bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Examination of Juvenile Probation Officers as Gateway Providers to Mental Health Care
Authors: Holloway Evan D. , Brown James R. , Suman Philip D. , Aalsma Matthew C.
Published: March 2012

Despite significant rates of psychopathology, less than 10% of court-involved youth are connected to appropriate care on release from detention. The majority are mandated to probation on release, providing the juvenile probation officer (PO) a unique opportunity to facilitate connection to mental health care. The current study supported this notion through analysis of qualitative interviews with recently detained youth, and their caregivers, who were identified with mental health concerns in detention. The juvenile PO was evaluated as a gateway provider (GP) in the pathway to mental health care. Results supported previous research discussing the conflicting roles inherent in juvenile probation: law enforcement and rehabilitation. A number of individual- and system-level factors specific to juvenile POs improved or impaired likelihood of connection to care. Further research should investigate how the interaction of the individual juvenile PO’s law enforcement orientation, and departmental culture and climate, affects youth’s connection to mental health care.
Performance-Support Bias and the Gender Pay Gap among Stockbrokers
Authors: Madden Janice Fanning
Published: March 2012

This article analyzes organizational mechanisms, and their contexts, leading to gender inequality among stockbrokers in two large brokerages. Inequality is the result of gender differences in sales, as both firms use performance-based pay, paying entirely by commissions. This article develops and tests whether performance-support bias, whereby women receive inferior sales support and sales assignments, causes the commissions gap. Newly available data on the brokerages’ internal transfers of accounts among brokers allows measurement of performance-support bias. Gender differences in the quality and quantity of transferred accounts provide a way to measure gender differences in the assignment of sales opportunities and support. Sales generated from internally transferred accounts, controlling for the accounts’ sales histories, provide a “natural experiment” testing for gender differences in sales capacities. The evidence for performance-support bias is (1) women are assigned inferior accounts and (2) women produce sales equivalent to men when given accounts with equivalent prior sales histories.
Clinicopathological insights into lupus nephritis in South Africans: a study of 251 patients
Authors: Okpechi IG , Swanepoel CR , Tiffin N , Duffield M , Rayner BL
Published: March 2012

There are few published studies on biopsy proven lupus nephritis (LN) from sub-Sahara Africa, mainly due to lack of expertise and pathology back-up for performing and interpreting renal biopsies in many centres. The purpose of this study was to document factors associated with biopsy proven LN and to determine clinical and laboratory models that best predict proliferative LN in South Africans. Of the 251 patients studied, 84.1% were females and 79.3% were of mixed ancestry. There were more observed cases of proliferative LN (63%) than non-proliferative LN. Factors associated with proliferative LN were male gender ( p = 0.049), haematuria on dipstix ( p < 0.0001), proteinuria on dipstix ( p = 0.042), low serum albumin ( p = 0.032), low complement C3 ( p < 0.0001), low complement C4 ( p = 0.009) and positive double-stranded DNA ( p = 0.039). Using four models designed from various combinations of the factors associated with proliferative LN, the specificity and positive predictive values were highest for the model that combined gender (male), presence of dipstix haematuria and proteinuria, hypoalbuminaemia, low C3 and low C4 and positive double-stranded DNA (100% respectively). Further study is recommended to identify the value of using these demographic and laboratory parameters in identifying patients with proliferative LN in resource limited centres where the performance of a biopsy is not possible.
Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients
Authors: Silva MF , Ribeiro AS , Fiorot FJ , Aikawa NE , Lotito AP , Campos LM , Mauad T , Silva CA
Published: March 2012

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8–16) and the median interval between diagnosis of JSLE and IA was 6 months (1–38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7–22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients.
Space for Transformation
Authors: Lysaker Judith T. , Furuness Shelly
Published: March 2012

Given the current and historical trends favoring the view of teachers as passive followers of “expert” directives, teachers are in need of continuing education that encourages them to be active change agents in educational reform. Teachers need professional education that helps them critique trends which question the legitimacy of their knowledge and experience as vital to critical conversations about school improvement. In this article, we elucidate the epistemic stance and the dialogic, relational approach to pedagogy that we adopt during the 3-week Summer Cohort experience. Second, we describe and analyze one of these activities—autobiographical writing which sets the framework for the course in terms of the relational and dialogic processes of our pedagogy and suggest ways in which such writing provides spaces for transformation in our students. We hope to demonstrate the ways in which a relational epistemology and dialogic, relationally oriented pedagogy provides one way to invite teachers to personal and professional transformation.
A unified framework for the prediction of cricket ball trajectories in spin and swing bowling
Authors: Baker Chris
Published: March 2012

