bluuebunny/crossref_metadata_2025 huggingface dataset:
Cape Verdean Immigrants’ Career Development and School Engagement
Authors: Coutinho Maria Teresa , Blustein David L.
Published: July 2013

This study examined the contribution of perceptions of discrimination, career planning, and vocational identity to the school engagement experiences of first- and second-generation immigrants among a sample of 125 Cape Verdean high school students. Perceived ethnic discrimination was found to moderate the association between both vocational factors and school engagement. Students who perceived high levels of discrimination and endorsed a strong vocational identity also endorsed high levels of school engagement. When endorsing high levels of career planning, individuals reporting different levels of perceived discrimination did not differ in school engagement. However, large differences in school engagement were noted at low levels of career planning, with individuals reporting low levels of perceived discrimination endorsing higher engagement in school than those who perceived higher levels of discrimination. The findings highlight the importance of considering perceptions of ethnic discrimination as one explores the academic and vocational functioning of immigrant students of color.
Workplace injury and voice: a comparison of management and union perceptions
Authors: Robinson Andrew M , Smallman Clive
Published: July 2013

This article moves beyond the existing institutional focus on union representation and workplace injury by looking at the substance of union representation and participation in the management of occupational health and safety (OHS). The effects on workplace injuries of different configurations of OHS voice (negotiation, consultation, information or ‘none’), as mapped by the perceptions of both management and unions in the same workplace, are explored using the British Workplace Employment Relations Survey 2004. The findings indicate that some participation is better than none, that more inclusive voice configurations are better than those that are less inclusive and that the alignment of voice between management and unions is fundamental to success. The impact of less inclusive participation is also found to be conditioned by the extent of trade union membership in the workplace.
Creativity and Technical Innovation
Authors: Kell Harrison J. , Lubinski David , Benbow Camilla P. , Steiger James H.
Published: July 2013

In the late 1970s, 563 intellectually talented 13-year-olds (identified by the SAT as in the top 0.5% of ability) were assessed on spatial ability. More than 30 years later, the present study evaluated whether spatial ability provided incremental validity (beyond the SAT’s mathematical and verbal reasoning subtests) for differentially predicting which of these individuals had patents and three classes of refereed publications. A two-step discriminant-function analysis revealed that the SAT subtests jointly accounted for 10.8% of the variance among these outcomes ( p < .01); when spatial ability was added, an additional 7.6% was accounted for—a statistically significant increase ( p < .01). The findings indicate that spatial ability has a unique role in the development of creativity, beyond the roles played by the abilities traditionally measured in educational selection, counseling, and industrial-organizational psychology. Spatial ability plays a key and unique role in structuring many important psychological phenomena and should be examined more broadly across the applied and basic psychological sciences.
Visual and Auditory Cue Effects on Risk Assessment in a Highway Training Simulation
Authors: Toet Alexander , Houtkamp Joske M. , van der Meulen Ralph
Published: July 2013

We investigated whether manipulation of visual and auditory depth and speed cues can affect a user’s sense of risk for a low-cost nonimmersive virtual environment (VE) representing a highway environment with traffic incidents. The VE is currently used in an examination program to assess procedural knowledge of highway patrol officers. In its original form, the VE did not convey the danger of the simulated incidents, and trainees did not experience a sense of risk, even though important elements which contribute to a sense of danger in reality (like the speed and proximity of vehicles) were accurately modeled. This deficiency seriously degrades the validity of the VE as an examination tool. To provide viewers a more compelling impression of a simulated highway incident, we added variability to traffic behavior, and enhanced and added several visual and auditory depth and speed cues in the VE, which are known to affect risk perception in reality. Participants passively watched video clips of both the original and the enhanced versions of the simulation, and actively performed a lane crossing task in both interactive versions of the VE. Then, they filled out questionnaires addressing their speed, distance, and risk perception. The implemented changes did not affect speed and distance estimates, but significantly increased perceived personal risk. These results show that relatively minor changes to the visual, auditory, and dynamic aspects of a VE, established through proper analysis of user requirements and tasks, can significantly influence a user’s experience, and thus determine the validity of the simulation for training and evaluation applications.
An adaptive pneumatic system for the attenuation of random vibrations
Authors: Morales Angel L , Nieto Antonio J , Chicharro José M , Pintado Publio
Published: July 2013

Adaptive suspensions can modify their filtering capacity to better accommodate excitations with different characteristics. The modification of stiffness (and, to a certain extent, damping) is particularly simple in pneumatic systems. The authors have proposed, modeled, analyzed, validated and tested a pneumatic suspension (composed of an air spring, an auxiliary tank and several connecting pipes) the transfer function of which can be modified simply by routing the air flow through the desired pipe. The method has been successfully tested in the case of unbalanced machinery. Procedures to estimate the input frequency have also been proposed for more general cases, but the question remains as to whether the adaptive scheme could be useful in the case of random excitations composed of a sizable range of frequencies. The focus of the work presented in this paper is to shed some light on this question. To this end, a suspension prototype is subjected to random inputs where the frequency content is tuned to increase the relative ‘weight’ of low frequencies, high frequencies or intermediate frequencies. The responses obtained using three different passive configurations, as well as an adaptive approach that can continuously choose among all three, are simulated, tested and compared. It will be shown that adaptation can minimize the root mean square displacement of the random response even in cases where there is significant overlap in the frequency content of the different types of input.
Sex and Straight Young Men
Authors: Doull Marion , Oliffe John , Knight Rod , Shoveller Jean A.
Published: July 2013

