bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of vancomycin pharmacokinetics in the adult acute myeloid leukemia population
Authors: Jarkowski Anthony , Forrest Alan , Sweeney Richard P , Tan Wei , Segal Brahm H , Almyroudis Nikolaos , Wang Eunice S , Wetzler Meir
Published: April 2011

Current vancomycin dosing guidelines in our acute myeloid leukemia population too often achieve suboptimal initial drug concentrations. Our aim was to assess vancomycin pharmacokinetic parameters in acute myeloid leukemia patients and develop an improved dosing equation to attain more accurate initial therapeutic trough levels. Acute myeloid leukemia patients receiving vancomycin for a presumed or documented gram positive infection were eligible. Patients hospitalized in the intensive care unit, those with creatinine clearance <30 mL/min or with limb amputation were excluded. Three samples were collected at the following post-infusion time ranges: 1 h, 3–8 h, and 8–24 h post-infusion, contingent on the dosing interval. Pharmacokinetic data were then fit using a Bayesian-based population pharmacokinetic model. A total of 25 acute myeloid leukemia patients were studied with a mean volume in the central compartment (Vc; L/65 kg), volume of distribution at steady state (Vss; L/65 kg) and distributional clearance (CLd; L/h/65 kg) of 15, 38.9, and 9.32, respectively. CLslope was 0.59 (mg of vancomycin clearance per unit of creatinine clearance in mL/min); this value is 21.4% lower than the established literature value (0.75). The derived equation, based upon these values, was reasonably precise at achieving the desired trough concentration using a priori dosing. The mean (CV%) of the achieved trough was 94% (29%) with a range of 66–188%; 3/25 at <75% and >125%]. We have established that the derived dosing equation can place ∼75% of adult acute myeloid leukemia patients at vancomycin trough levels within 75–125% of the target trough level.
The Application of a Three-Tier Model of Intervention to Parent Training
Authors: Phaneuf Leah , McIntyre Laura Lee
Published: April 2011

A three-tier intervention system was designed for use with parents with preschool children with developmental disabilities to modify parent–child interactions. A single-subject changing-conditions design was used to examine the utility of a three-tier intervention system in reducing negative parenting strategies, increasing positive parenting strategies, and reducing child behavior problems in parent–child dyads ( n = 8). The three intervention tiers consisted of (a) self-administered reading material, (b) group training, and (c) individualized video feedback sessions. Parental behavior was observed to determine continuation or termination of intervention. Results support the utility of a tiered model of intervention to maximize treatment outcomes and increase efficiency by minimizing the need for more costly time-intensive interventions for participants who may not require them.
The production of educational space: Heterotopia and the business university
Authors: Beyes Timon , Michels Christoph
Published: April 2011

This article responds to recent calls for rethinking management education and fostering a spatial understanding of educational practices. We propose to introduce Foucault’s notion of heterotopic space and the spatial thought of Lefebvre into the debate about the current and future state of business schools. In particular, we conceptually and empirically discuss the potential for understanding space in a way that addresses its productive force, its multiplicity and its inherent contradictions. Using the example of an experimental teaching project dedicated to the conception and physical design of a city of the future, we reflect upon the possibility of the emergence of ‘other’, heterotopic spaces within an institution of management learning. Our findings suggest that spatial interventions facilitate critically affirmative engagement with the business school by offering an imaginative approach to management education.
Hispanic Bachelor’s Degree Recipients in Connecticut: Effect of Major Field of Study on Expected Starting Salaries
Authors: Clifford Maryanne T. , Brown Jennifer L. , Free Rhona C.
Published: April 2011

Hispanics’ earnings remain below those of Whites, even after controlling for educational attainment. This article explores the effect of college major on estimated starting salaries of White and Hispanic bachelor’s-degree recipients from Connecticut colleges and universities. Results indicate that while the earnings gap between Hispanic and White workers will decrease as bachelor’s-degree attainment of Hispanics increases, differences in the distributions of students across college majors will mitigate that decrease.
Perceived Academic Preparedness of First-Generation Latino College Students
Authors: Boden Karen
Published: April 2011

First-generation Latino college students may be characterized as underprepared for college. Research points to low performance on placement tests. However, students may not perceive themselves as academically underprepared for college. This study explored first-generation Latino students’ perceptions of their academic preparedness. Seven students were interviewed with the following four themes to emerge—personal education planning, guides, academic skills, and personal impetus. Student answers show that they believed they were academically prepared for college.
Differences in Learning Styles of Dominican and Puerto Rican Students: We Are Latinos From the Caribbean; Our First Language Is Spanish, However; Our Learning Preferences Are Different
Authors: Maldonado-Torres Sonia E.
Published: April 2011

The purpose of this study was to examine the relationship between Dominican and Puerto Rican students’ learning style. Findings of the study demonstrated differences between the learning preferences of Dominican and Puerto Rican students in the elements of Motivation ( t = 2.846, p = .005), Several Ways of Learning ( t = 2.351, p = .020), and Tactile ( t = 3.469; p = .001).
Assessment of Stigma and Discrimination Experienced by People Living with HIV and AIDS Receiving Care/Treatment in University of Ilorin Teaching Hospital (UITH), Ilorin, Nigeria
Authors: Owolabi Rotimi S. , Araoye Margaret O. , Osagbemi Gordon K. , Odeigah Louis , Ogundiran Adeniyi , Hussain Nurudeen A.
Published: April 2011

