bluuebunny/crossref_metadata_2025 huggingface dataset:
Final Report on the Safety Assessment of Azulene
Authors: Andersen F. Alan
Published: September 2009

Azulene is an extract from the volatile oil of several perennial herbs and is detected in tobacco smoke. It functions as a skin conditioning agent in cosmetic formulations, including hair dyes. Azulene is reported to be used in a wide range of cosmetic formulations, but these reported uses are likely to be uses of guaiazulene, a chemically related colorant, because there are currently no suppliers of Azulene to the cosmetics industry. The anti-inflammatory action of Azulene has been demonstrated in several animal studies. Effects at the cellular level are reported to include inhibition of respiration and growth, but no effect on ciliary activity or membrane permeability. Relatively low oral toxicity was seen in acute animal studies. Azulene was not mutagenic in an Ames test, with and without metabolic acfivation. An allergic response to Azulene was noted in one case report. These data were clearly insufficient to support the safety of Azulene in cosmetics. Additional data needed to make a safety assessment include: methods of manufacture and impurities, especially naphthalenes; current concentration of use; skin penetration, if there is significant skin penetration, then both a 28-day dermal toxicity study to assess general skin and systemic toxicity and a reproductive and developmental toxicity study are needed; one genotoxicity study in a mammalian system, if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program methods is needed; skin irritation and sensitization in animals or humans; and ocular toxicity.
Final Report on the Safety Assessment of Isostearamidopropyl Morpholine Lactate
Authors: Andersen F. Alan
Published: September 2009

Isostearamidopropyl Morpholine Lactate is the lactic acid salt of isostearamidopropyl morpholine used as an antistatic agent in 20 cosmetic formulations, mostly hair preparations. The concentration of use in hair preparations is in the 1-5% range- Isostearamidopropyl Morpholine Lactate was nontoxic in acute oral toxicity studies in rats. Although Morpholine is considered a cutaneous, ocular, and mucous membrane irritant, and a sensitizer, Isostearamidopropyl Morpholine Lactate exhibits none of the sensitization and irritant reactions observed with Morpholine. Isostearamidopropyl Morpholine Lactate was minimally irritating to rabbit eyes, and mildly irritating to intact and abraded rabbit skin. Although sensitization was not seen in clinical tests, some irritancy was noted. Isostearamidopropyl Morpholine Lactate was not mutagenic in the Ames test, with or without metabolic activation, although cell killing was seen at most test concentrations. Although Morpholine is readily nitrosated to form carcinogenic nitrosamines, N-nitroso impurities were not detected in Isostearamidopropyl Morpholine Lactate. Mutagenicity data on Isostearamidopropyl Morpholine Lactate in a mammalian system were not available, nor were data available on skin penetration or toxicity associated with inhalation exposures. Accordingly, the safety of this ingredient in leave-on cosmetic formulations could not be determined. Based on the available data, this ingredient was considered safe for use in rinse-off cosmetic products. Additional data needed for assessing the safety of leave-on uses include: (i) skin penetration; if there is significant skin penetration, then both a 28-day dermal toxicity study to assess general skin and systemic toxicity, and a reproductive and developmental toxicity study are needed; (ii) one genotoxicity study in a mammalian system; if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program (NTP) methods may be needed; and (iii) inhalation toxicity data.
Sociocultural dimensions of HIV/AIDS among Middle Eastern immigrants in the US: bridging culture with HIV/AIDS programmes
Authors: Ehsanzadeh-Cheemeh Parvaneh , Sadeque Abul , Grimes Richard M , Essien E James
Published: September 2009

The population of Middle Eastern immigrants in the US has been increasing dramatically over the past 30 years, growing from 200,000 in 1970 to 1.5 million in 2000. These immigrants and their descendants constitute an important new population of interest for public health and other social programmes. With this addition to the cultural diversity of American society, it is important for healthcare programmes to be responsive to the unique cultural needs of those of Middle Eastern origin and to include them in healthcare curricula. This need is particularly imperative for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) intervention programmes, where the reduction of risky behaviours is essential to controlling the epidemic. When Middle Easterners emigrate to the US they must adjust to the American culture, which leads to preservation of some aspects of their culture and adjustment of behaviors to match American customs. This article aims to present sociocultural factors of HIV risk behaviours that are specific to Middle Eastern culture. The article also provides recommendations for HIV/AIDS-culturally appropriate intervention programmes.
An evaluation of performance-arts based HIV-prevention events in London with 13—16 year olds
Authors: Campbell Tomás , Bath Michael , Bradbear Rachel , Cottle Justine , Parrett Neil
Published: September 2009

Aim: The London borough of Newham is ethnically diverse and is one of the poorest regions in the UK. Rates of teenage pregnancy, sexually transmitted infections (STIs) and HIV are high compared to the rest of the country. One strand of the local school-based HIV-prevention programme for young people utilizes performance arts as a tool for HIV education and prevention. This study evaluated HIV knowledge, confidence and intention to use a condom in two groups of 13—16 year olds who had participated in performance-based events.

