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Background: We developed SPHERE, an electronic health record (EHR) data visualization application, to automatically populate with EHR data on the American Heart Association’s cardiovascular health (CVH) behaviors and factors. SPHERE was designed to increase patient-provider communication around Life’s Simple 7™, and utilized a stoplight color scheme as part of the visualization to indicate “ideal” (green), “intermediate” (yellow), and “poor” (red) CVH. Results from the SPHERE Study showed improvements in body mass index and diabetes status among eligible patients seen in the intervention clinic as compared to the control clinic. It remains unknown whether the use of SPHERE would be acceptable to oncologists in the survivorship care setting, even though cancer survivors are at high risk for developing cardiovascular disease. Methods: We conducted one-on-one interviews, using a think-aloud protocol, with 14 oncologists (10 community practice, 4 academic) who were practicing in the NCI Community Oncology Research Program (NCORP). During the 30-minute interview period, we asked each oncologist to use SPHERE and we obtained user feedback on the SPHERE application. Results: Half of the oncologists were male, and most (78%) were medical oncologists; 2 were gynecologic oncologists, and 1 was a radiation oncologist. When asked about discussing CVH with post-treatment, good-prognosis patients, no oncologists indicated that they “never” talked to patients about CVH or initiated those discussions. Eleven oncologists responded that discussing CVH was either “somewhat important” or “very important”, and 9 oncologists indicated they were “somewhat comfortable” or “very comfortable” discussing CVH with patients. Themes identified from transcripts of the 7 hours of interviews suggest 1) strong interest in the tool, 2) high perceived importance of discussing CVH with patients who had a good prognosis, 3) high usability, and 4) a belief that the tool would be helpful and not overly burdensome in practice. Duplication of preventative health efforts with the primary care provider as well as workflow and time constraints were identified as barriers by several oncology providers. Conclusions: Overall, these preliminary data demonstrate acceptability and feasibility of implementing the SPHERE application tool within NCORP community oncology practices. These qualitative data suggest great potential for automated EHR-based applications such as SPHERE to impact the CVH of cancer patients in survivorship care.

When searching for a target object presented in a context of other, irrelevant objects, the dissimilarity between target and surrounding context elements as well as the similarity between context elements themselves affect search efficiency. The present functional imaging study explored the cortical mechanisms involved in processing the same target when surrounded by context arrangements of varying homogeneity. Results showed that brain activity increased in the precuneus, cingulate gyrus, and the middle temporal gyrus as context homogeneity and local feature contrast increased. Contexts with low homogeneity and local feature contrast, compared to contexts with high homogeneity and local feature contrast, increasingly involved areas near the corpus callosum and the medial frontal gyrus. The results support the assumption that contextual grouping and local target detection both contribute to perform the visual search task. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

To attend successfully, a specification of what is currently relevant is necessary, but not sufficient. Irrelevant stimuli that are also present in the environment must be recognized as such and filtered out at the same time. Using functional magnetic resonance imaging, we showed that posterior brain regions in parietal, occipital and temporal cortex are recruited in order to ignore distracting visual stimuli, while the specification and selection of relevant stimuli is associated with differential activity in frontal cortex and hippocampal areas instead. The results thus suggest that the selection of relevant objects can be anatomically dissociated from the handling of competing irrelevant objects. The dissociation between the increased involvement of parietal and occipital cortex in handling distraction on one hand, and that of frontal cortex in target specification on the other provides neurophysiological support for models of attention that make this functional distinction. (C) 2010 Elsevier Ltd. All rights reserved.

Understanding the mechanisms that microbes exploit to invade host cells and cause disease is crucial if we are to eliminate their threat. Although pathogens use a variety of microbial factors to trigger entry into non-phagocytic cells, their targeting of the host cell process of endocytosis has emerged as a common theme. To accomplish this, microbes often rewire the normal course of particle internalization, frequently usurping theoretical maximal sizes to permit entry and reconfiguring molecular components that were once thought to be required for vesicle formation. Here, we discuss recent advances in our understanding of how toxins, viruses, bacteria, and fungi manipulate the host cell endocytic machinery to generate diseases. Additionally, we will reveal the advantages of using these organisms to expand our general knowledge of endocytic mechanisms in eukaryotic cells.

