bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐resolution genome‐wide copy‐number analysis suggests a monoclonal origin of multifocal prostate cancer
Authors: Boyd Lara K. , Mao Xueying , Xue Liyan , Lin Dongmei , Chaplin Tracy , Kudahetti Sakunthala C. , Stankiewicz Elzbieta , Yu Yongwei , Beltran Luis , Shaw Greg , Hines John , Oliver R. Tim D. , Berney Daniel M. , Young Bryan D. , Lu Yong‐Jie
Published: February 2012

Many human cancers present as multifocal lesions. Understanding the clonal origin of multifocal cancers is of both etiological and clinical importance. The molecular basis of multifocal prostate cancer has previously been explored using a limited number of isolated markers and, although independent origin is widely believed, the clonal origin of multifocal prostate cancer is still debatable. We attempted to address clonal origin using a genome‐wide copy‐number analysis of individual cancer and high‐grade prostatic intraepithelial neoplasia (HGPIN) lesions. Using Affymetrix array 6.0 copy‐number analysis, we compared the genomic changes detected in 48 individual cancer and HGPIN lesions, isolated from 18 clinically localized prostate cancer cases. Identical genomic copy‐number changes, shared by all same‐case cancer foci, were detected in all 13 informative cases displaying multiple tumor foci. In addition, individual HGPIN lesions in the two multifocal‐HGPIN cases available shared identical genomic changes. Commonly known genomic alterations, including losses at 6q15, 8p21.3‐8p21.2, 10q23.2‐10q23.31, 16q22.3, 16q23.2‐16q23.3 and 21q22.2‐21q22.3 regions and gain of 8q24.3 were the most frequently detected changes in this study and each was detected in all same‐case foci in at least one case. Microarray data were confirmed by fluorescence in situ hybridization in selected foci. Our high‐resolution genome‐wide copy‐number data suggest that many multifocal cases derive from a single prostate cancer precursor clone and that this precursor may give rise to separate HGPIN foci and may further progress to multifocal invasive prostate cancer. These findings, which demonstrate the monoclonal origin of multifocal prostate cancer, should significantly enhance our understanding of prostate carcinogenesis. © 2012 Wiley Periodicals, Inc.
Discovery of ALK‐PTPN3 gene fusion from human non‐small cell lung carcinoma cell line using next generation RNA sequencing
Authors: Jung Yeonjoo , Kim Pora , Jung Yeonhwa , Keum Juhee , Kim Soon‐Nam , Choi Yong Soo , Do In‐Gu , Lee Jinseon , Choi So‐Jung , Kim Sujin , Lee Jong‐Eun , Kim Jhingook , Lee Sanghyuk , Kim Jaesang
Published: February 2012

An increasing number of chromosomal aberrations is being identified in solid tumors providing novel biomarkers for various types of cancer and new insights into the mechanisms of carcinogenesis. We applied next generation sequencing technique to analyze the transcriptome of the non‐small cell lung carcinoma (NSCLC) cell line H2228 and discovered a fusion transcript composed of multiple exons of ALK (anaplastic lymphoma receptor tyrosine kinase) and PTPN3 (protein tyrosine phosphatase, nonreceptor Type 3). Detailed analysis of the genomic structure revealed that a portion of genomic region encompassing Exons 10 and 11 of ALK has been translocated into the intronic region between Exons 2 and 3 of PTPN3. The key net result appears to be the null mutation of one allele of PTPN3, a gene with tumor suppressor activity. Consistently, ectopic expression of PTPN3 in NSCLC cell lines led to inhibition of colony formation. Our study confirms the utility of next generation sequencing as a tool for the discovery of somatic mutations and has led to the identification of a novel mutation in NSCLC that may be of diagnostic, prognostic, and therapeutic importance. © 2012 Wiley Periodicals, Inc.
Risk factors for medication nonadherence in older adults with cognitive impairment who live alone
Authors: Thiruchselvam Thulasi , Naglie Gary , Moineddin Rahim , Charles Jocelyn , Orlando Laura , Jaglal Susan , Snow William , Tierney Mary C.
Published: February 2012

Objective

The aim of this study was to prospectively examine the influence of cognitive, medical, behavioral, and social risk factors on medication nonadherence in community‐dwelling older adults with cognitive impairment.

Methods

A sample of 339 elderly participants with cognitive impairment, who lived alone and took at least one medication, underwent baseline assessment which included the five subscales of the Dementia Rating Scale (DRS), number of medications, retrospective medication nonadherence, amount of formal and informal assistance, functional impairment, depression, perception of social resources, comorbidity, and alcohol consumption. The outcome was medication nonadherence during the 12‐month prospective period as reported by the participants' primary care physicians and caregivers at three‐month intervals.

Results

Fifty‐nine participants (17.4%) had, at least, one report of medication nonadherence. Logistic regression analyses indicated for every point increase on the DRS Conceptualization subscale (OR = 1.14; 95% CI = 1.02–1.27), there was a 14% increase in the odds of nonadherence. For every point increase on the DRS Memory subscale (OR = 0.89; 95% CI = 0.81–0.97) and DRS Initiation/Perseveration subscale (OR = 0.93; 95% CI = 0.87–1.00), there was an 11% decrease and 7% decrease in the odds, respectively. Having at least one previous occurrence of medication nonadherence (OR = 2.61; 95% CI = 1.18–5.62) and taking at least four medications (OR = 2.58; 95% CI = 1.31–5.29), both increased the odds by over 2.5‐fold.