Method: Group 1 ( n = 14) participated in a six-week programme of performance arts-based HIV education and prevention workshops, which culminated in a theatre-based performance. Group 2 ( n = 65) were audience members who attended the performance. Participants completed a short questionnaire containing both qualitative and quantitative items.

Results: Qualitative data suggested that the participants had learned about condoms and their efficacy in preventing acquisition of HIV and sexually transmitted diseases. Quantitative results indicated that after participation in the events, respondents had more information about HIV and condom use; were more confident that they could insist on condom use with partners; and planned to use condoms in the future. There was a statistically significant difference between Groups 1 and 2 but because of the small numbers in Group 1 this result should be interpreted cautiously.

Conclusions: Performance-based HIV-prevention activities may be a useful way to deliver HIV-prevention messages to young people. This evaluation will form the basis of a more systematic and robust evaluation of future events.
Overhead or opportunity?
Authors: Eagles David
Published: September 2009

David Eagles, a partner with PKF, a firm of accountants and business advisors, discusses the role of audit in the quest for continuous health improvement
Review: Therapeutic opportunities in noncutaneous melanoma
Authors: Wilkins D.K. , Nathan P.D.
Published: September 2009

Recent evidence suggests that the biology of noncutaneous melanoma differs significantly from cutaneous melanoma and may provide therapeutic opportunity. The most frequent sites of origin of noncutaneous melanoma are the eye and mucosal surfaces. Although noncutaneous melanomas are an uncommon group of cancers (representing less than 10% of all melanomas) a greater understanding of their genetic and molecular abnormalites is being translated into novel treatment strategies. These developments are important because there is currently no effective systemic therapy for noncutaneous melanoma. Significant attention has been focused on the role of c-kit (KIT, CD117), a transmembrane receptor with tyrosine kinase activity. In vitro and ex vivo evidence suggests that c-kit is frequently expressed/over expressed/mutated in noncutaneous melanoma. Anti-tumour effects with c-kit inhibitors are seen in pre-clinical models. A variety of multitargeted kinase inhibitors which have activity against c-kit are currently in early phase clinical trials in metastatic ocular, mucosal and acral melanoma. The few case reports of significant clinical activity with targeted therapies provides hope that greater understanding of the biology of noncutaneous melanoma can be translated into effective treatment.
Review: The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer
Authors: Schettino Clorinda , Bareschino Maria Anna , Rossi Antonio , Maione Paolo , Castaldo Vincenzo , Mazzeo Nicole , Sacco Paola Claudia , Ferrara Marianna Luciana , Palazzolo Giovanni , Ciardiello Fortunato , Gridelli Cesare
Published: September 2009

Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection - in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease.
Undifferentiated hematopoietic cells are characterized by a genome-wide undermethylation dip around the transcription start site and a hierarchical epigenetic plasticity
Authors: Chung Yun Shin , Kim Hye Joung , Kim Tae-Min , Hong Sung-Hyun , Kwon Kyung-Rim , An Sungwhan , Park Jung-Hoon , Lee Suman , Oh Il-Hoan
Published: September 2009

Evidence for the epigenetic regulation of hematopoietic stem cells (HSCs) is growing, but the genome-wide epigenetic signature of HSCs and its functional significance remain unclear. In this study, from a genome-wide comparison of CpG methylation in human CD34+ and CD34− cells, we identified a characteristic undermethylation dip around the transcription start site of promoters and an overmethylation of flanking regions in undifferentiated CD34+ cells. This “bivalent-like” CpG methylation pattern around the transcription start site was more prominent in genes not associated with CpG islands (CGI−) than CGI+ genes. Undifferentiated hematopoietic cells also exhibited dynamic chromatin associated with active transcription and a higher turnover of histone acetylation than terminally differentiated cells. Interestingly, inhibition of chromatin condensation by chemical treatment (5-azacytidine, trichostatin A) enhanced the self-renewal of “stimulated” HSCs in reconstituting bone marrows but not “steady-state” HSCs in stationary phase bone marrows. In contrast, similar treatments on more mature cells caused partial phenotypic dedifferentiation and apoptosis at levels correlated with their hematopoietic differentiation. Taken together, our study reveals that the undifferentiated state of hematopoietic cells is characterized by a unique epigenetic signature, which includes dynamic chromatin structures and an epigenetic plasticity that correlates to level of undifferentiation.
Epitopia: a web-server for predicting B-cell epitopes
Authors: Rubinstein Nimrod D , Mayrose Itay , Martz Eric , Pupko Tal
Published: September 2009

Background

Detecting candidate B-cell epitopes in a protein is a basic and fundamental step in many immunological applications. Due to the impracticality of experimental approaches to systematically scan the entire protein, a computational tool that predicts the most probable epitope regions is desirable.

