bluuebunny/crossref_metadata_2025 huggingface dataset:
Topoisomerase Mutations That Are Associated with High-Level Resistance to Earlier Fluoroquinolones in Staphylococcus aureus Have Less Effect on the Antibacterial Activity of Besifloxacin
Authors: Sanfilippo Christine M. , Hesje Christine K. , Haas Wolfgang , Morris Timothy W.
Published: October 2011

Background: The impact of mutations in DNA gyrase and topoisomerase IV on minimum inhibitory concentrations (MICs) was investigated to better understand why besifloxacin has a higher potency against Staphylococcus aureus when compared to other fluoroquinolones, which was especially pronounced against ciprofloxacin-resistant isolates. Methods: MICs were determined for 52 clinical isolates against besifloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and levofloxacin. The genes encoding GyrA, GyrB, ParC, and ParE were sequenced and the potential impact of mutations assessed in light of recent structural data. Results: For all fluoroquinolones tested, the MICs increased with the number of mutations in the quinolone resistance-determining regions. However, this increase was the smallest for besifloxacin and the largest for ciprofloxacin and levofloxacin. In addition to the commonly observed mutations in ParC and GyrA, more unusual mutations in ParE, such as Asp-432→His or Pro-585→Ser, were also detected. Conclusions: Compared to earlier fluoroquinolones, the higher potency of besifloxacin suggests that the drug’s unique combination of a 7-azepinyl ring and an 8-chloro-substituent results in unique interactions with DNA gyrase and topoisomerase IV.
Genetic Factors Influence Serological Measures of Common Infections
Authors: Rubicz Rohina , Leach Charles T. , Kraig Ellen , Dhurandhar Nikhil V. , Duggirala Ravindranath , Blangero John , Yolken Robert , Göring Harald H.H.
Published: October 2011

Background/Aims: Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods: IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and -2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses. Results: Serological phenotypes were significantly heritable for most pathogens (h2 = 0.17–0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c2 = 0.10–0.32). The underlying genetic etiology appears to be largely different for most pathogens. Conclusions: Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance.
Pseudomonas aeruginosa and Mortality after Hospital Admission for Chronic Obstructive Pulmonary Disease
Authors: Almagro Pedro , Salvadó Meritxell , Garcia-Vidal Carolina , Rodríguez-Carballeira Mónica , Cuchi Eva , Torres Juan , Ll Heredia Josep
Published: October 2011

Background:Pseudomonas aeruginosa (PA) is isolated in advanced stages of chronic obstructive pulmonary disease (COPD). Objectives: The aim of our study was to determine whether PA isolation during hospitalization for COPD exacerbation was associated with a poorer prognosis after discharge. Methods: We prospectively studied all patients with COPD exacerbation admitted between June 2003 and September 2004. A sputum culture was obtained at admission. Comorbidity, functional dependence, hospitalizations during the previous year, dyspnea, quality of life and other variables previously associated with mortality in COPD were studied. Spirometry and a 6-min walking test were performed 1 month after discharge. Mortality was evaluated 3 years after discharge. Results: A total of 181 patients were included in the study. Of these, 29 (16%) had PA in the sputum. The mean age was 72 years, and mean basal postbronchodilator forced expiratory volume in 1 s was 45.2% predicted (SD 14.4). The mean point value on the BODE index was 5.1 (SD 2.5). At 3 years, 17 of 29 patients (58.6%) in the PA group had died, compared to 53 of the 152 non-PA patients [34.9%; p < 0.004; hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.29–3.86]. In the multivariate analysis, PA remained statistically related to posthospital mortality (p = 0.02; HR 2.2, 95% CI 1.2–4.2) after adjustment for age (p < 0.02; HR 1.04, 95% CI 1.007–1.07), BODE index (p < 0.02; HR 1.15, 95% CI 1.02–1.3) and comorbidity (p < 0.02; HR 1.24, 95% CI 1.03–1.5). Conclusions: PA isolation in sputum in patients hospitalized for acute exacerbation of COPD is a prognostic marker of 3-year mortality. Poor prognosis is independent of other significant predictors of mortality such as BODE index, age and comorbidity, as measured by the Charlson index.
Methods of Cell Purification: A Critical Juncture for Laboratory Research and Translational Science
Authors: Amos Peter J. , Cagavi Bozkulak Esra , Qyang Yibing
Published: October 2011

Research in cell biology and the development of translational technologies are driven by competition, public expectations, and regulatory oversight, putting these fields at a critical juncture. Success in these fields is quickly becoming dependent on the ability of researchers to identify and isolate specific cell populations from heterogeneous mixtures accurately and efficiently. Many methods for cell purification have been developed, and each has advantages and disadvantages that must be considered in light of the intended application. Current cell separation strategies make use of surface proteins, genetic expression, and physics to isolate specific cells by phenotypic traits. Cell purification is also dependent on the cellular reagents available for use and the intended application, as these factors may preclude certain mechanisms used in the processes of labeling and sorting cells.
How Blood Vessel Networks Are Made and Measured
Authors: Chappell John C. , Wiley David M. , Bautch Victoria L.
Published: October 2011

