bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of radiosensitizing effects of the mammalian target of rapamycin inhibitor CCI-779 to cisplatin in experimental models of head and neck squamous cell carcinoma
Authors: Ekshyyan Oleksandr , Rong Youhua , Rong Xiaohua , Pattani Kavita M. , Abreo Fleurette , Caldito Gloria , Chang John Kai Siung , Ampil Federico , Glass Jonathan , Nathan Cherie-Ann O. 
Published: July 2009

Abstract
To determine if the mammalian target of rapamycin (mTOR) inhibitor CCI-779 can sensitize head and neck squamous cell carcinoma (HNSCC) to radiotherapy (XRT) and compare the radiosensitizing effects to cisplatin with its known considerable toxicity. Radiosensitizing effects of CCI-779 were assayed on HNSCC cell lines in vitro. CCI-779 (5 mg/kg), cisplatin (1 mg/kg), and XRT (2 Gy) alone and in combination were evaluated for antitumor activity in mice bearing FaDu and SCC40 xenografts. Effects of CCI-779 on radiation-induced activation of the Akt/mTOR pathway were analyzed. Although CCI-779 did not sensitize HNSCC cells to ionizing radiation in vitro, combination of CCI-779 and XRT significantly augmented the in vivo tumor growth-inhibitory effects of XRT and CCI-779 (P &lt; 0.05). In addition, CCI-779 + XRT suppressed tumor growth more effectively than cisplatin + XRT (P &lt; 0.05). CCI-779 + XRT significantly improved survival compared with XRT alone in both cisplatin-sensitive FaDu (P &lt; 0.01) and cisplatin-resistant SCC40 (P &lt; 0.05) xenograft mice. There were no additional benefits of adding cisplatin to CCI-779 + XRT. CCI-779 significantly attenuated irradiation-induced up-regulation of the mTOR pathway, increased apoptosis and displayed potent antiangiogenic activity in FaDu xenografts that was further enhanced by its combination with XRT (P &lt; 0.05), which may explain the mechanism of its selective radiosensitizing effects in vivo and not in vitro. Antitumor activity of XRT was enhanced when combined with CCI-779 in HNSCC xenograft model. CCI-779 + XRT showed antitumor activity superior to conventional chemoradiotherapy with cisplatin. These results pave the way for clinical trials using molecular targeted therapy with CCI-779 in combination with XRT for HNSCC treatment. [Mol Cancer Ther 2009;8(8):2255–65]
Foreign accent syndrome as a first sign of multiple sclerosis
Authors: Chanson JB , Kremer S , Blanc F , Marescaux C , Namer IJ , de Seze J 
Published: July 2009

BackgroundForeign accent syndrome (FAS) consists of a speech rhythm disorder different from dysarthia or aphasia. It is unusually met in multiple sclerosis (MS).ObjectiveWe report a case of FAS as an initial symptom of a MS.MethodsA right-handed French woman developed an isolated German foreign accent. Brain magnetic resonance imaging (MRI), SPECT and analysis of CSF were performed.ResultsBrain MRI revealed a large hypersignal on T2-weighted images in the left prerolandic white matter. Single photon emission computed tomography showed a right prerolandic hypoperfusion. Unmatched oligoclonal bands in cerebrospinal fluid and occurrence of new abnormal hypersignals on the following MRI led us to diagnose MS.ConclusionFAS may be the first symptom of MS. It could result from extensive disturbances of brain function involving the right hemisphere.
Extensive vasogenic edema of anti-aquaporin-4 antibody-related brain lesions
Authors: Matsushita T , Isobe N , Matsuoka T , Ishizu T , Kawano Y , Yoshiura T , Ohyagi Y , Kira J 
Published: July 2009

