bluuebunny/crossref_metadata_2025 huggingface dataset:
Culturally Relevant Prevention
Authors: Reese Le'Roy E. , Vera Elizabeth M.
Published: October 2007

For over a decade, there have been increasing efforts in counseling psychology and other areas of applied psychology to understand the role of culture in preventive and mental health services for ethnically, economically, and religiously diverse communities. In this Major Contribution, the authors offer examples of three prevention programs in which cultural relevance and competence were central to each program's development, implementation, and evaluation. The interventions each focus on an ethnic minority population, and they are offered in diverse settings. Participants differ in age and contexts in which they receive the intervention (e.g., individual, family, or classroom). Each article highlights similarities and differences likely in any prevention effort with diverse populations. In this introduction, the authors discuss the theoretical and empirical rationale for such interventions, as informed by literature on cultural competence and social justice, and the disproportionate health, educational, and economic disparities that poor and ethnic minority groups experience.
The Choices Program: Multisystemic Interventions for Enhancing the Personal and Academic Effectiveness of Urban Adolescents of Color
Authors: Vera Elizabeth M. , Caldwell Jennifer , Clarke Mary , Gonzales Rufus , Morgan Melissa , West Melissa
Published: October 2007

Through a collaboration with a public school in a poor, urban, largely Latino neighborhood, a multisystemic program was designed to foster positive youth development and promote school success. Aspects of the program highlighted include (a) the rationale; (b) interventions developed with and for youth, their parents, and their teachers; (c) the process of incorporating cultural issues into the program; and (d) evaluation strategies. Recommendations for future program development are provided along with general ideas for program evaluation.
Design and Implementation of a Grassroots Precollege Program for Latino Youth
Authors: Rivera-Mosquera Evelyn , Phillips Julia C. , Castelino Paul , Martin Juanita K. , Mowry Dobran Emily S.
Published: October 2007

This article discusses the design and implementation of a grassroots culturally and linguistically sensitive program designed to promote the pursuit of higher education among Latino youth. Latinos en Camino al Exito Universitario is an example of a culturally responsive program delivered out of a university counseling center as part of the training for multicultural competency for interns. Participants were 30 middle and high school students with supplementary parental involvement. Although outcome data were limited, positive outcomes included increased knowledge and confidence about college and precollege experiences. This article discusses how the program was developed, from recruitment to implementation, and how it was designed to meet the unique needs of Latino youth.
Moving From Contemplation to Preparation: Is Counseling Psychology Ready to Embrace Culturally Responsive Prevention?
Authors: Adams Eve M.
Published: October 2007

The confluence of prevention, multicultural competence and cultural responsiveness, and social justice is embryonic but holds much promise. The author uses the stages of change model to heighten awareness of how counseling psychologists are situated to provide well-developed system-level interventions and to examine the organizational and individual barriers to doing such work. The author then highlights the benefits for counseling psychology of engaging in preventive interventions. Strategies are provided to enhance the integration of prevention in training programs' curriculum in both the applied and research elements of the program. By providing learning opportunities that expose trainees to community interventions with disenfranchised populations, counseling psychology's commitment to social justice and multiculturalism will be more fully realized.
A Research Practitioner's Perspective on Culturally Relevant Prevention
Authors: Griffin James P. , Miller Erica
Published: October 2007

This article is a response to a number of articles that use a culturally relevant prevention (CRP) approach for ethnic and racial minorities. The reaction is from a research practitioner's viewpoint. The authors argue in favor of determining an operational definition of cultural relevance by implementing prevention services with fidelity in the field and understanding what structural components of CRPs are minimally necessary for the effective operation of the prevention programs. Field personnel also need to identify reliable ways to involve in planning those individuals who represent service recipient characteristics. The article closes with a recommendation that research practitioners pursue an active evaluation agenda aimed at further standardizing and quantifying the effectiveness of CRP strategies for underserved racial and ethnic groups.
An Experimental Juvenile Probation Program
Authors: Brank Eve , Lane Jodi , Turner Susan , Fain Terry , Sehgal Amber
Published: October 2007

In an effort to provide a wider range of services to youth and their families than is traditionally available in routine probation, the South Oxnard Challenge Project (SOCP) employed a team approach to service delivery of an intensive probation program. The researchers interviewed juveniles who were randomly assigned to either the SOCP experimental condition or the control condition of a routine probation program. The intensive probation program, among other goals, focused on improving parent–child relationships and teaching youth how to choose better peers. At 1 year post random assignment, experimental and control youth were not significantly different on key family or peer relationship measures. Level of program intensity, implementation issues, and other problems inherent in doing this type of research are provided as possible explanations for the lack of differences. These null findings are examined in light of the recent movement toward parental involvement legislation.
School Culture Change in the Making
Authors: Eilers Angela M. , Camacho Armando
Published: October 2007