Conclusions

Our unique finding that better conceptualization predicted nonadherence has important implications for healthcare providers' approaches to improve adherence in older adults with cognitive impairment. Replication in future studies is warranted. Copyright © 2012 John Wiley & Sons, Ltd.
REGIONAL VARIATION IN THE PRODUCTIVITY OF THE ENGLISH NATIONAL HEALTH SERVICE
Authors: Bojke Chris , Castelli Adriana , Street Andrew , Ward Padraic , Laudicella Mauro
Published: February 2012

Variation in the provision of health care has long been a policy concern. We adapt the framework for productivity measurement used in the National Accounts, making it applicable for sub‐national comparisons using cross‐sectional data. We assess the productivity of the National Health Service (NHS) across regions of England, termed Strategic Health Authorities (SHAs). Productivity is calculated by comparing the total amount of healthcare output to total inputs for each region, standardised to the national average. Healthcare output comprises 6500 different categories, capturing the number and type of NHS patients treated and the quality of care received. Healthcare inputs include NHS and agency staff, supplies, equipment and capital. We find that productivity varies from 5% above to 6% below the national average. Productivity is highest in South West SHA and lowest in East Midlands, South Central and Yorkshire and The Humber SHAs. We estimate that if all regions were as productive as the most productive region in England, the NHS could treat the same number of patients with £3.2bn fewer resources each year. The methods developed lend themselves to investigate variations in productivity in other types of healthcare organisations and health systems. Copyright © 2012 John Wiley & Sons, Ltd.
Source and characterization of hepatic macrophages in acetaminophen-induced acute liver failure in humans
Authors: Antoniades Charalambos Gustav , Quaglia Alberto , Taams Leonie S. , Mitry Ragai R. , Hussain Munther , Abeles Robin , Possamai Lucia A. , Bruce Matthew , McPhail Mark , Starling Christopher , Wagner Bart , Barnardo Adrian , Pomplun Sabine , Auzinger Georg , Bernal William , Heaton Nigel , Vergani Diego , Thursz Mark R. , Wendon Julia
Published: February 2012

Acetaminophen-induced acute liver failure (AALF) is associated with innate immunity activation, which contributes to the severity of hepatic injury and clinical outcome. A marked increase in hepatic macrophages (h-mφ) is observed in experimental models of AALF, but controversy exists regarding their role, implicating h-mφ in both aggravation and resolution of liver injury. The role of h-mφ in human AALF is virtually unexplored. We sought to investigate the role of chemokine (C-C motif) ligand 2 (CCL2) in the recruitment of circulating monocytes to the inflamed liver and to determine how the h-mφ infiltrate and liver microenvironment may contribute to tissue repair versus inflammation in AALF. We evaluated circulating monocytes, their chemokine (C-C motif) receptor 2 (CCR2) expression, and serum CCL2 levels in patients with AALF. Cell subsets and numbers of circulation-derived (MAC387+) or resident proliferating (CD68/Ki67+) h-mφ in hepatic immune infiltrates were determined by immunohistochemistry. Inflammatory cytokine levels were determined in whole and laser microdissected liver tissue by proteome array. In AALF, circulating monocytes were depleted, with the lowest levels observed in patients with adverse outcomes. CCL2 levels were high in AALF serum and hepatic tissue, and circulating monocyte subsets expressed CCR2, suggesting CCL2-dependent hepatic monocyte recruitment. Significant numbers of both MAC387+ and CD68+ h-mφ were found in AALF compared with control liver tissue with a high proportion expressing the proliferation marker Ki67. Levels of CCL2, CCL3, interleukin (IL)-6, IL-10, and transforming growth factor-β1 were significantly elevated in AALF liver tissue relative to chronic liver disease controls.

Conclusion

: In AALF, the h-mφ population is expanded in areas of necrosis, both through proliferation of resident cells and CCL2-dependent recruitment of circulating monocytes. The presence of h-mφ within an anti-inflammatory/regenerative microenvironment indicates that they are implicated in resolution of inflammation/tissue repair processes during AALF. (HEPATOLOGY 2012)
Long-term outcome of Japanese patients with type 1 autoimmune hepatitis
Authors: Yoshizawa Kaname , Matsumoto Akihiro , Ichijo Tetsuya , Umemura Takeji , Joshita Satoru , Komatsu Michiharu , Tanaka Naoki , Tanaka Eiji , Ota Masao , Katsuyama Yoshihiko , Kiyosawa Kendo , Abe Masanori , Onji Morikazu
Published: February 2012

The long-term outcome of patients with autoimmune hepatitis (AIH) in Japan has not been well-defined. The aim of this study was to clarify the outcome of this disease over a long follow-up period compared with that of the general Japanese population as well as that among patients. A total of 203 AIH patients were enrolled for a mean follow-up period of 131 months. All patients were treated with corticosteroids with or without azathioprine. The overall survival of AIH patients was similar to that of the general population in Japan. The prognosis of AIH subgroups divided according to disease severity, sex, incidence of relapse, liver histology, presence of cirrhosis, probable or definite AIH score, antibody to hepatitis B core antigen antibody positivity, or human leukocyte antigen DR4–positivity did not differ greatly among patients. However, the prognosis of patients experiencing two or more relapses was significantly poorer than that of patients with remission or a single relapse both in univariate (

P

< 0.001) and multivariate (

P

= 0.020) analyses. The development of liver malignancy was also a possibility among AIH patients with multiple relapses. Severe adverse effects of corticosteroids were rare, even in patients who underwent long-term treatment.