Objective Using neuroimaging, we analyzed the nature of extensive brain lesions in five anti-aquaporin-4 (AQP4) antibody-positive patients with neuromyelitis optica spectrum disorders. Results Extensive brain lesions involved white matter in three, and basal ganglia and corpus callosum in one each. Four patients showed high diffusivity on apparent diffusion coefficient maps and three demonstrated increased choline/creatine ratios and decreased N-acetyl-aspartate/creatine ratios on 1H-magnetic resonance spectroscopy. These findings suggested that the lesions were vasogenic edema associated with inflammation. Unusual brain symptoms associated with such lesions included recurrent limbic encephalitis, parkinsonism, and coma. Conclusion Anti-AQP4 antibody is considered to be associated with the neuroimaging appearances of vasogenic edema.
Multiple sclerosis risk: interaction between human leukocyte antigen and the environment in Sardinian population
Authors: Cocco E , Sardu C , Murru R , Frau J , Lorefice L , Mamusa E , Contu P , Marrosu MG 
Published: July 2009

Background The island of Sardinia features a high incidence of multiple sclerosis (MS) characterized by early age at onset and a progressively increasing trend. The current study was aimed at examining variations in human leukocyte antigen–risk genotypes occurring over time in a cohort of patients. Methods Susceptible and neutral DRB1-DQB1 genotypes were identified in 1660 patients. Age at onset was established in 1436 patients divided into two cohorts, an older cohort (subjects born before 1949, N = 233) and a younger one (subjects born from 1960 to 1989, N = 850). Patients from the older cohort were randomly assigned to patients of the same sex from the younger cohort, matched for age at onset. The final sample included 170 pairs. Logistic conditional analysis was performed to determine the probability of a neutral genotype in both cohorts. Kaplan–Meier analysis was applied to ascertain the influence of predisposing and neutral genotypes in age at onset for both cohorts. Findings The probability of carrying a neutral genotype was 1.76-fold higher in the younger than in the older cohort ( P = 0.02) and 3.67-fold higher in men ( P = 0.005). Kaplan–Meier analysis revealed an earlier age at onset in patients of the young cohort carrying the predisposing genotype ( P = 0.004). Interpretation In the Sardinian population, an environment more prone and propitious to autoimmunity may contribute toward the rising incidence of MS or anticipate overt manifestation of the disease in genetically predisposed subjects.
Heel Pain in the Athlete
Authors: Hunt Kenneth John , Anderson Robert B. 
Published: July 2009

Context: Heel pain, a relatively common problem in the athlete, can present a diagnostic and therapeutic dilemma. The purpose of this article is to review treatment techniques for common causes of heel pain in the athlete. Evidence Acquisition: Articles in the English literature through August 2008 were selected and reviewed in the context of the management of heel pain in the athlete. Clinical and surgical photographs are presented as an illustration of preferred techniques and pertinent pathologic findings. Results: Although nonoperative treatment remains the mainstay for most painful heel pathologies, a number of surgical interventions have shown encouraging results in carefully selected patients. Conclusions: The management of heel pain in the athlete requires diagnostic skill, appropriate imaging evaluation, and a careful, initially conservative approach to treatment. Surgical treatment can be successful in carefully selected patients.
YA is needed for proper nuclear organization to transition between meiosis and mitosis in Drosophila
Authors: Sackton Katharine L , Lopez Jacqueline M , Berman Cindy L , Wolfner Mariana F 
Published: July 2009

Abstract

Background
The Drosophila YA protein is required to initiate the embryonic cleavage divisions. After egg activation, YA enters nuclei and interacts with chromatin and the nuclear lamina. This study was designed to define more precisely the events prior to the first cleavage division that are dependent upon YA.

Results
We find that meiosis is completed normally in the absence of YA function. The first defects in embryos and eggs from mutant mothers first appear just after the completion of meiosis, and are seen as abnormal associations among the resultant haploid nuclei. These defects are associated with asynchronies in the cell cycle-dependent chromatin condensation state of the haploid nuclei. However, we find evidence of DNA replication in the absence of YA function.