Results

The Epitopia server is a web-based tool that aims to predict immunogenic regions in either a protein three-dimensional structure or a linear sequence. Epitopia implements a machine-learning algorithm that was trained to discern antigenic features within a given protein. The Epitopia algorithm has been compared to other available epitope prediction tools and was found to have higher predictive power. A special emphasis was put on the development of a user-friendly graphical interface for displaying the results.

Conclusion

Epitopia is a user-friendly web-server that predicts immunogenic regions for both a protein structure and a protein sequence. Its accuracy and functionality make it a highly useful tool. Epitopia is available athttp://epitopia.tau.ac.iland includes extensive explanations and example predictions.
Transcriptome analysis of the responses of Staphylococcus aureus to antimicrobial peptides and characterization of the roles of vraDE and vraSR in antimicrobial resistance
Authors: Pietiäinen Milla , François Patrice , Hyyryläinen Hanne-Leena , Tangomo Manuela , Sass Vera , Sahl Hans-Georg , Schrenzel Jacques , Kontinen Vesa P
Published: September 2009

Background

Understanding how pathogens respond to antimicrobial peptides, and how this compares to currently available antibiotics, is crucial for optimizing antimicrobial therapy. Staphylococcus aureus has several known resistance mechanisms against human cationic antimicrobial peptides (CAMPs). Gene expression changes in S. aureus strain Newman exposed to linear CAMPs were analyzed by DNA microarray. Three antimicrobial peptides were used in the analysis, two are derived from frog, temporin L and dermaseptin K4-S4(1-16), and the ovispirin-1 is obtained from sheep.

Results

The peptides induced the VraSR cell-wall regulon and several other genes that are also up-regulated in cells treated with vancomycin and other cell wall-active antibiotics. In addition to this similarity, three genes/operons were particularly strongly induced by the peptides: vraDE, SA0205 and SAS016, encoding an ABC transporter, a putative membrane-bound lysostaphin-like peptidase and a small functionally unknown protein, respectively. Ovispirin-1 and dermaseptin K4-S4(1-16), which disrupt lipid bilayers by the carpet mechanism, appeared to be strong inducers of the vraDE operon. We show that high level induction by ovispirin-1 is dependent on the amide modification of the peptide C-terminus. This suggests that the amide group has a crucial role in the activation of the Aps (GraRS) sensory system, the regulator of vraDE. In contrast, temporin L, which disrupts lipid bilayers by forming pores, revealed a weaker inducer of vraDE despite the C-terminal amide modification. Sensitivity testing with CAMPs and other antimicrobials suggested that VraDE is a transporter dedicated to resist bacitracin. We also showed that SA0205 belongs to the VraSR regulon. Furthermore, VraSR was shown to be important for resistance against a wide range of cell wall-active antibiotics and other antimicrobial agents including the amide-modified ovispirin-1, bacitracin, teicoplanin, cefotaxime and 10 other β-lactam antibiotics, chlorpromazine, thioridazine and EGTA.

Conclusion

Defense against different CAMPs involves not only general signaling pathways but also CAMP-specific ones. These results suggest that CAMPs or a mixture of CAMPs could constitute a potential additive to standard antibiotic treatment.
New insights into molecular pathways associated with flatfish ovarian development and atresia revealed by transcriptional analysis
Authors: Tingaud-Sequeira Angèle , Chauvigné François , Lozano Juanjo , Agulleiro María J , Asensio Esther , Cerdà Joan
Published: September 2009

Background

The Senegalese sole (Solea senegalensis) is a marine flatfish of increasing commercial interest. However, the reproduction of this species in captivity is not yet controlled mainly because of the poor knowledge on its reproductive physiology, as it occurs for other non-salmonid marine teleosts that exhibit group-synchronous ovarian follicle development. In order to investigate intra-ovarian molecular mechanisms in Senegalese sole, the aim of the present study was to identify differentially expressed genes in the ovary during oocyte growth (vitellogenesis), maturation and ovarian follicle atresia using a recently developed oligonucleotide microarray.