Conclusion:

Repeated relapses of AIH are significantly associated with a poorer long-term prognosis in Japan. AIH patients can expect a similar prognosis to that of the general population, provided they are adequately managed with continuous low doses of immunosuppressive therapy, especially after the first relapse. (HEPATOLOGY 2012)
Hepatitis delta virus infects the cells of hepadnavirus-induced hepatocellular carcinoma in woodchucks
Authors: Freitas Natalia , Salisse Jessica , Cunha Celso , Toshkov Ilia , Menne Stephan , Gudima Severin O.
Published: February 2012

Hepatitis delta virus (HDV) is a natural subviral agent of human hepatitis B virus (HBV). HDV enhances liver damage during concomitant infection with HBV. The molecular pathogenesis of HDV infection remains poorly understood. To advance our understanding of the relationship between HDV infection and liver cancer, it was determined whether HDV could infect in vivo the cells of hepadnavirus-induced hepatocellular carcinoma (HCC). Woodchucks (Marmota monax) that were chronically infected with HBV-related woodchuck hepatitis virus (WHV) and already developed HCCs were used as an experimental model. The locations of HCCs within the livers were determined using ultrasound imaging followed by open surgery. One week after surgery the WHV carrier woodchucks were superinfected with WHV-enveloped HDV (wHDV). Six weeks later the animals were sacrificed and HDV replication in normal liver tissues and in center masses of HCCs was evidenced by Northern analysis, real-time polymerase chain reaction assay, and immunohistochemistry. Based on accumulation levels of HDV RNAs and numbers of infected cells, the efficiency of wHDV infection appears to be comparable in most HCCs and normal liver tissues. Conclusion: Cells of WHV-induced HCCs are susceptible to HDV infection in vivo, and therefore express functional putative WHV receptors and support the steps of the attachment/entry governed by the hepadnavirus envelope proteins. Because others previously hypothesized that hepadnavirus-induced HCCs are resistant to reinfection with a hepadnavirus in vivo, our data suggest that if such a resistance exists it likely occurs via a block at the post-entry step. The demonstrated ability of HDV to infect already formed HCCs may facilitate development of novel strategies further dissecting the mechanism of liver pathogenesis associated with HDV infection. (HEPATOLOGY 2012;56:76–85)
Human apolipoprotein E peptides inhibit hepatitis C virus entry by blocking virus binding
Authors: Liu Shufeng , McCormick Kevin D. , Zhao Wentao , Zhao Ting , Fan Daping , Wang Tianyi
Published: February 2012

Hepatitis C virus (HCV) entry is a multiple-step process involving a number of host factors and hence represents a promising target for new antiviral drug development. In search of novel inhibitors of HCV infection, we found that a human apolipoprotein E (apoE) peptide, hEP, containing both a receptor binding fragment and a lipid binding fragment of apoE specifically blocked the entry of cell culture grown HCV (HCVcc) at submicromolar concentrations. hEP caused little cytotoxicity

in vitro

and remained active even if left 24 hours in cell culture. Interestingly, hEP inhibited neither human immunodeficiency virus (HIV)-HCV pseudotypes (HCVpp) nor HIV and Dengue virus (DENV) infection. Further characterization mapped the anti-HCV activity to a 32-residue region that harbors the receptor binding domain of apoE, but this fragment must contain a cysteine residue at the N-terminus to mediate dimer formation. The anti-HCV activity of the peptide appears to be dependent on both its length and sequence and correlates with its ability to bind lipids. Finally, we demonstrated that the apoE-derived peptides directly blocked the binding of both HCVcc and patient serum-derived virus to hepatoma cells as well as primary human hepatocytes.

Conclusion

: apoE peptides potently inhibit HCV infection and suggest a direct role of apoE in mediating HCV entry. Our findings also highlight the potential of developing apoE mimetic peptides as novel HCV entry inhibitors by targeting HCV-host interactions. (HEPATOLOGY 2012)
Modulation of regulatory T-cell activity in combination with interleukin-12 increases hepatic tolerogenicity in woodchucks with chronic hepatitis B
Authors: Otano Itziar , Suarez Lester , Dotor Javier , Gonzalez-Aparicio Manuela , Crettaz Julien , Olagüe Cristina , Vales Africal , Riezu Jose Ignacio , Larrea Esther , Borras Francisco , Benito Alberto , Hernandez-Alcoceba Ruben , Menne Stephan , Prieto Jesús , González-Aseguinolaza Gloria
Published: February 2012

Regulatory T cells (Treg) play a critical role in the modulation of immune responses to viral antigens in chronic viral hepatitis. Woodchucks (

Marmota monax

) infected with the woodchuck hepatitis virus (WHV) represent the best animal model for chronic hepatitis B virus (HBV) infection. Examination of intrahepatic and peripheral Treg in uninfected and WHV chronically infected woodchucks showed a significant increase of intrahepatic Treg numbers in chronically infected animals, whereas no differences were found in peripheral blood. In agreement with these data, higher expression levels of Forkhead box P3 (Foxp3), interleukin (IL)-10, transforming growth factor beta (TGF-β) were detected in the liver of chronic WHV carriers in comparison to uninfected animals. Furthermore, treatment of WHV-infected animals with an adenovirus encoding IL-12 failed to reduce viral load, a finding that was associated with lymphocyte unresponsiveness to IL-12 stimulation

in vitro

. We observed that TGF-β and Treg play a major role in the lack of lymphocyte response to IL-12 stimulation, as TGF-β inhibition and Treg depletion allowed recovery of T-cell responsiveness to this cytokine. Based on these results, woodchucks were treated with IL-12 in combination with a TGF-β inhibitory peptide or Treg depletion. However, no antiviral effect was achieved and, instead, an enhancement of the intrahepatic tolerogenic environment was observed.

