bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable kerbside recycling in the municipal garbage contract
Authors: Chowdhury Moe
Published: August 2009

In an era of global warming, rising energy costs and increasing volumes of wastes destined for landfills and incinerators, communities should set up environmentally sustainable services that are cost-effective for their citizens and revenue generators for municipalities. A win-win garbage collection and kerbside recycling program established more than eight years ago in a small rural community in Ohio, US is still going strong. It is offering a relatively inexpensive way for waste disposal by providing an incentive-based and highly participatory kerbside recycling and at the same time bringing in substantial franchise fees for the municipal coffers. Unlike garbage contracts in most communities that are designed for only residential waste collection, this program extends disposal and recycling services to non-residential establishments. It picks up hard-to-dispose household furniture, appliances and other bulky items without additional costs to the residents. By being creative and assessing local political and socio-economic milieu, public officials can implement a comprehensive service package for taking care of their community throwaways. However, before establishing such programs in partnership with a private firm, city administrators must understand the intricacies of bid specifications customized for municipal wastes and recyclable materials.
Privatization and Its Challenges for Human Resource Management in the Public Sector
Authors: Battaglio R. Paul
Published: August 2009

During the past three decades, extensive reforms have challenged public management by advocating private sector innovation as a more efficient alternative. New public management, the National Performance Review, and other market-based reforms champion private sector innovation as a means for improving accountability and quality of service in the public sector. Privatization is a key component of these reforms that takes advantage of private sector economy in the delivery of public services. Drawing from case studies and current research, the articles in this symposium issue offer new and valuable insights into the dynamics and details of outsourcing the human resource function in the public sector. This introduction provides readers with a synopsis of the contributions to this symposium and urges further research avenues in the wake of findings presented here.
Sympathetic Overstimulation During Critical Illness: Adverse Effects of Adrenergic Stress
Authors: Dünser Martin W. , Hasibeder Walter R.
Published: August 2009

The term ‘‘adrenergic’’ originates from ‘‘adrenaline’’ and describes hormones or drugs whose effects are similar to those of epinephrine. Adrenergic stress is mediated by stimulation of adrenergic receptors and activation of post-receptor pathways. Critical illness is a potent stimulus of the sympathetic nervous system. It is undisputable that the adrenergic-driven ‘‘fight-flight response’’ is a physiologically meaningful reaction allowing humans to survive during evolution. However, in critical illness an overshooting stimulation of the sympathetic nervous system may well exceed in time and scope its beneficial effects. Comparable to the overwhelming immune response during sepsis, adrenergic stress in critical illness may get out of control and cause adverse effects. Several organ systems may be affected. The heart seems to be most susceptible to sympathetic overstimulation. Detrimental effects include impaired diastolic function, tachycardia and tachyarrhythmia, myocardial ischemia, stunning, apoptosis and necrosis. Adverse catecholamine effects have been observed in other organs such as the lungs (pulmonary edema, elevated pulmonary arterial pressures), the coagulation (hypercoagulability, thrombus formation), gastrointestinal (hypoperfusion, inhibition of peristalsis), endocrinologic (decreased prolactin, thyroid and growth hormone secretion) and immune systems (immunomodulation, stimulation of bacterial growth), and metabolism (increase in cell energy expenditure, hyperglycemia, catabolism, lipolysis, hyperlactatemia, electrolyte changes), bone marrow (anemia), and skeletal muscles (apoptosis). Potential therapeutic options to reduce excessive adrenergic stress comprise temperature and heart rate control, adequate use of sedative/analgesic drugs, and aiming for reasonable cardiovascular targets, adequate fluid therapy, use of levosimendan, hydrocortisone or supplementary arginine vasopressin.
Availability of and Access to Career Development Activities for Transition-Age Youth With Disabilities
Authors: Carter Erik W. , Trainor Audrey A. , Cakiroglu Orhan , Swedeen Beth , Owens Laura A.
Published: August 2009

Equipping youth with and without disabilities for the world of work has been the focus of ongoing legislative and policy initiatives. The authors examined the extent to which career development and vocational activities were available to and accessed by youth with severe disabilities or emotional and behavioral disorders attending 34 urban, suburban, and rural high schools. Although school-level representatives (e.g., administrators, guidance counselors, student services directors) identified an array of career development opportunities offered by their schools, participation by youth with disabilities in these experiences was reported to be fairly limited. Potential factors influencing the participation of youth included disability-related needs and limited professional development opportunities for educators. The authors present recommendations for improving research and practice aimed at better preparing youth with disabilities for their future careers.
Cross-Validation of the Florida Cognitive Activities Scale (FCAS) in an Alzheimer’s Disease Research Center Sample
Authors: Schinka John A. , Raj Ashok , Loewenstein David A. , Small Brent J. , Duara Ranjan , Potter Huntington
Published: August 2009

