bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smac mimetic-derived augmentation of chemotherapeutic response in experimental pancreatic cancer
Authors: Awasthi Niranjan , Kirane Amanda , Schwarz Margaret A , Toombs Jason E , Brekken Rolf A , Schwarz Roderich E 
Published: January 2011

Abstract

Background
Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to conventional chemotherapy, in part due to the overexpression of inhibitors of apoptosis proteins (IAPs). Smac is an endogenous IAP-antagonist, which renders synthetic Smac mimetics attractive anticancer agents. We evaluated the benefits of combining a Smac mimetic, JP1201 (JP), with conventional chemotherapy agents used for PDAC management.

Methods
Cell viability assays and protein expression analysis were performed using WST-1 reagent and Western blotting, respectively. Apoptosis was detected by annexin V/propidium iodide staining. In vivo tumor growth and survival studies were performed in murine PDAC xenografts.

Results
JP and gemcitabine (Gem) inhibited PDAC cell proliferation with additive effects in combination. The percentage of early apoptotic cells in controls, JP, Gem and JP + Gem was 17%, 26%, 26% and 38%, respectively. JP-induced apoptosis was accompanied by PARP-1 cleavage. Similar additive anti-proliferative effects were seen for combinations of JP with doxorubicin (Dox) and docetaxel (DT). The JP + Gem combination caused a 30% decrease in tumor size in vivo compared to controls. Median animal survival was improved significantly in mice treated with JP + Gem (38 d) compared to controls (22 d), JP (28 d) or Gem (32 d) (p = 0.01). Animal survival was also improved with JP + DT treatment (32 d) compared to controls (16 d), JP (21 d) or DT alone (27 d).

Conclusions
These results warrant further exploration of strategies that promote chemotherapy-induced apoptosis of tumors and highlight the potential of Smac mimetics in clinical PDAC therapy.
Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study
Authors: Abdel Raheem Ahmad M , Hameed Diaa A , ElGanainy Ehab O , Mosad Eman , Abdelwanis Mostafa E , Kamel Nermen A , Hammouda Hisham M , Abdelaziz Mohammad A , Hemeyda Khaled 
Published: January 2011

Abstract

Background
Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL.

Methods
The study prospectively included 71 patients, (47 males, 24 females) with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0) who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1), while 33 patients did not receive adjuvant radiotherapy (group 2). Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded.

Results
The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03). The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p < 0.0001) and radiotherapy (odd ratio 0.19, 95% CI 0.05 - 0.78, p < 0.02). With Cox regression, the only independent multivariate predictor of radio-sensitivity was the Bcl-XL expression with odd ratio 4.6 and a p value < 0.0001. All patients tolerated the treatment with no life threatening or late complications during the period of follow up.

Conclusions
Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.
Study protocol: the sleeping sound with attention-deficit/hyperactivity disorder project
Authors: Sciberras Emma , Efron Daryl , Gerner Bibi , Davey Margot , Mensah Fiona , Oberklaid Frank , Hiscock Harriet 
Published: January 2011