Conclusion

: Our data show that TGF-β inhibition or Treg depletion had no added benefit over IL-12 therapy in chronic WHV infection. IL-12 immunostimulation induces a strong immunosuppressive reaction in the liver of chronic WHV carriers that counteracts the antiviral effect of the treatment. (HEPATOLOGY 2012)
Semi‐automated GIS techniques for detecting floodplain earthworks
Authors: Steinfeld Celine M. M. , Kingsford Richard T. , Laffan Shawn W.
Published: February 2012

Levees, channels and water storages built on the world's floodplain wetlands control flows for irrigation, flood mitigation and erosion management. Assessing their distribution and hydrological impacts through time and across broad extents is limited by significant costs and technical challenges. We tested the effectiveness of three new semi‐automated geographic information systems and traditional visual interpretation techniques for detecting earthworks. We used commercially or freely available two‐dimensional and three‐dimensional spatial imagery within 19 quadrats in an agricultural floodplain of the Murray–Darling Basin, southeastern Australia. Semi‐automated digital elevation model (DEM) analysis performed best for spatial accuracy (78% of earthworks correctly predicted within 25 m), overall classification accuracy (97.7%) and kappa (0.64), compared with traditional visual interpretation techniques using Landsat TM (52%, 96.3%, 0.39), SPOT (53%, 95.8%, 0.27) and aerial photography (72%, 97.2%, 0.31). DEM analysis also outperformed semi‐automated image segmentation (16%, 93%, 0.29) and integrated analysis (75%, 96.0%, 0.43) that used spectral information. Semi‐automated techniques were slow (DEM analysis: 27 418 s/km2; integrated analysis: 27 737 s/km2; and image segmentation: 1439 s/km2) compared with visual interpretation (Landsat TM: 109 s/km2; SPOT: 166 s/km2; and aerial photography: 276 s/km2); however, processing speed of semi‐automated techniques can be further increased without compromising accuracy. Semi‐automated techniques also offered operational autonomy following model calibration. High quality, cost‐effective earthwork mapping techniques, particularly the semi‐automated techniques in this study, are critical for understanding and managing ecosystem health, flood risk and water security in developed floodplains worldwide and should be implemented by governing institutions. Copyright © 2012 John Wiley & Sons, Ltd.
Characterizing the hydraulic properties of unsaturated sand considering various porosities and drying‐wetting paths of the retention curve
Authors: Ke Kai‐yuan , Tan Yih‐Chi , Chen Chu‐Hui , Lin Hsien‐Tsung
Published: February 2012

Previous studies have shown that water retention curve (WRC) and the hydraulic conductivity vary because of changes of the void ratio or porosity of soil. However, limited documents pointed out the change of hydraulic properties of soil when compacted to different porosities while considering both of the drying and wetting processes of the WRC. This information is sometimes necessary for research like finger flow analysis or the occurrence of wetting and drying cycles as what would be seen in the field. Therefore, this study aims to examine the change of WRC characteristics with varied porosity considering both of the drying and wetting path in WRC by conducting a sand box experiment. Results show that the same type of sand compacted to various porosities have different hydraulic parameters. Hydraulic conductivities generally decrease with reduced porosities; shape parameter α of the van Genuchten equation (1980) linearly decreases with declining porosity and shape parameter n in a reversal manner for the sands of interest whether in the drying process or wetting process. The unsaturated properties of sand are further characterized by inspecting the variations of moisture content, matric suction and vertical displacement of soil body subject to periodic changes of the water level by another sand box experiment. The outcomes suggest that the saturated water content and residual water content are changing during the wetting–drying process, which can be an implication of the changed properties of WRC. The characteristics of volumetric deformation might be varied as well because of the observation of the dissimilar patterns of the changing vertical displacements among each wetting–drying process. Infiltration patterns of the sands also are identified through numerical modelling by introducing a constant infiltration flux from the surface followed by a no‐influx condition. Results indicate that less water accumulates in the sand near the surface for the sand compacted to higher porosity, but water can move deeper. Hydraulic conductivity is found as the prime factor dominating the evolvement of wetting fronts. However, shape parameters of water retention curves also affect the infiltration pattern to some extent. In addition, different sands with similar porosities can have quite different infiltrating characteristics. Copyright © 2012 John Wiley & Sons, Ltd.
Tumorigenicity of acrylamide and its metabolite glycidamide in the neonatal mouse bioassay
Authors: Von Tungeln Linda S. , Doerge Daniel R. , Gamboa da Costa Gonçalo , Matilde Marques M. , Witt William M. , Koturbash Igor , Pogribny Igor P. , Beland Frederick A.
Published: February 2012

