bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA‐146a controls Th1‐cell differentiation of human CD4+ T lymphocytes by targeting PRKCε
Authors: Möhnle Patrick , Schütz Stefanie V. , van der Heide Verena , Hübner Max , Luchting Benjamin , Sedlbauer Julia , Limbeck Elisabeth , Hinske Ludwig C. , Briegel Josef , Kreth Simone
Published: October 2014

T‐cell functions must be tightly controlled to keep the balance between vital proinflammatory activity and detrimental overactivation. MicroRNA‐146a (miR‐146a) has been identified as a key negative regulator of T‐cell responses in mice. Its role in human T cells and its relevance to human inflammatory disease, however, remains poorly defined. In this study, we have characterized miR‐146a‐driven pathways in primary human T cells. Our results identify miR‐146a as a critical gatekeeper of Th1‐cell differentiation processes acting via molecular mechanisms not uncovered so far. MiR‐146a targets protein kinase C epsilon (PRKCε), which is part of a functional complex consisting of PRKCε and signal transducer and activator of transcription 4 (STAT4). Within this complex, PRKCε phosphorylates STAT4, which in turn is capable of promoting Th1‐cell differentiation processes in human CD4+ T lymphocytes. In addition, we observed that T cells of sepsis patients had reduced levels of miR‐146a and an increased PRKCε expression in the initial hyperinflammatory phase of the disease. Collectively, our results identify miR‐146a as a potent inhibitor of Th1‐cell differentiation in human T cells and suggest that dysregulation of miR‐146a contributes to the pathogenesis of sepsis.
IL‐27 stimulates human NK‐cell effector functions and primes NK cells for IL‐18 responsiveness
Authors: Ziblat Andrea , Domaica Carolina I. , Spallanzani Raúl G. , Iraolagoitia Ximena L. Raffo , Rossi Lucas E. , Avila Damián E. , Torres Nicolás I. , Fuertes Mercedes B. , Zwirner Norberto W.
Published: October 2014

IL‐27, a member of the IL‐12 family of cytokines, is produced by APCs, and displays pro‐ and anti‐inflammatory effects. How IL‐27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL‐27 and that blockade of IL‐27R (CD130) reduced the amount of IFN‐γ produced by NK cells during their coculture, showing the importance of IL‐27 during DC–NK‐cell crosstalk. Accordingly, human rIL‐27 stimulated IFN‐γ secretion by NK cells in a STAT1‐dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL‐18. Preincubation experiments demonstrated that IL‐27 primed NK cells for IL‐18‐induced IFN‐γ secretion, which was associated with an IL‐27‐driven upregulation of T‐bet expression. Also, IL‐27 triggered NKp46‐dependent NK‐cell‐mediated cytotoxicity against Raji, T‐47D, and HCT116 cells, and IL‐18 enhanced this cytotoxic response. Such NK‐cell‐mediated cytotoxicity involved upregulation of perforin, granule exocytosis, and TRAIL‐mediated cytotoxicity but not Fas‐FasL interaction. Moreover, IL‐27 also potentiated Ab‐dependent cell‐mediated cytotoxicity against mAb‐coated target cells. Taken together, IL‐27 stimulates NK‐cell effector functions, which might be relevant in different physiological and pathological situations.
Seleno‐Nucleobases and Their Water‐Soluble Ruthenium–Arene Half‐Sandwich Complexes: Chemistry and Biological Activity
Authors: Mitra Raja , Pramanik Anup K. , Samuelson Ashoka G.
Published: October 2014

Half‐sandwich organometallic ruthenium complexes of seleno‐nucleobases, 3 and 4, were synthesized and characterized. The structures of both complexes were determined by X‐ray crystallography and are the first crystal structures of ruthenium complexes with seleno‐nucleobases. Interestingly, 3 self‐assembles aided by adventitious water in DMF to give a tetranuclear square 3a·6H2O. Complex 4 is active against Jurkat and Molt‐4 cell lines but inactive against the K562 cell line, whereas 3 is completely inactive against all three cell lines. The free ligand 6‐selenopurine (1) and 6‐selenoguanine (2) are highly active against these cell lines. Compound 2, like its thio analogue, is unstable under UVA light, whereas 4 is stable under similar conditions, which suggests that the ruthenium complex could reduce problems associated with the instability of the free ligand, 2, under irradiation.
Numerical simulation of 3D free surface flows, with multiple incompressible immiscible phases. Applications to impulse waves
Authors: James N. , Boyaval S. , Caboussat A. , Picasso M.
Published: October 2014

A numerical method for the solution to the density‐dependent incompressible Navier–Stokes equations modeling the flow of N immiscible incompressible liquid phases with a free surface is proposed. It allows to model the flow of an arbitrary number of liquid phases together with an additional vacuum phase separated with a free surface. It is based on a volume‐of‐fluid approach involving N indicator functions (one per phase, identified by its density) that guarantees mass conservation within each phase. An additional indicator function for the whole liquid domain allows to treat boundary conditions at the interface between the liquid domain and a vacuum. The system of partial differential equations is solved by implicit operator splitting at each time step: first, transport equations are solved by a forward characteristics method on a fine Cartesian grid to predict the new location of each liquid phase; second, a generalized Stokes problem with a density‐dependent viscosity is solved with a FEM on a coarser mesh of the liquid domain. A novel algorithm ensuring the maximum principle and limiting the numerical diffusion for the transport of the N phases is validated on benchmark flows. Then, we focus on a novel application and compare the numerical and physical simulations of impulse waves, that is, waves generated at the free surface of a water basin initially at rest after the impact of a denser phase. A particularly useful application in hydraulic engineering is to predict the effects of a landslide‐generated impulse wave in a reservoir. Copyright © 2014 John Wiley & Sons, Ltd.
Multivariate decoding of cerebral blood flow measures in a clinical model of on‐going postsurgical pain
Authors: O'Muircheartaigh Jonathan , Marquand Andre , Hodkinson Duncan J. , Krause Kristina , Khawaja Nadine , Renton Tara F. , Huggins John P. , Vennart William , Williams Steven C.R. , Howard Matthew A.
Published: October 2014

