bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Ranibizumab monotherapy versus combination of Ranibizumab with photodynamic therapy with neovascular age‐related macular degeneration
Authors: Krebs Ilse , Vécsei Marlovits Veronika , Bodenstorfer Johannes , Glittenberg Carl , Ansari Shahrezaei Siamak , Ristl Robin , Binder Susanne
Published: December 2012

Purpose:  Modern therapy of neovascular age‐related macular degeneration consists in intravitreal injections of inhibitors of the vascular endothelial growth factor. An increasing number of these injections is required not only in monthly but also in as‐needed treatment regimen. In this study, it should be examined whether an additional administered photodynamic therapy (PDT) can considerably reduce the number of injection.

Methods:  In this prospective, randomized study carried out in three large hospitals of Vienna eyes with neovascular age‐related macula degeneration were included. Patients were randomized to either Ranibizumab monotherapy or combined standard fluence PDT and Ranibizumab therapy. All patients received a loading dose of three intravitreal Ranibizumab injections and were thereafter treated in an as‐needed regimen based on distance acuity and retinal thickness values. In the combined treatment group, PDT was administered 1 day after the first Ranibizumab injection.

Results:  Fifty‐one patients were randomized, 44 were finally included (four screening failures and three withdrawals). Twenty‐four patients were assigned to the monotherapy and 20 patients to the combined treatment group. Fewer injections were required in the combined treatment group (4.7 versus 6.3). Overall the patients lost 0.5 letters; in the combined treatment group, the patients lost mean 7.1 letters; in the monotherapy group, they gained mean 5.1 letters. Retinal thickness decreased significantly in both groups.

Conclusion:  A significant reduction of the number of required intravitreal injections could be achieved by the additional PDT treatment, but was accompanied by a worse functional outcome in this group.
Effects of meat species on the postprandial thermic effect in rats
Authors: Wakamatsu Jun‐ichi , Fujii Ryoji , Yamaguchi Kimikazu , Miyoshi Syouhei , Nishimura Takanori , Hattori Akihito
Published: December 2012

We examined animal species differences in the postprandial thermic effect of meat and investigated the postprandial thermic effect of mutton in rats. After intake of experimental diets containing each meat, body temperatures of rats fed mutton or venison were significantly higher than that of rats fed rabbit meat. After intake of experimental diets containing fractionized mutton, the body temperatures of rats fed diets containing lean mutton protein were higher than those of rats fed diets without lean mutton protein. In a two‐dimensional fluorescence difference gel electrophoresis study of brown adipose tissue, it was shown that the intake of mutton up‐regulated the expression of many signaling molecules that are involved in energy metabolism. The postprandial thermic effect of mutton seems to be due not to catecholamine and adrenocorticotropic hormone but to thyroid hormones. The results suggest that intake of lean mutton protein stimulates the secretion of thyroid hormones and facilitates energy metabolism in rats.
Satellite cells produce neural chemorepellent semaphorin 3A upon muscle injury
Authors: SATO Yusuke , DO Mai‐Khoi Q. , SUZUKI Takahiro , OHTSUBO Hideaki , MIZUNOYA Wataru , NAKAMURA Mako , FURUSE Mitsuhiro , IKEUCHI Yoshihide , TATSUMI Ryuichi
Published: December 2012

Regenerative mechanisms that regulate intramuscular motor innervation. including configuration of the neuromuscular connections are thought to reside in the spatiotemporal expression of axon‐guidance molecules. Our previous studies proposed a heretofore unexplored role of satellite cells as a key source of a secreted neural chemorepellent semaphorin 3A (Sema3A) expression. In order to verify this concept, there is still a critical need to provide direct evidence to show the up‐regulation of Sema3A protein in satellite cells in vivo upon muscle injury. The present study employed a Sema3A/MyoD double‐immunohistochemical staining for cryo‐sections prepared from cardiotoxin injected gastrocnemius muscle of adult mouse lower hind‐limb. Results clearly demonstrated that Sema3A expression was up‐regulated in myogenic differentiation‐positive satellite cells at 4–12 days post‐injury period, the time that corresponds to the cell differentiation phase characterized by increasing myogenin messenger RNA expression. This direct proof encourages a possible implication of satellite cells in the spatiotemporal regulation of extracellular Sema3A concentrations, which potentially ensures coordinating a delay in neurite sprouting and re‐attachment of motoneuron terminals onto damaged muscle fibers early in muscle regeneration in synchrony with recovery of muscle‐fiber integrity.
Thiopurine methyltransferase genotype–phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia
Authors: Lennard Lynne , Cartwright Cher Suzanne , Wade Rachel , Richards Susan M. , Vora Ajay
Published: December 2012

Aims

In children with acute lymphoblastic leukaemia (ALL) bone marrow activity can influence red blood cell (RBC) kinetics, the surrogate tissue for thiopurine methyltransferase (TPMT) measurements. The aim of this study was to investigate TPMT phenotype–genotype concordance in ALL, and the influence of TPMT on thiopurine metabolite formation.

Methods

We measured TPMT (activity, as units ml−1 packed RBCs and genotype) at diagnosis (n = 1150) and TPMT and thioguanine nucleotide (TGN) and methylmercaptopurine nucleotide (MeMPN) metabolites (pmol/8 × 108 RBCs) during chemotherapy (n = 1131) in children randomized to thioguanine or mercaptopurine on the United Kingdom trial ALL97.