Young men are considered to have power and to be powerful in many social settings and in particular within the realm of sexual relations. This article details research that directly asks young men how they perceive, interact with, and deploy power within intimate heterosexual relationships. Semi-structured interviews were conducted with 13 Canadian-based young men (aged 17-22 years) to explore how power was understood and enacted within their intimate heterosexual relationships. A social constructionist gendered analysis was used to inductively derive themes and situate the experiences of the participants within societal discourses of hegemonic masculinities and gender regimes. Power within relationships was most often described as operating equitably, with a few participants describing the deployment of power in coercive/controlling ways. Results reveal that the use of power by men can be understood as challenging or endorsing hegemonic masculinities and traditional heterosexual gender regimes. By including young men's voices in such discussions, our research contributes important understandings and some traction towards describing what might constitute more equitable gender and power relations.
The diagnosis of autism in community pediatric settings: Does advanced training facilitate practice change?
Authors: Swanson Amy R , Warren Zachary E , Stone Wendy L , Vehorn Alison C , Dohrmann Elizabeth , Humberd Quentin
Published: July 2013

The increased prevalence of autism spectrum disorder and documented benefits of early intensive intervention have created a need for flexible systems for determining eligibility for autism-specific services. This study evaluated the effectiveness of a training program designed to enhance autism spectrum disorder identification and assessment within community pediatric settings across the state. Twenty-seven pediatric providers participated in regional trainings across a 3.5-year period. Trainings provided clinicians with strategies for conducting relatively brief within-practice interactive assessments following positive autism spectrum disorder screenings. Program evaluation was measured approximately 1.5 years following training through (a) clinician self-reports of practice change and (b) blind diagnostic verification of a subset of children assessed. Pediatric providers participating in the training reported significant changes in screening and consultation practices following training, with a reported 85% increase in diagnostic identification of children with autism spectrum disorder within their own practice setting. In addition, substantial agreement (86%–93%) was found between pediatrician diagnostic judgments and independent, comprehensive blinded diagnostic evaluations. Collaborative training methods that allow autism spectrum disorder identification within broader community pediatric settings may help translate enhanced screening initiatives into more effective and efficient diagnosis and treatment.
Angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to psoriasis in a Chinese population
Authors: Yang KeDa , Zhang Fan , Li FangFang , Su Juan , Wen SaiLan , Liu Yang , Feng DeYun
Published: July 2013

Introduction:

The relationship between the angiotensin-converting enzyme ( ACE) insertion/deletion (I/D) polymorphism and psoriasis has previously been studied mainly in Caucasians and only once in Asians. The aim of this study is to evaluate the association between the ACE I/D polymorphism and the risk of psoriasis in a Chinese population.

Materials and methods:

The study population consisted of 668 psoriasis patients and 668 matched control subjects. The ACE I/D gene polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results:

The frequency of the ACE II genotype (odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.06, 1.63; P = 0.01) and I allele (OR = 1.25, 95% CI = 1.06, 1.48; P = 0.01) in patients with psoriasis was significantly higher than that in the control group. And the D allele frequency in patients with psoriasis was significantly lower (OR = 0.80, 95% CI = 0.68, 0.95; P = 0.01) than that in the control group. When stratified by family history, the frequency of the DD genotype was marginally significantly lower in patients with a positive family history of psoriasis (familial psoriasis) than in those with negative (sporadic psoriasis) (OR = 0.47, 95% CI = 0.23, 0.97; P = 0.04). When stratified by onset of the disease, type of psoriasis and the severity of psoriasis, no statistically significant result was observed.

Conclusion:

Our study suggested that the ACE II genotype and I allele might confer susceptibility to psoriasis in a Chinese population.
Grief in caregivers of persons with Alzheimer’s disease and related dementia: A qualitative synthesis
Authors: Large Samantha , Slinger Richard
Published: July 2013

This article provides a meta-synthesis of studies focusing on grief in caregivers of people with Alzheimer’s disease or related dementia. Through a systematic search, 11 articles met the inclusion criteria that care receivers had a diagnosis of Alzheimer’s disease or related dementia, caregivers were informal caregivers, and the study focused on caregiver grief. The meta-synthesis followed a meta-ethnography approach based on reciprocal translation. Six themes were identified, namely challenges of caregiving, losses and changes in the relationship, the role of dementia in grief, striving despite dementia, utilising social support and death as a relief from caregiving. Themes are discussed within an integrated framework showing the connected relationships between themes. The devised framework of themes illustrates the general experience of caregiver grief and can be used to devise specific, targeted interventions to help caregivers to identify and work through their grief.
Statistical analysis of sloshing-induced random impact pressures
Authors: Kim Sang-Yeob , Kim Yonghwan , Kim Kyong-Hwan
Published: July 2013