Recent reports of multivariate machine learning (ML) techniques have highlighted their potential use to detect prognostic and diagnostic markers of pain. However, applications to date have focussed on acute experimental nociceptive stimuli rather than clinically relevant pain states. These reports have coincided with others describing the application of arterial spin labeling (ASL) to detect changes in regional cerebral blood flow (rCBF) in patients with on‐going clinical pain. We combined these acquisition and analysis methodologies in a well‐characterized postsurgical pain model. The principal aims were (1) to assess the classification accuracy of rCBF indices acquired prior to and following surgical intervention and (2) to optimise the amount of data required to maintain accurate classification. Twenty male volunteers, requiring bilateral, lower jaw third molar extraction (TME), underwent ASL examination prior to and following individual left and right TME, representing presurgical and postsurgical states, respectively. Six ASL time points were acquired at each exam. Each ASL image was preceded by visual analogue scale assessments of alertness and subjective pain experiences. Using all data from all sessions, an independent Gaussian Process binary classifier successfully discriminated postsurgical from presurgical states with 94.73% accuracy; over 80% accuracy could be achieved using half of the data (equivalent to 15 min scan time). This work demonstrates the concept and feasibility of time‐efficient, probabilistic prediction of clinically relevant pain at the individual level. We discuss the potential of ML techniques to impact on the search for novel approaches to diagnosis, management, and treatment to complement conventional patient self‐reporting. Hum Brain Mapp 36:633–642, 2015. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.
Smoking increases risk of pain chronification through shared corticostriatal circuitry
Authors: Petre Bogdan , Torbey Souraya , Griffith James W. , De Oliveira Gildasio , Herrmann Kristine , Mansour Ali , Baria Alex T. , Baliki Marwan N. , Schnitzer Thomas J. , Apkarian Apkar Vania
Published: October 2014

Smoking is associated with increased incidence of chronic pain. However, the evidence is cross‐sectional in nature, and underlying mechanisms remain unclear. In a longitudinal observational study, we examined the relationship between smoking, transition to chronic pain, and brain physiology. In 160 subjects with subacute back pain (SBP: back pain lasting 4–12 weeks, and no prior back pain [BP] for at least 1 year) pain characteristics, smoking status, and brain functional properties were measured repeatedly over 1 year. Sixty‐eight completed the study, subdivided into recovering (SBPr, n = 31) and persisting (SBPp, n = 37), based on >20% decrease in BP over the year. Thirty‐two chronic back pain (CBP: duration > 5 years) and 35 healthy controls were similarly monitored. Smoking prevalence was higher in SBP and CBP but not related to intensity of BP. In SBP, smoking status at baseline was predictive of persistence of BP 1 year from symptom onset (differentiating SBPp and SBPr with 0.62 accuracy). Smoking status combined with affective properties of pain and medication use improved prediction accuracy (0.82). Mediation analysis indicated the prediction of BP persistence by smoking was largely due to synchrony of fMRI activity between two brain areas (nucleus accumbens and medial prefrontal cortex, NAc‐mPFC). In SBP or CBP who ceased smoking strength of NAc‐mPFC decreased from precessation to postcessation of smoking. We conclude that smoking increases risk of transitioning to CBP, an effect mediated by corticostriatal circuitry involved in addictive behavior and motivated learning. Hum Brain Mapp 36:683–694, 2015. © 2014 Wiley Periodicals, Inc.
Reduced CMRO2 and cerebrovascular reserve in patients with severe intracranial arterial stenosis: A combined multiparametric qBOLD oxygenation and BOLD fMRI study
Authors: Bouvier Julien , Detante Olivier , Tahon Florence , Attye Arnaud , Perret Thomas , Chechin David , Barbieux Marianne , Boubagra Kamel , Garambois Katia , Tropres Irène , Grand Sylvie , Barbier Emmanuel L. , Krainik Alexandre
Published: October 2014

Multiparametric quantitative blood oxygenation level dependent (mqBOLD) magnetic resonance Imaging (MRI) approach allows mapping tissular oxygen saturation (StO2) and cerebral metabolic rate of oxygen (CMRO2). To identify hemodynamic alteration related to severe intracranial arterial stenosis (SIAS), functional MRI of cerebrovascular reserve (CVR BOLD fMRI) to hypercapnia has been proposed. Diffusion imaging suggests chronic low grade ischemia in patients with impaired CVR. The aim of the present study was to evaluate how oxygen parameters (StO2 and CMRO2), assessed with mqBOLD approach, correlate with CVR in patients (n = 12) with SIAS and without arterial occlusion. The perfusion (dynamic susceptibility contrast), oxygenation, and CVR were compared. The MRI protocol conducted at 3T lasted approximately 1 h. Regions of interest measures on maps were delineated on segmented gray matter (GM) of middle cerebral artery territories. We have shown that decreased CVR is spatially associated with decreased CMRO2 in GM of patients with SIAS. Further, the degree of ipsilateral CVR reduction was well‐correlated with the amplitude of the CMRO2 deficit. The altered CMRO2 suggests the presence of a moderate ischemia explained by both a decrease in perfusion and in CVR. CVR and mqBOLD method may be helpful in the selection of patients with SIAS to advocate for medical therapy or percutaneous transluminal angioplasty‐stenting. Hum Brain Mapp 36:695–706, 2015. © 2014 Wiley Periodicals, Inc.
Analysis of self‐feeding in children with feeding disorders
Authors: Rivas Kristi M. , Piazza Cathleen C. , Roane Henry S. , Volkert Valerie M. , Stewart Victoria , Kadey Heather J. , Groff Rebecca A.
Published: October 2014