Results

Median TPMT activity at diagnosis (8.5 units) was significantly lower than during chemotherapy (13.8 units, median difference 5.1 units, 95% confidence interval (CI) 4.8, 5.4, P < 0.0001). At diagnosis genotype–phenotype was discordant. During chemotherapy the overall concordance was 92%, but this fell to 55% in the intermediate activity cohort (45% had wild‐type genotypes). For both thiopurines TGN concentrations differed by TPMT status. For mercaptopurine, median TGNs were higher in TPMT heterozygous genotype (754 pmol) than wild‐type (360 pmol) patients (median difference 406 pmol, 95% CI 332, 478, P < 0.0001), whilst median MeMPNs, products of the TPMT reaction, were higher in wild‐type (10 650 pmol) than heterozygous patients (3868 pmol) (P < 0.0001). In TPMT intermediate activity patients with a wild‐type genotype, TGN (median 366 pmol) and MeMPN (median 8590 pmol) concentrations were similar to those in wild‐type, high activity patients.

Conclusions

In childhood ALL, TPMT activity should not be used to predict heterozygosity particularly in blood samples obtained at disease diagnosis. Genotype is a better predictor of TGN accumulation during chemotherapy.
Development and validation of the supervisory relationship measure: A self‐report questionnaire for use with supervisors
Authors: Pearce Nathalie , Beinart Helen , Clohessy Sue , Cooper Myra
Published: December 2012

Objective

To develop a valid and reliable measure of the supervisory relationship (SR) from the perspective of the supervisor.

Design

A cross‐sectional self‐report questionnaire design was used with a repeated component for a subsample.

Method

Qualitative data from a previous study of the SR (collected by interviews with supervisors) were used to construct an 89‐item self‐report questionnaire measure (Supervisory Relationship Measure [SRM]). This was administered to 267 clinical psychology supervisors involved in supervising UK trainee clinical psychologists. One hundred and thirty‐four participants completed the measure a second time to establish its test–retest reliability.

Results

Principal components analysis was used. Five factors were identified and labelled ‘safe base’, ‘supervisor commitment’, ‘trainee contribution’, ‘external influences’, and ‘supervisor investment’. Fifty‐one items (comprising five subscales based on the factors identified) were selected for the final measure. Analyses revealed the SRM to have good internal consistency, good test–retest reliability, and good construct (convergent and divergent) validity. A preliminary test of predictive (statistical) validity (supervisor satisfaction with the relationship and trainee competence as perceived by the supervisor) yielded promising results.

Conclusion

The SRM is a valid and reliable measure of the SR from the supervisor perspective. It predicts supervisor satisfaction and preliminary evidence suggests that it may also predict trainee competence (as perceived by the supervisor). The findings are consistent with current theory on the SR. The SRM is, therefore, a promising tool for use in research, clinical, and training settings.

Practitioner points

The supervisory relationship measure (SRM) is a new psychometrically sound measure of the supervisory relationship (SR) with clinical and research uses.

Clinically, it is a useful and structured way for supervisors to provide constructive feedback to their trainees.

It can be used in conjunction with the Supervisory Relationship Questionnaire (SRQ) (completed by the supervisee) to support a dyadic discussion about clinical supervision.

Currently the measure is only validated on Clinical Psychology trainees and should be used with caution with qualified staff and other professional groups.

Participants were predominantly white British supervisors who chose to take part in an internet‐based study and thus the sample may not be fully representative of the population.
Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor‐bearing microparticles: a randomized‐controlled phase II trial (the Microtec study)
Authors: Zwicker Jeffrey I. , Liebman Howard A. , Bauer Kenneth A. , Caughey Thomas , Campigotto Federico , Rosovsky Rachel , Mantha Simon , Kessler Craig M. , Eneman Jonathan , Raghavan Vidya , Lenz Heinz‐Joseph , Bullock Andrea , Buchbinder Elizabeth , Neuberg Donna , Furie Bruce
Published: December 2012

Elevated levels of circulating tissue factor‐bearing microparticles (TFMP) have been associated with an increased risk of developing venous thromboembolism (VTE) in cancer patients. We performed a randomized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP randomized to enoxaparin or observation. The cumulative incidence of VTE at 2 months in the higher TFMP group randomized to enoxaparin (N = 23) was 5·6% while the higher TFMP group observation arm (N = 11) was 27·3% (Gray test P = 0·06). The cumulative incidence of VTE in the low TFMP was 7·2% (N = 32). No major haemorrhages were observed in the enoxaparin arm. The median survival for patients with higher levels of TFMP followed by observation was 11·8 months compared with 17·8 months on enoxaparin (P = 0·58). In a prospective randomized trial, increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE. Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP, with an overall rate of VTE similar in magnitude to the lower TFMP group.
Detection of BCR‐ABL1 mutations in chronic myeloid leukaemia by massive parallel sequencing
Authors: Eyal Eran , Tohami Tali , Amir Amnon , Cesarkas Karen , Jacob‐Hirsch Jasmine , Volchek Yuliya , Nagler Arnon , Rechavi Gideon , Amariglio Ninette
Published: December 2012

