Eda pathway lead to a human syndrome known as hypohidrotic ectodermal dysplasia (HED), which is characterized by missing and malformed teeth, sparse hair and reduced sweating. Individuals with HED suffer also from dry mouth because of reduced saliva flow. In order to understand the underlying mechanism, we analyzed salivary gland development in mouse models with altered Eda pathway activities. We have found that Eda regulates growth and branching of the SMG via transcription factor NF-κB in the epithelium, and that the hedgehog pathway is an important mediator of Eda/NF-κB. We also sought to determine whether a similar reciprocal interplay between the Eda and Wnt/β-catenin pathways, which are known to operate in other skin appendages, functions in developing SMG. Surprisingly and unlike in developing hair follicles and teeth, canonical Wnt signaling activity did not colocalize with Edar/NF-κB in salivary gland epithelium. Instead, we observed high mesenchymal Wnt activity and show that ablation of mesenchymal Wnt signaling either in vitro or in vivo compromised branching morphogenesis. We also provide evidence suggesting that the effects of mesenchymal Wnt/β-catenin signaling are mediated, at least in part, through regulation of Eda expression.
Evolutionary plasticity of segmentation clock networks
Authors: Krol Aurélie J. , Roellig Daniela , Dequéant Mary-Lee , Tassy Olivier , Glynn Earl , Hattem Gaye , Mushegian Arcady , Oates Andrew C. , Pourquié Olivier
Published: June 2011

The vertebral column is a conserved anatomical structure that defines the vertebrate phylum. The periodic or segmental pattern of the vertebral column is established early in development when the vertebral precursors, the somites, are rhythmically produced from presomitic mesoderm (PSM). This rhythmic activity is controlled by a segmentation clock that is associated with the periodic transcription of cyclic genes in the PSM. Comparison of the mouse, chicken and zebrafish PSM oscillatory transcriptomes revealed networks of 40 to 100 cyclic genes mostly involved in Notch, Wnt and FGF signaling pathways. However, despite this conserved signaling oscillation, the identity of individual cyclic genes mostly differed between the three species, indicating a surprising evolutionary plasticity of the segmentation networks.
A rare complication of radial artery catheterization
Authors: Inan Mustafa Bahadir , Acikgoz Burak , Yazicioglu Levent , Kaya Bulent , Ozyurda Umit
Published: June 2011

An arterial pseudoaneurysm is a cavity which does not consist of three layers of arterial wall and is generally seen at femoral and radial artery sites due to bone fractures, arterial injuries and iatrogenic reasons such as catheterization. The treatment choice may be either surgical or conservative. Patients with pseudoaneurysm should be carefully followed and the treatment choice should be immediately decided to avoid possible complications. We report a case of pseudoaneurysm formation in the radial artery that occurred one week after arterial catheterization for coronary angiography. The treatment choice for this patient was surgical and he was discharged without any complications.
Optimal contemporary management of symptomatic and asymptomatic carotid artery stenosis
Authors: Paraskevas Kosmas I , Mikhailidis Dimitri P , Moore Wesley S , Veith Frank J
Published: June 2011

This commentary addresses the issue of optimal contemporary management of symptomatic and asymptomatic carotid artery stenosis. Based on current data, carotid endarterectomy (CEA) should be performed in the majority of patients with symptomatic carotid artery stenosis. Carotid artery stenting (CAS) should be reserved for a minority of these symptomatic patients, in whom CEA is contraindicated. In asymptomatic patients, all should be placed on best medical treatment (BMT). With the use of one or more of the proposed stroke risk stratification models or some as yet undetermined method, the identification of those asymptomatic individuals may be possible in whom stroke risk is higher than usual with BMT. This asymptomatic subgroup, which may be small and is yet to be determined with certainty, could be offered an invasive carotid procedure (either CAS or CEA).
Testing Models of Strategic Behavior Characterized by Conditional Likelihoods
Authors: Otter Thomas , Gilbride Timothy J. , Allenby Greg M.
Published: June 2011

Marketing expenditures in the form of pricing, product development, promotion, and channel development are made to maximize profits. A challenge in evaluating the effectiveness of these expenditures is that decisions such as whether to lower prices or run promotions are made based on managers' knowledge of how sensitive consumers are to these marketing activities. Although marketing control variables are explanatory of sales, they are often set in anticipation of a market response, which reflects strategic behavior on the part of a firm. A challenge in developing a model of strategic behavior is that the process by which marketing expenditures are made is often not directly observable. We propose tests for comparing supply-side model formulations in which input variables are strategically determined. In these models, the joint likelihood of demand (y) and supply (x) can be factored into a conditional factor of demand given supply and into a marginal factor of supply. We illustrate our approach using data from a services company that operates in multiple geographic regions.
No Customer Left Behind: A Distribution-Free Bayesian Approach to Accounting for Missing Xs in Marketing Models
Authors: Qian Yi , Xie Hui
Published: June 2011