We conducted a cross-validation study of the Florida Cognitive Activities Scale (FCAS) in a sample of heterogeneously diagnosed elderly participants in the Florida Alzheimer’s Disease Research Center. FCAS scales were found to be significantly correlated with neuropsychological measures and with ratings of medial temporal atrophy (MTA). The pattern of significant differences in FCAS scores among groups of normals, those with mild cognitive impairment, and early-stage Alzheimer disease cases suggests that the cognitive activities tapped by the FCAS are affected throughout disease progression in the same way as the neuropsychological performance measures. Notably, FCAS score differences among these groups were as large as they were for ratings of MTA. The accumulation of reliability and validity data indicates that the FCAS scales are sensitive measures of individual differences in cognitive activity and would serve as valid longitudinal measures of change in the study of aging, cognitive decline, and degenerative dementia.
Behavioral Indicators of Postoperative Pain in Older Adults With Delirium
Authors: Decker Sheila A.
Published: August 2009

The undertreatment of postoperative pain in older adults with delirium is attributed, in part, to the inability to complete self-report pain assessment instruments. Patients’ loss of verbal skills to self-report pain and the lack of reliable and valid postoperative pain assessment instruments for use in older adults with delirium prompted the design of a study to identify common and subtle behavioral indicators of pain. Sixteen experienced registered nurses participating in four focus groups identified behavioral indicators of pain.Transcript analysis resulted in 89 behaviors indicative of pain. Seven researchers with expertise in pain and cognitive impairment in older adults reached 80% agreement on 22 behavioral indicators. The behavioral indicators were classified within one of four pain behavior categories (nonverbal cues/behaviors, vocalizations, facial expressions, and change in usual behavior), and each behavioral indicator was identified as common or subtle. Findings provide evidence of content validity for the pain behaviors.
Cerebral Venous and Sinus Thrombosis and Thrombophilic Mutations in Western Iran: Association With Factor V Leiden
Authors: Rahimi Zohreh , Mozafari Hadi , Amir Hossein Amiri Bigvand  , Reza Mohammad Doulabi  , Vaisi-Raygani Asad , Afshari Dariush , Razazian Nazanin , Rezaei Mansour
Published: August 2009

The present study aimed at investigating the prevalence of factor V Leiden G1691A, prothrombin G20210A, and MTHFR C677T in cerebral venous and sinus thrombosis (CVST) patients and their possible association with CVST in Western Iran. A total of 24 CVST patients with the mean age of 37.1 ± 11.7 years and 100 sex- and age-matched healthy individuals from Kermanshah Province of Iran with ethnic background of Kurd were studied for factor V Leiden G1691A, prothrombin G20210A and MTHFR C677T by PCR-RFLP method using Mnl I, Hind III, and Hinf I restriction enzymes, respectively. Prevalence of factor V Leiden was 16.7% in patients and 2% in control group. A significant association was found between factor V Leiden mutation and CVST with odds ratio (OR) of 9.8 (95% confidence intervals [CI] 1.68-57.2, P = .01). No prothrombin G20210A was found among patients. In patients, MTHFR C677T tended to be higher (58.3%) compared to control (44%), OR of 1.8 (95% CI 0.73-4.5, P = .2). Our study for the first time has determined the prevalence of inherited thrombophilia in a homogenous ethnic group of CVST patients and suggests that factor V Leiden, and not the prothrombin gene mutation is a risk factor for CVST in Western Iran.
Considering Changes in Exposure and Sensitivity in an Early Life Cumulative Risk Assessment
Authors: Howd Robert A.
Published: August 2009

A cumulative risk assessment is generally intended to address concurrent exposure by all exposure routes to a group of chemicals that share a common mechanism of toxicity. However, the contribution of different exposure routes will change over time. This is most critical when estimating risks to infants and children because their exposure sources change rapidly during the first few years of life because of dietary and behavioral changes. In addition, there may be changes in sensitivity to toxicants during this time period, associated with various developmental stages. Traditional risk assessments do not address this progression. Examples of how these factors might be incorporated into an early life risk assessment are provided for lead, dioxins and furans, and organophosphate pesticides. The same concepts may apply to other potentially susceptible subpopulations, such as the elderly.
Reconciling an Ethic of Care with Critical Management Pedagogy
Authors: Gabriel Yiannis
Published: August 2009