The ability to sequence nucleic acids at an unprecedented pace and decreased costs using massive parallel sequencing (MPS) strongly affects biomedical research. Here we applied MPS for the detection of rare, clinically relevant mutations in a chronic myeloid leukaemia (CML) patient. Tyrosine kinase inhibitors revolutionized CML therapy but in some patients the disease progresses due to resistance‐conferring mutations. MPS was applied herein to monitor such mutations in BCR‐ABL1 transcripts at different time points. The large volume of sequencing data increases sensitivity compared to direct sequencing and allows detection of marginally represented and previously uncharacterized mutations. We detected changes in the frequency of mutated clones including the emergence and disappearance of the resistance‐associated ABL1 T315I mutation. We also observed correlation in appearance of adjacent mutations, and exploited this observation to demonstrate the existence of mutated clones at the time of diagnosis. A tool is provided for detection of low frequency single nucleotide variants/mutations from deep coverage MPS data, applicable to clinical translation of advanced sequencing technologies.
Lymph node enlargement and risk of haematological and solid cancer
Authors: Frederiksen Henrik , Sværke Claus , Thomsen Reimar W. , Farkas Dóra K. , Pedersen Lars , Weiss Noel S. , Sørensen Henrik T.
Published: December 2012

Enlarged lymph nodes may be a marker of occult cancer, but accurate data on cancer risk are limited. We used population‐based Danish medical registries to assess cancer risk in a cohort of patients with a first‐time inpatient or outpatient hospital contact for enlarged lymph nodes during 1994–2008. Observed cancer incidences were compared with that expected in the general population. We observed 1750 cancers among 11 284 patients with enlarged lymph nodes during median follow up of 4·7 years. Only 389 cases were expected. Cancer risk was 11·5% [95% confidence interval (CI): 10·9–12·1%] during the first year of follow up, corresponding to an age‐ and sex‐standardized incidence ratio (SIR) of 21·1 (95% CI: 20·0–22·3). One‐year SIRs were more than 100 times increased for head and neck cancer and lymphomas. Beyond one year of follow up, overall cancer risk remained 1·4‐fold (95% CI: 1·3–1·5‐fold) higher than expected, while risk of lymphoma remained six to 10 times higher. Cancer risk was also elevated among patients with other conditions known to be associated with enlarged lymph nodes, such as infections and rheumatic disorders. We conclude that enlarged lymph nodes are a marker of occult cancer and long‐term risk of cancer.
Evaluation of an ICF‐based patient education programme for stroke patients: A randomized, single‐blinded, controlled, multicentre trial of the effects on self‐efficacy, life satisfaction and functioning
Authors: Sabariego Carla , Barrera Andrea E. , Neubert Silvia , Stier‐Jarmer Marita , Bostan Cristina , Cieza Alarcos
Published: December 2012

Objective

There is a current need for interventions that provide information to stroke survivors in a patient‐centred, interactive, personalized and flexible manner. To this purpose, a standardized but content‐flexible patient education programme based on the International Classification of Functioning, Disability and Health (ICF) was developed. This study evaluated the effect of this programme on perceived self‐efficacy.

Design

Single‐blind, randomized, multi‐centre controlled trial.

Methods

Stroke patients undergoing neurological rehabilitation were enrolled. Perceived self‐efficacy was measured with the Liverpool Self‐Efficacy Scale. Secondary outcomes were life satisfaction and self‐perception of the impact of the stroke on life, measured with the WHOQOL and the Stroke Impact Scale, respectively. Data obtained at baseline, post‐intervention and 6‐month follow‐up were analysed using multi‐level models of change.

Results

Two hundred and thirteen patients received either the ICF‐based patient education (n = 110) or an attention‐placebo (n = 103) control intervention. Over time, patients' self‐efficacy (p < .01) and participation (p < .01) improved, while emotional functioning (p < .01) deteriorated, although no significant between‐group differences were observed. Explorative analyses showed that gender, loci of control, difficulty in accessing health services after discharge and life satisfaction were significant predictors of self‐efficacy.

Conclusion

There was no significant benefit of the ICF‐based patient education in comparison with an attention‐placebo control group. Considering the importance of the programme for the further implementation of the ICF and the need of developing effective health education interventions for stroke, the methodology used was reviewed and an updated version proposed.

Statement of contribution

What is already known on this subject? Stroke survivors frequently report dissatisfaction about content, delivery and timing of information provision on several aspects of the disease as well as on available support. Although several interventions targeting information provision have been developed in the past years, an optimal format for such interventions has not been established yet. A recent review of health education interventions for stroke survivors encourages therefore the development of new programmes providing information in a patient‐centred, interactive, personalized, flexible and repetitive manner.

What does this study add? An innovative, standardized but content flexible patient education based on the ICF is evaluated. An implementation possibility of the ICF and of an ICF Core Set in clinical practice is presented. The usefulness of the ICF in providing a valuable framework to structure health education interventions is shown.
Inside Out: Targeting NHE1 as an Intracellular and Extracellular Regulator of Cancer Progression
Authors: Provost Joseph J. , Wallert Mark A.
Published: December 2012

The sodium hydrogen exchanger isoform one is a critical regulator of intracellular pH, serves as an anchor for the formation of cytoplasmic signaling complexes, and modulates cytoskeletal organization. There is a growing interest in the potential for sodium hydrogen exchanger isoform one as a therapeutic target against cancer. Sodium hydrogen exchanger isoform one transport drives formation of membrane protrusions essential for cell migration and contributes to the establishment of a tumor microenvironment that leads to the rearrangement of the extracellular matrix further supporting tumor progression. Here, we focus on the potential impact that an inexpensive, $100 genome would have in identifying prospective therapeutic targets to treat tumors based upon changes in gene expression and variation of sodium hydrogen exchanger isoform one regulators. In particular, we will focus on the ezrin, radixin, moesin family proteins, calcineurin B homologous proteins, Ras/Raf/MEK/ERK signaling, and phosphoinositide signaling as they relate to the regulation of sodium hydrogen exchanger isoform one in cancer progression.
Beyond the Hundred Dollar Genome – Drug Discovery Futures
Authors: Selwood David L.
Published: December 2012