In the current investigation, we evaluated a method for increasing self‐feeding with 3 children with a history of food refusal. The children never (2 children) or rarely (1 child) self‐fed bites of food when the choice was between self‐feeding and escape from eating. When the choice was between self‐feeding 1 bite of food or being fed an identical bite of food, self‐feeding was low (2 children) or variable (1 child). Levels of self‐feeding increased for 2 children when the choice was between self‐feeding 1 bite of food or being fed multiple bites of the same food. For the 3rd child, self‐feeding increased when the choice was between self‐feeding 1 bite of food or being fed multiple bites of a less preferred food. The results showed that altering the contingencies associated with being fed increased the probability of self‐feeding, but the specific manipulations that produced self‐feeding were unique to each child.
Bone substitute materials supplemented with prolyl hydroxylase inhibitors decrease osteoclastogenesis in vitro
Authors: Vinzenz Philipp , Schröckmair Stefan , Gruber Reinhard , Agis Hermann
Published: October 2014

Background and objective: Inhibition of prolyl hydroxylases stimulates bone regeneration. Consequently, bone substitute materials were developed that release prolyl hydroxylase inhibitors. However, the impact of prolyl hydroxylase inhibitors released from these carriers on osteoclastogenesis is not clear. We therefore assessed the effect of bone substitute materials that release prolyl hydroxylase inhibitors on osteoclastogenesis. Material and methods: Dimethyloxalylglycine, desferrioxamine, and l‐mimosine were lyophilized onto bovine bone mineral and hydroxyapatite, and supernatants were generated. Osteoclastogenesis was induced in murine bone marrow cultures in the presence of the supernatants from bone substitute materials. The formation of tartrate‐resistant acid phosphatase (TRAP)‐positive multinucleated cells and TRAP activity were determined. To test for possible effects on osteoclast progenitor cells, we measured the effect of the supernatants on proliferation and viability. In addition, experiments were performed where prolyl hydroxylase inhibitors were directly added to the bone marrow cultures. Results: We found that prolyl hydroxylase inhibitors released within the first hours from bone substitute materials reduce the number and activity of TRAP‐positive multinucleated cells. In line with this, addition of prolyl hydroxylase inhibitors directly to the bone marrow cultures dose‐dependently reduced the number of TRAP‐positive multinucleated cells and the overall resorption activity. Moreover, the released prolyl hydroxylase inhibitors decreased proliferation but not viability of osteoclast progenitor cells. Conclusion: Our results show that prolyl hydroxylase inhibitors released from bone substitute materials decrease osteoclastogenesis in murine bone marrow cultures. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1198–1203, 2015.
REVISITING THE SENSE OF COMMUNITY INDEX: A CONFIRMATORY FACTOR ANALYSIS AND INVARIANCE TEST
Authors: Flaherty Jeremy , Zwick Rodney R. , Bouchey Heather A.
Published: October 2014

The Sense of Community Index (SCI) has been the most widely used measure of Psychological Sense of Community (PSC), despite abundant evidence it does not adequately measure its intended dimensions. Alternative model specifications are rarely tested beyond their initial appearance in the literature, and the use of the SCI as a 1‐dimensional scale has been promoted without testing for invariance across groups. We use a sample of students from a small Northeastern state college to test the measurement properties of the SCI and to test for invariance across semesters of college and across waves of panel data. Neither the original 1‐ or 4‐factor solutions to the SCI nor an alternative 4‐factor solution provide an adequate fit to the data. Evidence of measurement invariance was mixed, with invariance found across waves of data, but not across semesters of school. Future research using PSC should employ measures other than the SCI.
IBERIAN AND LATIN AMERICAN ETHICS IN COMMUNITY PSYCHOLOGY: THE CONTRADICTION BETWEEN FACTS AND ACADEMICIAN'S PERCEPTION
Authors: Montero Maritza , Winkler María Inés
Published: October 2014

Changes in practices, action, roles, and professional functions confronted by community psychology (CP) bring new challenges to the discipline. We consulted 15 CP academicians about future challenges in CP practice, research, and education, mainly regarding ethics and values. A Delphi panel was applied to them. Qualitative and quantitative results were obtained from 3 circulations in response to 4 questions concerning the most relevant problems in CP and its training: basic competences, ethical aspects, and challenges. Results show relevant answers pointing out tasks already in practice within PC, as well as new subjects in, and for, intervention. High consensus presents as future ethic challenge, political engagement, and critical standing practices developed around Latin America and other places around the world. Superposing of CP and social psychology, definitions were also found, posing problems of identity, roles, and functions. Academic biases of participants limit the results obtained, presenting known problems already found in published papers.
The effect of sulforaphane on histone deacetylase activity in keratinocytes: Differences between in vitro and in vivo analyses
Authors: Dickinson Sally E. , Rusche Jadrian J. , Bec Sergiu L. , Horn David J. , Janda Jaroslav , Rim So Hyun , Smith Catharine L. , Bowden G. Timothy
Published: October 2014