The research was designed to assess the stigma and discrimination faced by People living with HIV and AIDS (PLWHA) that are receiving treatment in UITH, Ilorin. The study was a descriptive cross-sectional survey conducted on three hundred (300) people living with HIV and AIDS receiving care at the antiretroviral therapy (ART) clinics within University of Ilorin Teaching Hospital (which was the only ART site in Kwara State as at then). A quantitative method through the use of interviewer administered questionnaire was used for data collection. This study was a cross-sectional descriptive study design. All the patients who came to the clinic and met the selection criteria were recruited until the desired sample size was reached. Data were analyzed by EPI-INFO 2005 software package. The mean age of the respondents was 39 years (SD = 9.32), and their age ranged between 19 and 65 years. About two thirds (64.7%) of the respondents were females, 62.7% were married, and 62.9% were from monogamous family settings. Slightly less than half (47.3%) of the respondents were not informed before they were tested for HIV, majority (63.3%) were not counseled before the test, but only 11% did not receive posttest counseling. One quarter of the respondents had experienced stigmatization/discrimination. Various forms of stigmatization/discrimination experienced by the respondents include blame for being responsible for their HIV status, various name callings, telling them that they are no more useful to anybody, violation of confidentiality, social isolation, restriction of their participation in family/religious activities, rejection by their spouses/families, dismissal from place of work, isolating them from other patients, and denying them care at health centers. It is therefore recommended that government at all levels should develop and implement programs to educate health care providers about HIV and AIDS, ethics, and treatment and care; educate the general population on HIV and AIDS, put in place policies that will reduce/stop HIV-related stigma and discrimination at all levels of the society, educate PLWHA on their right to live and work without discrimination, and also ensure full community participation in HIV control programs.
Stigma and Access to HIV Care among HIV-Infected Women in Kolkata, West Bengal
Authors: Dasgupta Sharoda , Sullivan Patrick S. , Dasgupta Aparajita , Saha Bibhuti , Salazar Laura F.
Published: April 2011

Objectives:

Stigma is an important issue for marginalized HIV-infected populations. We describe stigma among HIV-infected women on antiretroviral therapy and associations with access to clinical care, demographic factors, and structural elements of support.

Methods:

HIV-infected women attending a government-supported clinic in Kolkata, India, were asked about experiences with stigma. Clinical information was abstracted from medical records. We described factors associated with stigma using ordinal logistic regression.

Results:

Among 198 women, higher levels of stigma were associated with lower CD4 count upon entry into care (aOR = 0.78; 95% confidence interval [CI]: [0.65, 0.94]), district of residence (aOR = 1.9; CI: [1.0, 3.4]), presence of extended family in the household (aOR = 0.57; CI: [0.32, 1.0]), and employment at the time of the interview (aOR = 0.48; CI: [0.26, 0.90]). Stigma was not associated with having missed scheduled HIV care appointments.

Conclusion:

Stigma is prevalent among Indian women with HIV, should be further explored, and may be important in considering public health interventions for better access to care.
The Immune Reconstitution Inflammatory Syndrome with Tuberculosis
Authors: Ali Kedir , Klotz Stephen A.
Published: April 2011

The Immune Reconstitution Inflammatory Syndrome (IRIS) in Ethiopian HIV-infected patients coinfected with tuberculosis (TB) was studied. HIV-infected outpatients initiating antiretroviral therapy (ART) at an HIV clinic in northern Ethiopia from January 2007 through September 2008 were identified (n = 1977). Patients with TB-IRIS occurring within 6 months of starting ART (n = 143) were compared with a control group of patients with HIV who began ART but did not develop TB-IRIS (n = 277). ART was not interrupted in any patient. Eleven (8%) patients with TB-IRIS died. New or “unmasked” TB with accompanying IRIS occurred in 132 or 92% of the cases. Worsening or “paradoxical” TB (ie, already known to be present and treated) was accompanied by IRIS in 11 (8%) patients. There was no significant difference between “unmasked” and “paradoxical” cases with respect to presentation of disease and outcome. Only a low baseline CD4 count (mean: 102 cells/μL) and a past history of World Health Organization (WHO) Clinical Stage 3 or 4 were associated with TB-IRIS ( P < .05). The clinical manifestations of TB-IRIS were diverse, requiring a high index of suspicion. For example, pleural disease occurred in 13 patients, TB lymphadenitis in 17, intracranial TB in 9 patients, and disseminated TB in 15 patients. The majority of patients (88%) responded to continuation of ART and TB therapy. Thus, TB-IRIS is common in Ethiopian patients beginning ART, occurring in 7% of patients initiating antiretroviral therapy.
Reducing Waiting Time at a Nigerian HIV Treatment Clinic
Authors: Olowookere Samuel Anu , Fatiregun Akinola Ayoola , Ladipo Modupe Martha-Alice , Akenova Yetunde Adebisi
Published: April 2011