The ethic of criticism has stood at the heart of western pedagogy for centuries. It has been the basis of science, morality and art as well as for the building of social and political institutions. The author argues that this ethic of criticism is sometimes at odds with the ethic of care, one that commits the carer to look after and take responsibility for the well-being of the cared-for. This ethic of care is further undermined by contemporary consumerism and its inroads into the fields of education and learning. The resulting perception of management as a field of study for young people is entirely instrumental— an effective stepping stone to launch a career, but one devoid of either intrinsic interest or social value. The author makes a plea for an enduring reconciliation of an ethic of care with an ethic of criticism as the basis for management education that is both interesting and socially useful.
Wild Frontiers—Reflections on Experiential Learning
Authors: Reynolds Michael
Published: August 2009

Experiential learning is currently prominent in management—including ‘critical’ management, pedagogy. This article reflects on the contribution of experiential learning to management education and on the resistance it has sometimes evoked, both from academics and managers. On the basis of these observations I suggest that the significance of experiential learning is not only as an alternative way of learning but in the social and political values that it brings to both educational and organizational contexts. In view of recent post-heroic developments in conceptions of leadership, I speculate that there could be currently a better match between experiential learning approaches and organizational practice than had previously been the case.
Accreditation Sickness in the Consumption of Business Education: The Vacuum in AACSB Standard Setting
Authors: Lowrie Anthony , Willmott Hugh
Published: August 2009

This article examines peer-administered accreditation in business education, taking AACSB (Association to Advance Collegiate Schools of Business) as its focus. Attention is directed to the educationally unhealthy consequences of an established regional mode of accreditation becoming an international benchmark for business education consumption. At the heart of the AACSB’s mission-linked approach is an evacuation of core content from business education. The change to a mission-linked architecture was motivated, it is argued, primarily by expansionist, rather than pedagogical, considerations. It coincided with a reduction in the number of US research-based schools unaccredited, the inability of many US-business schools to meet AACSB’s previous standards, the emergence of a rival accreditation agency (Association of Collegiate Business Schools and Programs) formed to target this market, and international competition from other accreditation bodies. We note that the mission-linked approach, underpinned by peer-review, has been good for AACSB growth but has, we suggest, been restrictive and unhealthy for business education that does not fit its ostensibly flexible and accommodating mould.
Acute effects of Yakson and Gentle Human Touch on the behavioral state of preterm infants
Authors: Im Hyesang , Kim Eunjung , Cain Kevin C.
Published: August 2009

Two weeks of touch intervention, either Yakson or Gentle Human Touch (GHT) have been shown to reduce the levels of stress hormones. This study evaluated the acute impact of both interventions on state during and immediately after touch. Forty preterm infants with a gestational age of ≤34 weeks received either Yakson or GHT for 15 days. A significantly greater sleeping state was identified in both groups after touch. This effect was significantly stronger with Yakson than GHT. During touch, about half the Yakson infants showed an arousal effect while the GHT infants showed little change. Both interventions left the babies calmer after touch. This calming effect is consistent with the previously observed effect on stress hormones and should be beneficial in terms of growth and development. Yakson had an arousing effect on a subset of the infants during touch, which possibly could be beneficial in terms of social development.
Paper-based versus computer-based records in the emergency department: Staff preferences, expectations, and concerns
Authors: Ayatollahi Haleh , Bath Peter A. , Goodacre Steve
Published: August 2009

Although the potential benefits of computer-based records have been identified in different areas of the healthcare environment, in many settings paper-based records and computer-based records are still used in parallel. In this article, emergency department (ED) staff perspectives about the use of paper- or computer-based records are presented. This was a qualitative study in which data were collected using in-depth semi-structured interviews with the ED staff. The interviews were transcribed verbatim and data were analysed using framework analysis. In total, 34 interviews were undertaken. The study identified a number of factors which might encourage or discourage the use of paper-based and computer-based records in the ED. Users also expressed their concerns and expectations. Although there is a tendency towards computerizing healthcare settings, user acceptance of technology should not be underestimated. To improve user acceptance, users’ concerns should be investigated and addressed appropriately.
Patterns of Abuse Disclosure among Youth
Authors: Ungar Michael , Barter Ken , McConnell Sheri M. , Tutty Leslie M. , Fairholm Judi
Published: August 2009

Evaluation forms completed by youth following participation in abuse prevention programming by the Canadian Red Cross (RespectED) offer a unique opportunity to explore disclosure strategies among a diverse national sample of 1621 young people. The sample comprised all youth in 5 regions who made anonymous written disclosures of abuse on evaluation forms administered after workshops delivered between 2000 and 2003. Focus groups, interviews and observational data were used to ensure the trustworthiness of the data analysis. Findings show that youth who have been abused or witnesses to abuse employ five disclosure strategies: using self-harming behaviours to signal the abuse to others; not talking at all about the abuse to prevent intrusive interventions by others; seeking help from peers; seeking help from informal adult supports; and seeking help from mandated service providers (social workers and police). Findings highlight young people’s use of indirect and direct means of disclosure to ensure their safety.
Committee Parallelism and Bicameral Agenda Coordination
Authors: Larocca Roger
Published: August 2009