AbstractBackgroundUp to 70% of children with Attention-Deficit/Hyperactivity Disorder (ADHD) experience sleep problems including difficulties initiating and maintaining sleep. Sleep problems in children with ADHD can result in poorer child functioning, impacting on school attendance, daily functioning and behaviour, as well as parental mental health and work attendance. The Sleeping Sound with ADHD trial aims to investigate the efficacy of a behavioural sleep program in treating sleep problems experienced by children with ADHD. We have demonstrated the feasibility and the acceptability of this treatment program in a pilot study.Methods/DesignThis randomised controlled trial (RCT) is being conducted with 198 children (aged between 5 to 12 years) with ADHD and moderate to severe sleep problems. Children are recruited from public and private paediatric practices across the state of Victoria, Australia. Upon receiving informed written consent, families are randomised to receive either the behavioural sleep intervention or usual care. The intervention consists of two individual, face-to-face consultations and a follow-up phone call with a trained clinician (trainee consultant paediatrician or psychologist), focusing on the assessment and management of child sleep problems. The primary outcome is parent- and teacher-reported ADHD symptoms (ADHD Rating Scale IV). Secondary outcomes are child sleep (actigraphy and parent report), behaviour, daily functioning, school attendance and working memory, as well as parent mental health and work attendance. We are also assessing the impact of children's psychiatric comorbidity (measured using a structured diagnostic interview) on treatment outcome.DiscussionTo our knowledge, this is the first RCT of a behavioural intervention aiming to treat sleep problems in children with ADHD. If effective, this program will provide a feasible non-pharmacological and acceptable intervention improving child sleep and ADHD symptoms in this patient group.Trial RegistrationCurrent Controlled Trials ISRCTN68819261.ISRCTN:ISRCTN68819261
Early life factors and being overweight at 4 years of age among children in Malmö, Sweden
Authors: Mangrio Elisabeth , Lindström Martin , Rosvall Maria 
Published: January 2011

Abstract

Background
Rising rates of obesity and overweight is an increasing public health problem all over the world. Recent research has shown the importance of early life factors in the development of child overweight. However, to the best of our knowledge there are no studies investigating the potential synergistic effect of early life factors and presence of parental overweight on the development of child overweight.

Methods
The study was population-based and cross-sectional. The study population consisted of children who visited the Child Health Care (CHC) centers in Malmö for their 4-year health check during 2003-2008 and whose parents answered a self-administered questionnaire (n = 9009 children).

Results
The results showed that having overweight/obese parents was strongly associated with the child being overweight or obese. Furthermore, there was an association between unfavorable early life factors (i.e., mother smoking during pregnancy, presence of secondhand tobacco smoke early in life, high birth weight) and the development of child overweight/obesity at four years of age, while breastfeeding seemed to have a protective role. For example, maternal smoking during pregnancy was associated with an odds ratio (OR) of 1.47 (95% CI: 1.22, 1.76) for overweight and 2.31 (95% CI: 1.68, 3.17) for obesity. The results further showed synergistic effects between parental overweight and exposure to unfavourable early life factors in the development of child overweight.

Conclusions
The present study shows the importance of early life factors in the development of child overweight and obesity, and thus puts focus on the importance of early targeted interventions.
Male commuters in north and south England: risk factors for the presence of faecal bacteria on hands
Authors: Dodrill Laura , Schmidt Wolf-Peter , Cobb Emma , Donachie Peter , Curtis Valerie , de Barra Mícheál 
Published: January 2011

Abstract

Background
A previous study found that the prevalence of contamination with bacteria of faecal-origin on the hands of men differed across UK cities, with a general trend of increased contamination in northern cities. The aim of this study was to (1) confirm the north-south trend (2) identify causes for the trend.

Methods
Hand swabs from commuters (n = 308) at train stations in 4 cities were tested for the presence of faecal bacteria.

Results
The prevalence of hand contamination with faecal bacteria was again higher in cities in the north compared to the south (5% in London, 4% in Birmingham, 10% in Liverpool and 19% in Newcastle). Contamination risk decreased with age and better personal hygiene (self-reported). Soil contact and shaking hands increased contamination with faecal bacteria. However, in multivariable analysis, none of these factors fully explained the variation in contamination across cities.