We assessed the waiting time and perceived satisfaction with care among people living with HIV/AIDS (PLHIV) at an antiretroviral clinic in Nigeria. A structured questionnaire was administered during interviews. Four hundred patients completed the questionnaire. The mean age of the respondents was 36.4 years (SD 9.7 years), and 61% of them were females. A majority, 72.9%, reported that the time elapsed between entry into the clinic and access to medical care services (waiting time) was more than an hour. However, a majority (77%) expressed satisfaction with the medical care they received. Although the majority of PLHIV were satisfied with their medical care, more needs to be done to reduce patient waiting time before access to medical services.
Understanding Early Functional Recovery After Robotic Prostatectomy
Authors: Skolarus Ted A. , Weizer Alon Z. , Hedgepeth Ryan C. , He Chang , Wood David P. , Hollenbeck Brent K.
Published: April 2011

Objectives. The time to regain urinary control and sexual function after robotic-assisted prostatectomy varies widely. The authors performed a study to prospectively assess relationships between intraoperative processes and early functional recovery after surgery. Methods. Prostate cancer patients undergoing robotic prostatectomy prospectively completed questionnaires (Expanded Prostate Cancer Index Composite–Short Form, Sexual Health Inventory for Men) preoperatively and at 3 months postoperatively. Relationships between intraoperative processes and early recovery were measured using multiple logistic regression. Results. At 3 months, 73.9% and 29.7% of patients had recovered urinary and sexual function, respectively. Bladder neck preservation was associated with early recovery of both urinary and sexual function ( P < .01). The quality of nerve sparing ( P = .01), seminal vesicle sparing ( P = .03), and the use of urethral suspension ( P = .04) were associated with early recovery of sexual function. Conclusions. Early functional recovery for patients undergoing robotic-assisted prostatectomy varies by both patient characteristics and process measures. The causal link between intraoperative processes and patient outcomes merits further study through quality improvement collaboratives.
Improving Surgical Outpatient Efficiency Through Mobile Phone Text Messaging
Authors: Corrigan Mark A. , McHugh Seamus M. , Murphy Rory K. J. , Dhillon Paul , Shah Abid , Hennessy Immanuel , Sheikh Athar , Lehane Elaine , Hill Arnold S. K.
Published: April 2011

Introduction. Currently, 175 000 people are on outpatient waiting lists in Irish hospitals. Many clinic slots are taken by patients returning for routine review postoperatively. Methods. A Nokia mobile phone was used to send an outpatient text (OPT) to patients 2 weeks postdischarge. Patients replying that they were well were discharged. If no reply after 2 attempts was received, they were scheduled for the next outpatient clinic. Results. Overall, 55 patients were offered the service over a 4-month period. Of these, 74.5% of patients were discharged from follow-up using text message surveillance. Patients were surveyed regarding their perception of the surveillance model, with all respondents ranking OPT surveillance as their preferred method of follow-up. There was a 13.6% decrease in outpatient visits over the study period. In addition, 6 emergency department visits were also avoided. Conclusion. Text message surveillance decreases outpatient waiting times and increases quality of care.
‘How do you get your voice heard when no-one will let you?’ Victimization at work
Authors: Snell Katy , Tombs Steve
Published: April 2011

A longstanding separation between corporate crime and ‘real’ or ‘conventional’ crime is both reflected in and institutionalized through state responses to corporate offending, excluding the victims of corporate crime from consideration or treatment as real victims of real crime. Experiences of this institutionalized disjuncture are treated in this article, through consideration of criminal justice, legal and regulatory responses to six cases of occupational death and those bereaved by it. Drawing upon data gleaned from semi-structured interviews, the article documents further processes of victimization through responses to this specific class of deaths, amounting to a denial of their very status as victims. The evidence presented here coheres with the wider, if hardly voluminous, literature on corporate crime victimization. The article concludes by discussing the wider significance of the struggle for victimhood, not least for criminology itself.
TIMP-1 deficiency subverts cell-cycle dynamics in murine long-term HSCs
Authors: Rossi Lara , Ergen Aysegul V. , Goodell Margaret A.
Published: April 2011

In addition to the well-recognized role in extracellular matrix remodeling, the tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be involved in the regulation of numerous biologic functions, including cell proliferation and survival. We therefore hypothesized that TIMP-1 might be involved in the homeostatic regulation of HSCs, whose biologic behavior is the synthesis of both microenvironmental and intrinsic cues. We found that TIMP-1−/− mice have decreased BM cellularity and, consistent with this finding, TIMP-1−/− HSCs display reduced capability of long-term repopulation. Interestingly, the cell cycle distribution of TIMP-1−/− stem cells appears distorted, with a dysregulation at the level of the G1 phase. TIMP-1−/− HSCs also display increased levels of p57, p21, and p53, suggesting that TIMP-1 could be intrinsically involved in the regulation of HSC cycling dynamics. Of note, TIMP-1−/− HSCs present decreased levels of CD44 glycoprotein, whose expression has been proven to be controlled by p53, the master regulator of the G1/S transition. Our findings establish a role for TIMP-1 in regulating HSC function, suggesting a novel mechanism presiding over stem cell quiescence in the framework of the BM milieu.
Depletion of CD25+ T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma
Authors: Jing Weiqing , Yan Xiaocai , Hallett William H. D. , Gershan Jill A. , Johnson Bryon D.
Published: April 2011