Results

Microarray analysis led to the identification of 118 differentially expressed transcripts, of which 20 and 8 were monitored by real-time PCR and in situ hybridization, respectively. During vitellogenesis, many up-regulated ovarian transcripts had putative mitochondrial function/location suggesting high energy production (NADH dehydrogenase subunits, cytochromes) and increased antioxidant protection (selenoprotein W2a), whereas other regulated transcripts were related to cytoskeleton and zona radiata organization (zona glycoprotein 3, alpha and beta actin, keratin 8), intracellular signalling pathways (heat shock protein 90, Ras homolog member G), cell-to-cell and cell-to-matrix interactions (beta 1 integrin, thrombospondin 4b), and the maternal RNA pool (transducer of ERBB2 1a, neurexin 1a). Transcripts up-regulated in the ovary during oocyte maturation included ion transporters (Na+-K+-ATPase subunits), probably required for oocyte hydration, as well as a proteinase inhibitor (alpha-2-macroglobulin) and a vesicle calcium sensor protein (extended synaptotagmin-2-A). During follicular atresia, few transcripts were found to be up-regulated, but remarkably most of them were localized in follicular cells of atretic follicles, and they had inferred roles in lipid transport (apolipoprotein C-I), chemotaxis (leukocyte cell-derived chemotaxin 2,), angiogenesis (thrombospondin), and prevention of apoptosis (S100a10 calcium binding protein).

Conclusion

This study has identified a number of differentially expressed genes in the ovary that were not previously found to be regulated during ovarian development in marine fish. Specifically, we found evidence, for the first time in teleosts, of the activation of chemoattractant, angiogenic and antiapoptotic pathways in hypertrophied follicular cells at the onset of ovarian atresia.
Interaction of ZEB and Histone Deacetylase with the PLDLS-binding cleft region of monomeric C-terminal Binding Protein 2
Authors: Zhao Ling-Jun , Kuppuswamy M , Vijayalingam S , Chinnadurai G
Published: September 2009

Background

Proteins of the C-terminal binding protein (CtBP) family, CtBP1 and CtBP2 are closely related transcriptional regulators that are coded by two different gene loci in the vertebrate genomes. They perform redundant and unique functions during animal development. CtBP proteins mediate their transcriptional function through interaction with various DNA-binding repressors that contain PLDLS-like motifs and chromatin modifying enzymes, such as class I histone deacetylases (HDAC) that do not contain such motifs. The N-terminal region of CtBP1/2 forms a hydrophobic cleft and is involved in interaction with both PLDLS-containing factors and non-PLDLS factors. CtBP proteins function as dimers to mediate transcriptional repression and dimerization is modulated by specific binding to NAD/NADH.

Results

In this study, we have investigated the role of dimerization of CtBP2 in recruitment of PLDLS-motif cofactors and non-PLDLS cofactors. Our results indicate that mutations in CtBP2 that interfere with dimerization abolish CtBP2 interaction with most cellular factors, except the PLDLS-motif factor zinc-finger E-box binding homeobox (ZEB) and the non-PLDLS factor HDAC2. Unlike most PLDLS-containing CtBP-binding proteins, ZEB contains three PLDLS-like motifs and all three contribute to the interaction with the CtBP2 monomer. Despite the ability to interact with ZEB and HDAC, the CtBP2 monomer fails to mediate ZEB-dependent transcriptional repression. The lack of repression activity of the CtBP2 monomer is correlated with the competition between ZEB and HDAC for interaction with the CtBP2 monomer.

Conclusion

These results suggest a competition between the canonical PLDLS-motif factors such as E1A and non-PLDLS factor HDAC for interaction with CtBP. They also indicate that the affinity for the CtBP monomer may be determined by the number as well as amino acid sequence compositions of the PLDLS-like motifs. Our results are consistent with a model that the CtBP2 dimer may interact with a PLDLS-containing repressor through one monomer and recruit HDAC and other chromatin modifying enzymes through the second monomer in the CtBP2 dimer.
Atherosclerosis profile and incidence of cardiovascular events: a population-based survey
Authors: Robinson Jennifer G , Fox Kathleen M , Bullano Michael F , Grandy Susan ,   the SHIELD Study Group
Published: September 2009

Background

Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD) events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals.

Methods

Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization). Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events.

Results

Of 17,640 respondents, 488 (2.8%) reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2) [all p < 0.05]. Incident CVD was twice as high in respondents with subclinical atherosclerosis (25.8%) as in those without atherosclerosis or clinical CVD (12.2%). In individuals with subclinical atherosclerosis, men (RR = 1.77, p = 0.050) and individuals with circulation problems (RR = 2.36, p = 0.003) were at greatest risk of experiencing CVD events in the next 2 years.