Sulforaphane is a natural product found in broccoli, which is known to exert many different molecular effects in the cell, including inhibition of histone deacetylase (HDAC) enzymes. Here, we examine for the first time the potential for sulforaphane to inhibit HDACs in HaCaT keratinocytes and compare our results with those found using HCT116 colon cancer cells. Significant inhibition of HDAC activity in HCT116 nuclear extracts required prolonged exposure to sulforaphane in the presence of serum. Under the same conditions HaCaT nuclear extracts did not exhibit reduced HDAC activity with sulforaphane treatment. Both cell types displayed down‐regulation of HDAC protein levels by sulforaphane treatment. Despite these reductions in HDAC family member protein levels, acetylation of marker proteins (acetylated Histone H3, H4, and tubulin) was decreased by sulforaphane treatment. Time‐course analysis revealed that HDAC6, HDAC3, and acetylated histone H3 protein levels are significantly inhibited as early as 6 h into sulforaphane treatment. Transcript levels of HDAC6 are also suppressed after 48 h of treatment. These results suggest that HDAC activity noted in nuclear extracts is not always translated as expected to target protein acetylation patterns, despite dramatic inhibition of some HDAC protein levels. In addition, our data suggest that keratinocytes are at least partially resistant to the nuclear HDAC inhibitory effects of sulforaphane, which is exhibited in HCT116 and other cells. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.
Cancer‐specific interruption of glucose metabolism by resveratrol is mediated through inhibition of Akt/GLUT1 axis in ovarian cancer cells
Authors: Gwak HyeRan , Haegeman Guy , Tsang Benjamin K. , Song Yong Sang
Published: October 2014

The metabolic phenotype of cancer is considered an ideal target for anticancer therapy. In ovarian cancer, glucose transporter 1 (GLUT1) is overexpressed and positron emission tomography (PET) using [18F] fluorodeoxyglucose (FDG), as a metabolic tumor parameter, has been found to be an effective diagnostic tool. In this study, we have characterized the selective cytotoxicity of resveratrol (RSV) in ovarian cancer cells through glucose metabolism regulation via GLUT1 modulation. We have demonstrated that, in contrast to primary normal ovarian epithelial cells, RSV selectively inhibited glucose uptake and induced apoptosis irrespective of p53 status in vitro. RSV had no affect on GLUT1 mRNA and protein expressions but interrupted intracellular GLUT1 trafficking to the plasma membrane. Suppressed plasma membrane GLUT1 localization in ovarian cancer was found to be associated with the inhibition of Akt activity by RSV, as confirmed by the action of the Akt inhibitors (LY294002 and Akt inhibitor IV), as well as overexpression of a constitutive active form of Akt. Taken together, these findings suggested that RSV induced apoptosis in ovarian cancer cells by impairing glucose uptake, a process involving Akt‐regulated plasma membrane GLUT1 trafficking. © 2014 Wiley Periodicals, Inc.
Pioglitazone, a PPARγ agonist, inhibits growth and invasion of human hepatocellular carcinoma via blockade of the rage signaling
Authors: Yang Yuan , Zhao Ling‐Hao , Huang Bo , Wang Ruo‐Yu , Yuan Sheng‐Xian , Tao Qi‐Fei , Xu Yong , Sun Han‐Yong , Lin Chuan , Zhou Wei‐Ping
Published: October 2014

Pioglitazone (PGZ), a synthetic PPARγ ligand, is known to have anti‐tumor activity. However, it is unclear how it acts against hepatocellular carcinoma (HCC). We hypothesized that the pathological receptor for advanced glycation end products (RAGE) is involved in the PGZ anti‐tumor process. To test this notion, human primary HCC tissues and corresponding adjacent non‐cancerous tissues (ANCT) from 75 consecutive cases were analyzed. The expression and clinical significance of RAGE was assessed by immunohistochemical assay through tissue microarray. After HCC cells were pretreated with different concentrations of PGZ, cell proliferation, apoptosis, cell invasion, and cell cycle distribution were evaluated by multiple assays. The results showed that, the positive expression of RAGE was significantly higher in HCC tissues than in ANCT (66.7% vs. 36.0%, P < 0.001), and was closely associated with pathological staging (P = 0.014) and lymph‐vascular space invasion (P = 0.003). Moreover, PGZ inhibited proliferative activity and invasive potential, and induced apoptosis and cell cycle arrest in HCC cells resulting in increased expression of PPARγ and decreased expression of RAGE, NF‐κB, HMGB1, p38MAPK, Ki‐67, MMP‐2, and CyclinD1. Furthermore, knockdown of RAGE or NF‐κB by siRNA effectively suppressed cell proliferation and invasion, and mediated the inhibitory effects of PGZ in HCC cells. Taken together, our findings suggest that, RAGE is overexpressed in human HCC tissues, and is closely associated with the pathological staging and tumor invasion of HCC. In addition, PGZ as a PPARγ agonist may inhibit growth and invasion of HCC cells via blockade of the RAGE signaling. © 2014 Wiley Periodicals, Inc.
7 tesla magnetic resonance imaging: A closer look at substantia nigra anatomy in Parkinson's disease
Authors: Lehéricy Stéphane , Bardinet Eric , Poupon Cyril , Vidailhet Marie , François Chantal
Published: October 2014