A multifaceted immunotherapeutic strategy that includes hematopoietic stem cell (HSC) transplantation, T-cell adoptive transfer, and tumor vaccination can effectively eliminate established neuroblastoma tumors in mice. In vivo depletion of CD4+ T cells in HSC transplantation recipients results in increased antitumor immunity when adoptively transferred T cells are presensitized, but development of T-cell memory is severely compromised. Because increased percentages of regulatory T (Treg) cells are seen in HSC transplantation recipients, here we hypothesized that the inhibitory effect of CD4+ T cells is primarily because of the presence of expanded Treg cells. Remarkably, adoptive transfer of presensitized CD25-depleted T cells increased tumor vaccine efficacy. The enhanced antitumor effect achieved by ex vivo depletion of CD25+ Treg cells was similar to that achieved by in vivo depletion of all CD4+ T cells. Depletion of CD25+ Treg cells resulted in elevated frequencies of tumor-reactive CD8 and CD4+ T cells and increased CD8-to-Treg cell ratios inside tumor masses. All mice given presensitized CD25-depleted T cells survived a tumor rechallenge, indicating the development of long-term CD8+ T-cell memory to tumor antigens. These observations should aid in the future design of immunotherapeutic approaches that promote the generation of both acute and long-term antitumor immunity.
Variance adjusted weighted UniFrac: a powerful beta diversity measure for comparing communities based on phylogeny
Authors: Chang Qin , Luan Yihui , Sun Fengzhu
Published: April 2011

Background

Beta diversity, which involves the assessment of differences between communities, is an important problem in ecological studies. Many statistical methods have been developed to quantify beta diversity, and among them, UniFrac and weighted-UniFrac (W-UniFrac) are widely used. The W-UniFrac is a weighted sum of branch lengths in a phylogenetic tree of the sequences from the communities. However, W-UniFrac does not consider the variation of the weights under random sampling resulting in less power detecting the differences between communities.

Results

We develop a new statistic termed variance adjusted weighted UniFrac (VAW-UniFrac) to compare two communities based on the phylogenetic relationships of the individuals. The VAW-UniFrac is used to test if the two communities are different. To test the power of VAW-UniFrac, we first ran a series of simulations which revealed that it always outperforms W-UniFrac, as well as UniFrac when the individuals are not uniformly distributed. Next, all three methods were applied to analyze three large 16S rRNA sequence collections, including human skin bacteria, mouse gut microbial communities, microbial communities from hypersaline soil and sediments, and a tropical forest census data. Both simulations and applications to real data show that VAW-UniFrac can satisfactorily measure differences between communities, considering not only the species composition but also abundance information.

Conclusions

VAW-UniFrac can recover biological insights that cannot be revealed by other beta diversity measures, and it provides a novel alternative for comparing communities.
Genetic analyses place most Spanish isolates of Beauveria bassiana in a molecular group with word-wide distribution
Authors: Garrido-Jurado Inmaculada , Márquez Marcela , Ortiz-Urquiza Almudena , Santiago-Álvarez Cándido , Iturriaga Enrique A , Quesada-Moraga Enrique , Monte Enrique , Hermosa Rosa
Published: April 2011

Background

The entomopathogenic anamorphic fungus Beauveria bassiana is currently used as a biocontrol agent (BCA) of insects. Fifty-seven Beauveria bassiana isolates -53 from Spain- were characterized, integrating group I intron insertion patterns at the 3'-end of the nuclear large subunit ribosomal gene (LSU rDNA) and elongation factor 1-alpha (EF1-α) phylogenetic information, in order to assess the genetic structure and diversity of this Spanish collection of B. bassiana.

Results

Group I intron genotype analysis was based on the four highly conserved insertion sites of the LSU (Ec2653, Ec2449, Ec2066, Ec1921). Of the 16 possible combinations/genotypes, only four were detected, two of which were predominant, containing 44 and 9 members out of 57 isolates, respectively. Interestingly, the members of the latter two genotypes showed unique differences in their growth temperatures. In follow, EF1-α phylogeny served to classify most of the strains in the B. bassiana s.s. (sensu stricto) group and separate them into 5 molecular subgroups, all of which contained a group I intron belonging to the IC1 subtype at the Ec1921 position. A number of parameters such as thermal growth or origin (host, geographic location and climatic conditions) were also examined but in general no association could be found.