The urban elementary school profiled in this case study was considered low performing based on state-mandated assessment scores from the time the school opened its doors in 1998 until very recently, putting the school on academic watch under the terms of the No Child Left Behind Act. However, in recent years the school realized a significant turnaround with the placement of a proactive principal and internal specialized supports accompanied by district office support. Survey data on school culture measures demonstrate an improvement in professional communities of practice, collaborative leadership, and evidence-based practice. This case study provides evidence that leadership coupled with multiple and coherent district supports can result in dramatic change at a school in a short period.
The Narrowing of Curriculum and Pedagogy in the Age of Accountability Urban Educators Speak Out
Authors: Crocco Margaret S. , Costigan Arthur T.
Published: October 2007

Under the curricular and pedagogical impositions of scripted lessons and mandated curriculum, patterns associated nationwide with high-stakes testing, the No Child Left Behind Act of 2001, and the phenomenon known as the “narrowing of curriculum,” new teachers in New York City (NYC) find their personal and professional identity thwarted, creativity and autonomy undermined, and ability to forge relationships with students diminished—all critical factors in their expressed job satisfaction. These indirect consequences of accountability regimen as it operates in NYC may exacerbate new teacher attrition, especially from schools serving low-income students. The data reported here suggest a mixed picture of frustration and anger, alongside determination, resistance, and resilience in the face of these impositions. Responses vary by school and grade level, lending support to the notion that the organizational environment serves as a critical factor in teachers' early career decisions about staying or leaving a school or the profession.
Overrepresentation of African American Students in Exclusionary Discipline The Role of School Policy
Authors: Fenning Pamela , Rose Jennifer
Published: October 2007

The overrepresentation of ethnic minority students, particularly African American males, in the exclusionary discipline consequences of suspension and expulsion has been consistently documented during the past three decades. Children of poverty and those with academic problems are also overrepresented in such discipline consequences. Sadly, a direct link between these exclusionary discipline consequences and entrance to prison has been documented and termed the school-to-prison pipeline for these most vulnerable students. In this article, the authors argue that ethnographic and interview data would support teachers' perceptions of loss of classroom control (and accompanying fear) as contributing to who is labeled and removed for discipline reasons (largely poor students of color). Exclusionary discipline consequences are the primary medium used once students are sent from the classroom. The authors recommend substantial revisions to discipline policies consistent with models of positive behavior support.
Empowering Parents and Building Communities
Authors: Shatkin Gavin , Gershberg Alec Ian
Published: October 2007

This article builds and explores the hypothesis that parent and community participation in school governance can have positive impacts on community development by fostering improvements in school performance and school— community relations and by acting as a catalyst for collective action around community-development issues. It does so through case studies of reforms for school-based management that have led to the creation of school-site councils that include parents and community representatives in Kentucky, Hawaii, Chicago, and El Paso. The article finds that the hypothesized outcomes can occur where parents are given meaningful decision-making authority in schools, nongovernmental organizations provide training and advocacy for parents, and principals actively facilitate parent involvement.
Living the Literature
Authors: Boston Genyne Henry , Baxley Traci
Published: October 2007

This article examines how gender construction and the literacy experiences of Black adolescent females can be shaped and motivated by their interaction with specific multicultural texts. This discussion further explores how current theories of race, identity and gender construction, and literacy learning in English language arts classrooms inform and provide additional clarity to the results of a content analysis study of four multicultural contemporary adolescent novels. As such, this discussion offers plausible insight for how a broader view of literacy learning theory may apply when discussing the literacy experiences of Black female adolescents and other marginalized readers.
Does It Really Matter If You Recognize Who I Am? The Implications of Identity Comprehension for Individuals in Work Teams†
Authors: Thatcher Sherry M. B. , Greer Lindred L.
Published: October 2007

A field study of 179 employees in an investment technology firm explores the relationship between identity comprehension and individual work outcomes. Identity comprehension is defined as the degree to which the relative importance of one's identities is recognized by important others. Results show that individuals with higher levels of identity comprehension in work teams are likely to have higher levels of creativity and satisfaction and lower levels of absenteeism.
Employee Commitment in Times of Change: Assessing the Importance of Attitudes Toward Organizational Change †
Authors: Elias Steven M.
Published: October 2007

Organizations are dynamic and changing entities. Variables associated with organizational change have been shown to serve as mediators of several individual difference variable/workrelated outcome relationships. This study examines three potential antecedents of 258 police officers' attitudes toward organizational change (ATOC), and whether ATOC mediates the relationships between these antecedents and affective organizational commitment (AOC). At the time of data collection, the officers' police department was restructuring its organizational design. Structural equation modeling indicates the growth need strength/AOC relationship is fully mediated, whereas the locus of control/AOC and internal work motivation/AOC relationships are partially mediated by ATOC. Implications and directions for future research are discussed.
Antecedents of Day-Level Proactive Behavior: A Look at Job Stressors and Positive Affect During the Workday†
Authors: Fritz Charlotte , Sonnentag Sabine
Published: October 2007