Conclusion
The study confirmed the north-south differences in faecal contamination of hands without finding a clear cause for the trend. Faecal contamination of hands was associated with personal hygiene indicators suggesting that microbiological testing may contribute to evaluating hygiene promotion campaigns.
A receptor fusion protein for the inhibition of murine oncostatin M
Authors: Brolund Liv , Küster Andrea , Korr Sabrina , Vogt Michael , Müller-Newen Gerhard 
Published: January 2011

AbstractBackgroundMost cytokines signal through heteromeric receptor complexes consisting of two or more different receptor subunits. Fusion proteins of the extracellular parts of receptor subunits turned out to be promising cytokine inhibitors useful in anti-cytokine therapy and cytokine research.ResultsWe constructed receptor fusion proteins (RFP) consisting of the ligand binding domains of the murine oncostatin M (mOSM) receptor subunits mOSMR and mgp130 connected by a flexible linker as potential mOSM inhibitors. mgp130 is a shared cytokine receptor that is also used by other cytokines such as IL-6 and leukemia inhibitory factor (LIF). In this study we compare four types of mOSM-RFPs that contain either domains D1-D3 or domains D2-D3 of mgp130 and are arranged in two ways. Domain D1 of mgp130 turned out to be dispensable for mOSM-binding. However, the arrangement of the two receptor subunits is essential for the inhibitory activity. We found mOSM induced STAT3 phosphorylation to be suppressed only when the mOSMR fragment was fused in front of the mgp130 fragment.ConclusionsmOSM-RFP consisting of D1-D4 of mOSMR and D2-D3 of mgp130 is a highly potent and specific inhibitor of mOSM. Since mOSM-RFP is encoded by a single gene it offers numerous possibilities for specific cytokine inhibition in gene delivery approaches based on viral vectors, transgenic animals and finally gene therapy.
Cardiovascular disease occurrence in two close but different social environments
Authors: Wennerholm Carina , Grip Björn , Johansson Annakarin , Nilsson Hans , Honkasalo Marja-Liisa , Faresjö Tomas 
Published: January 2011

Abstract

Background
Cardiovascular diseases estimate to be the leading cause of death and loss of disability-adjusted life years globally. Conventional risk factors for cardiovascular diseases only partly account for the social gradient. The purpose of this study was to compare the occurrence of the most frequent cardiovascular diseases and cardiovascular mortality in two close cities, the Twin cities.

Methods
We focused on the total population in two neighbour and equally sized cities with a population of around 135 000 inhabitants each. These twin cities represent two different social environments in the same Swedish county. According to their social history they could be labelled a "blue-collar" and a "white-collar" city. Morbidity data for the two cities was derived from an administrative health care register based on medical records assigned by the physicians at both hospitals and primary care. The morbidity data presented are cumulative incidence rates and the data on mortality for ischemic heart diseases is based on official Swedish statistics.

Results
The cumulative incidence of different cardiovascular diagnoses for younger and also elderly men and women revealed significantly differences for studied cardiovascular diagnoses. The occurrence rates were in all aspects highest in the population of the "blue-collar" twin city for both sexes.

Conclusions
This study revealed that there are significant differences in risk for cardiovascular morbidity and mortality between the populations in the studied different social environments. These differences seem to be profound and stable over time and thereby give implication for public health policy to initiate a community intervention program in the "blue-collar" twin city.
Increasing health worker capacity through distance learning: a comprehensive review of programmes in Tanzania
Authors: Nartker Anya J , Stevens Liz , Shumays Alyson , Kalowela Martin , Kisimbo Daniel , Potter Katy 
Published: January 2011

Abstract

Background
Tanzania, like many developing countries, faces a crisis in human resources for health. The government has looked for ways to increase the number and skills of health workers, including using distance learning in their training. In 2008, the authors reviewed and assessed the country's current distance learning programmes for health care workers, as well as those in countries with similar human resource challenges, to determine the feasibility of distance learning to meet the need of an increased and more skilled health workforce.

Methods
Data were collected from 25 distance learning programmes at health training institutions, universities, and non-governmental organizations throughout the country from May to August 2008. Methods included internet research; desk review; telephone, email and mail-in surveys; on-site observations; interviews with programme managers, instructors, students, information technology specialists, preceptors, health care workers and Ministry of Health and Social Welfare representatives; and a focus group with national HIV/AIDS care and treatment organizations.