Tissue and organ viability depends on the proper systemic distribution of cells, nutrients, and oxygen through blood vessel networks. These networks arise in part via angiogenic sprouting. Vessel sprouting involves the precise coordination of several endothelial cell processes including cell-cell communication, cell migration, and proliferation. In this review, we discuss zebrafish and mammalian models of blood vessel sprouting and the quantification methods used to assess vessel sprouting and network formation in these models. We also review the mechanisms involved in angiogenic sprouting, and we propose that the process consists of distinct stages. Sprout initiation involves endothelial cell interactions with neighboring cells and the environment to establish a specialized tip cell responsible for leading the emerging sprout. Furthermore, local sprout guidance cues that spatially regulate this outward migration are discussed. We also examine subsequent events, such as sprout fusion and lumenization, that lead to maturation of a nascent sprout into a patent blood vessel.
Clinical and Electrocardiography Changes in Patients Treated with Capecitabine
Authors: Koca Dogan , Salman Tarik , Unek Ilkay Tugba , Oztop Ilhan , Ellidokuz Hulya , Eren Murat , Yilmaz Ugur
Published: October 2011

Background: We aimed to identify the incidence of cardiac events with capecitabine treatment. Methods: The study included 52 patients (median age 59 years) with cancer treated at our Medical Oncology Clinic between 2009 and 2010. Cardiac events from capecitabine treatment were classified into 4 groups: cardiac symptoms, physical signs, electrocardiography (ECG) findings, and severe adverse cardiac effects. Results: The patients received either single-agent capecitabine or a combination chemotherapy including capecitabine. After initiation of capecitabine, 18 patients (34.6%) had new onset cardiovascular symptoms, 6 (11.5%) had new onset physical signs and 17 (32.6%) had new onset ECG findings. New onset ECG findings included prolonged corrected QT interval (n = 10, 19.2%) and prolonged PR interval (n = 3, 5.8%). Severe adverse capecitabine-induced cardiac side effects were observed in 5.8% of the patients, but none of the patients had myocardial infarction or died. Conclusion: Cardiac events are not rare during capecitebine treatment and patients should be followed closely to avoid cardiac morbidity and mortality.
Assessment of the Analgesic Effect of Centhaquin in Mouse Tail Flick and Hot-Plate Tests
Authors: Andurkar Shridhar V. , Gulati Anil
Published: October 2011

Background: Centhaquin is a centrally acting hypotensive drug like clonidine. Clonidine also produces analgesia and hypothermia in mice and potentiates morphine analgesia. Clonidine analgesia is blocked by idazoxan and naloxone while it is potentiated by BQ123 and sulfisoxazole. This study was conducted to determine the analgesic and hypothermic properties of centhaquin, and to assess whether it potentiates morphine analgesia. Yohimbine (α2-adrenergic antagonist), idazoxan (imidazoline/α2-adrenergic antagonist), naloxone (opioid antagonist), and BQ123 and sulfisoxazole (endothelin ETA antagonists) were used to study the involvement of these receptors in centhaquin analgesia and hypothermia. Methods: Analgesic (tail flick and hot-plate tests) latencies and body temperatures were measured in male Swiss Webster mice treated with vehicle plus centhaquin, antagonists plus centhaquin or centhaquin plus morphine. Results: Centhaquin produced dose-dependent analgesia which was partially blocked by yohimbine, idazoxan and naloxone. BQ123 and sulfisoxazole did not affect centhaquin analgesia. Morphine analgesia was not potentiated by centhaquin. Centhaquin produced mild hypothermia which was not blocked by yohimbine, idazoxan, naloxone, BQ123 or sulfisoxazole. Conclusions: This is the first report demonstrating the analgesic activity of centhaquin. The α2-adrenergic, imidazoline and opioid receptors are involved in mediating centhaquin analgesia. Endothelin ETA receptors do not play a role in centhaquin analgesia; centhaquin does not augment morphine analgesia.
Health-Related Quality of Life and Patient-Defined Benefit of Clobetasol 0.05% in Women with Chronic Lichen Sclerosus of the Vulva
Authors: Schwegler J. , Schwarz J. , Eulenburg C. , Blome C. , Ihnen M. , Mahner S. , Jaenicke F. , Augustin M. , Woelber L.
Published: October 2011