We examine why a significant proportion of the policy issues passed in either the U.S. House or Senate often fail to pass in the other chamber. We hypothesize that much of this failure of the House and Senate to coordinate their agendas occurs because committee jurisdictions are not parallel across chambers. To compare House and Senate agendas, we develop a comprehensive issue-level data set covering all bills introduced in the 103rd Congress. We estimate a multinomial logit model that reveals that the degree of jurisdictional parallelism across chambers is indeed one of the most important determinants of whether issues that pass in one chamber also pass in the other chamber.
Efficacy of Functional Strength Training on Restoration of Lower-Limb Motor Function Early After Stroke: Phase I Randomized Controlled Trial
Authors: Cooke Emma V. , Tallis Raymond C. , Clark Allan , Pomeroy Valerie M.
Published: August 2009

After stroke, physiotherapy can promote brain reorganization and motor recovery. Combining muscle strength and functional training (functional strength training, FST) may be beneficial. The aim of the authors was to compare FST with conventional physiotherapy (CPT) while controlling for the potential confounder of therapy intensity in a multicenter, randomized controlled observer-blind trial. The mean age of the participants was 68.3 (standard deviation [SD] = 12.03) years at a mean of 34 (SD = 20) days after stroke, with mean peak paretic knee extension torque (torque) of 22 (SD = 25) Nm. The estimated sample size was 102 to detect a between-group difference of 0.2 m/s in walking speed. After baseline measures, participants were allocated randomly to CPT or CPT + CPT or CPT + FST for 6 weeks. Additional experimental therapy was provided for up to 1 hour a day, 4 times each week. Outcomes were measured 6 weeks after baseline and at follow-up 12 weeks thereafter. Measures included walking speed, knee extensor torque, and functional mobility (Rivermead). At outcome, both extraintensity groups showed greater increases in walking speed than the CPT group, but this reached significance only for the CPT + CPT group ( P = .031). The CPT + CPT group also had a greater number of participants who walked at 0.8 m/s or above. No significant differences were observed for torque about the knee or for the Rivermead score. At follow-up, no significant differences were observed. These phase I results justify a subsequent trial of CPT + CPT versus CPT + FST.
TiO2 films prepared by ultrasonic spray pyrolysis
Authors: Nakaruk A. , Reece P. J. , Ragazzon D. , Sorrell C. C.
Published: August 2009

Fully dense anatase and rutile (TiO2) films were coated on (0001) α-quartz wafers using ultrasonic spray pyrolysis in air at 400°C for 2 h. The TiO2 films were annealed subsequently in air for 4 h at 600, 800 and 1000°C respectively. The films were characterised using X-ray diffraction (mineralogy), ultraviolet visible spectrophotometry (optical properties) and photoluminescence (structural defects). These data are interpreted in terms of phase transformation temperature, optical mean free path, refractive index and effect of heat treatment on the concentration of oxygen vacancies and/or silicon contamination.
Different NK cell–activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity
Authors: Wood Stephanie M. , Meeths Marie , Chiang Samuel C. C. , Bechensteen Anne Grete , Boelens Jaap J. , Heilmann Carsten , Horiuchi Hisanori , Rosthøj Steen , Rutynowska Olga , Winiarski Jacek , Stow Jennifer L. , Nordenskjöld Magnus , Henter Jan-Inge , Ljunggren Hans-Gustaf , Bryceson Yenan T.
Published: August 2009

The autosomal recessive immunodeficiencies Griscelli syndrome type 2 (GS2) and familial hemophagocytic lymphohistiocytosis type 3 (FHL3) are associated with loss-of-function mutations in RAB27A (encoding Rab27a) and UNC13D (encoding Munc13-4). Munc13-4 deficiency abrogates NK-cell release of perforin-containing lytic granules induced by signals for natural and antibody-dependent cellular cytotoxicity. We demonstrate here that these signals fail to induce degranulation in resting NK cells from Rab27a-deficient patients. In resting NK cells from healthy subjects, endogenous Rab27a and Munc13-4 do not colocalize extensively with perforin. However, phorbol 12-myristate 13-acetate and ionomycin stimulation or conjugation to susceptible target cells induced myosin-dependent colocalization of Rab27a and Munc13-4 with perforin. Unexpectedly, individual engagement of receptors leukocyte functional antigen-1, NKG2D, or 2B4 induced colocalization of Rab27a, but not Munc13-4, with perforin. Conversely, engagement of antibody-dependent cellular cytotoxicity receptor CD16 induced colocalization of Munc13-4, but not Rab27a, with perforin. Furthermore, colocalization of Munc13-4 with perforin was Rab27a-dependent. In conclusion, Rab27a or Munc13-4 recruitment to lytic granules is preferentially regulated by different receptor signals, demonstrating that individual target cell ligands regulate discrete molecular events for lytic granule maturation. The data suggest Rab27a facilitates degranulation at an early step yet highlight a reciprocal relationship between Munc13-4 and Rab27a for degranulation.
The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer–cell subsets associated with high levels of HIV-1 viremia
Authors: Brunetta Enrico , Fogli Manuela , Varchetta Stefania , Bozzo Luisa , Hudspeth Kelly L. , Marcenaro Emanuela , Moretta Alessandro , Mavilio Domenico
Published: August 2009