This article presents the statistical analysis of sloshing-induced random impact pressure. To obtain the pressure signal, three-dimensional sloshing model tests were conducted at two different filling depths. Several different methods were applied to identify sloshing peaks and to define the rise and decay times of the peak pressure signals. Statistical properties acquired from these methods were compared, and their consistency and/or discrepancy were observed. In addition, 200-h duration test data were acquired by running forty 5-h tests under each test condition. Based on the long-duration test data, the uncertainty of the test results with respect to the test duration was studied using the bootstrap method.
Recruitment and Transition of Construction Lecturers in Further Education
Authors: Page Damien
Published: July 2013

This article presents findings from a study of 14 heads of construction in further education colleges in England as they manage the transition of new construction lecturers from a culture of hypermasculinity to one of emotional labour and caring. It focuses firstly on the dilemmas faced by heads of construction at the recruitment stage before moving on to consider the difficulties faced by new lecturers as they change cultures and face the demands of administrative, academic and pedagogical challenges. The article concludes by discussing the implications of the research both for colleges and heads of construction themselves.
Neuropathic pain
Authors: Monkhouse Alexandra , Ali Tahir
Published: July 2013

The capacity to experience pain is valuable for survival; however, the development of neuropathic pain is maladaptive and may be the result of a variety of underlying clinical diagnoses. Neuropathic pain has a significant impact on the patient's quality of life, function and psychological well-being and creates a personal and societal financial burden. It is an important issue within primary care that is often underdiagnosed and undertreated. It is essential to have a systematic approach to the assessment of these patients with neuropathic pain within primary care. The patient and clinician should develop an individual management strategy involving behavioural and psychological support, functional rehabilitation and pharmacological therapy with the aim of optimising quality of life. This article aims to summarise the background to neuropathic pain, the common presentations within primary care and the current treatment options available.
The Great Recession
Authors: Park Heejung , Twenge Jean M. , Greenfield Patricia M.
Published: July 2013

Based on Greenfield’s theory of social change and human development, we predicted that adolescents’ values, behaviors, and self-assessments would become more collectivistic and less individualistic during the Great Recession (2008–2010) compared to the prerecession period (2004-2006), thereby reversing long-term trends from the 1970s. Data came from Monitoring the Future, a nationally representative yearly survey of 12th graders. Concern for others and environmentalism increased from the prerecession period to recession, reversing long-term declines. Long-term trends toward increasing materialism partially reversed: Wanting a job making lots of money continued to increase, the increase in the importance of money leveled off, and the increase in desiring to own expensive material items reversed. Long-term trends toward increasingly positive self-views continued. Correlations with economic indicators (median income, employment rate) over the entire time period (1976–2010) showed that collectivism was high and individualism was low during times of economic deprivation, consistent with Greenfield’s theory.
Use of a Wallet Written Asthma Action Plan Compared to a Full-Page Plan
Authors: Honey Brooke L. , Inhofe Nancy , Sullivan Peter , Martien Sarah , Swar Sajidah
Published: July 2013

Written asthma action plans (WAAPs) are recommended by national guidelines and health care accrediting bodies to help patients in early detection and treatment of asthma exacerbations. Furthermore, they provide a prescription for daily self-management. The objective of this study was to evaluate caregivers’ perception of the value and practical usage of a color-coded wallet WAAP compared to a full-page, black/white plan. Both WAAPs are given at every appointment with education for use. A survey regarding both WAAPs was completed by caregivers of children seen in a pediatric asthma clinic. Surveys included twenty-three multiple choice and two open-ended questions. A total of 32 surveys were completed. Ninety-seven percent and 90% of parents reported the full-page and wallet WAAP as extremely or somewhat useful, respectively. Despite instruction, only 19% of caregivers reported showing a WAAP to their pharmacy, even with 90% reporting they carried the wallet WAAP in their purse/wallet. Of those who use the WAAPs, both are used primarily when their child is sick (93% wallet card; 67% full-page) with a greater number using the wallet WAAP in the emergency department/urgent care/hospital. The full-page WAAP was used more often on a daily basis when taking green zone medications. Participants recognized the full-page plan to be more complete; however, the wallet WAAP was reported as easier to use. Based on this survey, caregivers value both formats. The next direction is to improve understanding of the wallet WAAP utility at the pharmacy, which may decrease medication refill errors and help improve asthma outcomes.
Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis
Authors: Fayon Michael , Kent Lisa , Bui Stephanie , Dupont Lieven , Sermet Isabelle
Published: July 2013

The Standardisation Committee of the European Cystic Fibrosis Society Clinical Trial Network has undertaken the evaluation of clinical end-points for therapeutic interventions regarding their use in multicentre clinical trials in cystic fibrosis (CF). This review of biomarkers in bronchoalveolar lavage (BAL) is part of the group’s work.