Conclusion

Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.
Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure
Authors: Hsieh Szu-Min , Chang Sui-Yuan , Hung Chien-Ching , Sheng Wang-Huei , Chen Mao-Yuan , Chang Shan-Chwen
Published: September 2009

Background

Tipranavir (TPV) is a recently approved nonpeptidic protease inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable.

Methods

To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively), but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score.

Results

Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r correlated with the duration of exposure to first-line PIs, whether in ATV or LPV/r group.

Conclusion

Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.
Complete absence of M2-pyruvate kinase expression in benign pancreatic ductal epithelium and pancreaticobiliary and duodenal neoplasia
Authors: Aloysius Mark M , Zaitoun Abed M , Bates Timothy E , Albasri Abdulkader , Ilyas Mohammad , Rowlands Brian J , Lobo Dileep N
Published: September 2009

Background

Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed to characterise the immunohistochemical expression of M2-PK in archived specimens of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic pancreatitis, and normal pancreas.

Methods

Immunohistochemical staining was performed with mouse anti-M2-PK monoclonal antibody (clone DF-4) at an optimal dilution of 1:25 on tissue microarrays constructed from formalin-fixed paraffin-embedded pancreatic tissue of 126 consecutive patients undergoing pancreatic resections between June 2001 and June 2006. 104 underwent resection for cancer and 22 for chronic pancreatitis. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. A further 11 premalignant pancreaticobiliary and duodenal lesions were studied. M2-PK expression was quantified with the immunohistochemical score (IHS; Range 0-12).

Results

Benign non-ductal tissue in chronic pancreatitis and normal pancreas showed variable expression of M2-PK (IHS = 1 in 25%, IHS = 2-3 in 40%, IHS>3 in 40%). Benign pancreatic ductal epithelium, all primary pancreaticobiliary and duodenal premalignant lesions and cancers (and lymph node metastasis) showed complete lack of expression (IHS = 0).

Conclusion

Complete lack of M2-PK expression was observed in benign pancreatic ducts, premalignant lesions and cancer. M2-PK is present only in benign non-ductal epithelium in normal pancreas and peri-tumoural tissue.
Correlates of quality of life of pre-obese and obese patients: a pharmacy-based cross-sectional survey
Authors: Laforest Laurent , Van Ganse Eric , Ritleng Cécile , Desamericq Gaelle , Letrilliart Laurent , Moreau Alain , Rosen Sarah , Mechin Hubert , Chamba Genevieve
Published: September 2009

Background

The correlates of quality of life (QOL), as measured by the OSQOL questionnaire were investigated in a convenience sample of overweight patients recruited in pharmacies.

Methods

A convenience sample of patients with a Body Mass Index ≥ 28 kg/m2 were recruited in community-based pharmacies. Baseline characteristics and QOL dimensions (1-Physical state, 2-Vitality-desire to do things, 3-Relations with others, 4-Psychological state) were reported in self-completed questionnaires from which the risk of obtaining a low QOL was assessed for each dimension.

Results

QOL was inadequate for all dimensions in the 494 patients included in the study (median age = 61, 48% women, 21% professional persons/top executives). Older pre-obese and obese patients were more likely to report impaired physical functioning (OR = 2.02, 95%CI = [1.10-3.70]), but were less severely affected socially (OR = 0.32, 95%CI = [0.15-0.69]). Pre-obese and obese professional persons and top executives showed better physical capabilities (OR = 0.35, 95%CI = [0.15-0.81]) and increased vitality (OR = 0.47, 95%CI = [0.23-0.95]). Overall, men's psychological state was better than females' (OR = 0.46, 95%CI = [0.25-0.82]). A body-mass index ≥ 35 kg/m2 was significantly associated with poorer QOL scores on physical, relational and psychological dimensions.

Conclusion

Our data highlighted the influence of the severity of excess weight, gender, age and socioeconomic status on QOL. These factors should be taken into account when interpreting QOL in pre-obese and obese persons.
A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes
Authors: Lewis Alexander D , Menezes Darryl A Braganza , McDermott Helen E , Hibbert Louise J , Brennan Sarah-Louise , Ross Elizabeth E , Jones Lisa A
Published: September 2009

Background

Medical students report high levels of stress related to their medical training as well as to other personal and financial factors. The aim of this study is to investigate whether there are differences in course-related stressors reported by medical students on undergraduate problem-based learning (PBL) and non-PBL programmes in the UK.