Acrylamide is a high‐volume industrial chemical, a component of cigarette smoke, and a product formed in certain foods prepared at high temperatures. Previously, we compared the extent of DNA adduct formation and mutations in B6C3F1/Tk mice treated neonatally with acrylamide or glycidamide to obtain information concerning the mechanism of acrylamide genotoxicity. We have now examined the tumorigenicity of acrylamide and glycidamide in mice treated neonatally. Male B6C3F1 mice were injected intraperitoneally on postnatal days 1, 8 and 15 with 0.0, 0.14 or 0.70 mmol acrylamide or glycidamide per kg body weight per day and the tumorigenicity was assessed after 1 year. Survival in each of the groups was >87%, there were no differences in body weights among the groups, and the only treatment‐related neoplasms involved the liver. The incidence of combined hepatocellular adenoma or carcinoma was 3.8% in the control group, 8.3% in the 0.14 mmol acrylamide and glycidamide per kg body weight groups, 4.2% in the 0.70 mmol acrylamide per kg body weight group and 71.4% in the 0.70 mmol glycidamide per kg body weight group. Analysis of the hepatocellular tumors indicated that the increased incidence observed in mice administered 0.70 mmol glycidamide per kg body weight was associated with A → G and A → T mutations at codon 61 of H‐ras. These results, combined with our previous data on DNA adduct formation and mutation induction, suggest that the carcinogenicity of acrylamide is dependent on its metabolism to glycidamide, a pathway that is deficient in neonatal mice.
Side‐Chain Metallocene‐Containing Polymers by Living and Controlled Polymerizations
Authors: Hardy Christopher G. , Ren Lixia , Zhang Jiuyang , Tang Chuanbing
Published: February 2012

This review summarizes recent work on side‐chain metallocene‐containing polymers prepared by controlled and living polymerizations, which include living anionic polymerization (LAP), ring‐opening metathesis polymerization (ROMP) and controlled radical polymerization (CRP) such as atom transfer radical polymerization (ATRP), reversible addition fragmentation chain transfer polymerization (RAFT), and nitroxide‐mediated polymerization (NMP). The majority of efforts in the field are focused on side‐chain ferrocene‐containing polymers, while cobaltocenium‐containing polymers have recently started to draw attention. Future direction on the development of other metallocene‐containing polymers is discussed.
Minnesota Employment Counselor Activities
Authors: RINGSMUTH PAUL L. , REDDING ARTHUR J.
Published: February 2012

Employment counselors, counselor supervisors, managers, and counselor educators were surveyed in Minnesota concerning the amounts of time that are now spent and should be spent in eleven employment counselor activities. All respondents generally agreed on the amounts of time that are now spent and should be spent in the activities. They also agreed that there should be significant increases (p > .05) in the amounts of time that should be spent in counseling, teaching, and research/follow‐up, and decreases in the amounts of time that should be spent in selection/intake and records/clerical activities. Employment counselors in main offices indicated that they now spend significantly less time than counselors in subordinate offices in counseling, consulting, and staff activities, and significantly more time in testing.
The Validity of the GATB for the Educationally Deficient
Authors: KUJOTH RICHARD
Published: February 2012

The General Aptitude Test Battery, used by many state employment services as a counseling tool, has been criticized as an unfair screening device. A less restrictive policy of pretest coaching and retesting, combined with action research on the effects of remedial education on aptitudes scores is suggested, rather than a return to subjective assessment.
Employer Preferences for the Form and Substance of Employment Application Cover Letters
Authors: STEPHENS DAVID B. , WATT JAMES T. , HOBBS WADE S.
Published: February 2012

This study investigates the effect some principal characteristics of employment application cover letters have on personnel officers. A sample of personnel executives from 100 major companies was queried as to their perception of the desirability of 12 common cover letter characteristics. The results indicate that the personnel officers do not consistently perceive letters in the manner suggested by the existing literature. Some characteristics are shown to elicit negative responses from personnel officers, and thus should be avoided by job applicants. Several characteristics are strongly preferred by the sample surveyed. The model for an employment cover letter derived from this study should enhance the applicant's chances for a favorable response, or at least prevent letter forms which might detract therefrom.
Treatment and Supervision of Probated Felons
Authors: MOORE JAMES B. , SHEARER ROBERT A.
Published: February 2012

Recently published results of a major personality study on probated felons furnish some directions for case‐load treatment and supervision. Probation programming guidelines based on these results—the specific personality constructs of manipulation, self‐control, and anxiety in probated felons—could enhance probation programming effectiveness.
Career Development Theories: What Help for Older Persons?
Authors: TOLBERT E. L.
Published: February 2012

Career development theory, although most highly developed for persons in the first two or three decades of life, can help counselors plan ways to work with older persons. The career development theories of Super, Tiedeman, Holland, Blau and other sociologists, Ginzberg, and Krumboltz, as well as the developmental theories of Levinson, Gould, and Neugarten are briefly reviewed to support this assertion. Although applications should be made with caution, concepts from these theories seem to have potential for enhancing the effectiveness of counseling of older persons. There seems, however, to be an increase in research and theory‐building on the career development of this age group; more helpful guidelines can be expected in the future.
Counseling the Disabled Older Person for the World of Work
Authors: MYERS JANE E.
Published: February 2012

Although work is meaningful to many older persons, numerous barriers exist that prohibit their active participation in the labor force. Employment counselors must possess a variety of attributes to help break down these barriers. This article discusses skills that the counselor needs when working with older adults and in particular with those who are disabled. Specialized approaches to job placement are discussed, including job modification and job restructuring. To become a successful advocate for the disabled elderly wishing to enter or remain in the labor market, the employment counselor is urged to become familiar with characteristics of older persons and federal laws relating to job development and placement for older and handicapped workers.
A Severe Employment Handicap: A Criminal Record
Authors: COELHO RICHARD J.
Published: February 2012