The advent of silicon chip based technologies for genome sequencing promises continuing exponential falls in the reagent costs of sequencing. When every patient has a full genome sequence as part of their medical records the science of drug discovery and drug design must adapt and improve to meet this challenge. This series covers computational, and experimental approaches for small molecules and biologics. From the virtual patient – a computational model of a complete human being, through in silico screening to RNA editing and antibody directed therapies.
Families Created by Reproductive Donation: Issues and Research
Authors: Golombok Susan
Published: December 2012

A growing number of children are being born through the donation of gametes (sperm or eggs) or embryos, or the hosting of a pregnancy for another woman (surrogacy), thus creating families in which children lack a gestational and/or genetic relationship with one or both parents. Research on these families suggests that concerns about adverse outcomes for parenting and child development are largely unfounded. Although less is known about nontraditional families formed through reproductive donation than about traditional families, these new family types likely are not at risk for parenting or child‐adjustment problems. Overall, findings suggest that the absence of a genetic or gestational connection between parents and children does not have an adverse effect on the quality of parent–child relationships or children's adjustment.
The Role of Sex of Peers and Gender‐Typed Activities in Young Children's Peer Affiliative Networks: A Longitudinal Analysis of Selection and Influence
Authors: Martin Carol Lynn , Kornienko Olga , Schaefer David R. , Hanish Laura D. , Fabes Richard A. , Goble Priscilla
Published: December 2012

A stochastic actor‐based model was used to investigate the origins of sex segregation by examining how similarity in sex of peers and time spent in gender‐typed activities affected affiliation network selection and how peers influenced children's (N = 292; Mage = 4.3 years) activity involvement. Gender had powerful effects on interactions through direct and indirect pathways. Children selected playmates of the same sex and with similar levels of gender‐typed activities. Selection based on gender‐typed activities partially mediated selection based on sex of peers. Children influenced one another's engagement in gender‐typed activities. When mechanisms producing sex segregation were compared, the largest contributor was selection based on sex of peers; less was due to activity‐based selection and peer influence. Implications for sex segregation and gender development are discussed.
Influence of self‐esteem and negative affectivity on oral health‐related quality of life in patients with partial tooth loss
Authors: Özhayat Esben B.
Published: December 2012

To meaningfully interpret oral health‐related quality of life (OHRQoL) measures, the influence of personality traits must be investigated.

Objectives

To investigate and quantify the influence of self‐esteem and negative affectivity (NA) on OHRQoL. It was hypothesized that low self‐esteem and high NA would be associated with worse OHRQoL.

Methods

OHRQoL measured by the Oral Health Impact Profile 49 (OHIP‐49), self‐esteem measured by the Rosenberg Self‐Esteem Scale (RSES), NA measured by the Eysenck Personality Inventory Questionnaire (EPI‐Q), global oral rating of oral comfort and controlling variables (gender, age, number of teeth, experience of wearing removable dental prostheses (RDP), location of missing teeth and zone of missing teeth) were collected from 81 patients with partial tooth loss, signed in for treatment with RDP.

Results

Bivariate analyses showed that the EPI‐Q score had the highest correlation with OHIP‐49 score (R = 0.5). Both EPI‐Q and RSES score had a stronger correlation with psychosocial items than physical/functional items of the OHIP‐49. In the multivariate analyses, the controlling variables alone explained 17.75% of the variance in OHIP‐49 score, while addition of EPI‐Q score, RSES score and both EPI‐Q and RSES score explained additionally 11.64%, 6.07% and 14.12%, respectively. For each unit increase in EPI‐Q score, the OHIP‐49 score increased 5.1 units and for each unit increase in RSES score, the OHIP‐49 score decreased 1.1. NA was statistically and clinically significantly higher and self‐esteem was statistically significantly lower in patients reporting worse oral comfort.

Conclusion

NA had the strongest and most clinically meaningful influence, but both NA and self‐esteem was found to influence OHRQoL; low self‐esteem and high NA was associated with worse OHRQoL. This indicates the possibility to explain some of the impact of tooth loss on OHRQoL based on personality traits.
Progesterone therapy increases free thyroxine levels—data from a randomized placebo‐controlled 12‐week hot flush trial
Authors: Sathi P. , Kalyan S. , Hitchcock C. L. , Pudek M. , Prior J. C.
Published: December 2012

Objective

Thyroid hormones and progesterone both influence core temperature, metabolism and are crucial during pregnancy. Our objective was to discover whether progesterone therapy caused changes in thyroid physiology compared with placebo.

Design

Post hoc analysis from a randomized (1:1) placebo‐controlled 12‐week trial of oral micronized progesterone (Progesterone, 300 mg/d at bedtime) for hot flushes (vasomotor symptoms, VMS) conducted in an academic medical centre.

Patients

Postmenopausal euthyroid, healthy (without cardiovascular diseases or risks) women, 1–11 years since last flow on no thyroid or ovarian hormone therapy with VMS participated.

Measurements

Primary outcomes were final and 12‐week changes in TSH, FreeT3 and FreeT4 on progesterone vs placebo.