Method

A cross-sectional study of second-year medical students in two UK medical schools (one PBL and one non-PBL programme) was conducted. A 16-question self-report questionnaire, derived from the Perceived Medical Student Stress Scale and the Higher Education Stress Inventory, was used to measure course-related stressors. Following univariate analysis of each stressor between groups, multivariate logistic regression was used to determine which stressors were the best predictors of each course type, while controlling for socio-demographic differences between the groups.

Results

A total of 280 students responded. Compared to the non-PBL students (N = 197), the PBL students (N = 83) were significantly more likely to agree that: they did not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03); there were too many small group sessions facilitated only by students resulting in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They were significantly more likely to disagree that: there was a lack of encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course fostered a sense of anonymity and feelings of isolation amongst students (OR = 3.42, p = 0.008).

Conclusion

There are significant differences in the perceived course-related stressors affecting medical students on PBL and non-PBL programmes. Course designers and student support services should therefore tailor their work to minimise, or help students cope with, the specific stressors on each course type to ensure optimum learning and wellbeing among our future doctors.
Function of caspase-14 in trophoblast differentiation
Authors: White Lloyd J , Declercq Wim , Arfuso Frank , Charles Adrian K , Dharmarajan Arun M
Published: September 2009

Background

Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored.

Methods

Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways.

Results

Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted.

Conclusion

Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.
Resveratrol inhibits prostaglandin formation in IL-1β-stimulated SK-N-SH neuronal cells
Authors: Wendeburg Lena , de Oliveira Antonio Carlos Pinheiro , Bhatia Harsharan S , Candelario-Jalil Eduardo , Fiebich Bernd L
Published: September 2009

Resveratrol, a polyphenol present in grapes and red wine, has been studied due to its vast pharmacological activity. It has been demonstrated that resveratrol inhibits production of inflammatory mediators in differentin vitroandin vivomodels. Our group recently demonstrated that resveratrol reduced the production of prostaglandin (PG) E2and 8-isoprostane in rat activated microglia. In a microglial-neuronal coculture, resveratrol reduced neuronal death induced by activated microglia. However, less is known about its direct roles in neurons. In the present study, we investigated the effects of resveratrol on interleukin (IL)-1β stimulated SK-N-SH cells. Resveratrol (0.1-5 μM) did not reduce the expression of cyclooxygenase (COX)-2 and microsomal PGE2synthase-1 (mPGES-1), although it drastically reduced PGE2and PGD2content in IL-1β-stimulated SK-N-SH cells. This effect was due, in part, to a reduction in COX enzymatic activity, mainly COX-2, at lower doses of resveratrol. The production of 8-iso-PGF2α, a marker of cellular free radical generation, was significantly reduced by resveratrol. The present work provides evidence that resveratrol reduces the formation of prostaglandins in neuroblastoma cells by reducing the enzymatic activity of inducible enzymes, such as COX-2, and not the transcription of the PG synthases, as demonstrated elsewhere.
National surveillance of Salmonella enterica in food-producing animals in Japan
Authors: Ishihara Kanako , Takahashi Toshio , Morioka Ayako , Kojima Akemi , Kijima Mayumi , Asai Tetsuo , Tamura Yutaka
Published: September 2009

A total of 518 fecal samples collected from 183 apparently healthy cattle, 180 pigs and 155 broilers throughout Japan in 1999 were examined to determine the prevalence and antimicrobial susceptibility ofSalmonella. The isolation rates were 36.1% in broilers, 2.8% in pigs and 0.5% in cattle.S. entericaInfantis was the most frequent isolate, found in 22.6% of broiler fecal samples. Higher resistance rates were observed against oxytetracycline (82.0%), dihydrostreptomycin (77.9%), kanamycin (41.0%) and trimethoprim (35.2%). Resistance rates to ampicillin, ceftiofur, bicozamycin, chloramphenicol and nalidixic acid were <10%. CTX-M-2 β-lactamase producingS. entericaSenftenberg was found in the isolates obtained from one broiler fecal sample. This is the first report of cephalosporin-resistantSalmonelladirectly isolated from food animal in Japan.
Transcriptional effects of CRP* expression in Escherichia coli
Authors: Khankal Reza , Chin Jonathan W , Ghosh Debashis , Cirino Patrick C
Published: September 2009

Background

Escherichia coliexhibits diauxic growth in sugar mixtures due to CRP-mediated catabolite repression and inducer exclusion related to phosphotransferase system enzyme activity. Replacement of the nativecrpgene with a catabolite repression mutant (referred to ascrp*) enables co-utilization of glucose and other sugars inE. coli. While previous studies have examined the effects of expressing CRP* mutants on the expression of specific catabolic genes, little is known about the global transcriptional effects of CRP* expression. In this study, we compare the transcriptome ofE. coliW3110 (expressing wild-type CRP) to that of mutant strain PC05 (expressing CRP*) in the presence and absence of glucose.