Having a criminal record can be viewed as a severe handicap that affects employment. Bonding and licensing regulations, employer attitudes, and psychological maladjustment of the ex‐offender are aspects of his or her employment problems. The understanding and active involvement of the rehabilitation counselor and the community can help overcome employment barriers and help the ex‐offender become an effective and contributing citizen.
The Stigma Associated with Various Criminal Offenses in Hiring Decisions
Authors: DeVINNEY DAVID J. , THOMAS KENNETH R.
Published: February 2012

The purpose of this study was to investigate the attitudes of prospective employers toward hiring ex‐offenders based on the nature of the crime committed. Thirty‐nine male and 30 female students in a personnel management class at a major Midwestern university were surveyed regarding their attitudes toward hiring persons convicted for the following crimes: kidnapping, armed robbery, homicide, assault and battery (nonsexual), automobile theft, rape, burglary, sale of hard narcotics, forgery, and child molesting. Statistical analyses revealed a significant difference in the total group's rankings of the 10 crimes but no significant differences between males and females.
The Male Midlife Crisis and Career Change
Authors: SAGAL KAREN , DeBLASSIE RICHARD
Published: February 2012

American males are known to find themselves in a stage similar to the turbulence and confusion of adolescence during the stage of mid‐life. This stage, referred to by some as “midadolescence,” occurs between the late 30s and early 50s. Mental, physical, emotional, and spiritual aspects of mid‐life males are frequently shaken to the core and have a definite impact on job satisfaction. Three major tasks are to be worked on during this time by men undergoing the aforementioned phenomenon: (a) terminating early adulthood, (b) dealing with polarities, and (c) initiating middle adulthood.
Some New Ideas on Employability Counseling
Authors: GOALDER JAMES S. , MANN WILLIAM H.
Published: February 2012

The article discusses common disadvantages of most current Employability Development Plans (EDPs) and suggests specific remedies that organize the decision‐making thrust of employability counseling. The authors present a theory‐based, developmental model for assessment and EDP systems, and review general problems in implementing this model.
Factors Affecting Employer Preference for Female Managerial Applicants
Authors: PEARSON BARBARA ELLEN , EVANS DONNA BROWN , MEHNERT WILLIAM O. , SANFORD ALPHEUS
Published: February 2012

This study examines aspects of job interview behavior that influence employer preference for a female applicant for a managerial position in the human service field. The authors used an analogue methodology simulating videotaped job interview vignettes to present a female applicant exhibiting varying leadership and personality styles, ranging from a “warm” cooperative style to a “cold” task‐oriented style. Employers in the human services field rated their preference for the simulated applicants. There were significant differences in preference for the various types of applicants; the most preferred were those who combined warmth with goal‐oriented leadership skills.
Interstitial interfaces show marked differences in regenerating tubules, matured tubules, and the renal stem/progenitor cell niche
Authors: Minuth Will W. , Denk Lucia
Published: February 2012

Stem/progenitor cells are promising candidates for the regeneration of parenchyma in acute and chronic renal failure. After an implantation stem/progenitor cells must migrate through the interstitial space to concentrate at the site of damage. However, information is lacking to what extent the interstitial interface is influencing the development of stem/progenitor cells into nephron structures. In consequence, tubule regeneration within an artificial polyester interstitium was analyzed by electron microscopy in comparison with the interstitial interface of matured tubules and the interstitium within the renal stem/progenitor cell niche. The experiments demonstrate that fixation of specimens with glutaraldehyde (GA) is leading in all cases to inconspicuously looking interstitial interfaces. In contrast, fixation of regenerating tubules in GA containing ruthenium red and tannic acid shows a dense network of fibers lining along the basal lamina. In contrast, matured tubules reveal after ruthenium red label an extremely thickened basal lamina, while only a punctate pattern is obtained after tannic acid treatment. Finally, within the renal stem/progenitor cell niche ruthenium red and tannic acid label reveals large amounts of extracellular matrix spanning through the interstitium. Thus, fixation of tissue in GA containing ruthenium red and tannic acid exhibits an unexpectedly regional heterogeneity of the renal interstitial interface. This fact has to be considered for an optimal therapeutic repair of parenchyma, since contacts between stem/progenitor cells with the interstitial interface influence further development. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Improvement in the colloidal stability of protein kinase‐responsive polyplexes by PEG modification
Authors: Tsuchiya Akira , Naritomi Yuki , Kushio Satoshi , Kang Jeong‐Hun , Murata Masaharu , Hashizume Makoto , Mori Takeshi , Niidome Takuro , Katayama Yoshiki
Published: February 2012

We have reported a disease‐cell specific gene expression system that is responsive to intracellular signaling proteins (e.g., protein kinases and proteases) hyperactivated in diseased cells. For this system, cationic peptide‐grafted polymers were synthesized for polyplex formation with genes. Here, we modified poly(ethylene glycol) (PEG) to a protein kinase A (PKA)‐responsive polymer to improve polyplex stability. PEG modification neutralized the surface charge of the polyplex and successfully increased polyplex stability at physiological conditions. However, PEG modification (PEG contents, 0.6 and 3.3 mol %) showed almost negligible effects on the reactivity of grafted peptides to PKA and the promotion of gene expression responding to PKA activity. Excessive modification of PEG (PEG contents, 6.8 mol %) inhibited polyplex formation. These results indicate that moderate modification of PEG to the enzyme‐responsive polymer improves polyplex stability without inhibiting the reaction with enzymes. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Advanced polymeric matrix for valvular complications
Authors: Acharya Gayathri , Hopkins Richard A. , Lee Chi H.
Published: February 2012