Background: This study investigates the health-related quality of life in patients with vulvar lichen sclerosus (LS) and the patient-defined therapeutic benefit of clobetasol. Methods: A survey analysis of 96 women with LS after treatment with clobetasol was performed. Quality of life was assessed with the Skindex-29. The Patient Benefit Index (PBI) was used to determine the therapeutic benefit. Results: The overall response rate was 59.2%. Quality of life was most impaired by somatic symptoms (scale ‘Symptoms’ score 3.2) and emotional stress (scale ‘Emotions’ score 3.1), while social interactions (scale ‘Functioning’ score 1.9) played an inferior role (p < 0.001). Primary therapeutic goals ‘to have confidence in the therapy’ and ‘to be free of itching’ were achieved in 73.2 and 69.0% of patients who indicated the goal applied to them. The global PBI score was 3.06. In 93.2% of patients it was >1, indicating a potential benefit from clobetasol. Conclusion: Topical clobetasol is of potential therapeutic benefit for patients with vulvar LS and might therefore improve quality of life.
Establishing Effect Size Guidelines for Interpreting the Results of Differential Bundle Functioning Analyses Using SIBTEST
Authors: Walker Cindy M. , Zhang Bo , Banks Kathleen , Cappaert Kevin
Published: October 2011

The purpose of this simulation study was to establish general effect size guidelines for interpreting the results of differential bundle functioning (DBF) analyses using simultaneous item bias test (SIBTEST). Three factors were manipulated: number of items in a bundle, test length, and magnitude of uniform differential item functioning (DIF) against the focal group in each item in a bundle. A secondary purpose was to validate the current effect size guidelines for interpreting the results of single-item DIF analyses using SIBTEST. The results of this study clearly demonstrate that ability estimation bias can only be attributed to DIF or DBF when a large number of items in a bundle are functioning differentially against focal examinees in a small way or a small number of items are functioning differentially against focal examinees in a large way. In either of these situations, the presence of DIF or DBF should be a cause for concern because it would lead one to erroneously believe that distinct groups differ in ability when in fact they do not.
Risk Factors for Supraglottoplasty Failure
Authors: Day Kristine E. , Discolo Christopher M. , Meier Jeremy D. , Wolf Bethany J. , Halstead Lucinda A. , White David R.
Published: October 2011

Objective

To review outcomes after supraglottoplasty for laryngomalacia and identify risk factors for supraglottoplasty failure.

Study Design

Case series with chart review.

Setting

Tertiary care children’s hospital.

Subjects and Methods

Retrospective case series evaluating patient outcomes after supraglottoplasty at an academic medical center between 2004 and 2010. Surgical failure was defined as need for revision surgery, tracheostomy tube placement, or gastrostomy tube insertion. Multivariable logistic regression was performed to identify risk factors for failure.

Results

The authors identified 95 children who underwent supraglottoplasty. After excluding patients with inadequate follow‐up data, 74 patients were included. On the basis of chart review, 12 (16%) of those patients were defined as failures according to the criteria above. Age, history of prematurity (<34 weeks’ gestational age), weight, growth curve percentile, neurologic/developmental problems, genetic syndrome, cardiac abnormality, synchronous airway lesions, and surgical technique were considered in risk factor analysis. Multivariable logistic regression was performed, revealing history of prematurity to be the only independent risk factor for failure (odds ratio = 4.85; 95% confidence interval, 1.07‐22.1; P =. 041).

Conclusions

Outcomes after supraglottoplasty were comparable to previous reports in the literature. History of prematurity should be considered a risk factor for surgical failure.
Challenging exclusionary paradigms in the traditional musical canon: Implications for music education practice
Authors: Kindall-Smith Marsha , McKoy Constance L. , Mills Susan W.
Published: October 2011

The authors propose that best practices in music education require a conceptual understanding of music teaching and learning based on a perspective of social justice and equitable access for all students. Examinations of the relationship between the tenets of culturally-responsive teaching and three dimensions of music teaching and learning (musical content, instruction, and context) are presented: (1) historically, through the identification of neglected African American contributions to Appalachian music; and (2) pedagogically, through the chronicling of social justice content and culturally-responsive instruction as taught in an urban university and public middle school. The implications of issues of power and social justice for music education are further contextualized within the lens of critical pedagogy to uncover possibilities for a 21st century canon of music teacher preparation that will maximize the potential to transform music education practice.
Finding the muse: Teaching musical expression to adolescents in the one-to-one studio environment
Authors: McPhee Eleanor A.
Published: October 2011

One-to-one music lessons are a common and effective way of learning a musical instrument. This investigation into one-to-one music teaching at the secondary school level explores the teaching of musical expression by two instrumental music teachers of brass and strings. The lessons of the two teachers with two students each were video recorded over a six-week period. This data were transcribed, coded and content analyzed. The results showed that the teachers used a variety of strategies to teach musical expression and the teacher’s choice of approach seems less important than ensuring that the student has a good understanding of the approach. Furthermore, the traditional strategies for teaching musical expression may benefit from the inclusion of approaches designed to enable young students to begin to create personal meaning in their music making. Teachers, therefore, might consider reading research findings on creative learning and devise strategies for its application in their music studios.
Validating the inhalation of 7.5% CO2 in healthy volunteers as a human experimental medicine: a model of generalized anxiety disorder (GAD)
Authors: Bailey Jayne E , Dawson Gerard R , Dourish Colin T , Nutt David J
Published: October 2011