This paper builds on earlier work of the author that calculated the trajectories of cricket balls under fast swing bowling conditions, and develops a unified analytical framework for the consideration of both slow spin bowling and fast swing bowling. A classification of different types of bowling delivery, in so far as they relate to the flight of the ball through the air, is set out, and from this classification four generic cases of seam and spin plane angle are identified for further consideration. The force coefficient characteristics on spinning balls due to auto-rotational effects (due to the spin of the ball) are then derived, and these are used to develop the full equations of motion that can predict both swing and spin bowling trajectories. The four generic cases are then investigated using approximate solutions of these equations, the trajectories of spin bowling in lateral and vertical directions are explored and the relative magnitudes of flight displacements due to the boundary layer asymmetry (the cause of swing bowling displacements) and auto-rotational forces are discussed. Finally, the effects of cross winds on spin bowling trajectories are considered. In summary the paper presents an overall methodology that enables the various flow phenomenon associated with cricket ball flight to be considered in a unified manner.
Rationale and design of PATRO Adults, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope® for the treatment of adult patients with growth hormone deficiency
Authors: Beck-Peccoz Paolo , Minuto Francesco , Leal-Cerro Alfonso , Zabransky Markus , Stalla Günter
Published: March 2012

Objective: To describe the rationale and design of PATRO Adults, a postmarketing surveillance study of the long-term efficacy and safety of somatropin (Omnitrope®) for the treatment of adult patients with growth hormone deficiency (GHD).

Methods: PATRO Adults is an observational, multicentre, open, longitudinal, noninterventional study being conducted in hospitals and specialized endocrinology clinics across several European countries. The primary objective is to assess the safety and efficacy of Omnitrope® in adults treated in routine clinical practice. Eligible patients are male or female adults who are receiving treatment with Omnitrope® and who have provided informed consent. Patients who have been treated with another human growth hormone (hGH) product before starting Omnitrope® therapy will also be eligible for inclusion. Efficacy assessments will be based on the analysis of the following: insulin-like growth factor-1 levels within age- and gender-adjusted normal ranges; anthropometric measures (weight, waist circumference, total fat mass, lean body mass, total body water); bone mineral density; lipids; effects on cardiovascular risk factors such as glucose metabolism, blood pressure and inflammatory markers (e.g. C-reactive protein); and quality of life. All adverse events will be monitored and recorded. Particular emphasis will be placed on long-term safety, the recording of malignancies, the occurrence and clinical impact of antirecombinant hGH antibodies, the incidence, severity and duration of hyperglycaemia, and the development of diabetes during treatment with Omnitrope®.

Conclusions: PATRO Adults is a large, long-term, postmarketing surveillance study that will extend the safety database for Omnitrope®, as well as contributing to the available data for all recombinant hGH products. Of particular interest, the study will provide important data on the impact of long-term GH replacement therapy on the development of diabetes mellitus, the recurrence/regrowth of hypothalamic–pituitary tumours, and de novo malignancy or recurrence of other (non-hypothalamic–pituitary) tumours.
Influences of welding parameters on mechanical properties of AZ31 friction stir spot welds
Authors: Sun N , North T H , Chen D R , Yin Y H
Published: March 2012

In this study, the influence of welding parameters, including tool rotational speed, plunge rate and dwell time, on the overlap tensile shear properties of AZ31 friction stir spot welds was investigated. The microstructures in stir zones and fracture surfaces were observed using optical microscope and scanning electron microscope respectively. The bonded width and h value (the distance from the tip of the partially bonded region to the top of the weld surface) were measured. The results indicated that larger bonded width and higher h value of the AZ31 weld result in better mechanical property. It is proposed that high tensile shear loads are produced when the tool rotational speed range of 1500–2250 rev min−1 and 1 s dwell time are applied during the friction stir spot welding of AZ31. The plunge rate range from 2·5 to 10 mm s−1 has insignificant influence on the tensile shear load of AZ31 joints under the present conditions. The failure mode changes from interfacial to pullout when the tool rotational speed is >2250 rev min−1. The fracture feature of AZ31 welds is brittle fracture.
Surface alloy depletion and martensite formation during glass to metal joining of austenitic stainless steels
Authors: Susan D F , Knorovsky G A , Robino C V , Michael J R , Rodriguez M A , Perricone M J
Published: March 2012