Results

Women with thyroid data (69 of 133 in original trial) were randomized to progesterone (n = 39) or placebo (n = 30)—baseline thyroid values were normal. There were no VMS‐thyroid interactions—VMS Score (number × intensity) did not correlate with TSH, FreeT3 or FreeT4 (Spearman's rank correlations: −0.03 to −0.19, respectively; all P > 0.15). At 12 weeks on progesterone, TSH levels tended to be lower (1.7 mU) than on placebo (2.2), P = 0.06; FreeT4 levels were higher (16.4 pmol/l) than on placebo (15.3), P = 0.02. FreeT3 was unchanged throughout. Analysis of covariance showed a significant increase in FreeT4 on progesterone (+2.5 pmol/l; 1.9–3.0) vs on placebo (+1.7; 1.1–2.4) with 95% CI of difference = 0.8 pmol/l [0.0, 1.6], P = 0.04.

Conclusions

Progesterone caused a significant FreeT4 increase that was discovered during this randomized controlled VMS trial. The clinical importance of this increased FreeT4 level remains to be documented. Registered at ClinialTrials.gov#NCT00152438.
Triptolide with Potential Medicinal Value for Diseases of the Central Nervous System
Authors: Zheng Yan , Zhang Wen‐Jing , Wang Xiao‐Min
Published: December 2012

Tripterygium wilfordii Hook.f. (TWHF) has a long history as a Traditional Chinese Medicine (TCM) herb that aids in treating inflammatory and autoimmune diseases. The major bioactive component of TWHF is triptolide, which has been recognized to possess a broad spectrum of biological profiles including antiinflammatory, immunosuppressive, antifertility, and antitumor activities, as well as neurotrophic and neuroprotective effects. Limitation of triptolide, such as poor water solubility and severe systemic toxicity, has postponed clinical development and trials; however, the wide range of medicinal value of triptolide has been drawing intensive worldwide attention. In particular, triptolide has been shown to have significant effects on central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, spinal cord and brain injury, and multiple sclerosis. This review focuses on the potential therapeutic role of triptolide on CNS diseases, and discusses the structural features, potential modifications, and the other pharmacological activities of triptolide.
Pifithrin‐α Enhances the Survival of Transplanted Neural Stem Cells in Stroke Rats by Inhibiting p53 Nuclear Translocation
Authors: Lei Xu‐Hui , Zhao Dan , Li Yong‐Li , Li Xian‐Feng , Sun Xu , Du Wen‐Zhong , Sun Ying , Hao Zhong‐Fei , Xin Shi‐Yue , Liu Cong , Zhang Zhi‐Ren , Jiang Chuan‐Lu
Published: December 2012

Aims

To examine a novel strategy to enhance the survival of grafted neural stem cells (NSCs) in stroke model.

Methods

Using a cell counting kit‐8 (CCK‐8) and TUNEL assay to test the protective effects of p53 inhibitor, pifithrin‐α (PFT‐α), on oxygen glucose deprivation (OGD) in NSCs. We compared the effects of vehicle + NSCs and FFT‐α + NSCs on the efficacy of transplantation in stroke rat model using behavioral analysis, immunohistochemistry, etc.

Results

Pifithrin‐α increased viability and decreased apoptosis in NSCs after OGD in vitro. By in vivo studies, we showed that the best recovery of neurological function in the stroke rats and the maximum survival of grafted NSCs were found in the PFT‐α + NSCs group. Twelve hours after cell transplantation, p53 was localized to the nuclei of grafted NSCs in the vehicle + NSCs group but was primarily localized to the cytoplasm in the PFT‐α + NSCs group. The p53‐upregulated modulator of apoptosis (PUMA) was highly expressed among the grafted cells in the vehicle + NSCs group compared with that in the PFT‐α + NSCs group.

Conclusion

Our results indicate that PFT‐α enhances the survival of grafted NSCs through the inhibition of p53 translocation into the nucleus.
Research Management Team (RMT): A Model for Research Support ‐Services at Duke University
Authors: Snyder Denise C. , Epps Shelly , Beresford Henry F. , Ennis Cory , Levens Justin S. , Woody Stephen K. , Tcheng James E. , Stacy Mark A. , Nahm Meredith
Published: December 2012

Collecting and managing data for clinical and translational research presents significant challenges for clinical and translational researchers, many of whom lack needed access to data management expertise, methods, and tools. At many institutions, funding constraints result in differential levels of research informatics support among investigators. In addition, the lack of widely shared models and ontologies for clinical research informatics and health information technology hampers the accurate assessment of investigators’ needs and complicates the efficient allocation of crucial resources for research projects, ultimately affecting the quality and reliability of research. In this paper, we present a model for providing flexible, cost‐efficient institutional support for clinical and translational research data management and informatics, the research management team, and describe our initial experiences with deploying this model at our institution. Clin Trans Sci 2012; Volume 5: 464–469
Collagenous sprue diagnosed by double balloon endoscopy
Authors: Yamamoto Yu , Yamada Takeshi , Akutsu Daisuke , Sugaya Akinori , Murashita Tetsuya , Matsuda Kenji , Yamamoto Yoshiyuki , Kusakabe Ryoko , Kaneko Tsuyoshi , Suzuki Hideo , Hyodo Ichinosuke , Sato Taiki , Takayashiki Norio , Murakoshi Naoto , Hara Ken , Mizokami Yuji
Published: December 2012