Anxiety is a complex phenomenon that can represent contextually different experiences to individuals. The experimental modelling in healthy volunteers of clinical anxiety experienced by patients is challenging. Furthermore, defining when and why anxiety (which is adaptive) becomes an anxiety disorder (and hence maladaptive) is the subject of much of the published literature. Observations from animal studies can be helpful in deriving mechanistic models, but gathering evidence from patients and reverse translating this to healthy volunteers and thence back to laboratory models is a more powerful approach and is likely to more closely model the clinical disorder. Thus the development and validation of a robust healthy volunteer model of anxiety may help to bridge the gap between the laboratory and the clinic and provide ‘proof of concept’ in screening for novel drug treatments. This review considers these concepts and outlines evidence from a validated healthy volunteer model of generalized anxiety disorder (GAD) following the inhalation of 7.5% CO2.
Traditional and Commercial Herb Use in Health Self-Management Among Rural Multiethnic Older Adults
Authors: Altizer Kathryn P. , Quandt Sara A. , Grzywacz Joseph G. , Bell Ronny A. , Sandberg Joanne C. , Arcury Thomas A.
Published: October 2011

This study analyzes the role of traditional and commercial herbs in older adults’ health self-management based on Leventhal’s Self-Regulatory Model conceptual framework. Sixty-two African American and White adults age 65 and older completed qualitative interviews describing the forms of herbs currently being used, sources of information about them, interpretations of health (acute symptoms or chronic conditions) that led to their use, and the initiation and suspension of use. Traditional herbs are native to the region or have been traditionally cultivated, usually taken raw or boiled to produce tea, and used for treating mild symptoms. Commercial herbs are prepared as pills, extracts, or teas; they are purchased at local stores or ordered by catalog or Internet and used for health promotion, illness prevention, or treatment of chronic conditions. Herbs are widely used among older adults; this analysis differentiates the types of herbs they use and their reasons for herbs use.
Fashion Leadership and Hedonic Shopping Motivations of Female Consumers
Authors: Kim Hye-Shin , Hong Heesook
Published: October 2011

Fashion leadership is an important consumer characteristic due to the interpersonal influence essential in the consumption process of apparel. Based on the human motivations theory and Sheth’s shopping preference theory, this study examines the hypothesized relationships of fashion leadership and five hedonic shopping motivations (gratification, value, social, idea, and adventure). This study advances current understanding of fashion leadership by studying a broad national female population base and offers empirical evidence into how fashion leadership shapes consumer need for emotional and experiential satisfaction in shopping. Results show fashion leadership to be significantly related to all but one hedonic shopping motivation. Additionally, this study finds that adventure shopping motivation may be derived from other types of hedonic shopping activities. Discussion concerning how current findings expand our understanding of fashion leadership within the context of shopping is presented.
Emotional Distress and Cognitive Functioning of Older Couples
Authors: Lee Jinkook , Paddock Susan M. , Feeney Kevin
Published: October 2011

Objective: This article examines the relationship between cognitive functioning and emotional distress in a sample of 2,684 married couples from the 2006 and 2008 Korean Longitudinal Study of Aging. Method: Using the Center for Epidemiologic Studies Depression (CESD) scale and the Mini-Mental State Exam (MMSE), we analyze the interrelation between emotional and cognitive health for individuals and spouses with with dyadic regression models. We test how emotional distress and cognitive impairment affect each other within individuals and from one spouse to another. Results: We find emotional distress contributes to cognitive impairment for wives but not for husbands. We also find emotional distress and cognitive impairment in one spouse affects that in the other. We find no evidence that emotional distress effects spouse’s cognitive impairment or that the cognitive ability impacts spouses’ emotional distress. Discussion: We discuss the results within the context of existing literature, focusing on the socioeconomic and clinical factors that explain these interrelations.
Swarm herding using a region holding sliding mode controller
Authors: Bacon Mark , Olgac Nejat
Published: October 2011

We introduce a control logic which allows a group of autonomous ‘pursuers’ to herd a single, non-hostile ‘evader’ along a desired trajectory. They achieve this with a general knowledge of the repulsion scheme on the evader and utilizing a feedback control, based on the evader state and the known desired trajectory of the evader. The quasi-decentralized control of the pursuers is a version of a region holding sliding mode controller (SMC). The novelty of this work lies in the decentralized distribution of pursuers within a desired region whose boundaries are maintained utilizing the robust properties of SMC. The dynamic pursuer distribution repels the evader with a desired force which reduces its tracking error. Illustrative examples are studied for validation.
Control of an uncertain fractional-order Liu system via fuzzy fractional-order sliding mode control
Authors: Faieghi Mohammad Reza , Delavari Hadi , Baleanu Dumitru
Published: October 2011