This study extends research on proactive behavior at work by examining the extent to which job stressors (time pressure and situational constraints) and affective experiences during the workday are associated with proactive behaviors on the same and the following workday. Results from civil service employees who filled in surveys over 4 consecutive workdays indicated that situational constraints were positively associated with proactive behavior on the same workday. In addition, positive mood was significantly related to proactive behavior on the same and the following workday.
A Power Perspective to Interunit Knowledge Transfer: Linking Knowledge Attributes to Unit Power and the Transfer of Knowledge
Authors: Wong Sze-Sze , Ho Violet T. , Chay Hoon Lee
Published: October 2007

This research investigates whether unit power affects interunit knowledge transfer. We propose that units are more likely to transfer their knowledge to other units with more critical, nonsubstitutable, and central knowledge because the latter have greater unit power upon the former. Findings from two firms reveal that differences in knowledge criticality and nonsubstitutability predict the degree of power one unit has upon another. However, only findings from one firm supported the mediating effect of unit power on knowledge transfer from a source to a seeker, suggesting that the role of unit power in affecting interunit knowledge transfer may be contingent on the degree of goal interdependence among units.
Gender Differences in Discipline of Nurses in Missouri
Authors: Evangelista Anita , Sims-Giddens Susan
Published: October 2007

Analysis of discipline of nurses by the Missouri Board of Nursing, 2000-2003, demonstrated differing rates by gender. Males received disproportionately high rates at 18.9%, although they represented 7.5% of Missouri nurses. Males received more severe discipline than females, with higher rates of license suspension and revocation, regardless of infractions or license level. Males surrendered licenses at higher rates. For 3 of the 28 infractions, males exceeded the number of females by a ratio of 2:1. Males committed one infraction that females did not. For three infractions, females outnumbered males by a ratio of 2:1. Females committed eight infractions not committed by males, including four murders. Consistent with previous studies, substance abuse was the behavior disciplined in the majority of cases (41.3%). Disparity in nurse discipline suggests the need for further study to analyze contributing factors, roles that nursing culture and gendered behaviors may play in the disciplinary process.
Culturally Competent Training Program: A Key to Training Lay Health Advisors for Promoting Breast Cancer Screening
Authors: Yu Mei-yu , Lixin Song  , Seetoo Amy , Cuijuan Cai  , Smith Gary , Oakley Deborah
Published: October 2007

The lay health advisor (LHA) training program for breast cancer screening was conducted among Chinese– English bilingual trainees residing in Southeast Michigan. Guided by Bandura's Social Learning Theory, the development of the training curriculum followed the health communication process recommended by the National Cancer Institute. Data analysis based on questionnaires completed by 79 LHAs indicated that the breast cancer screening training program significantly increased LHAs' knowledge and self-efficacy ( p < .01, t test, two-tailed) and LHAs had a positive perception with regard to the training manual. Regression analysis found that LHAs who were younger, employed, and demonstrated a positive perception of the training manual tended to have higher self-efficacy in promoting breast cancer screening ( R2 = .30). This study suggests that a culturally competent training program effectively increases LHAs' self-efficacy. The findings have implications for developing effective LHA training programs in Asian American communities where LHA interventions are rarely implemented.
Strategic Intercameral Behavior and the Sequence of Congressional Lawmaking
Authors: Taylor Andrew J.
Published: October 2007

In the vein of some fledgling theoretical work on Congress, I look for evidence of strategic intercameral behavior in the chamber sequence of the passage of 950 bills from 1955 to 2002. Specifically, I construct and test a semiformal model in which communication is assumed to take place between congressional majority party leaders capable of choreographing bill passage using their agenda control powers. These leaders allow the chamber with the majority whose ideal point is furthest from the president's to pass its version of the bill first. The empirical analysis corroborates the model.
Prognostic relevance of FLT3-TKD mutations in AML: the combination matters—an analysis of 3082 patients
Authors: Bacher Ulrike , Haferlach Claudia , Kern Wolfgang , Haferlach Torsten , Schnittger Susanne
Published: October 2007