A hallmark of Parkinson's disease (PD) is the progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Dopaminergic denervation is commonly imaged using radiotracer imaging in target structures such as the striatum. Until recently, imaging made only a modest contribution to detecting neurodegenerative changes in the substantia nigra (SN) directly. Histologically, the SN is subdivided into the ventral pars reticulata and the dorsal pars compacta, which is composed of dopaminergic neurons. In humans, dopaminergic neurons, which are known to accumulate neuromelanin, form clusters of cells (nigrosomes) that penetrate deep into the SN pars reticulata (SNr). The SNr contains higher levels of iron than the SNc in normal subjects. Neuromelanin and T2*‐weighted imaging therefore better detect the SNc and the SNr, respectively. The development of ultra‐high field 7 Tesla (7T) magnetic resonance imaging (MRI) provided the increase in spatial resolution and in contrast that was needed to detect changes in SN morphology. 7T MRI allows visualization of nigrosome‐1 as a hyperintense signal area on T2*‐weighted images in the SNc of healthy subjects and its absence in PD patients, probably because of the loss of melanized neurons and the increase of iron deposition. This review is designed to provide a better understanding of the correspondence between the outlines and subdivisions of the SN detected using different MRI contrasts and the histological organization of the SN. The recent findings obtained at 7T will then be presented in relation to histological knowledge. © 2014 International Parkinson and Movement Disorder Society
OAB epidemiological survey of general gynaecology outpatients and its effects on patient quality of life
Authors: An Fang , Yang Xin , Wang Yan J. , Chen Jian Y. , Wang Jian L.
Published: October 2014

Aims

To survey the prevalence rate of overactive bladder (OAB) among general gynaecology outpatients, it's connection to common benign gynaecological diseases and its effects on patient quality of life (QOL).

Method

A questionnaire survey on urination and its effects on QOL was administered to 2500 general gynaecology outpatients aged ≥18 who visited our hospital which is in Peking between October and November 2012. Additionally, their menstrual history and diseases were documented, according to their medical records.

Results

In total, 2161 effective questionnaires (86.4%) were collected from the respondents, who were aged 18–97 years. The overall OAB prevalence rate was 8.8% (191/2161), and the OAB prevalence rate in women >50 years was significantly higher (X2 = 7.656, P < 0.05). Moreover, the OAB prevalence rate (25.8%) among patients suffering from pelvic organ prolapse was significantly higher than the rate (8.6%) among patients without pelvic organ prolapse (X2 = 11.238, P < 0.05). Multi‐factor logistic regression indicated that age (OR = 1.504, 95% CI = 1.072–2.111) and pelvic organ prolapse (OR = 2.512, 95% CI = 1.109–5.688) were risk factors for OAB among the respondents. Additionally, with the rise of OAB severity, its effects on the QOL of OAB patients, like urinary urgency, nocturia, frequency and urge incontinence increased accordingly.

Conclusions

The OAB prevalence rate among general gynaecology outpatients was 8.8%, and the effects of OAB on QOL increased with the worsening of the disease. Neurourol. Urodynam. 35:29–35, 2016. © 2014 Wiley Periodicals, Inc.
Update on 2‐year outcomes of the TOMS™ transobturator male sling for the treatment of male stress urinary incontinence
Authors: Yiou Rene , Bütow Zentia , Parisot Juliette , Lingombet Odile , Augustin Déborah , de la Taille Alexandre , Salomon Laurent , Audureau Etienne
Published: October 2014

Aims

To update the 2‐year outcomes of the TOMS™ transobturator male sling for treating post‐prostatectomy urinary incontinence (pRP‐UI) in a group of patients previously evaluated at 1 year.

Methods

We prospectively followed 40 patients with pRP‐UI before and 6, 12, and 24 months after implantation of the TOMS™ transobturator male sling. Urinary symptoms were evaluated using the following questionnaires: USP, ICIQ, UCLA‐PCI (urinary bother domain), PGI‐I, and daily pad use. Success was defined as patients wearing no or only one security pad. We also report on any other surgical procedures for treating persistent incontinence during the follow‐up period.

Results

Of 40 patients included in the 1‐year follow‐up, seven required additional surgical treatment. In the remaining patients (n = 33), significant improvement (P < 0.001) compared to baseline was seen, and a subsequent tendency (non‐significant) toward impairment was noted throughout the three postoperative follow‐ups for the ICIQ (14.4 ± 4.4 [baseline], 7.6 ± 5.7 [6 months], 8.1 ± 5.6 [12 months], 8.9 ± 5.5 [24 months]), USP‐stress urinary (6.7 ± 2.2, 2.8 ± 2.4, 2.8 ± 2.4, 3.2 ± 2.8), ULCA‐PCI‐urinary bother (10.0 ± 12.5, 66.0 ± 33.0, 64.0 ± 31.5, 62.0 ± 30.7) scores, and pad use (2.5 ± 1.2, 0.7 ± 1.1, 0.8 ± 1.2, 0.9 ± 1.2). Significant impairment in postoperative PGI‐I (6.2 ± 0.9, 6.1 ± 0.9, 5.8 ± 1.1, P = 0.028) and USP‐overactive bladder symptoms scores (5.4 ± 3.6 [6 months] vs. 6.6 ± 3.7 [24 months], P = 0.046) were noted. A total of 18 (54.5%), 17 (51.5%), and 15 (45.5%) patients wore no postoperative pad, respectively.

Conclusion

Approximately half of the patients continue to wear no pad 2 years after TOMS™ transobturator male sling implantation. However, a tendency toward impaired continence, possibly associated with overactive bladder symptoms, was noted. Neurourol. Urodynam. 35:44–47, 2016. © 2014 Wiley Periodicals, Inc.
Prevalence of urinary incontinence and associated factors in nursing home residents
Authors: Jerez‐Roig Javier , Santos Marquiony M. , Souza Dyego L.B. , Amaral Fabienne Louise J.S. , Lima Kenio C.
Published: October 2014

Aims

To determine the prevalence of urinary incontinence (UI) and associated factors in the institutionalized elderly.