Robust control of fractional-order Liu system is addressed in this paper. The proposed approach relies on sliding mode control being established on a novel fractional-order integral type sliding surface. Theoretically, based on classical Lyapunov stability theorem, it has been shown that under suitable conditions, the proposed controller guarantees the system's stability. Further, it is shown that the method presented is capable for both commensurate and incommensurate systems. In order to reduce the chattering effect, a fuzzy logic controller is employed. Numerical simulations verify these results.
Risk Assessment With Victims of Intimate Partner Violence
Authors: Bennett Cattaneo Lauren , Chapman Aliya R.
Published: October 2011

In intimate partner violence (IPV) risk assessment, there is consensus that a large gap exists between research and practice. This exploratory study interviewed 13 practitioners working with IPV victims to generate ideas about the nature of this gap, and found that only two conducted standardized risk assessment. Others felt imposing structure might detract from the quality of their work. Results support the need for different techniques in different contexts; some adjust only speed of services according to their risk perception, whereas others use in-depth information to customize services. Perspectives appear particularly disparate regarding victim minimization of risk. Implications for future work are discussed.
Internet Use for Prediagnosis Symptom Appraisal by Colorectal Cancer Patients
Authors: Thomson Maria D. , Siminoff Laura A. , Longo Daniel R.
Published: October 2011

Background. This study explored the characteristics of colorectal cancer (CRC) patients who accessed Internet-based health information as part of their symptom appraisal process prior to consulting a health care provider. Method. Newly diagnosed CRC patients who experienced symptoms prior to diagnosis were interviewed. Brief COPE was used to measure patient coping. Logistic and linear regressions were used to assess Internet use and appraisal delay. Results. Twenty-five percent of the sample (61/242) consulted the Internet prior to visiting a health care provider. Internet use was associated with having private health insurance (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.20-5.43) and experiencing elimination symptoms (OR = 1.43; 95% CI = 1.14-1.80) and was marginally associated with age (OR = 0.96; 95% CI = 0.93-0.99). Internet use was not related to delayed medical care seeking. Conclusion. Internet use did not influence decisions to seek medical care. The Internet provided a preliminary information resource for individuals who experienced embarrassing CRC symptoms, had private health insurance, and were younger.
Sense and complexity: Initiatives in responsive performance audits
Authors: van der Knaap Peter
Published: October 2011

Many policy programmes yield disappointing results. Like policy evaluation, performance audit aims to help policy makers by uncovering barriers to success and suggesting improvements. Traditionally, performance audit relies heavily on policy objectives, norms, and criteria while focusing on the responsibility of a specific government entity (e.g. a ministry or an agency). More recently, however, performance auditors have recognized the need to be more open and responsive to the needs and preferences of target groups and stakeholders, and changes in context and knowledge – elements that have been central to responsive and realist evaluation for some years. This article describes new initiatives to bring more responsiveness into performance audits. Starting from the new international performance audit guidelines of INTOSAI, it discusses how this can work in practice by looking at recent initiatives of the Netherlands Court of Audit. The focus is on a new tool for performance audit, under the rather provocative label of ‘reality checks’: compact audits of the connection between policy programmes and stakeholders’ needs and preferences. By including more responsive research questions and methods and looking critically to existing monitoring and evaluation practices in policy programmes, performance audit has an important role to play in balancing the benefits and risks of policy objectives and performance indicators.
Toward Automated, At-Home Assessment of Mobility Among Patients With Parkinson Disease, Using a Body-Worn Accelerometer
Authors: Weiss Aner , Sharifi Sarvi , Plotnik Meir , van Vugt Jeroen P. P. , Giladi Nir , Hausdorff Jeffrey M.
Published: October 2011