Double balloon endoscopy (DBE) is useful for diagnosing many intestinal diseases and for endoscopic procedures. We report a case of chronic diarrhea in a 58‐year‐old Japanese man. He was initially suspected to have malabsorption syndrome. DBE showed reduction of folds, scalloping, mucosal nodularity and granularity. Pathological examinations of biopsies from the jejunum showed severe villous atrophy with subepithelial collagen bands. These findings led to the final diagnosis of collagenous sprue (CS). With1 month of total parenteral nutrition followed by a low‐gluten diet, his symptoms gradually improved. CS has never been reported before in Japan. DBE is useful for making a diagnosis of CS, and may be considered for patients who are suffering from diarrhea of unknown cause.
Atypical updating of face representations with experience in children with autism
Authors: Ewing Louise , Pellicano Elizabeth , Rhodes Gillian
Published: December 2012

Face identity aftereffects are significantly diminished in children with autism relative to typical children, which may reflect reduced perceptual updating with experience. Here, we investigated whether this atypicality also extends to non‐face stimulus categories, which might signal a pervasive visual processing difference in individuals with autism. We used a figural aftereffect task to measure directly perceptual updating following exposure to distorted upright faces, inverted faces and cars, in typical children and children with autism. A size‐change between study and test stimuli limited the likelihood that any processing atypicalities reflected group differences in adaptation to low‐level features of the stimuli. Results indicated that, relative to typical children, figural aftereffects for upright faces, but not inverted faces or cars, were significantly attenuated in children with autism. Moreover, the group difference was amplified when we isolated the ‘face‐selective’ component of the aftereffect, by partialling out the mid‐level shape adaptation common to upright and inverted face stimuli. Notably, the aftereffects of typical children were disproportionately larger for upright faces than for inverted faces and cars, but the magnitude of aftereffects of autistic children was not similarly modulated according to stimulus category. These findings are inconsistent with a pervasive adaptive coding atypicality relative to typical children, and suggest that reduced perceptual updating may constitute a high‐level, and possibly face‐selective, visual processing difference in children with autism.
Screening for diabetic retinopathy in pregnancy using photographic review clinics
Authors: Hampshire R. , Wharton H. , Leigh R. , Wright A. , Dodson P.
Published: December 2012

Aims

To assess the efficacy and value of the National Institute for Health and Clinical Excellence guidelines for digital photographic screening for diabetic retinopathy in pregnancy using photographic review clinics.

Methods

Pregnant patients (n = 186) with known diabetes were screened at first antenatal visit and at 28 weeks' gestation, if no retinopathy was noted at first visit, or at other intervals if retinopathy was present. Two 45° images (disc‐centred and macula‐centred views) were taken in both eyes and graded by trained graders and by an ophthalmologist.

Results

Ninety‐three patients (50%) remained free of diabetic retinopathy throughout pregnancy. Eighteen (10%) presented with sight‐threatening retinopathy at their first antenatal screen and were referred to the hospital eye service. Fifty patients (27%) were shown to have relatively stable retinopathy throughout pregnancy, with only two patients deteriorating and requiring referral to hospital eye service. Twenty‐three (12%) failed to complete the screening protocol after their first screen.

Conclusions

The study showed that pregnant patients screened for retinopathy in an ophthalmic photographic diabetic review clinic achieved National Institute for Health and Clinical Excellence guidelines in the majority and were clinically safe. Only 1% of patients required referral to ophthalmology after their initial screen, thus avoiding unnecessary hospital eye service appointments.
Is it Just a Bad Class? Assessing the Long‐term Stability of Estimated Teacher Performance
Authors: Goldhaber Dan , Hansen Michael
Published: December 2012

A number of teacher workforce policies implicitly assume that job performance is a relatively stable attribute within teachers. We use longitudinal data on 5th grade teachers in North Carolina to assess this using value‐added measures (VAMs) of job performance. We find that there is a permanent component of teacher performance that is stable in teachers over long periods—implying that workforce policies selecting teachers based on VAMs could effectively improve student achievement. But importantly, our time series model suggests that the permanent component of performance is considerably smaller than that which is often used to estimate workforce policy impacts.
Back to Baseline in Britain: Adaptation in the British Household Panel Survey
Authors: Clark Andrew E. , Georgellis Yannis
Published: December 2012

We look for evidence of adaptation in wellbeing to major life events using eighteen waves of British panel data. Adaptation to marriage, divorce, birth of child and widowhood appears to be rapid and complete; this is not so for unemployment. These findings are remarkably similar to those in previous work on German panel data. Equally, the time profiles with life satisfaction as the wellbeing measure are very close to those using a twelve‐item scale of psychological functioning. As such, the phenomenon of adaptation may be a general one, rather than being found only in German data or using single‐item wellbeing measures.
Exercise‐Induced Pulmonary Hypertension in Scleroderma Patients: A Common Finding but with Elusive Pathophysiology
Authors: Baptista Rui , Serra Sara , Martins Rui , Salvador Maria João , Castro Graça , Gomes Manuel , Santos Lèlita , Monteiro Pedro , da Silva Jose A. Pereira , Pêgo Mariano
Published: December 2012