We characterized the mutational status of the FLT3 tyrosine kinase domain (FLT3-TLD) in 3082 patients with newly diagnosed AML. FLT3-TKD mutations were detected in 147 of 3082 (4.8%) patients. Similar to the FLT3 juxtamembrane domain mutations (FLT3-LM), there was a high correlation of FLT3-TKD mutations with normal karyotype (88 of 1472; 6.0%). FLT3-TKD mutations were most frequent in the AML FAB subtypes M5b (15 of 114; 13.2%), M3v (6 of 51; 11.8%), and M4 (39 of 484; 8.1%). Similar to FLT3-LM, the FLT3-TKD mutations show elevated peripheral leukocytes compared with FLT3wt AML. FLT3-TKD had a high incidence in cases with NPM1 mutations (23 of 262; 8.8%), CEBPA mutations (6 of 76; 7.9%), and NRAS mutations (6 of 78; 7.7%). FLT3-TKD in combination with FLT3-LM (17 of 594 patients; 2.9%) and KITD816 (1 of 44; 2.3%) was rare. Unlike the FLT3-LM, which are associated with inferior survival, prognosis was not influenced by FLT3-TKD in the total cohort of 1720 cases, where follow-up data were available (97 FLT3-TKD; 1623 FLT3-WT). In t(15;17)/PML-RARA with FLT3-TKD mutations, in FLT3-LM/TKD double-mutated, and in MLL-PTD/TKD double-mutated cases prognosis was unfavorably influenced by FLT3-TKD mutations. In contrast, we found an additional favorable impact of FLT3-TKD on EFS in prognostically favorable AML with NPM1- or CEBPA mutations.
Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets
Authors: Gormley Michael , Dampier William , Ertel Adam , Karacali Bilge , Tozeren Aydin
Published: October 2007

Background

Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal) samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a) all genes on the microarray platform and b) a list of known disease-related genes (a priori selection). We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms.

Results

Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform.

Conclusion

Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine learning approaches. These findings are relevant to the use of molecular profiling for the identification of candidate biomarker panels.
Computational selection and prioritization of candidate genes for Fetal Alcohol Syndrome
Authors: Lombard Zané , Tiffin Nicki , Hofmann Oliver , Bajic Vladimir B , Hide Winston , Ramsay Michèle
Published: October 2007

Background

Fetal alcohol syndrome (FAS) is a serious global health problem and is observed at high frequencies in certain South African communities. Althoughin uteroalcohol exposure is the primary trigger, there is evidence for genetic- and other susceptibility factors in FAS development. No genome-wide association or linkage studies have been performed for FAS, making computational selection and -prioritization of candidate disease genes an attractive approach.

Results

10174 Candidate genes were initially selected from the whole genome using a previously described method, which selects candidate genes according to their expression in disease-affected tissues. Hereafter candidates were prioritized for experimental investigation by investigating criteria pertinent to FAS and binary filtering. 29 Criteria were assessed by mining various database sources to populate criteria-specific gene lists. Candidate genes were then prioritized for experimental investigation using a binary system that assessed the criteria gene lists against the candidate list, and candidate genes were scored accordingly. A group of 87 genes was prioritized as candidates and for future experimental validation. The validity of the binary prioritization method was assessed by investigating the protein-protein interactions, functional enrichment and common promoter element binding sites of the top-ranked genes.

Conclusion

This analysis highlighted a list of strong candidate genes from the TGF-β, MAPK and Hedgehog signalling pathways, which are all integral to fetal development and potential targets for alcohol's teratogenic effect. We conclude that this novel bioinformatics approach effectively prioritizes credible candidate genes for further experimental analysis.
Impact of prescription size on statin adherence and cholesterol levels
Authors: Batal Holly A , Krantz Mori J , Dale Rita A , Mehler Phillip S , Steiner John F
Published: October 2007

Background

Therapy with 3-Hydroxy-3-methylglutaryl Co-enzyme A reductase inhibitors (statins) improve outcomes in a broad spectrum of patients with hyperlipidemia. However, effective therapy requires ongoing medication adherence; restrictive pharmacy policies may represent a barrier to successful adherence, particularly among vulnerable patients. In this study we sought to assess the relationship between the quantity of statin dispensed by the pharmacy with patient adherence and total cholesterol.

Methods

We analyzed a cohort of 3,386 patients receiving more than one fill of statin medications through an integrated, inner-city health care system between January 1, 2000 and December 31, 2002. Our measure of adherence was days of drug acquisition divided by days in the study for each patient, with adequate adherence defined as ≥ 80%. Log-binomial regression was used to determine the relative risk of various factors, including prescription size, on adherence. We also assessed the relationship between adherence and total cholesterol using multiple linear regression.

Results

After controlling for age, gender, race, co-payment, comorbidities, and insurance status, patients who obtained a majority of fills as 60-day supply compared with 30-day supply were more likely to be adherent to their statin medications (RR 1.41, 95% CI 1.28–1.55, P < 0.01). We found that statin non-adherence less than 80% was predictive of higher total serum cholesterol by 17.23 ± 1.64 mg/dL (0.45 ± 0.04 mmol/L).

Conclusion

In a healthcare system serving predominantly indigent patients, the provision of a greater quantity of statin medication at each prescription fill contributes to improved adherence and greater drug effectiveness.
Impact of salinomycin on the intestinal microflora of broiler chickens
Authors: Johansen Charlotte H , Bjerrum Lotte , Pedersen Karl
Published: October 2007

Background

The ionophoric coccidiostat salinomycin is widely used in chicken feed. In the near future the use of ionophore coccidiostats may be banned as has been the case for other antimicrobial growth promoters. This study was conducted to examine the effect of salinomycin on Campylobacter jejuni infection and on the composition of the caecal microflora in broiler chickens.