Preoxidised and glass to metal (GtM) sealed austenitic stainless steels displayed a ferritic (bcc) layer near the metal/oxide interface, as determined by electron backscatter diffraction and X-ray diffraction. Through electron probe microanalysis, it was determined that this layer was depleted of alloying elements due to the oxidation and sealing processes. Characterisation of the layer morphology suggested that it formed through the martensite transformation mechanism. Thermochemical modelling with ThermoCalc also supported a martensitic transformation as opposed to diffusional ferrite formation. The composition gradient through the layer was correlated to the Eichelman and Hull empirical relationship for martensite start ( Ms) temperatures. Because of Cr, Mn and Si depletion during preoxidation and glass sealing, Ms temperatures near ambient are possible in this surface region. The martensite layer was non-uniform, however, with laths extending deeper into the alloy due to stabilised growth in the material above its Ms temperature. This behaviour was characterised by image analysis techniques and discussed in terms of martensite stability and microstructural effects. Possible negative aspects of bcc phase formation on GtM seal properties are discussed, and analyses of alternative alloys 21-6-9 (tradename Nitronic 40; Armco Holding Corp., West Chester, OH, USA) and 22-13-5 (Nitronic 50) showed reduction or elimination of martensite after GtM joining.
Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study
Authors: Lentzsch Suzanne , O'Sullivan Amy , Kennedy Ryan C. , Abbas Mohammad , Dai Lijun , Pregja Silvana Lalo , Burt Steve , Boyiadzis Michael , Roodman G. David , Mapara Markus Y. , Agha Mounzer , Waas John , Shuai Yongli , Normolle Daniel , Zonder Jeffrey A.
Published: March 2012

This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m2 (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704.
Runx1 deletion or dominant inhibition reduces Cebpa transcription via conserved promoter and distal enhancer sites to favor monopoiesis over granulopoiesis
Authors: Guo Hong , Ma Ou , Speck Nancy A. , Friedman Alan D.
Published: March 2012

Deletion of Runx1 in adult mice produces a myeloproliferative phenotype. We now find that Runx1 gene deletion increases marrow monocyte while reducing granulocyte progenitors and that exogenous RUNX1 rescues granulopoiesis. Deletion of Runx1 reduces Cebpa mRNA in lineage-negative marrow cells and in granulocyte-monocyte progenitors or common myeloid progenitors. Pu.1 mRNA is also decreased, but to a lesser extent. We also transduced marrow with dominant-inhibitory RUNX1a. As with Runx1 gene deletion, RUNX1a expands lineage−Sca-1+c-kit+ and myeloid cells, increased monocyte CFUs relative to granulocyte CFUs, and reduced Cebpa mRNA. Runx1 binds a conserved site in the Cebpa promoter and binds 4 sites in a conserved 450-bp region located at +37 kb; mutation of the enhancer sites reduces activity 6-fold in 32Dcl3 myeloid cells. Endogenous Runx1 binds the promoter and putative +37 kb enhancer as assessed by ChIP, and RUNX1-ER rapidly induces Cebpa mRNA in these cells, even in cycloheximide, consistent with direct gene regulation. The +37 kb region contains strong H3K4me1 histone modification and p300-binding, as often seen with enhancers. Finally, exogenous C/EBPα increases granulocyte relative to monocyte progenitors in Runx1-deleted marrow cells. Diminished CEBPA transcription and consequent impairment of myeloid differentiation may contribute to leukemic transformation in acute myeloid leukemia cases associated with decreased RUNX1 activity.
Perturbation of cytokinin and ethylene-signalling pathways explain the strong rooting phenotype exhibited by Arabidopsis expressing the Schizosaccharomyces pombe mitotic inducer, cdc25
Authors: Spadafora Natasha D , Parfitt David , Marchbank Angela , Li Sherong , Bruno Leonardo , Vaughan Rhys , Nieuwland Jeroen , Buchanan-Wollaston Vicky , Herbert Robert J , Bitonti Maria Beatrice , Doonan John , Albani Diego , Prinsen Els , Francis Dennis , Rogers Hilary J
Published: March 2012

Background

Entry into mitosis is regulated by cyclin dependent kinases that in turn are phosphoregulated. In most eukaryotes, phosphoregulation is through WEE1 kinase and CDC25 phosphatase. In higher plants a homologous CDC25 gene is unconfirmed and hence the mitotic inducer Schizosaccharomyces pombe (Sp) cdc25 has been used as a tool in transgenic plants to probe cell cycle function. Expression of Spcdc25 in tobacco BY-2 cells accelerates entry into mitosis and depletes cytokinins; in whole plants it stimulates lateral root production. Here we show, for the first time, that alterations to cytokinin and ethylene signaling explain the rooting phenotype elicited by Spcdc25 expression in Arabidopsis.