Results

The glucose effect is significantly suppressed in strain PC05 relative to strain W3110. The expression levels of glucose-sensitive genes are generally not altered by glucose to the same extent in strain PCO5 as compared to W3110. Only 23 of the 80 genes showing significant differential expression in the presence of glucose for strain PC05 are present among the 418 genes believed to be directly regulated by CRP. Genes involved in central carbon metabolism (including several TCA cycle genes) and amino acid biosynthesis, as well as genes encoding nutrient transport systems are among those whose transcript levels are most significantly affected by CRP* expression.

We present a detailed transcription analysis and relate these results to phenotypic differences between strains expressing wild-type CRP and CRP*. Notably, CRP* expression in the presence of glucose results in an elevated intracellular NADPH concentration and reduced NADH concentration relative to wild-type CRP. Meanwhile, a more drastic decrease in the NADPH/NADP+ratio is observed for the case of CRP* expression in strains engineered to reduce xylose to xylitol via a heterologously expressed, NADPH-dependent xylose reductase. Altered expression levels of transhydrogenase and TCA cycle genes, among others, are consistent with these observations.

Conclusion

While the simplest model of CRP*-mediated gene expression assumes insensitivity to glucose (or cAMP), our results show that gene expression in the context of CRP* is very different from that of wild-type in the absence of glucose, and is influenced by the presence of glucose. Most of the transcription changes in response to CRP* expression are difficult to interpret in terms of possible systematic effects on metabolism. Elevated NADPH availability resulting from CRP* expression suggests potential biocatalytic applications ofcrp*strains that extend beyond relief of catabolite repression.
Vascular injuries after blunt chest trauma: diagnosis and management
Authors: O'Connor James V , Byrne Christopher , Scalea Thomas M , Griffith Bartley P , Neschis David G
Published: September 2009

Background

Although relatively rare, blunt injury to thoracic great vessels is the second most common cause of trauma related death after head injury. Over the last twenty years, the paradigm for management of these devastating injuries has changed drastically. The goal of this review is to update the reader on current concepts of diagnosis and management of blunt thoracic vascular trauma.

Methods

A review of the medical literature was performed to obtain articles pertaining to both blunt injuries of the thoracic aorta and of the non-aortic great vessels in the chest. Articles were chosen based on authors' preference and clinical expertise.

Discussion

Blunt thoracic vascular injury remains highly lethal, with most victims dying prior to reaching a hospital. Those arriving in extremis require immediate intervention, which may include treatment of other associated life threatening injuries. More stable injuries can often be medically temporized in order to optimize definitive management. Endovascular techniques are being employed with increasing frequency and can often significantly simplify management in otherwise very complex patient scenarios.
ERG Expression Is an Independent Prognostic Factor and Allows Refined Risk Stratification in Cytogenetically Normal Acute Myeloid Leukemia: A Comprehensive Analysis of ERG, MN1, and BAALC Transcript Levels Using Oligonucleotide Microarrays
Authors: Metzeler Klaus H. , Dufour Annika , Benthaus Tobias , Hummel Manuela , Sauerland Maria-Cristina , Heinecke Achim , Berdel Wolfgang E. , Büchner Thomas , Wörmann Bernhard , Mansmann Ulrich , Braess Jan , Spiekermann Karsten , Hiddemann Wolfgang , Buske Christian , Bohlander Stefan K.
Published: September 2009

Purpose

Recently, several novel molecular prognostic markers were identified in cytogenetically normal acute myeloid leukemia (CN-AML). In addition to the well-known influence of FLT3, NPM1, and CEBPA mutations, high transcript levels of the ERG, BAALC, and MN1 genes have been associated with inferior outcomes, but the relative importance of these risk markers remains to be defined.

Patients and Methods

We analyzed ERG, BAALC, and MN1 expression levels in a cohort of 210 patients with CN-AML who received intensive chemotherapy. Expression levels of ERG, BAALC, and MN1 were determined in bone marrow samples by using oligonucleotide microarrays.