The aims of this project were: 1) to review the literature on reliability, validity and responsiveness of BAL in patients with CF; 2) to gain consensus of the group on the feasibility of BAL; and 3) to gain consensus on answers to key questions regarding the promotion of BAL to surrogate end-point status.

Assessment of BAL inflammatory markers in the literature indicates that their reliability, validity and responsiveness are adequate for clinical trials. After discussion of the practical characteristics it was concluded that BAL has an attractive validity profile, albeit with limited feasibility. It is particularly applicable to multicentre trials in preschool children with CF and early or mild lung disease. This is the first article to collate the literature in this manner. This provides a rationale to support the use of BAL in early clinical trials in preschool children with CF.
Target lobe volume reduction and COPD outcome measures after endobronchial valve therapy
Authors: Valipour Arschang , Herth Felix J.F. , Burghuber Otto C. , Criner Gerard , Vergnon Jean-Michel , Goldin Jonathan , Sciurba Frank , Ernst Armin
Published: July 2013

Endobronchial valve (EBV) therapy may be associated with improvements in chronic obstructive pulmonary disease-related outcomes and may therefore be linked to improvements in the body mass index, airflow obstruction, dyspnoea, exercise capacity (BODE) index.

Data from 416 patients with advanced emphysema and hyperinflation across Europe and USA, who were randomised to EBV (n=284) or conservative therapy (n=132) were analysed. Quantitative image analysis was used to compare the volume of the targeted lobe at baseline and at 6 months to determine target lobe volume reduction (TLVR).

44% of patients receiving EBV therapy (versus24.7% of controls) had clinically significant improvements in the BODE index (p<0.001). BODE index was significantly reduced by mean±sd1.4±1.8, 0.2±1.3 and 0.1±1.3 points in patients with TLVR >50%, 20%–50% and <20%, respectively (intergroup differences p<0.001), but increased by 0.3±1.2 points in controls. Changes in BODE were predicted by baseline BODE and correlated significantly with lobar exclusion and lung volumes at 6 months.

A greater proportion of patients in the treatment group than in the control group achieved a clinically meaningful improvement in BODE index; however, the likelihood of benefit was less than half in both groups. Patients in whom TLVR was obtained had greater improvements in clinical outcomes.
Targeting cell motility in pulmonary arterial hypertension
Authors: Paulin Roxane , Meloche Jolyane , Courboulin Audrey , Lambert Caroline , Haromy Alois , Courchesne Antony , Bonnet Pierre , Provencher Steeve , Michelakis Evangelos D. , Bonnet Sébastien
Published: July 2013

Pulmonary artery smooth muscle cells (PASMC), in pulmonary arterial hypertension (PAH), contribute to obliterative vascular remodelling and are characterised by enhanced proliferation, suppressed apoptosis and, a much less studied, increased migration potential. One of the major proteins that regulate cell migration is focal adhesion kinase (FAK), but its role in PAH is not fully understood. We hypothesised that targeting cell migration by FAK inhibition may be a new therapeutic strategy in PAH.

In vivo, inhalation of FAK-siRNA (n=5) or oral delivery of PF-228 (FAK inhibitor PF-573 228; n=5) inhibited rat monocrotaline induced PAH, improving the haemodynamics, vascular remodelling (media thickness), and right ventricular hypertrophy.In vitro, FAK was activated in PAH human lungs (n=8) or PASMC when compared to those form healthy subjects (Western blot, n=5), in a Src-dependent manner, as it was reversed by the specific Src inhibitor PP2. The degree of FAK phosphorylation at Y576 correlated positively with pulmonary vascular resistance in PAH patients. FAK inhibition (siRNA, PF-228 and PP2) in PAH-PASMCs induced a fivefold increase in apoptosis (percentage of terminal deoxynucleotidyl transferase dUTP nick end labelling), a 2.5-fold decrease in proliferation (%Ki67), an 18% decrease in cell migration (colorimetric assay) and a 50% decrease in cell invasion (wound healing).

Suppressing PASMC migration by FAK inhibition inhibits PAH progression and may open a new therapeutic window in PAH.
Genotyping and clinical characteristics of multidrug and extensively drug-resistant tuberculosis in a tertiary care tuberculosis hospital in China
Authors: Yuan Xiaoliang , Zhang Tiantuo , Kawakami Kazuyoshi , Zhu Jiaxin , Zheng Wenzheng , Li Hongtao , Deng Guofang , Tu Shaohua , Liu Weiyou
Published: July 2013

Background

There is a lack of information on the clinical characteristics of multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR) TB in the Jiangxi Province of China; furthermore, data have not been reported on the utility of mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) analyses in genotypingMycobacterium tuberculosisstrains isolated from this region. The aim of this study was to analyse the clinical features of patients with MDR and XDR TB from Jiangxi Province and to evaluate the discriminatory power of the 15-loci MIRU-VNTR method.

Methods

A retrospective study was conducted on patients diagnosed with MDR and XDR TB at the Jiangxi Chest Hospital from July 2010 to June 2011. The RD105 deletion-targeted multiplex PCR (DTM-PCR) and the 15-loci MIRU-VNTR method were used to determine the genetic background of the identified MDR and XDRM.tuberculosisclinical isolates.