Methods

An experimental infection study was carried out in isolators and the intestinal microflora was analyzed using quantitative cultivation, denaturant gradient gel electrophoresis (DGGE), cloning and sequencing.

Results

We found no effect of salinomycin on C. jejuni but salinomycin significantly affected the composition of the microflora. In addition, salinomycin significantly reduced the prevalence of Clostridium perfringens and we observed a significant increase (62%) in the mean body weight of salinomycin treated chickens compared to un-treated controls.

Conclusion

Termination of the use of ionophore coccidiostats will not affect food safety related to campylobacter, but will increase the risk of necrotic enteritis in the broilers.
Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia
Authors: Vargas-Alarcón Gilberto , Fragoso José-Manuel , Cruz-Robles David , Vargas Angélica , Vargas Alfonso , Lao-Villadóniga José-Ignacio , García-Fructuoso Ferrán , Ramos-Kuri Manuel , Hernández Fernando , Springall Rashidi , Bojalil Rafael , Vallejo Maite , Martínez-Lavín Manuel
Published: October 2007

Autonomic dysfunction is frequent in patients with fibromyalgia (FM). Heart rate variability analyses have demonstrated signs of ongoing sympathetic hyperactivity. Catecholamines are sympathetic neurotransmitters. Catechol-O-methyltransferase (COMT), an enzyme, is the major catecholamine-clearing pathway. There are several single-nucleotide polymorphisms (SNPs) in the COMT gene associated with the different catecholamine-clearing abilities of the COMT enzyme. These SNPs are in linkage disequilibrium and segregate as 'haplotypes'. Healthy females with a particular COMT gene haplotype (ACCG) producing a defective enzyme are more sensitive to painful stimuli. The objective of our study was to define whether women with FM, from two different countries (Mexico and Spain), have the COMT gene haplotypes that have been previously associated with greater sensitivity to pain. All the individuals in the study were female. Fifty-seven Mexican patients and 78 Spanish patients were compared with their respective healthy control groups. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Six COMT SNPs (rs2097903, rs6269, rs4633, rs4818, rs4680, and rs165599) were genotyped from peripheral blood DNA. In Spanish patients, there was a significant association between three SNPs (rs6269, rs4818, and rs4680) and the presence of FM when compared with healthy controls. Moreover, in Spanish patients with the 'high pain sensitivity' haplotype (ACCG), the disease, as assessed by the FIQ, was more severe. By contrast, Mexican patients displayed only a weak association between rs6269 and rs165599, and some FIQ subscales. In our group of Spanish patients, there was an association between FM and the COMT haplotype previously associated with high pain sensitivity. This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results.
Terminally differentiated neutrophils predominantly express Survivin-2α, a dominant-negative isoform of Survivin
Authors: Hu Huiyuan , Shikama Yayoi , Matsuoka Isao , Kimura Junko
Published: October 2007

Survivin, which is a member of the inhibitor of apoptosis protein family, was found originally in immature cells and cancer cells but not in non-neoplastic adult tissues. The subsequent identification of four other alternative splice variants that possess distinct functions and localizations suggested the diverse roles of survivin isoforms. An unspecified isoform of survivin was found recently to be induced in terminally differentiated neutrophils by cytokines that prolong the neutrophil lifespan, such as GM-CSF and G-CSF, suggesting the importance of survivin in blocking apoptosis in neutrophils. To examine the mechanism by which survivin inhibits neutrophil apoptosis, we attempted to induce survivin by GM-CSF/G-CSF in an HL60 cell line that was differentiated into neutrophils by all-trans retinoic acid and DMSO and freshly isolated human neutrophils. The antiapoptotic isoform “Survivin,” which was decreased during differentiation, was re-induced by GM-CSF in neutrophil-like, differentiated HL60. In contrast, in normal neutrophils, survivin mRNA was observed to increase spontaneously after 24 h incubation, and no additional elevation was induced by GM-CSF/G-CSF, which exerted their antiapoptotic effects on the neutrophils in 6 h, despite the lack of survivin induction. PCR and Western blotting detected Survivin-2α, a dominant-negative of antiapoptotic Survivin, with no other isoforms in the freshly isolated or incubated neutrophils. Our study revealed that the expressed isoforms and the response to GM-CSF were different between the HL60-derived and normal neutrophils, which predominantly expressed Survivin-2α, not likely involved in apoptosis inhibition by GM-CSF/G-CSF.
Streptococcus pyogenesactivates human plasmacytoid and myeloid dendritic cells
Authors: Veckman Ville , Julkunen Ilkka
Published: October 2007