Results

Expressing Spcdc25 in Arabidopsis results in increased formation of lateral and adventitious roots, a reduction of primary root width and more isodiametric cells in the root apical meristem (RAM) compared with wild type. Furthermore it stimulates root morphogenesis from hypocotyls when cultured on two way grids of increasing auxin and cytokinin concentrations. Microarray analysis of seedling roots expressing Spcdc25 reveals that expression of 167 genes is changed by > 2-fold. As well as genes related to stress responses and defence, these include 19 genes related to transcriptional regulation and signaling. Amongst these was the up-regulation of genes associated with ethylene synthesis and signaling. Seedlings expressing Spcdc25 produced 2-fold more ethylene than WT and exhibited a significant reduction in hypocotyl length both in darkness or when exposed to 10 ppm ethylene. Furthermore in Spcdc25 expressing plants, the cytokinin receptor AHK3 was down-regulated, and endogenous levels of iPA were reduced whereas endogeous IAA concentrations in the roots increased.

Conclusions

We suggest that the reduction in root width and change to a more isodiametric cell phenotype in the RAM in Spcdc25 expressing plants is a response to ethylene over-production. The increased rooting phenotype in Spcdc25 expressing plants is due to an increase in the ratio of endogenous auxin to cytokinin that is known to stimulate an increased rate of lateral root production. Overall, our data reveal important cross talk between cell division and plant growth regulators leading to developmental changes.
Quality of life of Chinese urban community residents: a psychometric study of the mainland Chinese version of the WHOQOL-BREF
Authors: Xia Ping , Li Ningxiu , Hau Kit-Tai , Liu Chaojie , Lu Yubo
Published: March 2012

Background

The short version of the World Health Organization's Quality of Life Instrument (WHOQOL-BREF) is widely validated and popularly used in assessing the subjective quality of life (QOL) of patients and the general public. We examined its psychometric properties in a large sample of community residents in mainland China.

Methods

The WHOQOL-BREF was administered to 1052 adult community residents in a major metropolitan city in southern China. The structural integrity of the 4-factor model in confirmatory factor analyses (CFA) and the relationship of QOL with demographic variables were examined. Validity was assessed using the known-group comparison (229 with vs. 823 without chronic illness), item-domain correlations, and CFA using the ML estimation in LISREL.

Results

Internal consistency reliability of the whole instrument (26 items) was 0.89, and the psychological, social, and environment domains had acceptable reliability (alpha = 0.76, 0.72, 0.78 respectively), while that of the physical domain was slightly lower (α = 0.67). The respective mean scores of these domains were 13.69, 14.11, 12.33 and 14.56. Item-domain correlations were much higher for corresponding domains than for non-corresponding domains, indicating good convergent validity. CFA provided a marginally acceptable fit to the a priori four-factor model when two matching content item pairs were allowed to be correlated; χ2 (244) = 1836, RMSEA = 0.088, NNFI = 0.898, CFI = 0.909. This factorial structure was shown to be equivalent between the participants with and without chronic illness. The differences in means between these two groups were significant but small in some domains; effect size = 0.55, 0.15, 0.18 in the physical, psychological, and social relationship domains respectively. Furthermore, males had significantly higher QOL scores than females in the psychological domain, while individuals with a younger age, higher income, and higher education levels also had significantly higher QOL. Compared with the international data, the Chinese in this study had relatively low QOL scores with about 5% of males and 16% of females being at risk for poor QOL.

Conclusions

This study has provided psychometric properties of the WHOQOL-BREF as used in China and should definitely be useful for researchers who would like to use or further refine the instrument.
Molecular characterization of glucose-6-phosphate dehydrogenase deficient variants in Baghdad city - Iraq
Authors: Al-Musawi Bassam MS , Al-Allawi Nasir , Abdul-Majeed Ban A , Eissa Adil A , Jubrael Jaladet MS , Hamamy Hanan
Published: March 2012

Background

Although G6PD deficiency is the most common genetically determined blood disorder among Iraqis, its molecular basis has only recently been studied among the Kurds in North Iraq, while studies focusing on Arabs in other parts of Iraq are still absent.

Methods

A total of 1810 apparently healthy adult male blood donors were randomly recruited from the national blood transfusion center in Baghdad. They were classified into G6PD deficient and non-deficient individuals based on the results of methemoglobin reduction test (MHRT), with confirmation of deficiency by subsequent enzyme assays. DNA from deficient individuals was studied using a polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) for four deficient molecular variants, namely G6PD Mediterranean (563 C→T), Chatham (1003 G→A), A- (202 G→A) and Aures (143 T→C). A subset of those with the Mediterranean variant, were further investigated for the 1311 (C→T) silent mutation.