HIV-1 has developed several strategies to evade natural killer (NK)–cell antiviral functions. One of these mechanisms is the HIV-1–induced expansion of highly dysfunctional NK-cell subsets. Here, we analyze a large cohort of HIV-1–infected patients in early or chronic phases of infection, both cross-sectionally and longitudinally. We demonstrate that a striking decrease in the surface expression of sialic acid–binding immunoglobulin-like lectin 7 (Siglec-7) represents the earliest marker of the aberrant NK-cell dysregulation, which precedes the down-modulation of CD56 mostly occurring in patients with chronic HIV-1 viremia. The combined detection of Siglec-7 and CD56 allows the identification of 2 new pathologic NK-cell subsets expanded preferentially in early (Siglec-7−/CD56+) or chronic (Siglec-7−/CD56−) stages of HIV-1 infection. Remarkably, these phenotypic abnormalities were directly associated with progressive and distinct impairments of NK-cell functions. The aforementioned NK-cell aberrancies could be observed only in the presence of high levels of viral replication and not in patients with low or undetectable HIV-1 viremia, such as long-term nonprogressors or patients having undergone antiretroviral therapy. High frequencies of Siglec-7−/CD56+ and Siglec-7−/CD56− pathologic NK cells reflect the immune and clinical status of HIV-1 infection and can also track the effectiveness of therapy.
Impairment of insulin-stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic Rats
Authors: Huang Jiung-Pang , Huang Shiang-Suo , Deng Jen-Ying , Hung Li-Man
Published: August 2009

In this study, we established systemic in-vivo evidence from molecular to organism level to explain how diabetes can aggravate myocardial ischemia-reperfusion (I/R) injury and revealed the role of insulin signaling (with specific focus on Akt/GLUT4 signaling molecules). The myocardial I/R injury was induced by the left main coronary artery occlusion for 1 hr and then 3 hr reperfusion in control, streptozotocin (STZ)-induced insulinopenic diabetes, and insulin-treated diabetic rats. The diabetic rats showed a significant decrease in heart rate, and a prolonged isovolumic relaxation (tau) which lead to decrease in cardiac output (CO) without changing total peripheral resistance (TPR). The phosphorylated Akt and glucose transporter 4 (GLUT 4) protein levels were dramatically reduced in both I/R and non-I/R diabetic rat hearts. Insulin treatment in diabetes showed improvement of contractile function as well as partially increased Akt phosphorylation and GLUT 4 protein levels. In the animals subjected to I/R, the mortality rates were 25%, 65%, and 33% in the control, diabetic, and insulin-treated diabetic group respectively. The I/R-induced arrhythmias and myocardial infarction did not differ significantly between the control and the diabetic groups. Consistent with its anti-hyperglycemic effects, insulin significantly reduced I/R-induced arrhythmias but had no effect on I/R-induced infarctions. Diabetic rat with I/R exhibited the worse hemodynamic outcome, which included systolic and diastolic dysfunctions. Insulin treatment only partially improved diastolic functions and elevated P-Akt and GLUT 4 protein levels. Our results indicate that cardiac contractile dysfunction caused by a defect in insulin-stimulated Akt/GLUT4 may be a major reason for the high mortality rate in I/R injured diabetic rats.
Extending the models for iron and sulfur oxidation in the extreme Acidophile Acidithiobacillus ferrooxidans
Authors: Quatrini Raquel , Appia-Ayme Corinne , Denis Yann , Jedlicki Eugenia , Holmes David S , Bonnefoy Violaine
Published: August 2009

Background

Acidithiobacillus ferrooxidans gains energy from the oxidation of ferrous iron and various reduced inorganic sulfur compounds at very acidic pH. Although an initial model for the electron pathways involved in iron oxidation has been developed, much less is known about the sulfur oxidation in this microorganism. In addition, what has been reported for both iron and sulfur oxidation has been derived from different A. ferrooxidans strains, some of which have not been phylogenetically characterized and some have been shown to be mixed cultures. It is necessary to provide models of iron and sulfur oxidation pathways within one strain of A. ferrooxidans in order to comprehend the full metabolic potential of the pangenome of the genus.