Conclusion

Most Spanish B. bassiana isolates (77.2%) are grouped into a major phylogenetic subgroup with word-wide distribution. However, high phylogenetic diversity was also detected among Spanish isolates from close geographic zones with low climatic variation. In general, no correlation was observed between the molecular distribution and geographic origin or climatic characteristics where the Spanish B. bassiana isolates were sampled.
Comparison of three tests of homogeneity of odds ratios in multicenter trials with unequal sample sizes within and among centers
Authors: Bagheri Zahra , Ayatollahi Seyyed Mohammad Taghi , Jafari Peyman
Published: April 2011

Background

Mixed effects logistic models have become a popular method for analyzing multicenter clinical trials with binomial data. However, the statistical properties of these models for testing homogeneity of odds ratios under various conditions, such as within-center and among-centers inequality, are still unknown and not yet compared with those of commonly used tests of homogeneity.

Methods

We evaluated the effect of within-center and among-centers inequality on the empirical power and type I error rate of the three homogeneity tests of odds ratios including likelihood ratio (LR) test of a mixed logistic model, DerSimonian-Laird (DL) statistic and Breslow-Day (BD) test by simulation study. Moreover, the impacts of number of centers (K), number of observations in each center and amount of heterogeneity were investigated by simulation.

Results

As compared with the equal sample size design, the power of the three tests of homogeneity will decrease if the same total sample size, which can be allocated equally within one center or among centers, is allocated unequally. The average reduction in the power of these tests was up to 11% and 16% for within-center and among-centers inequality, respectively. Moreover, in this situation, the ranking of the power of the homogeneity tests was BD≥DL≥LR and the power of these tests increased with increasing K.

Conclusions

This study shows that the adverse effect of among-centers inequality on the power of the homogeneity tests was stronger than that of within-center inequality. However, the financial limitations make the use of unequal sample size designs inevitable in multicenter trials. Moreover, although the power of the BD is higher than that of the LR when K≤6, the proposed mixed logistic model is recommended when K≥8 due to its practical advantages.
Engineering of a plasmid-free Escherichia coli strain for improved in vivo biosynthesis of astaxanthin
Authors: Lemuth Karin , Steuer Kristin , Albermann Christoph
Published: April 2011

Background

The xanthophyll astaxanthin is a high-value compound with applications in the nutraceutical, cosmetic, food, and animal feed industries. Besides chemical synthesis and extraction from naturally producing organisms like Haematococcus pluvialis, heterologous biosynthesis in non-carotenogenic microorganisms like Escherichia coli, is a promising alternative for sustainable production of natural astaxanthin. Recent achievements in the metabolic engineering of E. coli strains have led to a significant increase in the productivity of carotenoids like lycopene or β-carotene by increasing the metabolic flux towards the isoprenoid precursors. For the heterologous biosynthesis of astaxanthin in E. coli, however, the conversion of β-carotene to astaxanthin is obviously the most critical step towards an efficient biosynthesis of astaxanthin.

Results

Here we report the construction of the first plasmid-free E. coli strain that produces astaxanthin as the sole carotenoid compound with a yield of 1.4 mg/g cdw (E. coli BW-ASTA). This engineered E. coli strain harbors xanthophyll biosynthetic genes from Pantoea ananatis and Nostoc punctiforme as individual expression cassettes on the chromosome and is based on a β-carotene-producing strain (E. coli BW-CARO) recently developed in our lab. E. coli BW-CARO has an enhanced biosynthesis of the isoprenoid precursor isopentenyl diphosphate (IPP) and produces β-carotene in a concentration of 6.2 mg/g cdw. The expression of crtEBIY along with the β-carotene-ketolase gene crtW148 (NpF4798) and the β-carotene-hydroxylase gene (crtZ) under controlled expression conditions in E. coli BW-ASTA directed the pathway exclusively towards the desired product astaxanthin (1.4 mg/g cdw).

Conclusions

By using the λ-Red recombineering technique, genes encoding for the astaxanthin biosynthesis pathway were stably integrated into the chromosome of E. coli. The expression levels of chromosomal integrated recombinant biosynthetic genes were varied and adjusted to improve the ratios of carotenoids produced by this E. coli strain. The strategy presented, which combines chromosomal integration of biosynthetic genes with the possibility of adjusting expression by using different promoters, might be useful as a general approach for the construction of stable heterologous production strains synthesizing natural products. This is the case especially for heterologous pathways where excessive protein overexpression is a hindrance.
Chalcone-imidazolone conjugates induce apoptosis through DNA damage pathway by affecting telomeres
Authors: Ramaiah M Janaki , Pushpavalli SNCVL , Krishna G Rama , Sarma Pranjal , Mukhopadhyay Debasmita , Kamal Ahmed , Bhadra Utpal , Bhadra Manika Pal
Published: April 2011

Background

Breast cancer is one of the most prevalent cancers in the world and more than one million women are diagnosed leading to 410,000 deaths every year. In our previous studies new chalcone-imidazolone conjugates were prepared and evaluated for their anticancer activity in a panel of 53 human tumor cell lines and the lead compounds identified were 6 and 8. This prompted us to investigate the mechanism of apoptotic event.

Results

Involvement of pro-apoptotic protein (Bax), active caspase-9 and cleavage of retinoblastoma protein was studied. Interestingly, the compounds caused upregulation of p21, check point proteins (Chk1, Chk2) and as well as their phosphorylated forms which are known to regulate the DNA damage pathway. Increased p53BP1 foci by immunolocalisation studies and TRF1 suggested the possible involvement of telomere and associated proteins in the apoptotic event. The telomeric protein such as TRF2 which is an important target for anticancer therapy against human breast cancer was extensively studied along with proteins involved in proper functioning of telomeres.