Results

Of 804 M.tuberculosisclinical isolates, 159 (159/804, 19.8%) of the isolates were identified as MDR with first-line drug susceptibility testing. Of the 123 available MDR isolates, 13 (13/123, 10.6%) were XDR. The RD105 deletion-targeted multiplex PCR method identified 85 (85/110, 77.3%) MDR and 12 (12/13, 92.3%) XDR isolates as the Beijing genotype. MIRU-VNTR cluster analysis demonstrated that 101 MDR and 13 XDR strains had unique genotype patterns; the remaining 9 MDR strains were in 4 clusters, namely 1 cluster with 3 strains and 3 clusters with 2 strains, resulting in a low clustering rate (4.06%). The Hunter-Gaston discriminatory index (HGDI) of the 15-loci MIRU-VNTR method was as high as 0.992. In addition, clinical surveys showed that 87 (87/110, 79.1%) MDR TB patients and 10 (10/13, 76.9%) XDR TB patients had been previously treated. Diabetes mellitus was the most common comorbidity in both MDR TB (16/110, 14.5%) and XDR TB (2/13, 15.4%) patients.

Conclusions

Based on our preliminary data, the MDR and XDRM.tuberculosisclinical isolates identified at the Jiangxi Chest Hospital were genetically diverse and clustered at a low frequency. The 15-loci MIRU-VNTR method showed high discriminatory power and may be used as a first-line genotyping tool in investigating the molecular epidemiology ofM.tuberculosisin Jiangxi, China. Decisive measures are urgently needed to effectively prevent and manage MDR and XDR tuberculosis in this province.
Activation of SNAT1/SLC38A1 in human breast cancer: correlation with p-Akt overexpression
Authors: Wang Kuo , Cao Fang , Fang Wenzheng , Hu Yongwei , Chen Ying , Ding Houzhong , Yu Guanzhen
Published: July 2013

Background

SNAT1 is a subtype of the amino acid transport system A that has been implicated to play a potential role in cancer development and progression, yet its role in breast cancer remains unclear. In present study, we detected SNAT1 expression in breast cancers and explored its underlying mechanism in promoting breast carcinogenesis.

Methods

RT-PCR and Western blotting were performed to analyze the transcription and protein levels of SNAT1 in breast cancer cell lines and fresh tissues. Tissue microarray blocks containing breast cancer specimens obtained from 210 patients were constructed. Expression of SNAT1 in these specimens was analyzed using immunohistochemical studies. SNAT1 was down-regulated by SNAT1-shRNA in breast cancer cells and the functional significance was measured.

Results

SNAT1 was up-regulated in breast cancer cell lines and breast cancer tissues. Overexpression of SNAT1 was observed in 127 cases (60.5%). Expression of SNAT1 was significantly associated with tumor size, nodal metastasis, advanced disease stage, Ki-67, and ER status. Suppression of endogenous SNAT1 leads to cell growth inhibition, cell cycle arrest, and apoptosis of 4T1 cells and lowered the phosphorylation level of Akt. SNAT1 expression correlated significantly with p-Akt expression in human breast cancer samples.

Conclusions

The cross-talk between Akt signaling and SNAT1 might play a critical role in the development and progression of breast cancer, providing an important molecular basis for novel diagnostic markers and new attractive targets in the treatment of breast cancer patients.
Inhibition of advanced glycation end products by red grape skin extract and its antioxidant activity
Authors: Jariyapamornkoon Nattha , Yibchok-anun Sirintorn , Adisakwattana Sirichai
Published: July 2013

Background

The objective of the present study was to determine the phytochemical content and the protective effect of red grape skin extract (RGSE) against fructose-mediated protein oxidation. In addition, RGSE was screened for its potential as an antioxidant using various in vitro models.

Methods

Antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical scavenging activity, superoxide radical scavenging activity, trolox equivalent antioxidant capacity, ferric reducing antioxidant power (FRAP), ferrous ion chelating power. The total phenols content was measured by Folin–Ciocalteu assay, the flavonoids content by the AlCl3 colorimetric method. Antiglycation activity was determined using the formation of AGE fluorescence intensity, Nϵ-(carboxymethyl)lysine, and the level of fructosamine. The protein oxidation was examined using the level of protein carbonyl content and thiol group.

Results

The results showed that the content of total phenolics, flavonoids and total anthocyanins in RGSE was 246.3 ± 0.9 mg gallic acid equivalent/g dried extract, 215.9 ± 1.3 mg catechin equivalent/g dried extract, and 36.7 ± 0.8 mg cyanidin-3-glucoside equivalent/g dried extract, respectively. In the DPPH radical scavenging activity, hydroxyl radical scavenging activity, and superoxide radical scavenging activity, RGSE had the IC50 values of 0.03 ± 0.01 mg/ml, 5.40 ± 0.01 mg/ml, and 0.58 ± 0.01 mg/ml, respectively. In addition, RGSE had trolox equivalent antioxidant capacity assay (395.65 ± 1.61 mg trolox equivalent/g dried extract), ferric reducing antioxidant power (114.24 ± 0.03 mM FeSO4/g dried extract), and ferrous ion chelating power (3,474.05 ± 5.55 mg EDTA/g dried extract), respectively. The results showed that RGSE at different concentrations (0.031–0.500 mg/ml) has significantly inhibited the formation of AGEs in terms of the fluorescence intensity of glycated BSA during 4 weeks of study. The RGSE markedly decreased the level of fructosamine, which is directly associated with the reduction of AGE formation and Nϵ-(carboxymethyl)lysine (CML). The results demonstrated the significant effect of RGSE on preventing protein oxidative damages, including effects on the thiol and protein carbonyl oxidation.