Conclusion
Our data suggest YA function is needed at a control point, following meiosis II and the initiation of the first postmeiotic S phase, which is sensitive to the chromatin condensation state of the haploid meiotic products.
Proteins involved in difference of sorbitol fermentation rates of the toxigenic and nontoxigenic Vibrio choleraeEl Tor strains revealed by comparative proteome analysis
Authors: Wang Ruibai , Zhang Hongzhi , Qiu Haiyan , Gao Shouyi , Kan Biao 
Published: July 2009

Abstract

Background
The nontoxigenic V. cholerae El Tor strains ferment sorbitol faster than the toxigenic strains, hence fast-fermenting and slow-fermenting strains are defined by sorbitol fermentation test. This test has been used for more than 40 years in cholera surveillance and strain analysis in China. Understanding of the mechanisms of sorbitol metabolism of the toxigenic and nontoxigenic strains may help to explore the genome and metabolism divergence in these strains. Here we used comparative proteomic analysis to find the proteins which may be involved in such metabolic difference.

Results
We found the production of formate and lactic acid in the sorbitol fermentation medium of the nontoxigenic strain was earlier than of the toxigenic strain. We compared the protein expression profiles of the toxigenic strain N16961 and nontoxigenic strain JS32 cultured in sorbitol fermentation medium, by using fructose fermentation medium as the control. Seventy-three differential protein spots were found and further identified by MALDI-MS. The difference of product of fructose-specific IIA/FPR component gene and mannitol-1-P dehydrogenase, may be involved in the difference of sorbitol transportation and dehydrogenation in the sorbitol fast- and slow-fermenting strains. The difference of the relative transcription levels of pyruvate formate-lyase to pyruvate dehydrogenase between the toxigenic and nontoxigenic strains may be also responsible for the time and ability difference of formate production between these strains.

Conclusion
Multiple factors involved in different metabolism steps may affect the sorbitol fermentation in the toxigenic and nontoxigenic strains of V. cholerae El Tor.
Metapopulation structure for perpetuation of Francisella tularensis tularensis
Authors: Goethert Heidi K , Saviet Benjamin , Telford Sam R 
Published: July 2009

AbstractBackgroundOutbreaks of Type A tularemia due toFrancisella tularensis tularensisare typically sporadic and unstable, greatly hindering identification of the determinants of perpetuation and human risk. Martha's Vineyard, Massachusetts has experienced an outbreak of Type A tularemia which has persisted for 9 years. This unique situation has allowed us to conduct long-term eco-epidemiologic studies there. Our hypothesis is that the agent of Type A tularemia is perpetuated as a metapopulation, with many small isolated natural foci of transmission. During times of increased transmission, the foci would merge and a larger scale epizootic would occur, with greater likelihood that humans become exposed.MethodsWe sampled questing dog ticks from two natural foci on the island and tested them for tularemia DNA. We determined whether the force of transmission differed between the two foci. In addition, we examined the population structure ofF. tularensisfrom ticks by variable number tandem repeat (VNTR) analysis, which allowed estimates of diversity, linkage disequilibrium, and eBURST analysis.ResultsThe prevalence of tularemia DNA in ticks from our two field sites was markedly different: one site was stable over the course of the study yielding as many as 5.6% positive ticks. In contrast, infected ticks from the comparison site markedly increased in prevalence, from 0.4% in 2003 to 3.9% in 2006. Using 4 VNTR loci, we documented 75 different haplotypes (diversity = 0.91). eBURST analysis indicates that the stable site was essentially clonal, but the comparison site contained multiple unrelated lineages. The general bacterial population is evolving clonally (multilocus disequilibrium) and the bacteria in the two sites are reproductively isolated.ConclusionEven within an isolated island, tularemia natural foci that are no more than 15 km apart are uniquely segregated. One of our sites has stable transmission and the other is emergent. The population structure at the stable site is that of a clonal complex of circulating bacteria, whereas the emerging focus is likely to be derived from multiple founders. We conclude that the agent of tularemia may perpetuate in small stable natural foci and that new foci emerge as a result of spillover from such stable sites.
Burnout and use of HIV services among health care workers in Lusaka District, Zambia: a cross-sectional study
Authors: Kruse Gina R , Chapula Bushimbwa Tambatamba , Ikeda Scott , Nkhoma Mavis , Quiterio Nicole , Pankratz Debra , Mataka Kaluba , Chi Benjamin H , Bond Virginia , Reid Stewart E 
Published: July 2009

Abstract

Background
Well-documented shortages of health care workers in sub-Saharan Africa are exacerbated by the increased human resource demands of rapidly expanding HIV care and treatment programmes. The successful continuation of existing programmes is threatened by health care worker burnout and HIV-related illness.