Results

G6PD deficiency was detected in 109 of the 1810 screened male individuals (6.0%). Among 101 G6PD deficient males molecularly studied, the Mediterranean mutation was detected in 75 cases (74.3%), G6PD Chatham in 5 cases (5.0%), G6PD A- in two cases (2.0%), and G6PD Aures in none. The 1311 silent mutation was detected in 48 out of the 51 G6PD deficient males with the Mediterranean variant studied (94.1%).

Conclusions

Three polymorphic variants namely: the Mediterranean, Chatham and A-, constituted more than 80% of G6PD deficient variants among males in Baghdad. Iraq. This observation is to some extent comparable to other Asian Arab countries, neighboring Turkey and Iran.
A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease
Authors: Kaur Punit , Nagaraja Ganachari M , Zheng Hongying , Gizachew Dawit , Galukande Moses , Krishnan Sunil , Asea Alexzander
Published: March 2012

Background

Triple-negative breast cancer (TNBC) exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast cancer with higher percentages in premenopausal African-American and Hispanic women. The reason for this aggressive phenotype is currently the focus of intensive research. However, progress is hampered by the lack of suitable TNBC cell model systems.

Methods

To understand the mechanistic basis for the aggressiveness of TNBC, we produced a stable TNBC cell line by sorting for 4T1 cells that do not express the estrogen receptor (ER), progesterone receptor (PgR) or the gene for human epidermal growth factor receptor 2 (HER2). As a control, we produced a stable triple-positive breast cancer (TPBC) cell line by transfecting 4T1 cells with rat HER2, ER and PgR genes and sorted for cells with high expression of ER and PgR by flow cytometry and high expression of the HER2 gene by Western blot analysis.

Results

We isolated tumor-initiating cells (TICs) by sorting for CD24+/CD44high/ALDH1+ cells from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) stable cell lines. Limiting dilution transplantation experiments revealed that CD24+/CD44high/ALDH1+ cells derived from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) were significantly more effective at repopulating the mammary glands of naïve female BALB/c mice than CD24-/CD44-/ALDH1- cells. Implantation of the TNBC-TICs resulted in significantly larger tumors, which metastasized to the lungs to a significantly greater extent than TNBC, TPBC-TICs, TPBC or parental 4T1 cells. We further demonstrated that the increased aggressiveness of TNBC-TICs correlates with the presence of high levels of mouse twenty-five kDa heat shock protein (Hsp25/mouse HspB1) and seventy-two kDa heat shock protein (Hsp72/HspA1A).

Conclusions

Taken together, we have developed a TNBC-TICs model system based on the 4T1 cells which is a very useful metastasis model with the advantage of being able to be transplanted into immune competent recipients. Our data demonstrates that the TNBC-TICs model system could be a useful tool for studies on the pathogenesis and therapeutic treatment for TNBC.
JS-K, a glutathione/glutathione S-transferase-activated nitric oxide releasing prodrug inhibits androgen receptor and WNT-signaling in prostate cancer cells
Authors: Laschak Martin , Spindler Klaus-Dieter , Schrader Andres J , Hessenauer Andrea , Streicher Wolfgang , Schrader Mark , Cronauer Marcus V
Published: March 2012

Background

Nitric oxide (NO) and its oxidative reaction products have been repeatedly shown to block steroid receptor function via nitrosation of zinc finger structures in the DNA-binding domain (DBD). In consequence NO-donors could be of special interest for the treatment of deregulated androgen receptor(AR)-signaling in castration resistant prostate cancer (CRPC).

Methods

Prostate cancer (PCa) cells were treated with JS-K, a diazeniumdiolate derivate capable of generating large amounts of intracellular NO following activation by glutathione S-transferase. Generation of NO was determined indirectly by the detection of nitrate in tissue culture medium or by immunodetection of nitrotyrosine in the cytoplasm. Effects of JS-K on intracellular AR-levels were determined by western blotting. AR-dimerization was analyzed by mammalian two hybrid assay, nuclear translocation of the AR was visualized in PCa cells transfected with a green fluorescent AR-Eos fusion protein using fluorescence microscopy. Modulation of AR- and WNT-signalling by JS-K was investigated using reporter gene assays. Tumor cell proliferation following JS-K treatment was measured by MTT-Assay.