Human peripheral blood contains two major dendritic cell (DC) populations, namely CD11c–CD123+ plasmacytoid DCs (PDCs) and CD11c+CD123– myeloid DCs (MDCs). Although the activation of these DC types by various TLR ligands has been relatively well-characterized, less is known about the ability of whole live bacteria to induce PDC and MDC activation. In the present report, we have compared the activation of human PDCs and MDCs in response to major human bacterial pathogen Streptococcus pyogenes (group A streptococci) and influenza A virus. S. pyogenes stimulation resulted in the maturation of both DC types, as evidenced by enhanced expression of costimulatory molecules and production of proinflammatory cytokines and chemokines. Furthermore, S. pyogenes-stimulated PDCs and MDCs activated naïve CD4+ T cells and enhanced their Th1 cytokine production. Influenza A virus infection induced rapid PDC activation, whereas MDCs were extremely sensitive to influenza A virus-induced cell death. The most significant differences between DC types were seen in the production of IL-10 and IL-12, which were only produced by S. pyogenes-stimulated MDCs. Although S. pyogenes was able to induce PDC activation, only influenza A virus infection resulted in detectable IFN-α production. Our results show that depending on the infecting microbe, the functions of PDCs and MDCs may be partially overlapping, suggesting a considerable flexibility of the human DC system.
Selective cortical interneuron and GABA deficits in cyclin D2-null mice
Authors: Glickstein Sara B. , Moore Holly , Slowinska Bozena , Racchumi Joelle , Suh Minah , Chuhma Nao , Ross M. Elizabeth
Published: October 2007

In contrast to cyclin D1 nulls (cD1-/-), mice without cyclin D2 (cD2-/-) lack cerebellar stellate interneurons;the reason for this is unknown. In the present study in cortex, we found a disproportionate loss of parvalbumin (PV) interneurons in cD2-/- mice. This selective reduction in PV subtypes was associated with reduced frequency of GABA-mediated inhibitory postsynaptic currents in pyramidal neurons, as measured by voltage-clamp recordings, and increased cortical sharp activity in the EEGs of awake-behaving cD2-/- mice. Cell cycle regulation was examined in the medial ganglionic eminence (MGE), the major source of PV interneurons in mouse brain, and differences between cD2-/- and cD1-/- suggested that cD2 promotes subventricular zone(SVZ) divisions, exerting a stronger inhibitory influence on the p27 Cdk-inhibitor (Cdkn1b) to delay cell cycle exit of progenitors. We propose that cD2 promotes transit-amplifying divisions in the SVZ and that these ensure proper output of at least a subset of PV interneurons.
FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis
Authors: Wahl Matthias B. , Deng Chuxia , Lewandoski Mark , Pourquié Olivier
Published: October 2007

Fibroblast growth factor (FGF) signaling plays a crucial role in vertebrate segmentation. The FGF pathway establishes a posterior-to-anterior signaling gradient in the presomitic mesoderm (PSM), which controls cell maturation and is involved in the positioning of segmental boundaries. In addition, FGF signaling was shown to be rhythmically activated in the PSM in response to the segmentation clock. Here, we show that conditional deletion of the FGF receptor gene Fgfr1 abolishes FGF signaling in the mouse PSM,resulting in an arrest of the dynamic cyclic gene expression and ultimately leading to an arrest of segmentation. Pharmacological treatments disrupting FGF signaling in the PSM result in an immediate arrest of periodic WNT activation, whereas NOTCH-dependent oscillations stop only during the next oscillatory cycle. Together, these experiments provide genetic evidence for the role of FGF signaling in segmentation, and identify a signaling hierarchy controlling clock oscillations downstream of FGF signaling in the mouse.
A combinatorial code of maternal GATA, Ets and β-catenin-TCF transcription factors specifies and patterns the early ascidian ectoderm
Authors: Rothbächer Ute , Bertrand Vincent , Lamy Clement , Lemaire Patrick
Published: October 2007

Our understanding of the maternal factors that initiate early chordate development, and of their direct zygotic targets, is still fragmentary. A molecular cascade is emerging for the mesendoderm, but less is known about the ectoderm, giving rise to epidermis and nervous tissue. Our cis-regulatory analysis surprisingly places the maternal transcription factor Ci-GATAa(GATA4/5/6) at the top of the ectodermal regulatory network in ascidians. Initially distributed throughout the embryo, Ci-GATAa activity is progressively repressed in vegetal territories by accumulating maternalβ-catenin. Once restricted to the animal hemisphere, Ci-GATAa directly activates two types of zygotic ectodermal genes. First, Ci-fog is activated from the 8-cell stage throughout the ectoderm, then Ci-otxis turned on from the 32-cell stage in neural precursors only. Whereas the enhancers of both genes contain critical and interchangeable GATA sites, their distinct patterns of activation stem from the additional presence of two Ets sites in the Ci-otx enhancer. Initially characterized as activating elements in the neural lineages, these Ets sites additionally act as repressors in non-neural lineages, and restrict GATA-mediated activation of Ci-otx. We thus identify a precise combinatorial code of maternal factors responsible for zygotic onset of a chordate ectodermal genetic program.
Association between human oocyte developmental competence and expression levels of some cumulus genes
Authors: Cillo Fabiana , Brevini Tiziana A L , Antonini Stefania , Paffoni Alessio , Ragni Guido , Gandolfi Fulvio
Published: October 2007