Methods
From March to June 2007, we studied occupational burnout and utilization of HIV services among health providers in the Lusaka public health sector. Providers from 13 public clinics were given a 36-item, self-administered questionnaire and invited for focus group discussions and key-informant interviews.

Results
Some 483 active clinical staff completed the questionnaire (84% response rate), 50 staff participated in six focus groups, and four individuals gave interviews. Focus group participants described burnout as feeling overworked, stressed and tired. In the survey, 51% reported occupational burnout. Risk factors were having another job (RR 1.4 95% CI 1.2–1.6) and knowing a co-worker who left in the last year (RR 1.6 95% CI 1.3–2.2). Reasons for co-worker attrition included: better pay (40%), feeling overworked or stressed (21%), moving away (16%), death (8%) and illness (5%). When asked about HIV testing, 370 of 456 (81%) reported having tested; 240 (50%) tested in the last year. In contrast, discussion groups perceived low testing rates. Both discussion groups and survey respondents identified confidentiality as the prime reason for not undergoing HIV testing.

Conclusion
In Lusaka primary care clinics, overwork, illness and death were common reasons for attrition. Programmes to improve access, acceptability and confidentiality of health care services for clinical providers and to reduce workplace stress could substantially affect workforce stability.
Molecular epidemiology of sexually transmitted human papillomavirus in a self referred group of women in Ireland
Authors: Menton John F , Cremin Suzanne M , Canier Lydie , Horgan Mary , Fanning Liam J 
Published: July 2009

Abstract

Background
Human papillomavirus (HPV) causes cervical cancer and external genital warts. The purpose of this study is to document the genotype distribution of HPV in females aged between 18 and 34 who self-referred to an STI clinic with visible external genital warts (EGW). Scrapings were taken from visible external genital warts (EGW). These scrapings were analysed by PCR for the presence of HPV DNA. Positive samples were then genotyped by means of a commercially available assay (LiPA). A comparison of genotyping results determined by the LiPA assay and direct amplicon DNA sequencing was also performed.

Results
Ninety-two patients out of 105 samples (88%) had detectable levels of HPV DNA. The majority of individuals with EGW (66%) showed the presence of two or more genotypes. The most common HPV genotypes present in the study population were HPV-6, HPV-11, HPV-16, HPV-18, HPV-33 and HPV-53. Potential effects of vaccination on HPV molecular epidemiology indicate that 40% of the patients could have been protected from the high risk genotypes HPV-16 and HPV-18.

Conclusion
This is the first report of the molecular epidemiology of external genital warts in women aged between 18 and 34 from Ireland based on results from a LiPA assay. The study shows that most individuals are infected with multiple genotypes including those with high oncogenic potential and that the newly available HPV vaccines could have a significant impact on prevalence of the most common HPV genotypes in this study population.
Genetic diversity of the E Protein of Dengue Type 3 Virus
Authors: Amarilla Alberto A , de Almeida Flavia T , Jorge Daniel M , Alfonso Helda L , de Castro-Jorge Luiza A , Nogueira Nadia A , Figueiredo Luiz T , Aquino Victor H 
Published: July 2009

Abstract

Background
Dengue is the most important arbovirus disease in tropical and subtropical countries. The viral envelope (E) protein is responsible for cell receptor binding and is the main target of neutralizing antibodies. The aim of this study was to analyze the diversity of the E protein gene of DENV-3. E protein gene sequences of 20 new viruses isolated in Ribeirao Preto, Brazil, and 427 sequences retrieved from GenBank were aligned for diversity and phylogenetic analysis.

Results
Comparison of the E protein gene sequences revealed the presence of 47 variable sites distributed in the protein; most of those amino acids changes are located on the viral surface. The phylogenetic analysis showed the distribution of DENV-3 in four genotypes. Genotypes I, II and III revealed internal groups that we have called lineages and sub-lineages. All amino acids that characterize a group (genotype, lineage, or sub-lineage) are located in the 47 variable sites of the E protein.