Conclusions

The apoptotic proteins such as Bax, active caspase-9 and cleaved RB are up-regulated in the compound treated cells revealing the apoptotic nature of the compounds. Down regulation of TRF2 and upregulation of the TRF1 as well as telomerase assay indicated the decrease in telomeric length revealing telomeric dysfunction and thereby controlling the rapid rate of cell proliferation. In summary, chalcone-imidazolone conjugates displayed significant DNA damage activity particularly at telomeres and caused both apoptosis and senescence-like growth arrest which suggested that these compounds have potential activity against breast carcinoma.
Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium
Authors: Rao Rajiv G , Sudhakar Deepthi , Hogue Claire P , Amici Stephanie , Gordon Lynn K , Braun Jonathan , Notterpek Lucia , Goodglick Lee , Wadehra Madhuri
Published: April 2011

Background

PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characterized the expression of PMP22 in the human menstrual cycle and began to characterize its function in the endometrium.

Methods

Using a combination of immunohistochemistry and quantitative PCR, we characterized the expression of PMP22 in both proliferative and secretory endometrium. Differences in PMP22 expression between proliferative and secretory endometrium were determined using a Mann-Whitney U test. In order to investigate the influence of PMP22 on α6 integrin expression, cells were created that ectopically overexpressed PMP22 or expressed a siRNA to inhibit its expression. These cells were analyzed for changes in integrins and binding to extracellular matrices.

Results

In this study, we show that PMP22 expression is higher in proliferative phase than secretory phase. Functionally, we have begun to characterize the functional significance of this expression. Previous studies have suggested a link between PMP22 and α6 integrin, and therefore we asked whether PMP22 could associate or potentially modulate the expression of α6 integrin. Expression of both PMP22 and α6 integrin were detectable in endometrial epithelial and stromal cells, and we show that both proteins can associate and colocalize with each other. To understand if PMP22 directly altered the expression of a6 integrin, we examined cell lines with modulated levels of the protein. Overexpression of PMP22 was sufficient to increase α6 integrin surface expression with a concominant increase in binding to the extracellular matrix laminin, while a reduction in PMP22 suppressed α6 integrin surface expression.

Conclusion

These findings suggest a physiologic role for PMP22 on the expression of α6 integrin. We predict that this may be important for the maintainence of endometrial integrity and to the disease biology associated with altered levels of α6 integrin expression in the endometrium.
Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs
Authors: Chen Tian Sheng , Arslan Fatih , Yin Yijun , Tan Soon Sim , Lai Ruenn Chai , Choo Andre Boon Hwa , Padmanabhan Jayanthi , Lee Chuen Neng , de Kleijn Dominique PV , Lim Sai Kiang
Published: April 2011

Background

Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells (hESC-MSCs) have been shown to reduce myocardial ischemia/reperfusion injury in animal models. However, as hESC-MSCs are not infinitely expansible, large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes.

Methods

The hESC-MSCs were transfected by lentivirus carrying a MYC gene. The transformed cells were analyzed for MYC transgene integration, transcript and protein levels, and surface markers, rate of cell cycling, telomerase activity, karyotype, genome-wide gene expression and differentiation potential. The exosomes were isolated by HPLC fractionation and tested in a mouse model of myocardial ischemia/reperfusion injury, and infarct sizes were further assessed by using Evans' blue dye injection and TTC staining.

Results

MYC-transformed MSCs largely resembled the parental hESC-MSCs with major differences being reduced plastic adherence, faster growth, failure to senesce, increased MYC protein expression, and loss of in vitro adipogenic potential that technically rendered the transformed cells as non-MSCs. Unexpectedly, exosomes from MYC-transformed MSCs were able to reduce relative infarct size in a mouse model of myocardial ischemia/reperfusion injury indicating that the capacity for producing therapeutic exosomes was preserved.

Conclusion

Our results demonstrated that MYC transformation is a practical strategy in ensuring an infinite supply of cells for the production of exosomes in the milligram range as either therapeutic agents or delivery vehicles. In addition, the increased proliferative rate by MYC transformation reduces the time for cell production and thereby reduces production costs.
Conjugate heat transfer of laminar mixed convection of a nanofluid through an inclined tube with circumferentially non-uniform heating
Authors: Allahyari Shahriar , Behzadmehr Amin , Sarvari Seyed Masoud Hosseini
Published: April 2011

Laminar mixed convection of a nanofluid consisting of water and Al2O3in an inclined tube with heating at the top half surface of a copper tube has been studied numerically. The bottom half of the tube wall is assumed to be adiabatic (presenting a tube of a solar collector). Heat conduction mechanism through the tube wall is considered. Three-dimensional governing equations with using two-phase mixture model have been solved to investigate hydrodynamic and thermal behaviours of the nanofluid over wide range of nanoparticle volume fractions. For a given nanoparticle mean diameter the effects of nanoparticle volume fractions on the hydrodynamics and thermal parameters are presented and discussed at different Richardson numbers and different tube inclinations. Significant augmentation on the heat transfer coefficient as well as on the wall shear stress is seen.
Design process of the nanofluid injection mechanism in nuclear power plants
Authors: Kang Myoung-suk , Jee Changhyun , Park Sangjun , Bang In Choel , Heo Gyunyoung
Published: April 2011