Background: The etiology of exercise‐induced pulmonary hypertension (exPH) in systemic sclerosis (SSc) remains a complex task, as both left ventricle (LV) diastolic dysfunction and pulmonary vascular disease can contribute to its development. We determined the incidence of exPH in SSc and examined the association between pulmonary artery systolic pressure (PASP) and tissue Doppler‐derived indexes of pulmonary capillary wedge pressure (PCWP). Methods: Thirty‐eight patients with SSc were studied, using a cycloergometer protocol; 10 were excluded due to resting PH or absence of tricuspid regurgitation (TR); TR and mitral E‐wave velocities, LV outflow tract time‐velocity integral and LV septal E′‐wave were measured before and in peak exercise to calculate cardiac output (CO), PCWP and pulmonary vascular resistance (PVR). Results: Mean age of diagnosis was 57.9 ± 8.9 years. At a mean workload of 64 ± 29 Watts, 48% of patients increased PASP ≥ 50 mmHg. PCWP, assessed by the E/e′ ratio, did not change significantly during exercise (10.2 ± 3.1–10.0 ± 5.1; P = NS). Only 3 patients had elevations of the E/e′ ratio ≥ 13 during exercise; 2 of them had an exercise PASP ≥ 50 mmHg, yielding a proportion of exPH due to elevated LV filling pressures of 2/11 (18%). Patients with exPH had lower DLCO and had more frequently the diffuse SSc. Conclusion: The elevation of PASP during exercise in most patients of this cohort seems to be related to a reduced pulmonary vascular reserve, and not to an increase in PCWP. Further studies are warranted to determine the therapeutic, as well as prognostic implications of these findings.
Risk prediction of very early recurrence, death and progression after acute ischaemic stroke
Authors: Maier I. L. , Bauerle M. , Kermer P. , Helms H.‐J. , Buettner T.
Published: December 2012

Background and purpose

Early recurrent strokes lead to extended hospitalization and high number of complications. We investigated three stroke scores, the Essen Stroke Risk Score (ESRS), the ABCD² and the Recurrence Risk Estimator at 90 days (RRE‐90) for their prognostic value to predict early recurrent stroke, death and progressive stroke.

Methods

Clinical and radiological data from 1727 consecutive patients with ischaemic stroke, being admitted to the stroke unit, were evaluated retrospectively. Predictive value of stroke scores was tested for early recurrence within 7 days, death and progressive stroke expressed as observational risk and area under the receiver operator curve (AUROC).

Results

Early recurrent stroke occurred in 56 patients (3.2%), 40 patients (2.3%) died within the first 7 days and 125 patients (7.2%) had a progressive stroke. ESRS was not predictive for early recurrence, death or progressive stroke. ABCD² score was predictive for death (P < 0.01; χ²; AUROC, 0.65; 0.58–0.72), and progressive stroke (P < 0.001; χ²; AUROC, 0.70; 0.66–0.74). RRE‐90 predicted early recurrent stroke (P < 0.001; χ²; AUROC, 0.65; 0.58–0.73), early death (P < 0.001; χ²; AUROC, 0.72; 0.66–0.78) and progressive stroke (P < 0.001; χ²; AUROC, 0.66; 0.61–0.71).

Conclusions

RRE‐90 bears high potential to not only predict early recurrence but also death and progression after ischaemic stroke. ABCD² appears to be useful to predict risk of death and progression. These findings have relevant clinical implications for early triage of patients being admitted to stroke units.
Genetic variation in the receptor for advanced glycation end‐products (RAGE) gene and ischaemic stroke
Authors: Olsson S. , Jood K.
Published: December 2012

Background and purpose

The multi‐ligand receptor for advanced glycation end‐products (RAGE, alias AGER) is suggested to contribute to the pathogenesis of vascular disease, but its potential role in stroke is unclear. The aim of this study was to investigate whether genetic variation in RAGE gene is associated with ischaemic stroke (IS).

Methods

The Sahlgrenska Academy Study on Ischaemic Stroke comprises 844 Caucasian patients with first ever (n = 732) and recurrent (n = 112) IS, and 668 Caucasian controls. Three tagSNPs were selected to capture genetic variation in the RAGE gene. IS subtypes were determined using TOAST criteria.

Results

One SNP, rs1035798, showed significant association with the subtype of small‐vessel disease (SVD) after correction for multiple testing (OR 1.56, 95% CI 1.16–2.09), adjusted P‐value < 0.05). This association was independent of hypertension, diabetes and smoking. None of the SNPs was associated with overall IS.

Conclusion

In this sample of patients with IS, genetic variation in RAGE is associated with the IS subtype SVD, but not overall IS.
Six‐year follow‐up of a case series with non‐communicating syringomyelia in multiple sclerosis
Authors: Weier K. , Naegelin Y. , Amann M. , Magon S. , Mueller‐Lenke N. , Radue E.‐W. , Kappos L. , Stippich C. , Gass A. , Sprenger T.
Published: December 2012

Background

Non‐communicating syringomyelia (NCS) has occasionally been described in case reports and small case series as an incidental finding of spinal cord (SC) pathology in patients with multiple sclerosis (MS), but only little is known on the clinical course and progression of NCS, and in more general terms on the prognosis of patients with MS and NCS.

Methods

Nine patients with MS with known NCS at baseline and a control group of 18 age‐, sex‐ and disease course‐matched patients with MS without NCS were recruited for a follow‐up visit after 6 years. All 27 patients underwent clinical examination and brain magnetic resonance imaging (MRI), and 8/9 patients with NCS were additionally studied with MRI of the SC. MRI data were analysed for changes in length and maximal cross‐sectional area of the NCS, lesion volumes of the brain and cord as well as for volumetric metrics of the whole brain (using SIENAX), the cerebellum and medulla oblongata (using ECCET).

Results

NCS did not significantly change in size when corrected for multiple comparisons. The clinical data (annual relapse rate, EDSS and disease duration) and MRI metrics (T2 and T1 lesion load; whole brain, cerebellar and medulla oblongata volumes as well as their percentage volume change per year) did not significantly differ between patients with MS with or without NCS.