Objective. To develop an automated and objective method to assess mobility in Parkinson disease (PD) patients in daily-life settings and to investigate whether accelerometer-derived measures discriminate between PD and healthy controls as they walk and simulate activities of daily living (ADL). Methods. Healthy older adults (17) and patients with PD (22) wore a triaxial accelerometer on their lower back during short walks (validation study) and during a walk around the medical center to simulate daily activities (ADL simulation). The variability (consistency and rhythmicity) of stepping was assessed. The patients completed the walks before and after taking their anti-Parkinsonian medications. Frequency-based acceleration measures included dominant frequency, amplitude (strength of signal frequency), width (frequency dispersion), and slope (a combination reflecting amplitude and width) of the main frequency of the power spectral density in the 0.5- to 3.0-Hz band. A subset of the Unified Parkinson-Disease Rating Scale provided a clinical measure of gait impairment (UPDRS-Gait5). A PD patient and control wore the sensors for 3 days at home. Results. The width was larger, and the amplitude and slope were smaller in the PD patients compared to the controls in the validation study and ADL simulation ( P < .02). The width decreased, and the amplitude and slope increased when patients took anti-Parkinsonian medications ( P < .007). Significant correlations were observed between acceleration-derived measures and UPDRS-Gait5. The data obtained at home was similar to the clinic data. Conclusions. Frequency-derived measures are valid and sensitive estimates of stride-to-stride variability that can be used to assess the quality and consistency of walking in patients with PD in real-life settings.
The Role of Mindfulness and Psychological Flexibility in Somatization, Depression, Anxiety, and General Psychological Distress in a Nonclinical College Sample
Authors: Masuda Akihiko , Tully Erin C.
Published: October 2011

The current study investigated whether mindfulness and psychological flexibility uniquely and separately accounted for variability in psychological distress (somatization, depression, anxiety, and general psychological distress). An ethnically diverse, nonclinical sample of college undergraduates (N = 494, 76% female) completed a Web-based survey that included the self-report measures of interest. Consistent with prior research, psychological flexibility and mindfulness were positively associated with each other, and tested separately, both variables were negatively associated with somatization, depression, anxiety, and general psychological distress. Results also revealed that psychological flexibility and mindfulness accounted for unique variance in all 4 measures of distress. These findings suggest that mindfulness and psychological flexibility are interrelated but not redundant constructs and that both constructs are important for understanding the onset and maintenance of somatization, depression, anxiety, and general distress.
Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine and chemokine secretion in CD56bright and CD56dim NK cells
Authors: Morandi Fabio , Ferretti Elisa , Castriconi Roberta , Dondero Alessandra , Petretto Andrea , Bottino Cristina , Pistoia Vito
Published: October 2011

Soluble HLA-G (sHLA-G) inhibits natural killer (NK) cell functions. Here, we investigated sHLA-G–mediated modulation of (1) chemokine receptor and NK receptor expression and function and (2) cytokine and chemokine secretion in CD56bright and CD56dim NK cells. sHLA-G-treated or untreated peripheral blood (PB) and tonsil NK cells were analyzed for chemokine receptor and NK receptor expression by flow cytometry. sHLA-G down-modulated (1) CXCR3 on PB and tonsil CD56bright and CD56dim, (2) CCR2 on PB and tonsil CD56bright, (3) CX3CR1 on PB CD56dim, (4) CXCR5 on tonsil CD56dim, and (5) CD94/NKG2A on PB and tonsil CD56bright and CD56dim NK cells. Such sHLA-G–mediated down-modulations were reverted by adding anti–HLA-G or anti–ILT2 mAbs. sHLA-G inhibited chemotaxis of (1) PB NK cells toward CXCL10, CXCL11, and CX3CL1 and (2) PB CD56bright NK cells toward CCL2 and CXCL10. IFN-γ secretion induced by NKp46 engagement was inhibited by NKG2A engagement in untreated but not in sHLA-G–treated NK cells. sHLA-G up-regulated secretion of (1) CCL22 in CD56bright and CD56dim and (2) CCL2, CCL8, and CXCL2-CXCL3 in CD56dim PB NK cells. Signal transduction experiments showed sHLA-G–mediated down-modulation of Stat5 phosphorylation in PB NK cells. In conclusion, our data delineated novel mechanisms of sHLA-G–mediated inhibition of NK-cell functions.
Three genes expressing Kunitz domains in the epididymis are related to genes of WFDC-type protease inhibitors and semen coagulum proteins in spite of lacking similarity between their protein products
Authors: Clauss Adam , Persson Margareta , Lilja Hans , Lundwall Åke
Published: October 2011

Background

We have previously identified a locus on human chromosome 20q13.1, encompassing related genes of postulated WFDC-type protease inhibitors and semen coagulum proteins. Three of the genes with WFDC motif also coded for the Kunitz-type protease inhibitor motif. In this report, we have reinvestigated the locus for homologous genes encoding Kunitz motif only. The identified genes have been analyzed with respect to structure, expression and function.

Results

We identified three novel genes; SPINT3, SPINT4 and SPINT5, and the structure of their transcripts were determined by sequencing of DNA generated by rapid amplification of cDNA ends. Each gene encodes a Kunitz domain preceded by a typical signal peptide sequence, which indicates that the proteins of 7.6, 8.7, and 9.7 kDa are secreted. Analysis of transcripts in 26 tissues showed that the genes predominantly are expressed in the epididymis. The recombinantly produced proteins could not inhibit the amidolytic activity of trypsin, chymotrypsin, plasmin, thrombin, coagulation factor Xa, elastase, urokinase and prostate specific antigen, whereas similarly made bovine pancreatic trypsin inhibitor (BPTI) had the same bioactivity as the protein isolated from bovine pancreas.