Results

The NO-releasing compound JS-K was shown to inhibit AR-mediated reporter gene activity in 22Rv1 CRPC cells. Inhibition of AR signaling was neither due to an inhibition of nuclear import nor to a reduction in AR-dimerization. In contrast to previously tested NO-donors, JS-K was able to reduce the intracellular concentration of functional AR. This could be attributed to the generation of extremely high intracellular levels of the free radical NO as demonstrated indirectly by high levels of nitrotyrosine in JS-K treated cells. Moreover, JS-K diminished WNT-signaling in AR-positive 22Rv1 cells. In line with these observations, castration resistant 22Rv1 cells were found to be more susceptible to the growth inhibitory effects of JS-K than the androgen dependent LNCaP which do not exhibit an active WNT-signaling pathway.

Conclusions

Our results suggest that small molecules able to inhibit WNT- and AR-signaling via NO-release represent a promising platform for the development of new compounds for the treatment of CRPC.
Potential relevance of pre-operative quality of life questionnaires to identify candidates for surgical treatment of genital prolapse: a pilot study
Authors: Chauvin Christian , Chéreau Elisabeth , Ballester Marcos , Daraï Emile
Published: March 2012

Background

To evaluate prolapse-related symptoms, quality of life and sexuality of patients with validated questionnaires before and after surgery for genital prolapse and assess relevance of such an evaluation to select women for surgery.

Methods

From November 2009 to April 2010, 16 patients operated on for genital prolapse of grade greater than or equal to 2 (POP-Q classification) were evaluated prospectively by three questionnaires of quality of life Pelvic Floor Distress Inventory (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7) and Pelvic Organ Prolaps/Urinary Incontinence Sexual Questionnaire (PISQ-12). Data were collected the day before surgery and 6 weeks postoperatively.

Results

Eleven patients had laparoscopic surgery and five vaginal surgery. There was a significant decrease in pelvic heaviness, vaginal discomfort and urinary symptoms after surgery. The score of symptoms of prolapse, the PFDI-20 score was 98.5 preoperatively and 31.8 postoperatively (p < 0.0001). The score for quality of life, the PFIQ-7 score was 54.5 preoperatively and 7.4 postoperatively (p = 0.001). The score of sexuality, the PISQ-12 score was 35.3 preoperatively and 37.5 postoperatively (p = 0.1). Two of the 3 patients with a PFIQ 7 under or equal to 20 were not improved while all the women with a preoperative PFIQ-7 over 20 were improved after surgery.

Conclusions

This study suggests that surgery improves quality of life of patients with genital prolapse. Quality of life questionnaires could help select good candidates for surgery. Further studies are required to determine threshold to standardize indications of surgery.
Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models
Authors: Plengsuriyakarn Tullayakorn , Viyanant Vithoon , Eursitthichai Veerachai , Picha Porntipa , Kupradinun Piengchai , Itharat Arunporn , Na-Bangchang Kesara
Published: March 2012

Background

Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed.

Methods/Design

The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification.

Results

Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities.

Conclusion

Plants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA.
Specific tagging of the egress-related osmiophilic bodies in the gametocytes of Plasmodium falciparum
Authors: Sannella Anna Rosa , Olivieri Anna , Bertuccini Lucia , Ferrè Fabrizio , Severini Carlo , Pace Tomasino , Alano Pietro
Published: March 2012

Background

Gametocytes, the blood stages responsible for Plasmodium falciparum transmission, contain electron dense organelles, traditionally named osmiophilic bodies, that are believed to be involved in gamete egress from the host cell. In order to provide novel tools in the cellular and molecular studies of osmiophilic body biology, a P. falciparum transgenic line in which these organelles are specifically marked by a reporter protein was produced and characterized.

Methodology

A P. falciparum transgenic line expressing an 80-residue N-terminal fragment of the osmiophilic body protein Pfg377 fused to the reporter protein DsRed, under the control of pfg377 upstream and downstream regulatory regions, was produced.

Results

The transgenic fusion protein is expressed at the appropriate time and stage of sexual differentiation and is trafficked to osmiophilic bodies as the endogenous Pfg377 protein. These results indicate that a relatively small N-terminal portion of Pfg377 is sufficient to target the DsRed reporter to the gametocyte osmiophilic bodies.

Conclusions

This is the first identification of a P. falciparum aminoacid sequence able to mediate trafficking to such organelles. To fluorescently tag such poorly characterized organelles opens novel avenues in cellular and imaging studies on their biogenesis and on their role in gamete egress.
Loss of HLTF function promotes intestinal carcinogenesis
Authors: Sandhu Sumit , Wu Xiaoli , Nabi Zinnatun , Rastegar Mojgan , Kung Sam , Mai Sabine , Ding Hao
Published: March 2012

Background

HLTF (Helicase-like Transcription Factor) is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown.