Poly(L‐lactic acid) (PLLA) matrix systems incorporated with poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) containing nitric oxide (NO) donors (DETA NONOate) were developed for prevention of heart valve complications through sustained and controlled release of NO. PLLA matrices were prepared using the salt leaching method and the properties and drug release profiles were characterized. For assessment of the effects of PLLA systems on the pharmacological responses and cytotoxicity, various factors, such as calcium content, alkaline phosphatase (ALP) activity, cyclic guanosine monophosphate (cGMP) expression, intercellular adhesion molecule (ICAM‐1) expression and cell viability of porcine aortic valve interstitial cells (PAVICs), were evaluated. PLLA matrices embedded with PLGA‐ NPs demonstrated its usefulness in alleviating the calcification rate of the VICs. The cGMP levels under osteoblastic conditions significantly increased, supporting that anticalcification activity of NO is mediated through NO‐cGMP signaling pathway. The level of ICAM‐1 expression in cells exposed to NO was lowered, suggesting that NO has an inhibitory activity against tissue inflammation. NO releases from PLLA matrix embedded with PLGA NPs prevented valvular calcification and inflammation without causing any cytotoxic activities. PLLA matrix system loaded with NPs containing NO donors could provide a new platform for sustained and controlled delivery of NO, significantly reducing valvular complications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Altering surface characteristics of polypropylene mesh via sodium hydroxide treatment
Authors: Regis Shawn , Jassal Manisha , Mukherjee Nilay , Bayon Yves , Scarborough Nelson , Bhowmick Sankha
Published: February 2012

Incisional hernias represent a serious and common complication following laparotomy. The use of synthetic (e.g. polypropylene) meshes to aid repair of these hernias has considerably reduced recurrence rates. While polypropylene is biocompatible and has a long successful clinical history in treating hernias and preventing reherniation, this material may suffer some limitations, particularly in challenging patients at risk of wound failure due to, for example, an exaggerated inflammation reaction, delayed wound healing, and infection. Surface modification of the polypropylene mesh without sacrificing its mechanical properties, critical for hernia repair, represents one way to begin to address these clinical complications. Our hypothesis is treatment of a proprietary polypropylene mesh with sodium hydroxide (NaOH) will increase in vitro NIH/3T3 cell attachment, predictive of earlier and improved cell colonization and tissue integration of polypropylene materials. Our goal is to achieve this altered surface functionality via enhanced removal of chemicals/oils used during material synthesis without compromising the mechanical properties of the mesh. We found that NaOH treatment does not appear to compromise the mechanical strength of the material, despite roughly a 10% decrease in fiber diameter. The treatment increases in vitro NIH/3T3 cell attachment within the first 72 h and this effect is sustained up to 7 days in vitro. This research demonstrates that sodium hydroxide treatment is an efficient way to modify the surface of polypropylene hernia meshes without losing the mechanical integrity of the material. This simple procedure could also allow the attachment of a variety of biomolecules to the polypropylene mesh that may aid in reducing the complications associated with polypropylene meshes today. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Growth, differentiation, and migration of osteoblasts on transparent Ni doped TiO2thin films deposited on borosilicate glass
Authors: Dhayal Marshal , Kapoor Renu , Sistla Pavana Goury , Kant Chander , Pandey Ravi Ranjan , Govind  , Saini Krishan Kumar , Pande Gopal
Published: February 2012

A simple and cost effective dip coating method was used to deposit thin films of amorphous (AM) or anatase (AN) titanium dioxide (TiO2) on borosilicate glass substrates, either with or without prior doping of TiO2with nickel (Ni) cations by a specially designed sol gel technique. The objective of the study was to compare the physicochemical and biological properties of these films and assess their use in orthopedic implants or forin vitrocell biological studies. Analytical techniques such as XRD and XPS, in combination with ATR‐FTIR and SEM revealed that only AN films, prepared by controlled heating up to 450°C, irrespective of prior doping with Ni, contained significant crystalline structures of variable morphologies. This observation could be linked to the carbon and oxygen contents and the availability of functional groups in the films. Cell biological studies revealed that Ni doping of TiO2in both AM and AN films improved the adhesion, spreading, proliferation, differentiation, and migration of MC3T3 cells. Our studies provide a new approach to prepare optically transparent metal surfaces, with tunable physicochemical properties, which could be suitable for eliciting optimal osteoinductive cell responses and permit the detailedin vitrocell biological studies of osteoblasts. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces
Authors: Hofstetter Birgit , Gamsjaeger Sonja , Phipps Roger J , Recker Robert R , Ebetino Frank H , Klaushofer Klaus , Paschalis Eleftherios P
Published: February 2012