Results
Challenges include lack of guidelines for administrators, instructors and preceptors of distance learning programmes regarding roles and responsibilities; absence of competencies for clinical components of curricula; and technological constraints such as lack of access to computers and to the internet. Insufficient funding resulted in personnel shortages, lack of appropriate training for personnel, and lack of materials for students.
Nonetheless, current and prospective students expressed overwhelming enthusiasm for scale-up of distance learning because of the unique financial and social benefits offered by these programs. Participants were retained as employees in their health care facilities, and remained in their communities and supported their families while advancing their careers. Space in health training institutions was freed up for new students entering in-residence pre-service training.

Conclusions
A blended print-based distance learning model is most feasible at the national level due to current resource and infrastructure constraints. With an increase in staffing; improvement of infrastructure, coordination and curricula; and decentralization to the zonal or district level, distance learning can be an effective method to increase both the skills and the numbers of qualified health care workers capable of meeting the health care needs of the Tanzanian population.
Differential endothelial cell gene expression by African Americans versusCaucasian Americans: a possible contribution to health disparity in vascular disease and cancer
Authors: Wei P , Milbauer LC , Enenstein J , Nguyen J , Pan W , Hebbel RP 
Published: January 2011

AbstractBackgroundHealth disparities and the high prevalence of cardiovascular disease continue to be perplexing worldwide health challenges. This study addresses the possibility that genetic differences affecting the biology of the vascular endothelium could be a factor contributing to the increased burden of cardiovascular disease and cancer among African Americans (AA) compared to Caucasian Americans (CA).MethodsFrom self-identified, healthy, 20 to 29-year-old AA (n = 21) and CA (n = 17), we established cultures of blood outgrowth endothelial cells (BOEC) and applied microarray profiling. BOEC have never been exposed toin vivoinfluences, and their gene expression reflects culture conditions (meticulously controlled) and donor genetics. Significance Analysis of Microarray identified differential expression of single genes. Gene Set Enrichment Analysis examined expression of pre-determined gene sets that survey nine biological systems relevant to endothelial biology.ResultsAt the highly stringent threshold of False Discovery Rate (FDR) = 0, 31 single genes were differentially expressed in AA.PSPHexhibited the greatest fold-change (AA > CA), but this was entirely accounted for by a homolog (PSPHL) hidden within thePSPHprobe set. Among other significantly different genes were: for AA > CA,SOS1, AMFR, FGFR3; and for AA < CA, ARVCF, BIN3, EIF4B.Many more (221 transcripts for 204 genes) were differentially expressed at the less stringent threshold of FDR <.05. Using the biological systems approach, we identified shear response biology as being significantly different for AA versus CA, showing an apparent tonic increase of expression (AA > CA) for 46/157 genes within that system.ConclusionsMany of the genes implicated here have substantial roles in endothelial biology. Shear stress response, a critical regulator of endothelial function and vascular homeostasis, may be different between AA and CA. These results potentially have direct implications for the role of endothelial cells in vascular disease (hypertension, stroke) and cancer (via angiogenesis). Also, they are consistent with our over-arching hypothesis that genetic influences stemming from ancestral continent-of-origin could impact upon endothelial cell biology and thereby contribute to disparity of vascular-related disease burden among AA. The method used here could be productively employed to bridge the gap between information from structural genomics (for example, disease association) and cell function and pathophysiology.
Influenza A virus NS1 gene mutations F103L and M106I increase replication and virulence
Authors: Dankar Samar K , Wang Shuai , Ping Jihui , Forbes Nicole E , Keleta Liya , Li Yishan , Brown Earl G 
Published: January 2011

Abstract

Background
To understand the evolutionary steps required for a virus to become virulent in a new host, a human influenza A virus (IAV), A/Hong Kong/1/68(H3N2) (HK-wt), was adapted to increased virulence in the mouse. Among eleven mutations selected in the NS1 gene, two mutations F103L and M106I had been previously detected in the highly virulent human H5N1 isolate, A/HK/156/97, suggesting a role for these mutations in virulence in mice and humans.