ObjectiveThe attaching and effacing (A/E) pathogens enterohaemorrhagic Escherichia coli, enteropathogenic E coli and Citrobacter rodentium colonise intestinal tracts, attach to enterocytes, collapse infected cell microvilli and alter numerous host cell processes during infection. Enterocyte alterations result in numerous small molecules being released from host cells that likely contribute to diarrhoeal phenotypes observed during these infections. One possible route for small molecules to be released from intestinal cells may be through functional gap junction hemichannels. Here we examine the involvement of these hemichannels during the diarrhoeal disease caused by A/E pathogens in vivo.DesignMice were infected with the diarrhoea-causing murine A/E pathogen C rodentium for 7 days. Connexin43 (Cx43) protein levels and immunolocalisation in the colon were initially used to determine alterations during A/E bacterial infections in vivo. Connexin mimetic peptides and connexin permeable tracer molecules were used to gage the presence and function of unpaired connexin hemichannels. The role of Cx43 in diarrhoea generation was assessed by comparing infections of wild-type mice to Cx43 mutant mice and determining the water abundance in the colonic luminal material.ResultsWe demonstrate that Cx43 protein levels are increased in colonocytes during in vivo A/E bacterial infections, resulting in functionally open connexon hemichannels in apical membranes of infected cells. Moreover, infected Cx43 +/− mice do not suffer from diarrhoeal disease.ConclusionsThis study provides the first evidence that functional connexon hemichannels can occur in the intestine and are a novel molecular mechanism of water release during infectious diarrhoea.

Purpose To study the retinal nerve fiber layer thickness difference between high-tension primary open angle glaucoma (HT-POAG) and primary angle closure glaucoma (PACG) eyes using scanning laser polarimetry-variable corneal compensation (GDx VCC) in Taiwan-Chinese population; to evaluate the usefulness of the GDx VCC for detecting POAG and PACG eyes in Taiwan-Chinese population. Patients and methods The study comprised 88 early to moderate glaucomatous eyes (one randomly selected eye from 47 HT-POAG patients and 41 PACG patients) and the control group consisted of 45 age-matched eyes from 45 normal individuals. Each subject underwent retinal nerve fiber layer thickness measurement by GDx VCC and Humphrey Field Analyzer visual field testing. Measured GDx VCC parameters were compared among groups. We also calculated the area under the receive operator characteristic (AROC) curve, corresponding sensitivity/specificity and best cut off value for each parameter in differentiating normal from POAG and PACG eyes. Results There was no significant difference between HT-POAG and PACG eyes in each parameter. The parameter with the best AROC curve for differentiating normal from POAG eye was nerve fiber indicator (AROC, 0.779; sensitivity=57.4%, specificity=100%; best cut off value >27). The parameter with the best AROC curves for differentiating normal from PACG eyes was temporal-superior-nasal-inferior-temporal average (AROC, 0.829; sensitivity=46.3%, specificity=100%, best cut off value Conclusions There was no significant difference between the HT-POAG and PACG eyes as far as the various parameters were concerned. GDx VCC shows fair discriminating ability in distinguishing normal from POAG and PACG eyes in Taiwan Chinese population.

Purpose: Persistent interleukin-8 (IL-8) production contributes to chronic inflammation of the stomach. The proinflammatory IL-1β polymorphisms, which enhance the cytokine production, are associated with increased risk of gastric cancer. The −251A/T polymorphism of the IL-8 promoter is involved in several human diseases. Particularly, the −251A is associated with decreased risk of colorectal cancer. We aimed to determine whether the −251 allele resulting in high IL-8 expression was associated with increased risk of gastric carcinoma.Experimental Design: The −251A/T promoters were cloned and analyzed by luciferase assay. Binding of nuclear proteins to the −251A/T promoters was analyzed by electrophoretic mobility shift assay. The −251A/T promoters were differentiated by PCR-RFLP. Comparison of gastric cancer risk between the −251A/T promoters was done by a case-control study.Results: The −251T allele possessed transcriptional activity 2- to 5-fold stronger than the −251A counterpart. Electrophoretic mobility shift assay showed that the −251A promoter had strong ability to bind to an unknown protein or multiprotein complex. The −251T allele was associated with increased risk of noncardia (Ptrend = 0.012) and cardia (Ptrend = 0.029) carcinomas. Gastric carcinoma patients with the low-risk AA genotype had a tendency to sustain intestinal-type carcinomas (χ2 = 6.816; P = 0.033); however, the high-risk −251T allele was associated with >2-fold increased risk of diffuse-type (AA versus AT + TT: odds ratio, 2.52; 95% confidence interval, 1.16-5.49; P = 0.017) and mixed-type (AA versus AT + TT: odds ratio, 2.22; 95% confidence interval, 1.12-4.40; P = 0.019) carcinomas.Conclusions: The IL-8 −251T allele is significantly associated with increased risk of gastric carcinoma, particularly the diffuse and mixed types in Chinese population.