We used Raman and Fourier transform infrared microspectroscopy (FTIRM) analysis to examine the intrinsic bone material properties at actively bone-forming trabecular surfaces in iliac crest biopsies from women with postmenopausal osteoporosis (PMO) who were treated with either alendronate (ALN) or risedronate (RIS). At eight study sites, women were identified who had postmenopausal osteoporosis (PMO), were at least 5 years postmenopause, and had been on long-term therapy (either 3–5 years or >5 years) with daily or weekly ALN or RIS. Following standard tetracycline labeling, biopsies were collected from 102 women (33 treated with ALN for 3–5 years [ALN-3], 35 with ALN for >5 years [ALN-5], 26 with RIS for 3–5 years [RIS-3], and 8 with RIS for >5 years [RIS-5]) and were analyzed at anatomical areas of similar tissue age in bone-forming areas (within the fluorescent double labels). The following outcomes were monitored and reported: mineral to matrix ratio (corresponding to ash weight), relative proteoglycan content (regulating mineralization commencement), mineral maturity (indicative of the mineral crystallite chemistry and stoichiometry, and having a direct bearing on crystallite shape and size), and the ratio of two of the major enzymatic collagen cross-links (pyridinoline/divalent). In RIS-5 there was a significant decrease in the relative proteoglycan content (−5.83% compared to ALN-5), while in both RIS-3 and RIS-5 there was significantly lower mineral maturity/crystallinity (−6.78% and −13.68% versus ALN-3 and ALN-5, respectively), and pyridinoline/divalent collagen cross-link ratio (−23.09% and −41.85% versus ALN-3 and ALN-5, respectively). The results of the present study indicate that ALN and RIS exert differential effects on the intrinsic bone material properties at actively bone-forming trabecular surfaces. © 2012 American Society for Bone and Mineral Research.
Biomechanical stimulation of osteoblast gene expression requires phosphorylation of the RUNX2 transcription factor
Authors: Li Yan , Ge Chunxi , Long Jason P , Begun Dana L , Rodriguez Jose A , Goldstein Steven A , Franceschi Renny T
Published: February 2012

Bone can adapt its structure in response to mechanical stimuli. At the cellular level, this involves changes in chromatin organization, gene expression, and differentiation, but the underlying mechanisms are poorly understood. Here we report on the involvement of RUNX2, a bone-related transcription factor, in this process. Fluid flow shear stress loading of preosteoblasts stimulated translocation of extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) to the nucleus where it phosphorylated RUNX2 on the chromatin of target genes, and increased histone acetylation and gene expression. MAPK signaling and two RUNX2 phosphoacceptor sites, S301 and S319, were critical for this response. Similarly, in vivo loading of mouse ulnae dramatically increased ERK and RUNX2 phosphorylation as well as expression of osteoblast-related genes. These findings establish ERK/MAPK-mediated phosphorylation of RUNX2 as a critical step in the response of preosteoblasts to dynamic loading and define a novel mechanism to explain how mechanical signals induce gene expression in bone. © 2012 American Society for Bone and Mineral Research.
Caffeic acid 3,4-dihydroxy-phenethyl ester suppresses receptor activator of NF-κB ligand–induced osteoclastogenesis and prevents ovariectomy-induced bone loss through inhibition of mitogen-activated protein kinase/activator protein 1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 signaling pathways
Authors: Wu Xian , Li Zhenxi , Yang Zhengfeng , Zheng Chunbing , Jing Ji , Chen Yihua , Ye Xiyun , Lian Xiaoyuan , Qiu Wenwei , Yang Fan , Tang Jie , Xiao Jianru , Liu Mingyao , Luo Jian
Published: February 2012

Receptor activator of NF-κB ligand (RANKL) stimulation leads to the activation of mitogen-activated protein kinase (MAPK)/AP-1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) signaling pathways in osteoclastogenesis. Targeting these pathways has been an encouraging strategy for bone-related diseases, such as postmenopausal osteoporosis. In this study, we examined the effects of caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) on osteoclastogenesis. In mouse bone marrow monocytes (BMMs) and RAW264.7 cells, CADPE suppressed RANKL-induced osteoclast differentiation and actin-ring formation in a dose-dependent manner within non–growth inhibitory concentrations at the early stage, while CADPE had no effect on macrophage colony-stimulating factor (M-CSF)-induced proliferation and differentiation. At the molecular level, CADPE inhibited RANKL-induced phosphorylation of MAPKs, including extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK), without significantly affecting the NF-κB signaling pathway. CADPE abrogated RANKL-induced activator protein 1 (AP-1)/FBJ murine osteosarcoma viral oncogene homolog (c-Fos) nuclear translocation and activation. Overexpression of c-Fos prevented the inhibition by CADPE of osteoclast differentiation. Furthermore, CADPE suppressed RANKL-induced the tumor necrosis factor receptor associated factor 6 (TRAF6) interaction with c-src tyrosine kinase (c-Src), blocked RANKL-induced the phosphorylation of protein kinase B (AKT), and inhibited RANKL-induced Ca2+ oscillation. As a result, CADPE decreased osteoclastogenesis-related marker gene expression, including NFATc1, TRAP, cathepsin K, and c-Src. To test the effects of CADPE on osteoclast activity in vivo, we showed that CADPE prevented ovariectomy-induced bone loss by inhibiting osteoclast activity. Together, our data demonstrate that CADPE suppresses osteoclastogenesis and bone loss through inhibiting RANKL-induced MAPKs and Ca2+-NFATc1 signaling pathways. CADPE is a novel agent in the treatment of osteoclast-related diseases, such as osteoporosis. © 2012 American Society for Bone and Mineral Research.