Conclusions

The present study revealed that RGSE would exert beneficial effects by virtue of its antioxidants and antiglycation. The findings could provide a new insight into the naturally occurring antiglycation properties of RGSE for preventing AGE-mediated diabetic complication.
Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease
Authors: Kim Hyeon Jin , Hong Young Bin , Park Jin-Mo , Choi Yu-Ri , Kim Ye Jin , Yoon Bo Ram , Koo Heasoo , Yoo Jeong Hyun , Kim Sang Beom , Park Minhwa , Chung Ki Wha , Choi Byung-Ok
Published: July 2013

Background

Mutations in thePleckstrin homology domain-containing, family G member 5(PLEKHG5) gene has been reported in a family harboring an autosomal recessive lower motor neuron disease (LMND). However, thePLEKHG5mutation has not been described to cause Charcot-Marie-Tooth disease (CMT).

Methods

To identify the causative mutation in an autosomal recessive intermediate CMT (RI-CMT) family with childhood onset, whole exome sequencing (WES), histopathology, and lower leg MRIs were performed. Expression and activity of each mutant protein were analyzed.

Results

We identified novel compound heterozygous (p.Thr663Met and p.Gly820Arg) mutations in thePLEKHG5gene in the present family. The patient revealed clinical manifestations of sensory neuropathy. Fatty replacements in the distal lower leg muscles were more severe than in the thigh muscles. Although the symptoms and signs of this patient harboring slow nerve conduction velocities suggested the possibility of demyelinating neuropathy, a distal sural nerve biopsy was compatible with axonal neuropathy. Immunohistochemical analysis revealed that the patient has a low level of PLEKHG5 in the distal sural nerve and an in vitro assay suggested that the mutant proteins have a defect in activating the NF-κB signaling pathway.

Conclusions

This study identifies compound heterozygousPLEKHG5mutations as the cause of RI-CMT. We suggest that PLEKHG5 might play a role in the peripheral motor and sensory nervous system. This study expands the phenotypic spectrum ofPLEKHG5mutations.
Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome
Authors: Donadille Bruno , D’Anella Pascal , Auclair Martine , Uhrhammer Nancy , Sorel Marc , Grigorescu Romulus , Ouzounian Sophie , Cambonie Gilles , Boulot Pierre , Laforêt Pascal , Carbonne Bruno , Christin-Maitre Sophie , Bignon Yves-Jean , Vigouroux Corinne
Published: July 2013

Background

Laminopathies, due to mutations in LMNA, encoding A type-lamins, can lead to premature ageing and/or lipodystrophic syndromes, showing that these diseases could have close physiopathological relationships. We show here that lipodystrophy and extreme insulin resistance can also reveal the adult progeria Werner syndrome linked to mutations in WRN, encoding a RecQ DNA helicase.

Methods

We analysed the clinical and biological features of two women, aged 32 and 36, referred for partial lipodystrophic syndrome which led to the molecular diagnosis of Werner syndrome. Cultured skin fibroblasts from one patient were studied.

Results

Two normal-weighted women presented with a partial lipodystrophic syndrome with hypertriglyceridemia and liver steatosis. One of them had also diabetes. Both patients showed a peculiar, striking lipodystrophic phenotype with subcutaneous lipoatrophy of the four limbs contrasting with truncal and abdominal fat accumulation. Their oral glucose tolerance tests showed extremely high levels of insulinemia, revealing major insulin resistance. Low serum levels of sex-hormone binding globulin and adiponectin suggested a post-receptor insulin signalling defect. Other clinical features included bilateral cataracts, greying hair and distal skin atrophy. We observed biallelic WRN null mutations in both women (p.Q748X homozygous, and compound heterozygous p.Q1257X/p.M1329fs). Their fertility was decreased, with preserved menstrual cycles and normal follicle-stimulating hormone levels ruling out premature ovarian failure. However undetectable anti-müllerian hormone and inhibin B indicated diminished follicular ovarian reserve. Insulin-resistance linked ovarian hyperandrogenism could also contribute to decreased fertility, and the two patients became pregnant after initiation of insulin-sensitizers (metformin). Both pregnancies were complicated by severe cervical incompetence, leading to the preterm birth of a healthy newborn in one case, but to a second trimester-abortion in the other. WRN-mutated fibroblasts showed oxidative stress, increased lamin B1 expression, nuclear dysmorphies and premature senescence.