In marketing applications, it is common that some key covariates in a regression model, such as marketing mix variables or consumer profiles, are subject to missingness. The convenient method that excludes the consumers with missingness in any covariate can result in a substantial loss of efficiency and may lead to strong selection bias in the estimation of consumer preferences and sensitivities. To solve these problems, we propose a new Bayesian distribution-free approach, which can ensure that no customer is left behind in the analysis as a result of missing covariates. In this way, all customers are being considered in devising managerial policies. The proposed approach allows for flexible modeling of a joint distribution of multidimensional interrelated covariates that can contain both continuous and discrete variables. At the same time, it minimizes the impact of distributional assumptions involved in covariate modeling because the method does not require researchers to specify parametric distributions for covariates and can automatically generate suitable distributions for missing covariates. We have developed an efficient Markov chain Monte Carlo algorithm for inference. Besides robustness and flexibility, the proposed approach reduces modeling and computational efforts associated with missing covariates and therefore makes the missing covariate problems easier to handle. We evaluate the performance of the proposed method using extensive simulation studies. We then illustrate the method in two real data examples in which missing covariates occur: a mixed multinomial logit discrete-choice model in a ketchup data set and a hierarchical probit purchase incidence model in a retail store data set. These analyses demonstrate that the proposed method overcomes several important limitations of existing approaches for solving missing covariate problems and offers opportunities to make better managerial decisions with the current available marketing databases. Although our applications focus on consumer-level data, the proposed method is general and can be applied to other marketing applications where other types of marketing players are the units of analysis.
Thrombocytopathy: an update1
Authors: Drogies Tim , Braunert Leanthe , Thiery Joachim , Brügel Mathias
Published: June 2011

“Thrombocytopathia” describes inherited or acquired functional disorders of platelets. The complexity of functional and metabolic processes in platelets is associated with a multitude of possible pathologic disturbances, showing a high variability in the clinical picture. The diagnosis of thrombocytopathies by existing laboratory methods is limited by variable sensitivities and specificities for various pathophysiologic backgrounds. Furthermore, the clinical evaluation of laboratory results is complex because of high intra- and interindividual variability of the platelet function. In daily routine diagnostics, a detailed patient history and clinical examination combined with aggregometry-based laboratory methods remains the central approach to diagnose a platelet function disorder.
Liraglutide as additional treatment for type 1 diabetes
Authors: Varanasi Ajay , Bellini Natalie , Rawal Deepti , Vora Mehul , Makdissi Antoine , Dhindsa Sandeep , Chaudhuri Ajay , Dandona Paresh
Published: June 2011

Objective

To determine whether the addition of liraglutide to insulin to treat patients with type 1 diabetes leads to an improvement in glycemic control and diminish glycemic variability.

Subjects and methods

In this study, 14 patients with well-controlled type 1 diabetes on continuous glucose monitoring and intensive insulin therapy were treated with liraglutide for 1 week. Of the 14 patients, eight continued therapy for 24 weeks.

Results

In all the 14 patients, mean fasting and mean weekly glucose concentrations significantly decreased after 1 week from 130±10 to 110±8 mg/dl (P<0.01) and from 137.5±20 to 115±12 mg/dl (P<0.01) respectively. Glycemic excursions significantly improved at 1 week. The mean s.d. of glucose concentrations decreased from 56±10 to 26±6 mg/dl (P<0.01) and the coefficient of variation decreased from 39.6±10 to 22.6±7 (P<0.01). There was a concomitant fall in the basal insulin from 24.5±6 to 16.5±6 units (P<0.01) and bolus insulin from 22.5±4 to 15.5±4 units (P<0.01).

In patients who continued therapy with liraglutide for 24 weeks, mean fasting, mean weekly glucose concentrations, glycemic excursions, and basal and bolus insulin dose also significantly decreased (P<0.01). HbA1c decreased significantly at 24 weeks from 6.5 to 6.1% (P=0.02), as did the body weight by 4.5±1.5 kg (P=0.02).

Conclusion

Liraglutide treatment provides an additional strategy for improving glycemic control in type 1 diabetes. It also leads to weight loss.
Excessive ovarian production of nerve growth factor elicits granulosa cell apoptosis by setting in motion a tumor necrosis factor α/stathmin-mediated death signaling pathway
Authors: Garcia-Rudaz Cecilia , Dorfman Mauricio , Nagalla Srinivasa , Svechnikov Konstantin , Söder Olle , Ojeda Sergio R , Dissen Gregory A
Published: June 2011

Excessive nerve growth factor (NGF) production by the ovary, achieved via a transgenic approach, results in arrested antral follicle growth, reduced ovulatory capacity, and a predisposition to cyst formation in response to mildly elevated LH levels. Two salient features in these mutant mice (termed 17NF) are an elevated production of 17α-hydroxyprogesterone (17-OHP4), testosterone, and estradiol (E2) in response to gonadotropins, and an increased frequency of granulosa cell (GC) apoptosis. In this study, we show that the increase in steroidal response is associated with enhanced expression ofCyp17a1,Hsd17b, andCyp19a1, which encode the enzymes catalyzing the synthesis of 17-OHP4, testosterone, and E2respectively. Using a proteomic approach, we identified stathmin (STMN1), as a protein that is overproduced in 17NF ovaries. In its phosphorylated state, STMN1 mediates a cell death signal initiated by tumor necrosis factor α (TNF). STMN1 is expressed in GCs and excessive NGF increases its abundance as well as that of its forms phosphorylated at serine (Ser) 16, 25, and 38. TNF synthesis is also increased in 17NF ovaries, and this change is abolished by blocking neurotrophic tyrosine kinase receptors. Inhibiting TNF actionsin vivoby administering a soluble TNF receptor prevented the increase in total and phosphorylated STMN1 production, as well as GC apoptosis in NGF-overproducing ovaries. These results indicate that an excess of NGF in the ovary promotes steroidogenesis by enhancing the expression of enzyme genes involved in 17-OHP4, testosterone, and E2synthesis, and causes GC apoptosis by activating a TNF/ STMN1-mediated cell death pathway.