Results

Bioinformatic-based metabolic reconstruction supported by microarray transcript profiling and quantitative RT-PCR analysis predicts the involvement of a number of novel genes involved in iron and sulfur oxidation in A. ferrooxidans ATCC23270. These include for iron oxidation: cup (copper oxidase-like), ctaABT (heme biogenesis and insertion), nuoI and nuoK (NADH complex subunits), sdrA1 (a NADH complex accessory protein) and atpB and atpE (ATP synthetase F0 subunits). The following new genes are predicted to be involved in reduced inorganic sulfur compounds oxidation: a gene cluster (rhd, tusA, dsrE, hdrC, hdrB, hdrA, orf2, hdrC, hdrB) encoding three sulfurtransferases and a heterodisulfide reductase complex, sat potentially encoding an ATP sulfurylase and sdrA2 (an accessory NADH complex subunit). Two different regulatory components are predicted to be involved in the regulation of alternate electron transfer pathways: 1) a gene cluster (ctaRUS) that contains a predicted iron responsive regulator of the Rrf2 family that is hypothesized to regulate cytochrome aa
3 oxidase biogenesis and 2) a two component sensor-regulator of the RegB-RegA family that may respond to the redox state of the quinone pool.

Conclusion

Bioinformatic analysis coupled with gene transcript profiling extends our understanding of the iron and reduced inorganic sulfur compounds oxidation pathways in A. ferrooxidans and suggests mechanisms for their regulation. The models provide unified and coherent descriptions of these processes within the type strain, eliminating previous ambiguity caused by models built from analyses of multiple and divergent strains of this microorganism.
Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population
Authors: Uchida Tomohisa , Nguyen Lam Tung , Takayama Akiko , Okimoto Tadayoshi , Kodama Masaaki , Murakami Kazunari , Matsuhisa Takeshi , Trinh Tuan Dung , Ta Long , Ho Dang Quy Dung , Hoang Hoa Hai , Kishida Tetsuko , Fujioka Toshio , Moriyama Masatsugu , Yamaoka Yoshio
Published: August 2009

Background

The incidence of gastric cancer differs among countries in Asia, and it has been suggested that virulence factors associated with Helicobacter pylori are partly responsible. The aim of this study was to investigate several genetic factors regarded as virulence or molecular epidemiologic markers in H. pylori isolates from Vietnamese subjects.

Results

The cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh.

Conclusion

Pre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.
Direct and negative regulation of the sycO-ypkA-ypoJ operon by cyclic AMP receptor protein (CRP) in Yersinia pestis
Authors: Zhan Lingjun , Yang Lei , Zhou Lei , Li Yingli , Gao He , Guo Zhaobiao , Zhang Lianfeng , Qin Chuan , Zhou Dongsheng , Yang Ruifu
Published: August 2009

Background

Pathogenic yersiniae, including Y. pestis, share a type III secretion system (T3SS) that is composed of a secretion machinery, a set of translocation proteins, a control system, and six Yop effector proteins including YpkA and YopJ. The cyclic AMP receptor protein (CRP), a global regulator, was recently found to regulate the laterally acquired genes (pla and pst) in Y. pestis. The regulation of T3SS components by CRP is unknown.

Results

The sycO, ypkA and yopJ genes constitute a single operon in Y. pestis. CRP specifically binds to the promoter-proximate region of sycO, and represses the expression of the sycO-ypkA-yopJ operon. A single CRP-dependent promoter is employed for the sycO-ypkA-yopJ operon, but two CRP binding sites (site 1 and site 2) are detected within the promoter region. A CRP box homologue is found in site 1 other than site 2. The determination of CRP-binding sites, transcription start site and core promoter element (-10 and -35 regions) promotes us to depict the structural organization of CRP-dependent promoter, giving a map of CRP-promoter DNA interaction for sycO-ypkA-yopJ.

Conclusion

The sycO-ypkA-yopJ operon is under the direct and negative regulation of CRP in Y. pestis. The sycO-ypkA-yopJ promoter-proximate regions are extremely conserved in Y. pestis, Y. pseudotuberculosis and Y. enterocolitica. Therefore, data presented here can be generally applied to the above three pathogenic yersiniae.
Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage
Authors: Jeon Hyojin , Ai Jinglu , Sabri Mohamed , Tariq Asma , Shang Xueyuan , Chen Gang , Macdonald R Loch
Published: August 2009