Nanofluids, which are engineered suspensions of nanoparticles in a solvent such as water, have been found to show enhanced coolant properties such as higher critical heat flux and surface wettability at modest concentrations, which is a useful characteristic in nuclear power plants (NPPs). This study attempted to provide an example of engineering applications in NPPs using nanofluid technology. From these motivations, the conceptual designs of the emergency core cooling systems (ECCSs) assisted by nanofluid injection mechanism were proposed after following a design framework to develop complex engineering systems. We focused on the analysis of functional requirements for integrating the conventional ECCSs and nanofluid injection mechanism without loss of performance and reliability. Three candidates of nanofluid-engineered ECCS proposed in previous researches were investigated by applying axiomatic design (AD) in the manner of reverse engineering and it enabled to identify the compatibility of functional requirements and potential design vulnerabilities. The methods to enhance such vulnerabilities were referred from TRIZ and concretized for the ECCS of the Korean nuclear power plant. The results show a method to decouple the ECCS designs with the installation of a separate nanofluids injection tank adjacent to the safety injection tanks such that a low pH environment for nanofluids can be maintained at atmospheric pressure which is favorable for their injection in passive manner.
Electro-synthesis of novel nanostructured PEDOT films and their application as catalyst support
Authors: Zhou Cuifeng , Liu Zongwen , Yan Yushan , Du Xusheng , Mai Yiu-Wing , Ringer Simon
Published: April 2011

Poly(3,4-ethylenedioxythiophene) (PEDOT) films doped with nitric and chlorine ions have been electrochemically deposited simply by a one-step electrochemical method in an aqueous media in the absence of any surfactant. The fabricated PEDOT films were characterized by scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. The results indicate that the hierarchical structured PEDOT film doped with nitric ions displays a 'lunar craters' porous morphology consisting of PEDOT nano-sheets with a thickness of less than 2 nm. The effect of counter ions on the electro-polymerization, the electrochemistry, and the morphology of the polymer film was studied. Compared with PEDOT film doped with nitric acid, PEDOT film deposited in the presence of chlorine ions shows irregular morphology and less electrochemical activity. The specific nanostructure of the polymer was further studied as catalyst support for platinum nanoparticles to methanol electro-oxidation.
A situational analysis of HIV and AIDS in Pakistan
Authors: Ilyas Muhammad , Asad Sultan , Ali Liaqat , Shah Masaud , Badar Sadaf , Sarwar Muhammad Tahir , Sumrin Aleena
Published: April 2011

HIV (Human immunodeficiency virus) transmission has been reduced by protected sex and screening of blood products and other body fluids in the developed countries. It has been reported that Pakistan is at high risk of HIV/AIDS infection but presently the prevalence rate is considerably low. The number of reported cases of HIV/AIDS in Pakistan has been continuously increasing since 1987. By 2010 the total number of registered cases has reached to 6000 and this figure is on the rise with the passage of time. Some serious strategies must be implemented to control this deadly disease.
Impact of sphingomyelin levels on coronary heart disease and left ventricular systolic function in humans
Authors: Chen Xueying , Sun Aijun , Zou Yunzeng , Ge Junbo , Lazar Jason M , Jiang Xian-Cheng
Published: April 2011

Sphingomyelin (SM) is an abundant phospholipid in cell membranes and in lipoproteins. In human plasma, SM is mainly found in atherogenic lipoproteins; therefore, higher levels of SM may promote atherogenesis. We investigated the relations between plasma SM levels and the presence of angiographic coronary heart disease (CHD) and left ventricular systolic dysfunction. We studied 732 patients referred for coronary angiography. Median SM levels were higher among patients with CHD and in those with LV systolic dysfunction (LVEF<50%) than in patients without CHD or LV dysfunction. SM levels were significantly correlated with fibrinogen levels, diabetes, apoB, and triglyceride levels. On multivariate analyses, higher median SM levels were associated with a higher risk of CHD and lower LV ejection fraction. The pro-atherogenic property of plasma SM might be related to 1) CHD; 2) LV systolic dysfunction; and 3) metabolism of apoB-containing or triglyceride-rich lipoproteins.
Thoracic aorta pseudoaneurysm with hemopericardium: unusual presentation of warfarin overdose
Authors: Tien Ya-Chih , Chen Ying-Cheng , Liao Chiung-Ying , Chang Chia-Chu
Published: April 2011