Conclusions

We show here for the first time that partial lipodystrophy with severe insulin resistance can reveal WRN-linked premature aging syndrome. Increased expression of lamin B1 with altered lamina architecture observed in WRN-mutated fibroblasts could contribute to premature cellular senescence. Primary alterations in DNA replication and/or repair should be considered as possible causes of lipodystrophic syndromes.
Estimation of plasma fibrinogen levels based on hemoglobin, base excess and Injury Severity Score upon emergency room admission
Authors: Schlimp Christoph J , Voelckel Wolfgang , Inaba Kenji , Maegele Marc , Ponschab Martin , Schöchl Herbert
Published: July 2013

Introduction

Fibrinogen plays a key role in hemostasis and is the first coagulation factor to reach critical levels in massively bleeding trauma patients. Consequently, rapid estimation of plasma fibrinogen (FIB) is essential upon emergency room (ER) admission, but is not part of routine coagulation monitoring in many centers. We investigated the predictive ability of the laboratory parameters hemoglobin (Hb) and base excess (BE) upon admission, as well as the Injury Severity Score (ISS), to estimate FIB in major trauma patients.

Methods

In this retrospective study, major trauma patients (ISS ≥16) with documented FIB analysis upon ER admission were eligible for inclusion. FIB was correlated with Hb, BE and ISS, alone and in combination, using regression analysis.

Results

A total of 675 patients were enrolled (median ISS 27). FIB upon admission correlated strongly with Hb, BE and ISS. Multiple regression analysis showed that Hb and BE together predicted FIB (adjusted R2 = 0.46; loge(FIB) = 3.567 + 0.223.Hb - 0.007.Hb2 + 0.044.BE), and predictive strength increased when ISS was included (adjusted R2 = 0.51; loge(FIB) = 4.188 + 0.243.Hb - 0.008.Hb2 + 0.036.BE - 0.031.ISS + 0.0003.ISS2). Of all major trauma patients admitted with Hb <12 g/dL, 74% had low (<200 mg/dL) FIB and 54% had critical (<150 mg/dL) FIB. Of patients admitted with Hb <10 g/dL, 89% had low FIB and 73% had critical FIB. These values increased to 93% and 89%, respectively, among patients with an admission Hb <8 g/dL. Sixty-six percent of patients with only a weakly negative BE (<−2 mmol/L) showed low FIB. Of patients with BE <−6 mmol/L upon admission, 81% had low FIB and 63% had critical FIB. The corresponding values for BE <−10 mmol/L were 89% and 78%, respectively.

Conclusions

Upon ER admission, FIB of major trauma patients shows strong correlation with rapidly obtainable, routine laboratory parameters such as Hb and BE. These two parameters might provide an insightful and rapid tool to identify major trauma patients at risk of acquired hypofibrinogenemia. Early calculation of ISS could further increase the ability to predict FIB in these patients. We propose that FIB can be estimated during the initial phase of trauma care based on bedside tests.
Renal macro- and microcirculation autoregulatory capacity during early sepsis and norepinephrine infusion in rats
Authors: Burban Mélanie , Hamel Jean-François , Tabka Maher , de La Bourdonnaye Mathilde Renou , Duveau Agnès , Mercat Alain , Calès Paul , Asfar Pierre , Lerolle Nicolas
Published: July 2013

Introduction

The relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity.

Methods

Ventilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions.

Results

Positive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion.

Conclusion

In our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion.
Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients
Authors: Gonzalez Leslie , Cravoisy Aurélie , Barraud Damien , Conrad Marie , Nace Lionel , Lemarié Jérémie , Bollaert Pierre-Edouard , Gibot Sébastien
Published: July 2013

Introduction

A rational use of antibiotics is of paramount importance in order to prevent the emergence of multidrug resistant bacteria that can lead to therapeutic impasse, especially in intensive care units (ICUs). A de-escalation strategy is therefore naturally advocated as part of better antibiotics usage. However, the clinical impact of such a strategy has not been widely studied. We aimed to assess the feasibility and the clinical impact of a de-escalation strategy in a medical ICU and to identify factors associated when de-escalation was possible.

Methods

We performed a retrospective study of patients hospitalized in a medical ICU over a period of six months. Independent factors associated with de-escalation and its clinical impact were assessed.

Results

Two hundred and twenty-nine patients were included in the study. Antibiotics were de-escalated in 117 patients (51%). The appropriateness of initial antibiotic therapy was the only independent factor associated with the performance of de-escalation (OR = 2.9, 95% CI, 1.5-5.7; P = 0.002). By contrast, inadequacy of initial antibiotic therapy (OR = 0.1, 0.0 to 0.1, P <0.001) and the presence of multidrug resistant bacteria (OR = 0.2, 0.1 to 0.7, P = 0.006) prevented from de-escalation. There were no differences in terms of short (ICU) or long-term (at 1 year) mortality rates or any secondary criteria such as ICU length of stay, duration of antibiotic therapy, mechanical ventilation, incidence of ICU-acquired infection, or multi-drug resistant bacteria emergence.

