Professional working at computer notebooks is associated with high requirements on the body posture in the seated position. By the high continuous static muscle stress resulting from this position at notebooks, professionals frequently working at notebooks for long hours are exposed to an increased risk of musculoskeletal complaints. Especially in subjects with back pain, new notebooks should be evaluated with a focus on rehabilitative issues.
In a field study a new notebook design with adjustable screen was analyzed and compared to standard notebook position.
There are highly significant differences in the visual axis of individuals who are seated in the novel notebook position in comparison to the standard position. Also, differences are present between further alternative notebook positions. Testing of gender and glasses did not reveal influences.
This study demonstrates that notebooks with adjustable screen may be used to improve the posture. Future studies may focus on patients with musculoskeletal diseases.
In August and September 2005, Hurricanes Katrina and Rita caused breeches in the New Orleans, LA, levee system, resulting in catastrophic flooding. The city remained flooded for several weeks, leading to extraordinary mold growth in homes. To characterize the potential risks of mold exposures, we measured airborne molds and markers of molds and bacteria in New Orleans area homes. In October 2005, we collected air samples from 5 mildly water-damaged houses, 15 moderately to heavily water-damaged houses, and 11 outdoor locations. The air filters were analyzed for culturable fungi, spores, (1→3,1→6)-β-d-glucans, and endotoxins. Culturable fungi were significantly higher in the moderately/heavily water-damaged houses (geometric mean = 67,000 CFU/m3) than in the mildly water-damaged houses (geometric mean = 3,700 CFU/m3) (P = 0.02). The predominant molds found were Aspergillus niger, Penicillium spp., Trichoderma, and Paecilomyces. The indoor and outdoor geometric means for endotoxins were 22.3 endotoxin units (EU)/m3 and 10.5 EU/m3, respectively, and for (1→3,1→6)-β-d-glucans were 1.7 μg/m3 and 0.9 μg/m3, respectively. In the moderately/heavily water-damaged houses, the geometric means were 31.3 EU/m3 for endotoxins and 1.8 μg/m3 for (1→3,1→6)-β-d-glucans. Molds, endotoxins, and fungal glucans were detected in the environment after Hurricanes Katrina and Rita in New Orleans at concentrations that have been associated with health effects. The species and concentrations were different from those previously reported for non-water-damaged buildings in the southeastern United States.
With massive amounts of data being generated in electronic format, there is a need in basic science laboratories to adopt new methods for tracking and analyzing data. An electronic laboratory notebook (ELN) is not just a replacement for a paper lab notebook, it is a new method of storing and organizing data while maintaining the data entry flexibility and legal recording functions of paper notebooks. Paper notebooks are regarded as highly flexible since the user can configure it to store almost anything that can be written or physically pasted onto the pages. However, data retrieval and data sharing from paper notebooks are labor intensive processes and notebooks can be misplaced, a single point of failure that loses all entries in the volume. Additional features provided by electronic notebooks include searchable indices, data sharing, automatic archiving for security against loss and ease of data duplication. Furthermore, ELNs can be tasked with additional functions not commonly found in paper notebooks such as inventory control. While ELNs have been on the market for some time now, adoption of an ELN in academic basic science laboratories has been lagging. Issues that have restrained development and adoption of ELN in research laboratories are the sheer variety and frequency of changes in protocols with a need for the user to control notebook configuration outside the framework of professional IT staff support. In this commentary, we will look at some of the issues and experiences in academic laboratories that have proved challenging in implementing an electronic lab notebook.
Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency (13/20) and multi-drug resistance. Here, we show that the same cells respond very differently when adapted to RITA, a drug that, like nutlin-3, also disrupts the p53/Mdm2 interaction. All of the 11 UKF-NB-3 sub-lines adapted to RITA that we established retained functional wild-type p53 although RITA induced a substantial p53 response. Moreover, all RITA-adapted cell lines remained sensitive to nutlin-3, whereas only five out of 10 nutlin-3-adapted cell lines retained their sensitivity to RITA. In addition, repeated adaptation of the RITA-adapted sub-line UKF-NB-3rRITA10 μM to nutlin-3 resulted in p53 mutations. The RITA-adapted UKF-NB-3 sub-lines displayed no or less pronounced resistance to vincristine, cisplatin, and irradiation than nutlin-3-adapted UKF-NB-3 sub-lines. Furthermore, adaptation to RITA was associated with fewer changes at the expression level of antiapoptotic factors than observed with adaptation to nutlin-3. Transcriptomic analyses indicated the RITA-adapted sub-lines to be more similar at the gene expression level to the parental UKF-NB-3 cells than nutlin-3-adapted UKF-NB-3 sub-lines, which correlates with the observed chemotherapy and irradiation sensitivity phenotypes. In conclusion, RITA-adapted cells retain functional p53, remain sensitive to nutlin-3, and display a less pronounced resistance phenotype than nutlin-3-adapted cells.
RITA; nutlin-3; p53; p53 activator; drug resistance; radiation
The use of low-molecular-weight, non-peptidic molecules that disrupt the interaction between the p53 tumor suppressor and its negative regulator MDM2 has provided a promising alternative for the treatment of different types of cancer. Among these compounds, RITA (reactivation of p53 and induction of tumor cell apoptosis) has been shown to be effective in the selective induction of apoptosis, and this effect is due to its binding to the p53 tumor suppressor. Since biological systems are highly dynamic and MDM2 may bind to different regions of p53, new alternatives should be explored. On this basis, the computational "blind docking" approach was employed in this study to see whether RITA would bind to MDM2.
It was observed that RITA binds to the MDM2 p53 transactivation domain-binding cleft. Thus, RITA can be used as a lead compound for designing improved "multi-target" drugs. This novel strategy could provide enormous benefits to enable effective anti-cancer strategies.
This study has demonstrated that a single molecule can target at least two different proteins related to the same disease.
multi-target drugs; RITA; cancer treatment; blind docking; MDM2; p53 tumor suppressor
The results of these experiments show, in short, that, by the method employed, adrenalin could neither be demonstrated in the specimen of blood, nor in either of the two specimens of malignant hypernephroma, nor in the specimen of metastatic tissue from the adrenal tumor which closely resembled a malignant hypernephroma. The results agree with those of Greer and Wells in showing that no adrenalin is found in malignant renal hypernephromas; and the further observation is made that no adrenalin content of the blood of a patient with malignant renal hypernephroma could be shown by the rabbit uterus strip test. Those rare tumors which arise from medullary adrenal tissue might be expected to contain adrenalin; but as pointed out by Greer and Wells, since the ordinary malignant renal hypernephroma arises from adrenal rests which consist of cortical tissue, and since the cortex of adrenal contains no adrenalin, no adrenalin should be expected in the tumors arising from such cortical tissue.
In order to create a worker-friendly environment for institutional foodservice, facilities operating with a dry kitchen system have been recommended. This study was designed to compare the work safety and work environment of foodservice between wet and dry kitchen systems. Data were obtained using questionnaires with a target group of 303 staff at 57 foodservice operations. Dry kitchen facilities were constructed after 2006, which had a higher construction cost and more finishing floors with anti-slip tiles, and in which employees more wore non-slip footwear than wet kitchen (76.7%). The kitchen temperature and muscular pain were the most frequently reported employees' discomfort factors in the two systems, and, in the wet kitchen, "noise of kitchen" was also frequently reported as a discomfort. Dietitian and employees rated the less slippery and slip related incidents in dry kitchens than those of wet kitchen. Fryer area, ware-washing area, and plate waste table were the slippery areas and the causes were different between the functional areas. The risk for current leakage was rated significantly higher in wet kitchens by dietitians. In addition, the ware-washing area was found to be where employees felt the highest risk of electrical shock. Muscular pain (72.2%), arthritis (39.1%), hard-of-hearing (46.6%) and psychological stress (47.0%) were experienced by employees more than once a month, particularly in the wet kitchen. In conclusion, the dry kitchen system was found to be more efficient for food and work safety because of its superior design and well managed practices.