At present, oocyte selection is mainly based upon morphological criteria but it is generally acknowledged that its reliability requires further improvement. The aim of this study was to determine whether transcript levels in cumulus cells can provide a useful marker of oocyte developmental competence in vitro. A retrospective study was performed on cumulus cells isolated from 90 oocytes retrieved from 45 patients. Upon fertilization, 35 oocytes originated good-quality embryos and 36 developed into poor-quality embryos, whereas 19 failed to be fertilized. Semi-quantitative measurement of hyaluronic acid synthase 2 (HAS2), gremlin1 (GREM1), and pentraxin 3 (PTX3) mRNAs was performed and data for all genes were obtained from all the samples. Cumulus cells isolated from oocytes that originated high-quality embryos on day 3 of culture had HAS2 and GREM1 transcript levels higher than those detected in cells from oocytes that did not fertilize or developed into poor-quality embryos. No differences were observed in PTX3 levels. Results indicate that the measurement of HAS2 and GREM1 levels in cumulus cells would reliably complement the morphological evaluation providing a useful tool for selecting oocytes with greater chances to be fertilized and develop in vitro.
Follistatin serum concentrations during full-term labour in women – significant differences between spontaneous and induced labour
Authors: Rae K , Hollebone K , Chetty V , Clausen D , McFarlane J
Published: October 2007

Follistatin has been isolated from human placenta and has been identified in human foetal membranes and fluids. Serum follistatin levels in women rise during pregnancy particularly near term. In this study, we examined the effect of induction and stage of labour on maternal plasma concentrations of follistatin. Women who gave birth after a normal pregnancy were retrospectively divided into three groups: those who went in labour spontaneously (n = 33), needed induction by amniotomy and IV oxytocin (n = 18) or underwent planned caesarean section (n = 10). Serum was collected at 38–40 weeks of gestation, periodically through labour with a vaginal examination and once within 36 h postpartum and assayed for oestradiol, progesterone, prolactin and C-reactive protein. Follistatin was measured using a rabbit antiserum (#204) raised against purified 35 kDa bovine follistatin. Human recombinant follistatin was used as both standard and tracer. Concentrations of follistatin at 38–40 weeks of gestation were significantly different between groups. Those who had a spontaneous labour had concentrations higher than those who were induced. Similarly, those who were induced had concentrations higher than those who underwent a caesarean. In the spontaneous group, follistatin rose during labour, peaking at 57.9 ± 5.48 ng/ml at > 3 cm of cervical dilation, and after delivery follistatin decreased to 26.16 ± 3.4 ng/ml at 24 h post-delivery. In induced patients follistatin continued increasing to peak following delivery at 26.9 ± 3.0 ng/ml and decreased at > 3 h post-delivery. Follistatin concentrations in caesarean section patients at 24 h post-surgery (18.53 ± 3.74 ng/ml) were not different from that before the surgery and were comparable with the other two groups. Follistatin is clearly implicated in the onset of labour; however, further studies with a larger cohort of women are necessary to determine the nature of its role.
The role of angiotensin II in the early stages of bovine ovulation
Authors: Ferreira Rogério , Oliveira João Francisco , Fernandes Rafael , Moraes José Ferrugem , Gonçalves Paulo Bayard
Published: October 2007

There is evidence that the renin–angiotensin system plays an important role in ovulation in cattle. Using an in vivo model, we investigated the role of angiotensin (Ang) II in bovine ovulation by injecting Ang II receptor antagonists into ovulatory follicles. Animals (n = 102) were pre-synchronized and, when the follicles reached 12 mm, they were given the respective treatment and the cows received GnRH agonist (i.m.) to induce ovulation. The ovulation rate was significantly lower when 100 μ M saralasin (Ang II receptor antagonist) was intrafollicularly injected (14.3%) in comparison with saline solution (83.3%). Based on these results, a second experiment was carried out to determine the timing of Ang II’s critical role in ovulation. Saralasin inhibited ovulation only when applied at 0 and 6 h (16.7 and 42.9% ovulation rate in the 0- and 6-h groups respectively), but not at 12 h (100%) following GnRH agonist treatment. To investigate the subtypes of Ang II receptors implicated in the LH-induced ovulation, losartan (LO; AT1-Ang II receptor antagonist), PD123 319 (AT2-Ang II receptor antagonist), LO+PD123 319, or saline were intrafollicularly injected when the cows were challenged with GnRH agonist. Ovulation was inhibited by PD123 319 and LO+PD123 319 (50.0 and 33.3% on ovulation rate respectively), but not by LO or saline solution (100% ovulation in both groups). From these results, we suggest that Ang II plays a pivotal role in the early mechanism of bovine ovulation via the AT2 receptor subtype.
Humoral Immune Responses to Influenza Vaccination in Patients with Obstructive Sleep Apnea
Authors: Dopp John M. , Wiegert Nicholas A. , Moran John J. , Muller Daniel , Weber Steven , Hayney Mary S.
Published: October 2007

Study Objective. To compare humoral immune responses to influenza vaccination in subjects with obstructive sleep apnea (OSA) and in healthy volunteers (control subjects).