Results

To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apc

min/+
mutant background, Hltf

-
deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf
-/-
/Apc

min/+
mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apc

min/+
mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased.

Conclusion

Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.
Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis
Authors: Pan Bing , Ren Hui , Lv Xiaofeng , Zhao Yangyu , Yu Baoqi , He Yubin , Ma Yijing , Niu Chenguang , Kong Jinge , Yu Fangzhu , Sun Wen-bing , Zhang Youyi , Willard Belinda , Zheng Lemin
Published: March 2012

Background

Previous studies suggest that oxidative stress plays an important role in the development of breast cancer. There is a significant inverse relationship between HDL and the risk and mortality of breast cancer. However, it is well known that under conditions of oxidative stress, such as breast cancer, HDL can be oxidatively modifiedand these modifications may have an effect on the functions of HDL. The purpose of this study is to determine the different effects of normal and oxidized (caused by hypochlorite-induced oxidative stress) HDL on breast cancer cell metastasis.

Methods

Human breast cancer cell lines were treated with normal and hypochlorite-oxidized HDL, and then cell metastasis potency in vivo and the abilities of migration, invasion, adhesion to HUVEC and ECM in vitro were examined. Integrin expression and PKC activity were evaluated, and PKC inhibitor and PKC siRNA was applied.

Results

We found hypochlorite-oxidized HDL dramatically promotes breast cancer cell pulmonary metastasis (133.4% increase at P < 0.0 l for MDA-MB-231 by mammary fat pad injection; 164.3% increase at P < 0.01 for MCF7 by tail vein injection) and hepatic metastasis (420% increase at P < 0.0 l for MDA-MB-231 by mammary fat pad injection; 1840% fold increase at P < 0.001 for MCF7 by tail vein injection) in nude mice, and stimulates higher cell invasion (85.1% increase at P < 0.00 l for MDA-MB-231; 88.8% increase at P < 0.00 l for MCF7;), TC-HUVEC adhesion (43.4% increase at P < 0.00 l for MDA-MB-231; 35.2% increase at P < 0.00 l for MCF7), and TC-ECM attachment (41.0% increase at P < 0.00 l for MDA-MB-231; 26.7% increase at P < 0.05 for MCF7) in vitro compared with normal HDL. The data also shows that the PKC pathway is involved in the abnormal actions of hypochlorite-oxidized HDL.

Conclusions

Our study demonstrated that HDL under hypochlorite-induced oxidative stress stimulates breast cancer cell migration, invasion, adhesion to HUVEC and ECM, thereby promoting metastasis of breast cancer. These results suggest that HDL-based treatments should be considered for treatment of breast cancer patients.
Modeling interaction using trust and recommendation in ubiquitous computing environment
Authors: Iltaf Naima , Ghafoor Abdul , Hussain Mukhtar
Published: March 2012

To secure computing in pervasive environment, an adaptive trust and recommendation based access control model (based on human notion of trust) is proposed. The proposed model provides support to calculate direct as well as indirect trust based on recommendations. It handles situations (by itself) both in which the requesting entity has a past experience with the service and a stranger entity requesting to access the service without any past interaction with the service. It encompasses the ability to reason human cognitive behavior and has the capability to adjust in accordance with behavioral pattern changes. X-bar control chart is used to handle malicious recommendation. The defense mechanisms incorporated by proposed model against attacks such as bad mouthing attack, oscillating behavior attack and conflicting behavior attack are also demonstrated.
The effects of multi-domain versus single-domain cognitive training in non-demented older people: a randomized controlled trial
Authors: Cheng Yan , Wu Wenyuan , Feng Wei , Wang Jiaqi , Chen You , Shen Yuan , Li Qingwei , Zhang Xu , Li Chunbo
Published: March 2012

Background

Whether healthy older people can benefit from cognitive training (CogTr) remains controversial. This study explored the benefits of CogTr in community dwelling, healthy, older adults and compared the effects of single-domain with multi-domain CogTr interventions.

Methods

A randomized, controlled, 3-month trial of CogTr with double-blind assessments at baseline and immediate, 6-month and 12-month follow-up after training completion was conducted. A total of 270 healthy Chinese older people, 65 to 75 years old, were recruited from the Ganquan-area community in Shanghai. Participants were randomly assigned to three groups: multi-domain CogTr, single-domain CogTr, and a wait-list control group. Twenty-four sessions of CogTr were administrated to the intervention groups over a three-month period. Six months later, three booster training sessions were offered to 60% of the initial training participants. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Form A), the Color Word Stroop test (CWST), the Visual Reasoning test and the Trail Making test (TMT) were used to assess cognitive function.