Results

High transcript levels of ERG, BAALC, and MN1 were predictors for inferior overall survival (OS) and a lower rate of complete remissions (CRs). There were significant positive correlations between the expression levels of all three genes. ERG expression levels predicted OS in elderly patients (ie, age 60 years or older) with CN-AML (P = .006) as well as in younger patients (P = .013). In multivariate analyses, high ERG expression was independently associated with a lower CR rate (P = .013), shorter event-free survival (P = .008), and shorter OS (P = .005). Patients who had low ERG levels and absent FLT3 internal tandem duplication (ITD) had a 5-year OS of 44%, and patients who had high ERG expression and FLT3 ITD had a 5-year OS of only 5%.

Conclusion

We analyzed a comprehensive set of molecular risk factors in a large, homogeneous CN-AML patient cohort. In this study, high ERG expression levels emerged as a strong negative prognostic factor and provided prognostic information in addition to established molecular markers.
Circulating Tumor Cells: A Useful Predictor of Treatment Efficacy in Metastatic Breast Cancer
Authors: Liu Minetta C. , Shields Peter G. , Warren Robert D. , Cohen Philip , Wilkinson Mary , Ottaviano Yvonne L. , Rao Suman B. , Eng-Wong Jennifer , Seillier-Moiseiwitsch Francoise , Noone Anne-Michelle , Isaacs Claudine
Published: September 2009

Purpose

Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging.

Patients and Methods

Serial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals.

Results

Sixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment.

Conclusion

We provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.
Estrogen-Progestagen Menopausal Hormone Therapy and Breast Cancer: Does Delay From Menopause Onset to Treatment Initiation Influence Risks?
Authors: Fournier Agnès , Mesrine Sylvie , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise
Published: September 2009

Purpose

To investigate whether the relation between estrogen-progestagen menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to the delay between menopause onset and treatment initiation.

Participants and Methods

Between 1992 and 2005, 1,726 invasive breast cancers were identified among 53,310 postmenopausal women from the French E3N cohort (mean duration of follow-up, 8.1 years). Hazard ratios (HRs) and CIs were estimated using Cox models, with MHT never users as the reference.

Results

Among recent users of EP-MHT, the risk of breast cancer varied according to the timing of treatment initiation. This variation was confined to short durations of use (≤ 2 years): the HR was 1.54 (95% CI, 1.28 to 1.86) for short treatments initiated in the 3-year period following menopause onset and 1.00 (95% CI, 0.68 to 1.47) for short treatments initiated later (P = .04 for homogeneity). However, this pattern of risks was not observed in users of EP-MHT containing progesterone, among whom there was no significantly increased risk associated with short duration of use (HR was 0.87 [95% CI, 0.57 to 1.32] for treatments initiated ≤ 3 years after menopause, and HR was 0.90 [95% CI, 0.45 to 1.81] for treatments initiated later). Longer durations of EP-MHT use were generally associated with increases in breast cancer risk, whatever the gap time.

Conclusion

Our results suggest that, for some EP-MHT, the timing of treatment initiation transiently modulates the risk of breast cancer and that, when initiated close to menopause, even short durations of use are associated with an increased breast cancer risk. Estrogen + progesterone combinations might be an exception in this regard.
Survival Disparities in Patients With Lymphoma According to Place of Residence and Treatment Provider: A Population-Based Study
Authors: Loberiza Fausto R. , Cannon Anthony J. , Weisenburger Dennis D. , Vose Julie M. , Moehr Matt J. , Bast Martin A. , Bierman Philip J. , Bociek R. Gregory , Armitage James O.
Published: September 2009

Purpose

Health disparities exist according to an individual's place of residence. We evaluated the association between primary area of residence (urban v rural) according to treatment provider (university based v community based) and overall survival in patients with lymphoma and determined whether there are patient groups that could benefit from better coordination of care.

Patients and Methods

Population-based, retrospective cohort study of 2,330 patients with centrally confirmed lymphoma from Nebraska and surrounding states and treated by university-based or community-based oncologists from 1982 to 2006.

Results

Among urban residents, 321 (14%) were treated by university-based providers (UUB) and 816 (35%) were treated by community-based providers (UCB). Among rural residents, 332 (14%) were treated by university-based providers (RUB), and 861 (37%) were treated by community-based providers (RCB). The relative risk (RR) of death among UUB, UCB, and RUB were not statistically different. However, RCB had a higher risk of death (RR, 1.37; 95% CI, 1.14 to 1.65; P = .01; and RR, 1.26; 95% CI, 1.06 to 1.49; P = .01) when compared with UUB and RUB, respectively. This association was true in both low- and intermediate-risk patients. Among high-risk patients, UCB, RUB, and RCB were all at higher risk of death when compared with UUB.

Conclusion

Survival outcomes of patients with lymphoma may be associated with place of residence and treatment provider. High-risk patients from rural areas may benefit from better coordination of care.