Methods

A cross‐sectional study is presented herein, conducted between October and December 2013, in 10 nursing homes in the city of Natal (Northeast Brazil). Individuals over the age of 60, who reside in institutions, were included. Hospitalized individuals and those at end of life were excluded. Data collection included sociodemographic information, UI characterization, as well as variables related to the institution itself and to health conditions (comorbidities, medication, pelvic floor surgery, Barthel Index for functional capacity, and Pfeiffer test for cognitive status). UI was verified through the Minimum Data Set (MDS) version 3.0, which was also used to assess urinary devices and UI toileting programs. The Chi‐square test (or Fisher's exact test), the linear Chi‐square test, and logistic regression were utilized to model associations.

Results

The final sample consisted of 321 elderly, mostly females, with a mean age of 81.5 years. The prevalence of UI was 58.88% (CI 95%: 53.42–64.13) and the final model revealed a statistically significant association between UI and white race, physical inactivity, stroke, mobility impairment, and cognitive decline. The most frequent UI type was functional UI and toileting programs (prompted voiding) were only applied to approximately 8% of residents.

Conclusions

It is concluded that UI is a health issue that affects more than half of the institutionalized elderly, and is associated with white race, physical inactivity, stroke, and other geriatric syndromes such as immobility and cognitive disability. Neurourol. Urodynam. 35:102–107, 2016. © 2014 Wiley Periodicals, Inc.
A posteriori error analysis for nonconforming approximations of an anisotropic elliptic problem
Authors: Achchab Boujemâa , Agouzal Abdellatif , Majdoubi Adil , Meskine Driss , Souissi Ali
Published: October 2014

We develop in this article an a posteriori error estimator for the P1‐nonconforming finite element approximation, for a diffusion‐reaction equation. We adopt the error in a constitutive law approach in two and three dimensional space, for not necessary piecewise constant data of problems. The efficiency and the reliability of our estimators are proved, neither Helmholtz decomposition of the error nor saturation assumption. The constants are explicitly given, which prove the robustness of these estimators. © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 950–976, 2015
The ecology of internal workplace giving at Indiana University: a case study of faculty and staff campus campaign communications and fundraising
Authors: Shaker Genevieve G. , Kienker Brittany L. , Borden Victor M. H.
Published: October 2014

This collective case study examines university‐specific philanthropic cultures, campus fundraising campaigns, and their impact on faculty and staff giving to the university. Drawing on both qualitative and quantitative data, the study documents fundraising strategies through interviews and materials analysis and assesses their results through quantitative data on characteristics of donors and their philanthropic gifts. Examination of fundraising methods reveals differences between demand and supply‐side communication strategies with faculty and staff members as internal stakeholders and donors. Concentrating on the campuses of Indiana University, a large, highly diverse public institution in the American Midwest, this study includes analysis of the outcomes of the fundraising process across institutions of different sizes, demographics, and philanthropic cultures. The findings underscore the importance of exploring the characteristics that influence employee donation behaviors as context for the creation and enactment of fundraising campaigns and highlight the need for future research in the area of workplace giving.

Copyright © 2014 John Wiley & Sons, Ltd.
Ifosfamide and vinorelbine is an effective reinduction regimen in children with refractory/relapsed Hodgkin lymphoma, AHOD00P1: A children's oncology group report
Authors: Trippett Tanya M. , Schwartz Cindy L. , Guillerman R. Paul , Gamis Alan S. , Gardner Sharon , Hogan Shirley , London Wendy B. , Chen Lu , de Alarcon Pedro
Published: October 2014

Background

We assessed the safety and efficacy of ifosfamide and vinorelbine (IV) as a less toxic and effective reinduction regimen for pediatric patients with relapsed or refractory Hodgkin Lymphoma.

Procedure

This multi‐center Children's Oncology Group phase II pilot study enrolled patients <30 years of age with biopsy‐proven Hodgkin Lymphoma in relapse or refractory disease after front‐line therapy. Treatment consisted of ifosfamide 3,000 mg/m2 intravenous infusion over 24 hr on Days 1–4 and vinorelbine 25 mg/m2/dose intravenous push on Days 1 and 5 of each 21 day cycle with cytokine support. The study endpoints included estimation of key toxicities (cardiac, hepatic, or renal toxicity or toxic death), the rate of successful peripheral stem cell harvesting, and response after two cycles of therapy.

Results

Sixty‐six patients received a median of two cycles of IV. Sixty‐four of 66 were heavily pretreated, 4 had refractory disease, 55% were male and 79% had nodular sclerosis HL. The primary toxicities were hematologic. Harvested peripheral stem cells were sufficient for autologous transplantation in 46 of 54 patients for whom stem cell collection was attempted. The overall response rate (72%; 95% CI 59–83%) permitted the majority of patients to undergo subsequent stem cell transplantation.

Conclusions

IV is a safe and effective re‐induction regimen for salvage of pediatric patients with relapsed or refractory Hodgkin Lymphoma with an excellent response rate and success of post chemotherapy stem cell harvest. It avoids the use of etoposide, an agent associated with secondary malignancy after stem cell transplantation. Pediatr Blood Cancer 2015;62:60–64. © 2014 Wiley Periodicals, Inc.
Targeting histone deacetylases (HDACs) and Wee1 for treating high‐risk neuroblastoma
Authors: Hanmod Santosh S. , Wang Guan , Edwards Holly , Buck Steven A. , Ge Yubin , Taub Jeffrey W. , Wang Zhihong
Published: October 2014

Background

Despite advances in treatment regimens, patients with high‐risk neuroblastoma have long‐term survival rates of < 40%. Wee1 inhibition in combination with CHK1 inhibition has shown promising results in neuroblastoma cells. In addition, it has been demonstrated that panobinostat can downregulate CHK1. Therefore, combination of panobinostat and MK‐1775 may result in synergistic cytotoxicity against neuroblastoma cell lines.