Results

Multi-domain CogTr produced statistically significant training effects on RBANS, visual reasoning, and immediate and delayed memory, while single-domain CogTr showed training effects on RBANS, visual reasoning, word interference, and visuospatial/constructional score (all P < 0.05). At the 12-month posttest, the multi-domain CogTr showed training effects on RBANS, delayed memory and visual reasoning, while single-domain CogTr only showed effects on word interference. Booster training resulted in effects on RBANS, visual reasoning, time of trail making test, and visuospatial/constructional index score.

Conclusions

Cognitive training can improve memory, visual reasoning, visuospatial construction, attention and neuropsychological status in community-living older people and can help maintain their functioning over time. Multi-domain CogTr enhanced memory proficiency, while single-domain CogTr augmented visuospatial/constructional and attention abilities. Multi-domain CogTr had more advantages in training effect maintenance.

Clinical Trial Registration

Chinese Clinical Trial Registry. Registration number: ChiCTR-TRC-09000732.
The effect of the ratio of standardized ileal digestible lysine to metabolizable energy on growth performance, blood metabolites and hormones of lactating sows
Authors: Xue Lingfeng , Piao Xiangshu , Li Defa , Li Pengfei , Zhang Rongfei , Kim Sung Woo , Dong Bing
Published: March 2012

A total of 335 lactating sows (Landrace × Large White) were used in two experiments to determine the optimum ratio of standardized ileal digestible lysine (SID-Lys) to metabolizable energy (ME) for mixed parity sows during lactation. In Exp. 1, 185 sows (weighing an average of 256.2 ± 6.5 kg and having an average parity of 3.4 ± 0.3) were allocated to one of six experimental diets in a completely randomized block design within parity groups (1, 2, and 3+). The experimental diets were formulated to contain 3.06, 3.16, 3.20, 3.25, 3.30 or 3.40 Mcal/kg of ME and each diet was fed to the sows throughout a 28 day lactation. All diets provided a similar SID-lysine level (0.86%). As a result, the diets provided a SID-Lys:ME ratio of 2.81, 2.72, 2.69, 2.65, 2.61 or 2.53 g/Mcal ME. Sow feed intake was significantly (P < 0.01) affected by the energy content of the diet as well as by sow parity. Using regression analysis, feed intake was shown to be maximized at 3.25, 3.21, 3.21 and 3.21 Mcal/kg of ME for parity 1, 2, 3+ sows and the entire cohort of sows respectively (quadratic; P < 0.01). In addition, the result of feed intake can be expressed as 2.65, 2.69, 2.69 and 2.68 g/Mcal based on analysis of SID-Lys:ME ratio. Litter weight gain was affected by dietary treatment for parity 3+ sows and the entire cohort (P < 0.01). Based on regression analysis, litter weight gain was maximized at 3.25 and 3.24 Mcal/kg of ME for parity 3+ (quadratic; P < 0.01) and the entire cohort (quadratic; P < 0.01). Similarly, the result of litter weight gain could be expressed as 2.65 and 2.66 g/Mcal of SID-Lys:ME ratio. Therefore, 3.25 Mcal/kg of ME was selected for Exp. 2 in which 150 sows (weighing 254.6 ± 7.3 kg and having an average parity of 3.4 ± 0.4) were allocated to one of five treatments in a completely randomized block design within parity (1, 2, and 3+). The experimental diets were formulated to contain 2.1, 2.4, 2.7, 3.0 or 3.3 g/Mcal of SID-Lys:ME ratio with all diets providing 3.25 Mcal/kg of ME. The diets were fed to the sows throughout a 28 day lactation. Sow body weight loss was affected by dietary treatment (parity 3+ sows, P = 0.02; entire cohort, P < 0.01) and by sow parity (P < 0.01). Litter weight at weaning and litter weight gain were affected by dietary treatment for parity 1, 2, 3+ sows and the entire cohort (P < 0.01) as well as by sow parity (P < 0.01). Plasma urea nitrogen (P < 0.01), creatinine (P < 0.01) and non-esterifide fatty acids (P = 0.04) were decreased as the SID-Lys:ME ratio of the diet increased. Insulin-like growth factor-1 (P = 0.02), estradiol (P < 0.01) and luteinizing hormone (P = 0.02) were increased as the SID-Lys:ME ratio in diet increased. Based on a broken-line model, the estimated SID-Lys:ME ratio to maximize litter weight gain was estimated to be 3.05 g/Mcal.