Conclusions

The similar organization, chromosomal location and site of expression, suggests that the novel genes are homologous with the genes of WFDC-type protease inhibitors and semen coagulum proteins, despite the lack of similarity in primary structure of their protein products. Their restricted expression to the epididymis suggests that they could be important for male reproduction. The recombinantly produced proteins are presumably bioactive, as demonstrated with similarly made BPTI, but may have a narrower spectrum of inhibition, as indicated by the lacking activity against eight proteases with differing specificity. Another possibility is that they have lost the protease inhibiting properties, which is typical of Kunitz domains, in favor of hitherto unknown functions.
Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy
Authors: Pavlík Tomáš , Janoušová Eva , Pospíšil Zdeněk , Mužík Jan , Žáčková Daniela , Ráčil Zdeněk , Klamová Hana , Cetkovský Petr , Trněný Marek , Mayer Jiří , Dušek Ladislav
Published: October 2011

Background

The current situation in the treatment of chronic myeloid leukaemia (CML) presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment.

Methods

Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data.

Results

The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively) at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter.

Conclusions

Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in this paper. Both quantities reliably illustrate a patient's disease status in time because they account for the proportion of patients in the second and subsequent disease remissions. Moreover, the model is also applicable in the future, regardless of what the progress in the CML treatment will be and how many treatment options will be available, respectively.
Applying the Stages of Change model to Type 2 diabetes care in Trinidad: A randomised trial
Authors: Partapsingh VA , Maharaj RG , Rawlins JM
Published: October 2011

Objective

To improve glycaemic control among Type 2 diabetics using patient-physician consultations guided by the Stages of Change (SOC) model.

Design and Methods

A randomised trial was conducted. After ensuring concealment of allocation, Type 2 diabetics were randomly assigned to receive the intervention or the control. The intervention consisted of identifying each patient's Stage of Change for managing their diabetes by diet, exercise and medications, and applying personalised, stage-specific care during the patient-physician consultations based on the SOC model. Patients in the control group received routine care. The variables of interest were effect on glycaemic control (measured by the difference in HbA1c levels) and patients' readiness to change (measured by identifying patients' SOC for managing their diabetes by diet, exercise and medications).

Results

Participants were primarily over age 50, male and Indo-Trinidadian. Most had received only a primary school education and over 65% had a monthly income of $320 USD/month or less. Sixty-one Type 2 diabetics participated in each arm. Three patients were lost to follow-up in the intervention arm. After 48 weeks, there was an overall increase in HbA1c of 0.52% (SE 0.17) and 1.09% (SE 0.18) for both the intervention and control groups respectively. There was a relative reduction in HbA1c of 0.57% (95% CI 0.07, 1.07) with the intervention group compared to the control (p = 0.025). For exercise and diet there was an overall tendency for participants in the intervention arm to move to a more favourable SOC, but little change was noted with regards medication use.

Conclusions

The result suggests a tendency to a worsening of glycaemic control in this population despite adopting more favourable SOC for diet and exercise. We hypothesized that harsh social conditions prevailing at the time of the study overrode the clinical intervention.
Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies
Authors: Hess Michael , Stritzker Jochen , Härtl Barbara , Sturm Julia B , Gentschev Ivaylo , Szalay Aladar A
Published: October 2011

Background

Oncolytic viral tumor therapy is an emerging field in the fight against cancer with rising numbers of clinical trials and the first clinically approved product (Adenovirus for the treatment of Head and Neck Cancer in China) in this field. Yet, until recently no general (bio)marker or reporter gene was described that could be used to evaluate successful tumor colonization and/or transgene expression in other biological therapies.

Methods

Here, a bacterial glucuronidase (GusA) encoded by biological therapeutics (e.g. oncolytic viruses) was used as reporter system.

Results

Using fluorogenic probes that were specifically activated by glucuronidase we could show 1) preferential activation in tumors, 2) renal excretion of the activated fluorescent compounds and 3) reproducible detection of GusA in the serum of oncolytic vaccinia virus treated, tumor bearing mice in several tumor models. Time course studies revealed that reliable differentiation between tumor bearing and healthy mice can be done as early as 9 days post injection of the virus. Regarding the sensitivity of the newly developed assay system, we could show that a single infected tumor cell could be reliably detected in this assay.