Work safety; dry kitchen; functional area; slipperiness; work environment in foodservice
Part diary, part scientific record, biological field notebooks often contain details necessary to understanding the location and environmental conditions existent during collecting events. Despite their clear value for (and recent use in) global change studies, the text-mining outputs from field notebooks have been idiosyncratic to specific research projects, and impossible to discover or re-use. Best practices and workflows for digitization, transcription, extraction, and integration with other sources are nascent or non-existent. In this paper, we demonstrate a workflow to generate structured outputs while also maintaining links to the original texts. The first step in this workflow was to place already digitized and transcribed field notebooks from the University of Colorado Museum of Natural History founder, Junius Henderson, on Wikisource, an open text transcription platform. Next, we created Wikisource templates to document places, dates, and taxa to facilitate annotation and wiki-linking. We then requested help from the public, through social media tools, to take advantage of volunteer efforts and energy. After three notebooks were fully annotated, content was converted into XML and annotations were extracted and cross-walked into Darwin Core compliant record sets. Finally, these recordsets were vetted, to provide valid taxon names, via a process we call “taxonomic referencing.” The result is identification and mobilization of 1,068 observations from three of Henderson’s thirteen notebooks and a publishable Darwin Core record set for use in other analyses. Although challenges remain, this work demonstrates a feasible approach to unlock observations from field notebooks that enhances their discovery and interoperability without losing the narrative context from which those observations are drawn.
“Compose your notes as if you were writing a letter to someone a century in the future.”
Perrine and Patton (2011)
Field notes; notebooks; crowd sourcing; digitization; biodiversity; transcription; text-mining; Darwin Core; Junius Henderson; annotation; taxonomic referencing; natural history; Wikisource; Colorado; species occurrence records
AIMS: To evaluate the effect of the Calman reforms on SpRs in urology with respect to their educational goals, their experience of the RITA process and its value in preparing them for their chosen consultant careers. Participants and Methods: All urological trainees holding national training numbers who had completed at least one RITA review, but had not yet been awarded a CCST, were sampled. RESULTS: A total of 100 completed replies were received. Of those replying, 87% had an appointed educational supervisor with marked variation between regions. Training expectations in the four main categories of knowledge, vocational skills, operative competencies and personal development for each particular year of training were clear to only 40%, 35%, 44% and 60% of trainees, respectively. In general, trainee satisfaction with their most recent RITA review was fair with a mean of 6 (range, 4-8) on an arbitrary 10-point scale. Of the trainees, 83% felt that they would be adequately trained for consultant practice at the end of their training although this confidence varied between years of training. CONCLUSIONS: Unification in the registrar grade has initiated an improvement in urological education for SpRs. There has, however, been haphazard delivery of that education due to a lack of objectivity in definition and assessment of the educational goals in individual training years. The RITA process should be more prescriptive in its administration and the setting of annual targeted training objectives should help to optimise the training opportunities for individual SpRs.
Biomarker-based cross-sectional incidence estimation requires a Recent Infection Testing Algorithm (RITA) with an adequately large mean recency duration, to achieve reasonable survey counts, and a low false-recent rate, to minimise exposure to further bias and imprecision. Estimating these characteristics requires specimens from individuals with well-known seroconversion dates or confirmed long-standing infection. Specimens with well-known seroconversion dates are typically rare and precious, presenting a bottleneck in the development of RITAs.
The mean recency duration and a ‘false-recent rate’ are estimated from data on seroconverting blood donors. Within an idealised model for the dynamics of false-recent results, blood donor specimens were used to characterise RITAs by a new method that maximises the likelihood of cohort-level recency classifications, rather than modelling individual sojourn times in recency.
For a range of assumptions about the false-recent results (0% to 20% of biomarker response curves failing to reach the threshold distinguishing test-recent and test-non-recent infection), the mean recency duration of the Vironostika-LS ranged from 154 (95% CI: 96–231) to 274 (95% CI: 234–313) days in the South African donor population (n = 282), and from 145 (95% CI: 67–226) to 252 (95% CI: 194–308) days in the American donor population (n = 106). The significance of gender and clade on performance was rejected (p−value = 10%), and utility in incidence estimation appeared comparable to that of a BED-like RITA. Assessment of the Vitros-LS (n = 108) suggested potentially high false-recent rates.