About 50% of humans with aneurysmal subarachnoid hemorrhage (SAH) die and many survivors have neurological and neurobehavioral dysfunction. Animal studies usually focused on cerebral vasospasm and sometimes neuronal injury. The difference in endpoints may contribute to lack of translation of treatments effective in animals to humans. We reviewed prior animal studies of SAH to determine what neurological and neurobehavioral endpoints had been used, whether they differentiated between appropriate controls and animals with SAH, whether treatment effects were reported and whether they correlated with vasospasm. Only a few studies in rats examined learning and memory. It is concluded that more studies are needed to fully characterize neurobehavioral performance in animals with SAH and assess effects of treatment.
Limitations in a frataxin knockdown cell model for Friedreich ataxia in a high-throughput drug screen
Authors: Calmels Nadège , Seznec Hervé , Villa Pascal , Reutenauer Laurence , Hibert Marcel , Haiech Jacques , Rustin Pierre , Koenig Michel , Puccio Hélène
Published: August 2009

Background

Pharmacological high-throughput screening (HTS) represents a powerful strategy for drug discovery in genetic diseases, particularly when the full spectrum of pathological dysfunctions remains unclear, such as in Friedreich ataxia (FRDA). FRDA, the most common recessive ataxia, results from a generalized deficiency of mitochondrial and cytosolic iron-sulfur cluster (ISC) proteins activity, due to a partial loss of frataxin function, a mitochondrial protein proposed to function as an iron-chaperone for ISC biosynthesis. In the absence of measurable catalytic function for frataxin, a cell-based assay is required for HTS assay.

Methods

Using a targeted ribozyme strategy in murine fibroblasts, we have developed a cellular model with strongly reduced levels of frataxin. We have used this model to screen the Prestwick Chemical Library, a collection of one thousand off-patent drugs, for potential molecules for FRDA.

Results

The frataxin deficient cell lines exhibit a proliferation defect, associated with an ISC enzyme deficit. Using the growth defect as end-point criteria, we screened the Prestwick Chemical Library. However no molecule presented a significant and reproducible effect on the proliferation rate of frataxin deficient cells. Moreover over numerous passages, the antisense ribozyme fibroblast cell lines revealed an increase in frataxin residual level associated with the normalization of ISC enzyme activities. However, the ribozyme cell lines and FRDA patient cells presented an increase in Mthfd2 transcript, a mitochondrial enzyme that was previously shown to be upregulated at very early stages of the pathogenesis in the cardiac mouse model.

Conclusion

Although no active hit has been identified, the present study demonstrates the feasibility of using a cell-based approach to HTS for FRDA. Furthermore, it highlights the difficulty in the development of a stable frataxin-deficient cell model, an essential condition for productive HTS in the future.
In-vivo imaging of retinal nerve fiber layer vasculature: imaging - histology comparison
Authors: Scoles Drew , Gray Daniel C , Hunter Jennifer J , Wolfe Robert , Gee Bernard P , Geng Ying , Masella Benjamin D , Libby Richard T , Russell Stephen , Williams David R , Merigan William H
Published: August 2009

Background

Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO) scanning laser ophthalmoscopy (SLO), that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed.

Methods

We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue.

Results

Superficial focus (innermost retina) at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs). However, at a deeper focus beneath the NFL, (toward outer retina) the polygonal pattern typical of the ganglion cell layer (inner) and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections.

Conclusion

This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal vascular disorders and other eye diseases, such as glaucoma.
Modulation of expression and cellular distribution of p21 by macrophage migration inhibitory factor
Authors: Taranto Elliott , Xue Jin R , Morand Eric F , Leech Michelle
Published: August 2009

Background

The pleiotropic protein MIF, (macrophage migration inhibitory factor), has been demonstrated to modulate several key proteins governing cell cycle control and is considered to contribute to cell growth and differentiation. In this study we investigated the effect of MIF on the expression and cellular distribution of the CDK inhibitor p21.

Methods

The effect of endogenous MIF on p21 expression and distribution was examined by comparing murine dermal fibroblasts derived fromwtand MIF -/- mice. The effect of MIF on cell growth and apoptotic rates was compared using3H-Thymidine incorporation assays and annexin V/PI assays respectively. Total p21 protein levels were compared using flow cytometry and western blotting. p21 mRNA was assessed by RT-PCR. Intracellular p21 staining was performed to assess cellular distribution of total protein. To further confirm observations siRNA was used to knockdown MIF protein inwtcells. Cell cycle analysis was performed using PI incorporation assays.

Results

MIF-/- murine dermal fibroblasts exhibited reduced proliferative responses and were more susceptible to apoptosis. This was associated with reduced p21 expression and nuclear distribution. Treatment with recombinant MIF protein was demonstrated to reduce both basal and induced apoptosis and increase nuclear p21 expression. Reduced nuclear p21 expression was also observed in MIF siRNA treatedwtcells.