Conclusion
Our results provide information about the most frequent amino acid changes and diversity of the E protein of DENV-3.
Implementation experience during an eighteen month intervention to improve paediatric and newborn care in Kenyan district hospitals
Authors: Nzinga Jacinta , Ntoburi Stephen , Wagai John , Mbindyo Patrick , Mbaabu Lairumbi , Migiro Santau , Wamae Annah , Irimu Grace , English Mike 
Published: July 2009

Abstract

Background
We have conducted an intervention study aiming to improve hospital care for children and newborns in Kenya. In judging whether an intervention achieves its aims, an understanding of how it is delivered is essential. Here, we describe how the implementation team delivered the intervention over 18 months and provide some insight into how health workers, the primary targets of the intervention, received it.

Methods
We used two approaches. First, a description of the intervention is based on an analysis of records of training, supervisory and feedback visits to hospitals, and brief logs of key topics discussed during telephone calls with local hospital facilitators. Record keeping was established at the start of the study for this purpose with analyses conducted at the end of the intervention period. Second, we planned a qualitative study nested within the intervention project and used in-depth interviews and small group discussions to explore health worker and facilitators' perceptions of implementation. After thematic analysis of all interview data, findings were presented, discussed, and revised with the help of hospital facilitators.

Results
Four hospitals received the full intervention including guidelines, training and two to three monthly support supervision and six monthly performance feedback visits. Supervisor visits, as well as providing an opportunity for interaction with administrators, health workers, and facilitators, were often used for impromptu, limited refresher training or orientation of new staff. The personal links that evolved with senior staff seemed to encourage local commitment to the aims of the intervention. Feedback seemed best provided as open meetings and discussions with administrators and staff. Supervision, although sometimes perceived as fault finding, helped local facilitators become the focal point of much activity including key roles in liaison, local monitoring and feedback, problem solving, and orientation of new staff to guidelines. In four control hospitals receiving a minimal intervention, local supervision and leadership to implement new guidelines, despite their official introduction, were largely absent.

Conclusion
The actual content of an intervention and how it is implemented and received may be critical determinants of whether it achieves its aims. We have carefully described our intervention approach to facilitate appraisal of the quantitative results of the intervention's effect on quality of care. Our findings suggest ongoing training, external supportive supervision, open feedback, and local facilitation may be valuable additions to more typical in-service training approaches, and may be feasible.
Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort
Authors: Gottenberg Jacques-Eric , Miceli-Richard Corinne , Ducot Béatrice , Goupille Philippe , Combe Bernard , Mariette Xavier 
Published: July 2009

Abstract
Introduction
Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort.

Methods
In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at 1 year and either met the 1987 American College of Rheumatology criteria for RA (n = 578) or had undifferentiated arthritis (n = 132). Baseline serum samples of patients naïve to corticosteroid and disease-modifying antirheumatic drug treatment were assessed for beta2-microglobulin, IgG, IgA, IgM, immunoglobulin free light chains of immunoglobulins, and B-cell activating factor of the tumor necrosis factor family (BAFF). The BAFF gene 871T>C polymorphism was genotyped in all patients.

Results
All markers of B-cell activation except BAFF and IgM were significantly higher in patients with early RA than those with undifferentiated arthritis. Anti-cyclic citrullinated peptide (anti-CCP) and beta2-microglobulin were associated with a diagnosis of early RA in the multivariate analysis. Markers of B-cell activation, except BAFF, were associated with disease activity, rheumatoid factor and anti-CCP secretion. The BAFF gene polymorphism was not associated with early RA.

Conclusions
Markers of B-cell activation are elevated in patients with early RA, compared with undifferentiated arthritis, independently of any systemic increase in BAFF secretion, and correlate with disease activity. This study sheds new light on the early pathogenic role of B-lymphocytes in RA and suggests that targeting them might be a useful therapeutic strategy in early RA.