Conclusion

The stable findings regarding size and shape of the syrinx and lack of distinguishing MRI and clinical features support the assumption that NCS is not defining a prognostically or pathogenetically distinct subgroup of patients with MS.
Advanced age and liability to oxaliplatin‐induced peripheral neuropathy: post hoc analysis of a prospective study
Authors: Argyriou A. A. , Briani C. , Cavaletti G. , Bruna J. , Alberti P. , Velasco R. , Lonardi S. , Cortinovis D. , Cazzaniga M. , Campagnolo M. , Santos C. , Kalofonos H. P.
Published: December 2012

Background and purpose

The aim of this post hoc analysis of data extracted from a prospective, multicenter study is to test in a large homogenous population of chemotherapy‐naïve patients with colorectal cancer (CRC) treated with oxaliplatin (OXA)‐based chemotherapy whether advanced age increases the risk of developing OXA‐induced peripheral neuropathy (OXAIPN).

Methods

One‐hundred and forty‐five patients with CRC, without other significant co‐morbidities predisposing to peripheral neuropathy, were divided according to their age into two groups: patients aged between 50 and 68 years (group I, n = 75); and patients aged ≥ 69 years (group II, n = 70). Patients were prospectively monitored at baseline and followed‐up during chemotherapy using the motor and neurosensory National Cancer Institute Common Toxicity criteria, the clinical version of the Total Neuropathy Score and neurophysiology. The incidence and severity of both the acute and cumulative OXAIPN was thoroughly determined and then compared between age groups.

Results

No statistically significant difference was observed in the incidence of both the acute (n = 64/75 vs. 56/70; P = 0.510) and cumulative OXAIPN (n = 51/75 vs. 49/70; P = 0.858) between age groups. The severity of OXAIPN was also similar between age groups. In line with the clinical data, the neurophysiological results between age groups were also comparable.

Conclusion

The results of this study indicate that advanced age does not seem to represent a significant risk factor of OXAIPN in patients with CRC without any other significant co‐morbidities.
An investigation of the relationship between hindlimb lameness and saddle slip
Authors: Greve L. , Dyson S. J.
Published: December 2012

Reasons for performing study

We have observed saddle slip consistently to one side because of a crooked rider, an ill‐fitting saddle, asymmetry in a horse's thoracolumbar shape and lameness. Currently, there are no objective data to permit assessment of the relative importance of each factor.

Objectives

To document the frequency of occurrence of saddle slip in horses with hindlimb lameness compared with other horses. To describe the effect of lameness characteristics and grade, the abolition of lameness by diagnostic analgesia, breed, size, thoracolumbar shape and symmetry and the rider's weight.

Methods

One hundred and twenty‐eight horses were assessed prospectively, and lameness and saddle slip were assigned a grade before and after diagnostic analgesia. The thoracolumbar shape and symmetry were measured objectively. In 3 horses, the force distribution and magnitude underneath the saddle were measured before and after diagnostic analgesia.

Results

The saddle consistently slipped to one side in 38 of 71 horses (54%) with hindlimb lameness, compared with one of 26 horses (4%) with forelimb lameness, none of 20 (0%) with back pain and/or sacroiliac joint region pain and none of 11 sound horses (0%). The association between saddle slip and hindlimb lameness was significant (Spearman's rank correlation coefficient, ρ = 0.548, P<0.001). Diagnostic analgesia abolishing the hindlimb lameness eliminated the saddle slip in 37 of 38 horses (97%). In 2 horses, the saddle continued to slip after resolution of lameness; one horse had bilateral forelimb lameness and the other horse had concurrent hindlimb and forelimb lameness. The saddle of both these horses was asymmetrically flocked. The saddle slipped to the side of the lamer hindlimb in most horses (32 of 37 [86%]). No horse with saddle slip had significant left–right asymmetry of the back at 4 predetermined sites.

Conclusions and clinical relevance

Hindlimb lameness is an important factor in inducing saddle slip. Saddle slip may be an indicator of the presence of hindlimb lameness.
The six amino acid antimicrobial peptide bLFcin6 penetrates cells and delivers siRNA
Authors: Fang Bing , Guo Hui Y , Zhang Ming , Jiang Lu , Ren Fa Z
Published: December 2012

Cell‐penetrating peptides (CPPs) are a new class of vectors with high pharmaceutical potential to deliver bioactive cargos into cells. Here, we characterized bLFcin6, a six amino acid peptide derived from bovine lactoferricin, as a CPP. Uptake of bLFcin6 was measured by flow cytometry. The ability to delivery siRNA was analyzed in HeLa cells. bLFcin6 exhibited concentration‐dependent uptake and intracellular distribution. Below 7.5 μm, uptake of bLFcin6 was significantly lower than uptake of TAT (P < 0.05) because bLFcin6 has fewer cationic amino acids. Compared to CPP5 (RLRWR) and CPP6 (PFVYLI), bLFcin6 had a significantly higher internalization ratio above 2.5 μm because it has two tryptophan residues. Uptake of bLFcin6 starts with an ionic cell‐surface interaction. It is then rapidly internalized by lipid raft‐dependent macropinocytosis, followed by release from macropinosomes into the cytosol and nucleus. Moreover, bLFcin6 formed stable electrostatic complexes with siRNA and delivered siRNA into cells, resulting in significant knockout activity at both the mRNA and protein levels. The knockout activity of siRNA delivered by bLFcin6 was similar to that mediated by TAT, although knockout by bLFcin6 required a higher molar ratio. In this study, bLFcin6 was tested for its ability to act as an siRNA‐delivering CPP.