Design. Prospective, controlled, parallel‐design study.

Setting. Sleep disorders center at a university hospital.

Subjects. Fourteen untreated subjects with moderate‐to‐severe OSA (apnea hypopnea index > 15 events/hr) and 17 healthy volunteers (control subjects).

Intervention. All subjects were given the influenza vaccine for the years 2004–2005 or 2005–2006.

Measurements and Main Results. Blood samples were obtained before and 2–4 weeks after vaccination to measure serum antibody titers for the A/New Caledonia/20/99 (H1N1)‐like and B/Shanghai/361/2002‐like viral strains by using the hemagglutination inhibition assay. Seroconversion was defined as an increase in the antibody titer by more than 4‐fold, whereas seroprotection was defined as an antibody titer greater than 40 hemagglutination units. The mean ± standard error of the mean apnea hypopnea index, calculated as the number of abnormal respiratory events divided by the number of hours of total sleep time, was 56 ± 12 events/hour in the OSA group and 1.0 ± 0.4 oxygen desaturations/hour in the control group (p<0.05). However, no significant differences were observed in changes in antibody concentration, frequencies of seroconversion, or rates of seroprotection between subjects with OSA and control subjects. Polysomnographic measures of OSA were not correlated with immune responses.

Conclusion. Although pathophysiologic characteristics of OSA may influence immune responses, moderate‐to‐severe OSA did not impair humoral responses to the influenza vaccine in these subjects.
Effects of Gatifloxacin and Levofloxacin on Rates of Hypoglycemia and Hyperglycemia Among Elderly Hospitalized Patients
Authors: Lodise Thomas , Graves Jeffrey , Miller Chris , Mohr John F , Lomaestro Ben , Smith Raymond P.
Published: October 2007

Study Objectives. To compare rates of hypoglycemia and hyperglycemia among elderly hospitalized patients with normal blood glucose concentrations at baseline who were receiving either gatifloxacin or levofloxacin, and to determine if appropriateness of their doses, according to their package inserts, was associated with hypoglycemia or hyperglycemia.

Design. Retrospective cohort study.

Setting. Integrated Veterans Administration (VA) health care system.

Patients. Nine hundred thirty‐seven elderly (≥ 65 yrs) patients with documented blood glucose levels of 65–140 mg/dl before receiving a fluoroquinolone.

Measurements and Main Results. Between January 2003 and April 2004, 405 patients receiving levofloxacin met study criteria. In April 2004, gatifloxacin was substituted for levofloxacin on the formulary of this VA system. Thus, between April 2004 and December 2004, 532 patients received gatifloxacin. All blood glucose concentrations during hospitalization that were measured during fluoroquinolone therapy or within 72 hours of completion of therapy were reviewed. Demographic characteristics, comorbidities, insulin and oral hypoglycemic therapies, disease severity, blood glucose levels, and outcomes were recorded and compared between groups. The two groups were similar at baseline for all characteristics examined except previous hospitalization. In the logistic regression, gatifloxacin was independently associated with both hypoglycemia (adjusted odds ratio [AOR] 2.5, 95% confidence interval [CI] 1.2–5.7, p=0.04) and hyperglycemia (AOR 2.4, 95% CI 1.5‐3.6, p<0.001). Improper dosage adjustment based on renal function was not associated with higher rates of hypoglycemia and hyperglycemia for either drug. Of the 532 patients receiving gatifloxacin, 465 (87.4%) received appropriate doses, yet gatifloxacin was associated with higher rates of hypoglycemia and hyperglycemia compared with patients receiving levofloxacin.

Conclusions. Higher rates of both hypoglycemia and hyperglycemia were noted among elderly hospitalized patients who received gatifloxacin compared with those receiving levofloxacin, irrespective of dosing.
Drug Removal by Plasmapheresis: An Evidence‐Based Review
Authors: Ibrahim Rami B. , Liu Chin , Cronin Simon M. , Murphy Bridgette C. , Cha Raymond , Swerdlow Paul , Edwards David J.
Published: October 2007

Contrary to the literature about drug removal during hemodialysis, data regarding drug removal during plasmapheresis are sparse. Over the last 40 years, approximately 70 publications—mostly case reports of overdoses—have described the effects of plasmapheresis on pharmaceutical agents. Important issues are drug extraction during plasma exchange with chemotherapy, as well as drug classes such as antiinfectives, anticoagulants, antiepileptics, cardiovascular agents, and immunosuppressants. Other considerations are the merits and pitfalls of the different methods used in published reports and recommendations for future pharmacokinetic studies in this field.