Conclusions

De-escalation appears feasible in most cases without any obvious negative clinical impact in a medical ICU.
Effects of synthetic colloids on oxidative stress and inflammatory response in hemorrhagic shock: comparison of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin
Authors: Chen Gan , You Guoxing , Wang Ying , Lu Mingzi , Cheng Weina , Yang Jing , Zhao Lian , Zhou Hong
Published: July 2013

Introduction

This study compared the effects of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin on oxidative stress and the inflammatory response in a rodent hemorrhagic shock model.

Methods

Sodium pentobarbital-anesthetized adult male Wistar rats (200 g to 220 g) were subjected to a severe volume-controlled hemorrhage using arterial blood withdrawal (30 mL/kg to 33 mL/kg) and resuscitated with a colloid solution at the same volume as blood withdrawal (hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, or succinylated gelatin). Arterial blood gas parameters were monitored. Malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the liver, lungs, intestine, and brain were measured two hours after resuscitation. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 in the intestine were also measured.

Results

Infusions of hydroxyethyl starch 130/0.4, but not hydroxyethyl starch 200/0.5 or succinylated gelatin, significantly reduced MDA levels and MPO activity in the liver, intestine, lungs and brain, and it also inhibited the production of TNF-α in the intestine two hours after resuscitation. However, no significant difference between hydroxyethyl starch 200/0.5 and succinylated gelatin was observed.

Conclusions

Hydroxyethyl starch 130/0.4, but not hydroxyethyl starch 200/0.5 or succinylated gelatin, treatment after hemorrhagic shock ameliorated oxidative stress and the inflammatory response in this rat model. No significant differences were observed after hydroxyethyl starch 200/0.5 or succinylated gelatin administration at doses of approximately 33 mL/kg.
Combined impact of smoking and heavy alcohol use on cognitive decline in early old age: Whitehall II prospective cohort study
Authors: Hagger-Johnson Gareth , Sabia Séverine , Brunner Eric John , Shipley Martin , Bobak Martin , Marmot Michael , Kivimaki Mika , Singh-Manoux Archana
Published: July 2013

Background

Identifying modifiable risk factors for cognitive decline may inform prevention of dementia.

Aims

To examine the combined impact of cigarette smoking and heavy alcohol consumption on cognitive decline from midlife.

Method

Prospective cohort study (Whitehall II cohort) with three clinical examinations in 1997/99, 2002/04 and 2007/09. Participants were 6473 adults (72% men), mean age 55.76 years (s.d. = 6.02) in 1997/99. Four cognitive tests, assessed three times over 10 years, combined into a global z-score (mean 0, s.d. = 1).

Results

Age-related decline in the global cognitive score was faster in individuals who were smoking heavy drinkers than in non-smoking moderate alcohol drinkers (reference group). The interaction term (P = 0.04) suggested that the combined effects of smoking and alcohol consumption were greater than their individual effects. Adjusting for age, gender, education and chronic diseases, 10-year decline in global cognition was −0.42 z-scores (95% Cl −0.45 to −0.39) for the reference group. In individuals who were heavy alcohol drinkers who also smoked the decline was −0.57 z-scores (95% Cl −0.67 to −0.48); 36% faster than the reference group.

Conclusions

Individuals who were smokers who drank alcohol heavily had a 36% faster cognitive decline, equivalent to an age-effect of 2 extra years over 10-year follow-up, compared with individuals who were non-smoking moderate drinkers.
Structural and Functional Analysis of the Amphioxus IGFBP Gene Uncovers Ancient Origin of IGF-Independent Functions
Authors: Zhou Jianfeng , Xiang Jianhai , Zhang Shicui , Duan Cunming
Published: July 2013

IGFs play key roles in regulating vertebrate development, growth, reproduction, and aging. In extracellular fluids, IGFs are bound and regulated by a family of IGF-binding proteins (IGFBPs). Although all known IGFBPs are secreted proteins, some are also found in the nucleus and possess IGF-independent activities. When and how these distinct modes of biological actions have evolved is unknown. In this study, we identified and analyzed an IGFBP gene from amphioxus. Amphioxus shares a common ancestor with the modern vertebrate lineage that dates back to more than 520 million years ago. The amphioxus IGFBP shares all major structural characteristics of vertebrate IGFBPs. Phylogenetic analyses place it in a basal position in the IGFBP lineage. Ligand blot analysis reveals that amphioxus IGFBP does not bind to IGF-I or -II. Changing its Phe70 into Leu, however, is sufficient to convert it into a functional IGF binder. When tested in cultured cells, amphioxus IGFBP is localized in the nucleus, and this is attributed to 2 redundant nuclear localization sequences in its L domain. Furthermore, the amphioxus IGFBP N-terminal domain has strong transcriptional activation activity. Forced expression of amphioxus IGFBP in zebrafish embryos results in dorsalized phenotypes. This action requires nuclear localization. These results suggest that the nuclear localization and transcription activation activity of IGFBPs are ancient functions and the IGF-binding function may have been acquired by opportunistic gain-of-functional mutations later in evolution.