Conclusion

The results demonstrate that in the absence of MIF p21 expression and nuclear distribution is reduced which is associated with a reduction in cell growth and increased apoptosis. MIF may therefore play a role in maintaining homeostatic control of p21.
Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes
Authors: Merkley Mark A , Hildebrandt Ellen , Podolsky Robert H , Arnouk Hilal , Ferris Daron G , Dynan William S , Stöppler Hubert
Published: August 2009

Background

Infection with high-risk type human papilloma viruses (HPVs) is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features.

Results

Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE). The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23%) of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2%) were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1); and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27).

Conclusion

This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.
HIV and hepatitis C virus infections among hanka injection drug users in central Ukraine: a cross-sectional survey
Authors: Dumchev Kostyantyn V , Soldyshev Ruslan , Qian Han-Zhu , Zezyulin Olexandr O , Chandler Susan D , Slobodyanyuk Pavel , Moroz Larisa , Schumacher Joseph E
Published: August 2009

Background

Ukraine has experienced an increase in injection drug use since the 1990s. An increase in HIV and hepatitis C virus infections has followed, but not measures of prevalence and risk factors. The purposes of this study are to estimate the prevalence of HIV, HCV, and co-infection among injection drug users (IDUs) in central Ukraine and to describe risk factors for HIV and HCV.

Methods

A sample of 315 IDUs was recruited using snowball sampling for a structured risk interview and HIV/HCV testing (81.9% male, 42% single, average age 28.9 years [range = 18 to 55]).

Results

HIV and HCV antibodies were detected in 14.0% and 73.0%, respectively, and 12.1% were seropositive for both infections. The most commonly used drug was hanka, home-made from poppy straw and often mixed with other substances including dimedrol, diazepines, and hypnotics. The average period of injecting was 8.5 years; 62.5% reported past-year sharing needles or injection equipment, and 8.0% shared with a known HIV-positive person. More than half (51.1%) reported multiple sexual partners, 12.9% buying or selling sex, and 10.5% exchanging sex and drugs in the past year. Those who shared with HIV positive partners were 3.4 times more likely to be HIV positive than those who did not. Those who front- or back-loaded were 4 times more likely to be HCV positive than those who did not.

Conclusion

Harm reduction, addiction treatment and HIV prevention programs should address risk factors to stop further spread of both HIV and HCV among IDUs and to the general population in central Ukraine.
Matrix metalloproteinase-2 is elevated in midtrimester amniotic fluid prior to the development of preeclampsia
Authors: Lavee Michal , Goldman Shlomit , Daniel-Spiegel Etty , Shalev Eliezer
Published: August 2009

Objective

To evaluate levels of matrix metalloproteinases (MMP) and their inhibitors (TIMP) in second trimester amniotic fluid of women with hypertensive disorders compared to normotensive women.

Study Design

Amniotic fluid was obtained from 133 women undergoing genetic second trimester amniocentesis. Zymography was performed for MMP characterization and an MMP-2 ELISA kit was used to determine MMP-2 levels. TIMP-2 expression was evaluated using western blot.

Results

Mean amniotic fluid MMP-2 and TIMP-2 levels were significantly higher in women who developed a hypertensive disorder compared to normotensive women (P < 0.0004 and P < 0.01, respectively). When subdivided into subgroups, amniotic fluid from women who eventually developed preeclampsia or superimposed preeclampsia showed significantly higher MMP-2 levels than normotensive women (P < 0.05). However, no statistical difference in MMP-2 levels was found between patients with gestational hypertension and normotensive patients.

Conclusion

Higher amniotic fluid MMP-2 and TIMP-2 levels are found in women who eventually develop preeclampsia.
Training needs assessment for clinicians at antiretroviral therapy clinics: evidence from a national survey in Uganda
Authors: Lutalo Ibrahim M , Schneider Gisela , Weaver Marcia R , Oyugi Jessica H , Sebuyira Lydia Mpanga , Kaye Richard , Lule Frank , Namagala Elizabeth , Scheld W Michael , McAdam Keith PWJ , Sande Merle A
Published: August 2009

Background

To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted.

Methods

The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics.

Results

Thirty of 33 doctors (91%), 24 of 40 clinical officers (60%), 16 of 114 nurses (14%) and 13 of 54 midwives (24%) who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p < 0.001). Sixty-four percent of the people who prescribed antiretroviral therapy were not doctors. Among professionals who prescribed it, 76% of doctors, 62% of clinical officers, 62% of nurses and 51% of midwives were trained in initiating patients on antiretroviral therapy (p = 0.457); 73%, 46%, 50% and 23%, respectively, were trained in monitoring patients on the therapy (p = 0.017). Seven percent of doctors, 42% of clinical officers, 35% of nurses and 77% of midwives assessed that their overall knowledge of antiretroviral therapy was lower than good (p = 0.001).

Conclusion

Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date.