Music is considered a remedy for the body body, psychological therapy, and a mental release. During World War Two, health medical professionals held concerts to appease the wounded soldiers’ emotions and to initiate the research and discussion of music and emotion applied to various fields in academia. This chapter attempts to use the music emotion model as the media to introduce the possible emotional response during music listening via music structure, listener’s background, and surroundings, to do the research for human physical and psychological influence by automatic generated electronic sound, and to discuss the emotional releasie effect of music. This chapter also discusses various emotional responses derived by various colors applied to the music emotion model to break the limitation of the existing music forms and to develop the possible music color synesthesia applied to all aspects, in order to lay the foundation for next generation users.

Purpose Aging has become a significant problem in the recent years, due to the aging baby boomers. Most of the supervision systems use vision to perform care functions. However people usually cannot watch video all the time, therefore the proposed sonification for aging Taiwanese is used to express a particular situation at the children or nursing home, including both acoustic instrumental sound for the eventtriggered actions, and algorithmic composition to represent various environment situations. The nursing system can easily retrieve their seniors’ situation anytime according to the transmitted audio signal and music via a network. Method The proposed Chinese music sonification system (CMSS) for older people can be implemented into two sections. Section 1: Eventtriggered sound is designed using Chinese instrumental audio samples performed by pipa, erhu, etc. Event-triggered sound is based on the input of various actions of aging people, such as watering, exercising, toileting, dining, sleeping, etc. Section 2: Computer-composed music, is designed using automated stochastic process of MIDI-data with various moods and situations mapped into music features, including musical scale, harmony, tonality, and rhythm. There are five Chinese music modes used for the musical scale. Among them Gong, Jiao, and Jiao are closer to the major mode in western music, while Shang and Yu are similar to the minor mode, therefore positive emotions will be mapped into a major-mode music, and the negative emotions will be correlated to a minor-mode music. Results & Discussion CMSS is based on the hybrid event-triggered sound and computer composed music. Event-triggered sound is the pre-recorded discrete audio samples, while computer composed music is the calculated continuous MIDIrendered audio in real-time. A questionnaire is designed for the seniors to listen to the result of the CMSS, and most of them are satisfied with this innovated design. Action data is used for computer composed music calculation via CCD, RF ID, or any other wireless technology, and environment data is determined by sensors such as bio-feedback, temperature, etc., providing data for event-triggered sound. CMSS are implemented with computer music software Max/MSP, to perform CMSS for the seniors living in Taiwan.

Francisella tularensis are highly infectious microbes that cause the disease tularemia. Although much of the bacterial burden is carried in non-phagocytic cells, the strategies these pathogens use to invade these cells remains elusive. To examine these mechanisms we developed two in vitro Francisella-based infection models that recapitulate the non-phagocytic cell infections seen in livers of infected mice. Using these models we found that Francisella novicida exploit clathrin and cholesterol dependent mechanisms to gain entry into hepatocytes. We also found that the clathrin accessory proteins AP-2 and Eps15 co-localized with invading Francisella novicida as well as the Francisella Live Vaccine Strain (LVS) during hepatocyte infections. Interestingly, caveolin, a protein involved in the invasion of Francisella in phagocytic cells, was not required for non-phagocytic cell infections. These results demonstrate a novel endocytic mechanism adopted by Francisella and highlight the divergence in strategies these pathogens utilize between non-phagocytic and phagocytic cell invasion.

Recent work has demonstrated that the spectrin cytoskeleton is a host cell target, exploited during intestinal bacterial disease. Here we show that the highly virulent intestinal pathogen enterohaemorrhagic Escherichia coli (EHEC) is also reliant upon the spectrin cytoskeleton during key pathogenic events. Immunofluorescent microscopy demonstrated that the core components of the spectrin cytoskeleton (spectrin, adducin, and protein 4.1 [p4.1]) are recruited to sites of EHEC attachment and localized at pedestal structures along with the EHEC pedestal specific proteins IRSp53 and IRTKS. Further studies involving siRNA-mediated knockdowns of spectrin, adducin, or p4.1 revealed that those proteins are needed for efficient docking of EHEC to host cells, are involved in recruiting IRSp53 to the pedestal and are necessary for pedestal formation. These findings identify the spectrin cytoskeleton as a major host cell cytoskeletal network involved in critical EHEC pathogenic events.

Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.