Procedure

In vitro cytotoxicities of panobinostat and MK‐1775 at clinically achievable concentrations, either alone or in combination, were evaluated in SK‐N‐AS, SK‐N‐DZ, and SK‐N‐BE(2) high‐risk neuroblastoma cell lines using MTT assays. The mechanism of antitumor interaction was investigated using propidium iodide (PI) staining and flow cytometry analysis to determine apoptosis, as well as Western blotting to assess expression of phosphorylated CDK1/2, CHK1, and H2AX.

Results

Treatment of neuroblastoma cell lines with 500 nM MK‐1775 caused growth arrest and apoptosis in SK‐N‐DZ and SK‐N‐AS, while it had minimal effect on the SK‐N‐BE(2) cell line. The combination of panobinostat and MK‐1775 resulted in synergistic antitumor interactions in all three of the cell lines tested. MK‐1775 treatment in SK‐N‐BE(2) cells induced increased levels of p‐CHK1S345, which could be decreased by the addition of panobinostat. This was accompanied by increased DNA damage and apoptosis.

Conclusions

The combination of panobinostat and MK‐1775 has synergistic antitumor activity against neuroblastoma cell lines and holds promise as a potential treatment strategy for the management of high‐risk neuroblastoma patients. Pediatr Blood Cancer 2015;62:52–59. © 2014 Wiley Periodicals, Inc.
Phase I trial of Seneca Valley Virus (NTX‐010) in children with relapsed/refractory solid tumors: A report of the Children's Oncology Group
Authors: Burke Michael J. , Ahern Charlotte , Weigel Brenda J. , Poirier John T. , Rudin Charles M. , Chen Yingbei , Cripe Timothy P. , Bernhardt M. Brooke , Blaney Susan M.
Published: October 2014

Background

To determine the MTD of Seneca Valley Virus (NTX‐010) in children with relapsed/refractory solid tumors. Patients (≥3–≤21 years) with neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features were eligible.

Procedure

Part A (single dose of NTX‐010) enrolled 13 patients at three dose levels (1 × 109 viral particles (vp)/kg [n = 6], 1 × 1010 vp/kg [n = 3], 1 × 1011 vp/kg [n = 4]). Diagnoses included neuroblastoma (n = 9), rhabdomyosarcoma (n = 2), carcinoid tumor (n = 1), and adrenocorticocarcinoma (n = 1). Part B added cyclophosphamide (CTX) (oral CTX (25 mg/m2/day) days 1–14 and IV CTX (750 mg/m2) days 8 and 29) to two doses of NTX‐010 (1 × 1011 vp/kg, days 8 and 29). Nine patients enrolled to Part B. Diagnoses included neuroblastoma (n = 3), rhabdomyosarcoma (n = 1), Wilms tumor (n = 3), and adrenocorticocarcinoma (n = 2).

Results

Twelve patients on Part A were evaluable for toxicity. There was a single DLT (grade 3 pain) at dose level 1. Additional grade ≥3 related adverse events (AEs) included leukopenia (n = 1), neutropenia (n = 3), lymphopenia (n = 3), and tumor pain (n = 1). No DLTs occurred on part B. Other grade ≥3 related AEs on Part B included: Leukopenia (n = 3), nausea (n = 1), emesis (n = 1), anemia (n = 1), neutropenia (n = 4), platelets (n = 1), alanine aminotransferase (n = 1), and lymphopenia (n = 2). All patients cleared NTX‐010 from blood and stool by 3 weeks with 17/18 patients developing neutralizing antibodies.

Conclusion

NTX‐010 is feasible and tolerable at the dose levels tested in pediatric patients with relapsed/refractory solid tumors either alone or in combination with cyclophosphamide. However, despite the addition of cyclophosphamide, neutralizing antibodies appeared to limit applicability. Pediatr Blood Cancer 2015;62:743–750. © 2014 Wiley Periodicals, Inc.
Challenges in managing infections among pediatric cancer patients: Suboptimal national essential medicines lists for low and middle income countries
Authors: Kirby Jeannette , Ojha Rohit P. , Johnson Kyle M. , Bittner Elizabeth C. , Caniza Miguela A.
Published: October 2014

Infection management for pediatric cancer patients may be compromised in low and middle income countries (LMICs) if key antimicrobials are not included in national essential medicines lists. We screened national essential medicines lists for 81 LMICs, and assessed the frequency and corresponding 95% confidence limits (CL) of countries that included the 15 International Society of Paediatric Oncology‐recommended antimicrobial agents. Only 19% (95% CL: 11%, 28%) of countries included all recommended antimicrobials in their national essential medicines lists. The selection of antimicrobial agents for national essential medicines lists in LMICs warrants attention from a pediatric cancer perspective. Pediatr Blood Cancer 2015;62:204–207. © 2014 Wiley Periodicals, Inc.
A rapid method for preparation of the cerebrospinal fluid proteome
Authors: Larssen Eivind , Brede Cato , Hjelle Anne Bjørnstad , Øysæd Kjell Birger , Tjensvoll Anne Bolette , Omdal Roald , Ruoff Peter
Published: October 2014