Results
To determine the selective advantage of these mutations, reverse genetics was used to rescue viruses containing each of the NS1 mouse adapted mutations into viruses possessing the HK-wt NS1 gene on the A/PR/8/34 genetic backbone. Both F103L and M106I NS1 mutations significantly enhanced growth in vitro (mouse and canine cells) and in vivo (BALB/c mouse lungs) as well as enhanced virulence in the mouse. Only the M106I NS1 mutation enhanced growth in human cells. Furthermore, these NS1 mutations enhanced early viral protein synthesis in MDCK cells and showed an increased ability to replicate in mouse interferon β (IFN-β) pre-treated mouse cells relative to rPR8-HK-NS-wt NS1. The double mutant, rPR8-HK-NS-F103L + M106I, demonstrated growth attenuation late in infection due to increased IFN-β induction in mouse cells. We then generated a rPR8 virus possessing the A/HK/156/97 NS gene that possesses 103L + 106I, and then rescued the L103F + I106M mutant. The 103L + 106I mutations increased virulence by >10 fold in BALB/c mice. We also inserted the avian A/Ck/Beijing/1/95 NS1 gene (the source lineage of the A/HK/156/97 NS1 gene) that possesses 103L + 106I, onto the A/WSN/33 backbone and then generated the L103F + I106M mutant. None of the H5N1 and H9N2 NS containing viruses resulted in increased IFN-β induction. The rWSN-A/Ck/Beijing/1/95-NS1 gene possessing 103L and 106I demonstrated 100 fold enhanced growth and >10 fold enhanced virulence that was associated with increased tropism for lung alveolar and bronchiolar tissues relative to the corresponding L103F and I106M mutant.

Conclusions
The F103L and M106I NS1 mutations were adaptive genetic determinants of growth and virulence in both human and avian NS1 genes in the mouse model.
Exposure to Diethylstilbestrol During Embryonic and Larval Stages of Medaka Fish (Oryzias latipes) Leads to Sex Reversal in Genetic Males and Reduced Gonad Weight in Genetic Females
Authors: Paul-Prasanth Bindhu , Shibata Yasushi , Horiguchi Ryo , Nagahama Yoshitaka 
Published: January 2011

Abstract
Molecular and cellular mechanisms involved in artificially induced ovarian differentiation were analyzed by exposing embryos of medaka (Oryzias latipes) to a potent nonsteroidal estrogen, diethylstilbestrol (DES). Embryos were exposed for short-exposure (SE) [from 0 to 8 d postfertilization (dpf)] and long-exposure (LE) periods (from 0 to 18/28 dpf) to 1 ng/ml of DES, and status of sexual differentiation in somatic and germ cells of these gonads was analyzed at 8, 18, and 28 dpf by histology, cell proliferation assays, TUNEL assay, and in situ hybridization using sex-specific somatic and germ cell markers. Additionally, gonads of exposed fry were examined after withdrawal of DES to see whether effects of DES in exposed fish were reversible or not. DES induced germ cell proliferation and meiosis in XY fry of SE and LE groups. However, SE induced only a partial reduction in expression of gonadal soma-derived factor, the male-dominant somatic cell marker, and was not sufficient to induce ovarian development after withdrawal of DES. On the contrary, LE resulted in complete loss of such male-specific gene expression in somatic cells of XY gonads, and these gonads underwent sustained ovarian development even after withdrawal of DES. Importantly, LE to DES affected germ cell proliferation in XX gonads adversely during early stages of sexual differentiation, leading to reduced gonad weight in adulthood. Interestingly, apoptosis was not the cause for reduction in germ cell number. Taken together, these results indicated that DES exposure has long-lasting effects on the gonadal development in genetic males (sex reversal) and females (reduced gonad weight) of medaka.