There have been few case reports which discuss a relationship between warfarin overdose and aortic pseudoaneurysm leakage. We report the case of a female receiving warfarin who presented with dsypnea. Her international normalized ratio was > 10. Chest radiograph revealed cardiomegaly, and chest computed tomography (CT) showed a bulging pouch-like lesion below the aortic arch greater than 6x6 cm in size and a fluid collection suggesting blood in the pericardium. Thoracic endovascular aneurysm repair (TEVAR) was successfully performed by a cardiovascular surgeon. Aortic pseudoaneurysm formation and leakage may be considered as a rare complication in patients receiving warfarin therapy. Further study regarding warfarin use and the incidence of pseudoaneurysm leakage is needed.
Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms
Authors: Chkioua Latifa , Khedhiri Souhir , Kassab Asma , Bibi Amina , Ferchichi Salima , Froissart Roseline , Vianey-Saban Christine , Laradi Sandrine , Miled Abdelhedi
Published: April 2011

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in alpha-L-iduronidase (IDUA) which is involved in the degradation of dermatan and heparan sulfates. The disease has severe and milder phenotypic subtypes. The aim of this study was the detection of mutations in the IDUA gene from 12 additional MPS I patients with various clinical phenotypes (severe, 8 cases; intermediate, 3 cases; mild, 1 case).

Patients and methods

In this study, the IDUA mutations in eight unrelated Tunisian families were performed by amplifying and sequencing the IDUA exons and intron-exon jonctions.

Results

Five IDUA mutations were detected: one is the L578Q, a novel mutation found, in milder patient. The others were the previously described: P533R, Y581X, F602X and R628X that produce a severe and intermediate phenotype. In addition, eighteen variants, including eight previously unreported polymorphisms (IVS6+21c > a, IVS7+79c > t, IVS7-45 g > c, IVS9+36t > c, IVS10+140c > a, IVS11+33c > t, IVS12+13c > t and IVS12-31c > g), were detected.

Conclusion

This paper, showed a heterogeneous pattern of mutations and polymorphisms among Tunisian patients.
Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients
Authors: Westbury Charlotte B , Sahlberg Kristine Kleivi , Borresen-Dale Anne-Lise , Isacke Clare M , Yarnold John R
Published: April 2011

Background

Gene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be used to differentiate radiation sensitive patients and controls in patients who had previously received radiotherapy for early breast cancer.

Findings

Eight patients who developed marked late radiation change assessed by photographic breast appearance and 8 matched patients without any change were selected from women entered in a prospective randomised trial of breast radiotherapy fractionation. Gene expression profiling of primary skin fibroblasts exposed in vitro to bleomycin sulphate and mock treated fibroblast controls was performed. 973 genes were up-regulated and 923 down-reguated in bleomycin sulphate treated compared to mock treated control fibroblasts. Gene ontology analysis revealed enriched groups were cellular localisation, apoptosis, cell cycle and DNA damage response for the deregulated genes. No transcriptional differences were identified between fibroblasts from radiation sensitive cases and control patients; subgroup analysis using cases exhibiting severe radiation sensitivity or with high risk alleles present in TGF β1 also showed no difference.

Conclusions

The transcriptional response of human dermal fibroblasts to bleomycin sulphate has been characterised. No differences between clinically radiation sensitive and control patients were detected using this approach.
Steroid-triggered, cell-autonomous death of a Drosophila motoneuron during metamorphosis
Authors: Winbush Ari , Weeks Janis C
Published: April 2011

Background

The metamorphosis of Drosophila melanogaster is accompanied by elimination of obsolete neurons via programmed cell death (PCD). Metamorphosis is regulated by ecdysteroids, including 20-hydroxyecdysone (20E), but the roles and modes of action of hormones in regulating neuronal PCD are incompletely understood.

Results

We used targeted expression of GFP to track the fate of a larval motoneuron, RP2, in ventral ganglia. RP2s in abdominal neuromeres two through seven (A2 to A7) exhibited fragmented DNA by 15 hours after puparium formation (h-APF) and were missing by 20 h-APF. RP2 death began shortly after the 'prepupal pulse' of ecdysteroids, during which time RP2s expressed ecdysteroid receptors (EcRs). Genetic manipulations showed that RP2 death required the function of EcR-B isoforms, the death-activating gene, reaper (but not hid), and the apoptosome component, Dark. PCD was blocked by expression of the caspase inhibitor p35 but unaffected by manipulating Diap1. In contrast, aCC motoneurons in neuromeres A2 to A7, and RP2s in neuromere A1, expressed EcRs during the prepupal pulse but survived into the pupal stage under all conditions tested. To test the hypothesis that ecdysteroids trigger RP2's death directly, we placed abdominal GFP-expressing neurons in cell culture immediately prior to the prepupal pulse, with or without 20E. 20E induced significant PCD in putative RP2s, but not in control neurons, as assessed by morphological criteria and propidium iodide staining.

Conclusions

These findings suggest that the rise of ecdysteroids during the prepupal pulse acts directly, via EcR-B isoforms, to activate PCD in RP2 motoneurons in abdominal neuromeres A2 to A7, while sparing RP2s in A1. Genetic manipulations suggest that RP2's death requires Reaper function, apoptosome assembly and Diap1-independent caspase activation. RP2s offer a valuable 'single cell' approach to the molecular understanding of neuronal death during insect metamorphosis and, potentially, of neurodegeneration in other contexts.