The cerebrospinal fluid (CSF) proteome is of great interest for investigation of diseases and conditions involving the CNS. However, the presence of high‐abundance proteins (HAPs) can interfere with the detection of low‐abundance proteins, potentially hindering the discovery of new biomarkers. Therefore, an assessment of the CSF subproteome composition requires depletion strategies. Existing methods are time consuming, often involving multistep protocols. Here, we present a rapid, accurate, and reproducible method for preparing the CSF proteome, which allows the identification of a high number of proteins. This method involves acetonitrile (ACN) precipitation for depleting HAPs, followed by immediate trypsination. As an example, we demonstrate that this method allows discrimination between multiple sclerosis patients and healthy subjects.
Extracellular vesicles including exosomes are mediators of signal transduction: Are they protective or pathogenic?
Authors: Gangoda Lahiru , Boukouris Stephanie , Liem Michael , Kalra Hina , Mathivanan Suresh
Published: October 2014

Extracellular vesicles (EVs) are signaling organelles that are released by many cell types and is highly conserved in both prokaryotes and eukaryotes. Based on the mechanism of biogenesis, these membranous vesicles can be classified as exosomes, shedding microvesicles, and apoptotic blebs. It is becoming clearer that these EVs mediate signal transduction in both autocrine and paracrine fashion by the transfer of proteins and RNA. While the role of EVs including exosomes in pathogenesis is well established, very little is known about their function in normal physiological conditions. Recent evidences allude that EVs can mediate both protective and pathogenic effects depending on the precise state. In this review, we discuss the involvement of EVs as mediators of signal transduction in neurodegenerative diseases and cancer. In addition, the role of EVs in mediating Wnt and PI3K signaling pathways is also discussed. Additional findings on the involvement of EVs in homeostasis and disease progression will promote a better biological understanding, advance future therapeutic, and diagnostic applications.
Confidence interval estimation for number of patient‐years needed to treat
Authors: Zhu Haiyuan , Wu Xiao
Published: October 2014

The number of patient‐years needed to treat (NPYNT), also called the event‐based number needed to treat, to avoid one additional exacerbation has been reported in recently published respiratory trials, but the confidence intervals are not routinely reported. The challenge of constructing confidence intervals for NPYNT is due to the fact that exacerbation data or count data in general are usually analyzed using Poisson‐based models such as Poisson or negative binomial regression and the rate ratio is the natural metric for between‐treatment comparison, while NPYNT is based on rate difference, which is not usually calculated for those models. Therefore, the variance estimates from these analysis models are directly related to the rate ratio rather than the rate difference. In this paper, we propose several methods to construct confidence intervals for the NPYNT, assuming that the event rates are estimated using Poisson or negative binomial regression models. The coverage property of the confidence intervals constructed with these methods is assessed by simulations. Copyright © 2014 John Wiley & Sons, Ltd.
Effects of starch alkenylsuccinylation on the grafting efficiency, paste viscosity, and film properties of alkenylsuccinylated starch‐g‐poly(acrylic acid)
Authors: Zhu Zhifeng , Zhang Longqiu , Li Manli , Zhou Yongsheng
Published: October 2014

Commercial cornstarch was alkenylsuccinylated with alkenylsuccinic anhydride to different degrees of substitution (DS) and then the products were graft‐copolymerized with acrylic acid for investigating the effects of starch alkenylsuccinylation on the graft copolymerization with vinyl monomer, as well as on paste viscosity and film properties of alkenylsuccinylated starch‐g‐poly(acrylic acid) (ASS‐g‐PAA). The number of carbon atom of alkenyl in alkenylsuccinates considered was 8 and 12, corresponding to octenylsuccinylation and dodecenylsuccinylation of starch, respectively. The graft copolymerization was accessed by grafting efficiency, grafting ratio, and conversion of monomer to polymer, and the film properties of ASS‐g‐PAA considered included tensile strength, breaking elongation, and work‐to‐break. Experimental results demonstrated that the alkenylsuccinylation showed marked effects on the copolymerization, paste viscosity, and film properties. It resulted in increased grafting efficiency, stable paste viscosity, and strong starch film. Carbon‐chain length of the alkenyl and DS value of the alkenylsuccinates also exhibited evident effects on the copolymerization and film properties. Octenylsuccinylation of starch before the copolymerization was superior to dodecenylsuccinylation in improving the efficiency and film properties. Low levels of octenylsuccinylation could be utilized to increase the efficiency of the copolymerization and improve the properties of starch film.
Effect of phosphorylation of the maize starch on thermal generation of stable and short‐living radicals
Authors: Bidzińska Ewa , Błaszczak Wioletta , Dyrek Krystyna , Fornal Józef , Kruczała Krzysztof , Michalec Marek , Rozwora Robert , Szczygieł Jadwiga , Wenda Elżbieta
Published: October 2014

Effect of hydrolysis, phosphorylation and treatment with high hydrostatic pressure on thermal generation of stable and short‐living radicals in maize starch was studied by X‐ray diffraction (XRD), electron paramagnetic resonance (EPR) spectroscopy, differential scanning calorimetry and polarized light microscopy. Phosphorus was introduced into maize starch as mono‐ and distarch phosphates. XRD indicated localization of phosphate groups in amorphous part of the granule whereas calorimetric data suggested some cross‐linking of the distarch phosphates. Stable and short‐living radicals with unpaired electron localized at carbon atom were generated in all investigated samples in the temperature range commonly used for processing food. The number of detected short‐living radicals, stabilized by a spin trap, is of two orders of magnitude greater than that of the stable radical species. Hydrolysis and phosphorylation strongly increase the number of stable radicals while pretreatment of the starch with high hydrostatic pressure diminishes their amount. The EPR spectra of stable radicals consist of two components, single line and another one with hyperfine structure, indicating interaction of unpaired electron with neighboring hydrogen atom. The EPR spectra of the spin trap adducts with short‐living radicals contain three components from species differing in their dynamic properties depending on localization in zones of various degree of crystallinity.