Conclusion

GusA therefore has the potential to be used as a general marker in the preclinical and clinical evaluation of (novel) biological therapies as well as being useful for the detection of rare cells such as circulating tumor cells.
Toll-like receptor 2 -196 to -174 del polymorphism influences the susceptibility of Han Chinese people to Alzheimer's disease
Authors: Yu Jin-Tai , Mou Shan-Mao , Wang Li-Zhu , Mao Cai-Xia , Tan Lan
Published: October 2011

Background

Toll-like receptor 2 (TLR2) represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD) as it is located under the linkage region of AD on chromosome 4q, and functionally is involved in the microglia-mediated inflammatory response and amyloid-β clearance. The -196 to -174 del polymorphism affects the TLR2 gene and alters its promoter activity.

Methods

We recruited 800 unrelated Northern Han Chinese individuals comprising 400 late-onset AD (LOAD) patients and 400 healthy controls matched for gender and age. The -196 to -174 del polymorphism in the TLR2 gene was genotyped using the polymerase chain reaction (PCR) method.

Results

There were significant differences in genotype (P = 0.026) and allele (P = 0.009) frequencies of the -196 to -174 del polymorphism between LOAD patients and controls. The del allele was associated with an increased risk of LOAD (OR = 1.31, 95% CI = 1.07-1.60, Power = 84.9%). When these data were stratified by apolipoprotein E (ApoE) ε4 status, the observed association was confined to ApoE ε4 non-carriers. Logistic regression analysis suggested an association of LOAD with the polymorphism in a recessive model (OR = 1.64, 95% CI = 1.13-2.39, Bonferroni corrected P = 0.03).

Conclusions

Our data suggest that the -196 to -174 del/del genotype of TLR2 may increase risk of LOAD in a Northern Han Chinese population.
Regeneration of Centella asiatica plants from non-embryogenic cell lines and evaluation of antibacterial and antifungal properties of regenerated calli and plants
Authors: Bibi Yamin , Zia Muhammad , Nisa Sobia , Habib Darima , Waheed Abdul , Chaudhary Fayyaz M
Published: October 2011

Background

The threatened plant Centella asiatica L. is traditionallyused for a number of remedies. In vitro plant propagation and enhanced metabolite production of active metabolites through biotechnological approaches has gained attention in recent years.

Results

Present study reveals that 6-benzyladenine (BA) either alone or in combination with 1-naphthalene acetic acid (NAA) supplemented in Murashige and Skoog (MS) medium at different concentrations produced good quality callus from leaf explants of C. asiatica. The calli produced on different plant growth regulators at different concentrations were mostly embryogenic and green. Highest shoot regeneration efficiency; 10 shoots per callus explant, from non-embryogenic callus was observed on 4.42 μM BA with 5.37 μM NAA. Best rooting response was observed at 5.37 and 10.74 μM NAA with 20 average number of roots per explant. Calli and regenerated plants extracts inhibited bacterial growth with mean zone of inhibition 9-13 mm diameter when tested against six bacterial strains using agar well diffusion method. Agar tube dilution method for antifungal assay showed 3.2-76% growth inhibition of Mucor species, Aspergillus fumigatus and Fusarium moliniformes.

Conclusions

The present investigation reveals that non-embryogenic callus can be turned into embryos and plantlets if cultured on appropriate medium. Furthermore, callus from leaf explant of C. asiatica can be a good source for production of antimicrobial compounds through bioreactor.
Giardia duodenalis assemblages and Entamoeba species infecting non-human primates in an Italian zoological garden: zoonotic potential and management traits
Authors: Berrilli Federica , Prisco Cristina , Friedrich Klaus G , Di Cerbo Pilar , Di Cave David , De Liberato Claudio
Published: October 2011

Background

Giardia duodenalis and Entamoeba spp. are among the most common intestinal human protozoan parasites worldwide and they are frequently reported in captive non-human primates (NHP). From a public health point of view, infected animals in zoos constitute a risk for animal caretakers and visitors. In this study we carried out the molecular identification of G. duodenalis and Entamoeba spp. from nine species of primates housed in the zoological garden of Rome, to better ascertain their occurrence and zoonotic potential.

Results

G. duodenalis was found only in Lemur catta (47.0%). Entamoeba spp. were detected in all species studied, with the exception of Eulemur macaco and Varecia rubra. The number of positive pools ranged from 5.9% in L. catta to 81.2% in Mandrillus sphinx; in Pan troglodytes the observed prevalence was 53.6%. A mixed Entamoeba-Giardia infection was recorded only in one sample of L. catta. All G. duodenalis isolates belonged to the zoonotic assemblage B, sub assemblage BIV. Three Entamoeba species were identified: E. hartmanni, E. coli and E. dispar.

Conclusions

Our results highlight the importance of regularly testing animals kept in zoos for the diagnosis of zoonotic parasites, in order to evaluate their pathogenic role in the housed animals and the zoonotic risk linked to their presence. A quick detection of the arrival of pathogens into the enclosures could also be a prerequisite to limit their spread into the structure via the introduction of specific control strategies. The need for molecular identification of some parasite species/genotype in order to better define the zoonotic risk is also highlighted.