The new method facilitates RITA characterisation using widely available specimens that were previously overlooked, at the cost of possible artefacts. While accuracy and precision are insufficient to provide estimates suitable for incidence surveillance, a low-cost approach for preliminary assessments of new RITAs has been demonstrated. The Vironostika-LS and Vitros-LS warrant further analysis to provide greater precision of estimates.
We have recently shown that induction of the p53 tumour suppressor protein by the small-molecule RITA (reactivation of p53 and induction of tumour cell apoptosis; 2,5-bis(5-hydroxymethyl-2-thienyl)furan) inhibits hypoxia-inducible factor-1α and vascular endothelial growth factor expression in vivo and induces p53-dependent tumour cell apoptosis in normoxia and hypoxia. Here, we demonstrate that RITA activates the canonical ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related DNA damage response pathway. Interestingly, phosphorylation of checkpoint kinase (CHK)-1 induced in response to RITA was influenced by p53 status. We found that induction of p53, phosphorylated CHK-1 and γH2AX proteins was significantly increased in S-phase. Furthermore, we found that RITA stalled replication fork elongation, prolonged S-phase progression and induced DNA damage in p53 positive cells. Although CHK-1 knockdown did not significantly affect p53-dependent DNA damage or apoptosis induced by RITA, it did block the ability for DNA integrity to be maintained during the immediate response to RITA. These data reveal the existence of a novel p53-dependent S-phase DNA maintenance checkpoint involving CHK-1.
p53; hypoxia; HIF-1α; DNA damage; CHK-1
The low frequency of p53 alterations e.g., mutations/deletions (∼10%) in multiple myeloma (MM) makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK) signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP) analysis showed that activated c-Jun binds to the activator protein-1 (AP-1) binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA) against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with JNK activators in the treatment of MM.
Determining the taxonomic lineage of DNA sequences is an important step in metagenomic analysis. Short DNA fragments from next-generation sequencing projects and microbes that lack close relatives in reference sequenced genome databases pose significant problems to taxonomic attribution methods. Our new classification algorithm, RITA (Rapid Identification of Taxonomic Assignments), uses the agreement between composition and homology to accurately classify sequences as short as 50 nt in length by assigning them to different classification groups with varying degrees of confidence. RITA is much faster than the hybrid PhymmBL approach when comparable homology search algorithms are used, and achieves slightly better accuracy than PhymmBL on an artificial metagenome. RITA can also incorporate prior knowledge about taxonomic distributions to increase the accuracy of assignments in data sets with varying degrees of taxonomic novelty, and classified sequences with higher precision than the current best rank-flexible classifier. The accuracy on short reads can be increased by exploiting paired-end information, if available, which we demonstrate on a recently published bovine rumen data set. Finally, we develop a variant of RITA that incorporates accelerated homology search techniques, and generate predictions on a set of human gut metagenomes that were previously assigned to different ‘enterotypes’. RITA is freely available in Web server and standalone versions.
Hurricanes Katrina, Rita, Gustav, and Ike deposited large quantities of sediment on coastal wetlands after making landfall in the northern Gulf of Mexico. We sampled sediments deposited on the wetland surface throughout the entire Louisiana and Texas depositional surfaces of Hurricanes Katrina, Rita, Gustav, and the Louisiana portion of Hurricane Ike. We used spatial interpolation to model the total amount and spatial distribution of inorganic sediment deposition from each storm. The sediment deposition on coastal wetlands was an estimated 68, 48, and 21 million metric tons from Hurricanes Katrina, Rita, and Gustav, respectively. The spatial distribution decreased in a similar manner with distance from the coast for all hurricanes, but the relationship with distance from the storm track was more variable between events. The southeast-facing Breton Sound estuary had significant storm-derived sediment deposition west of the storm track, whereas sediment deposition along the south-facing coastline occurred primarily east of the storm track. Sediment organic content, bulk density, and grain size also decreased significantly with distance from the coast, but were also more variable with respect to distance from the track. On average, eighty percent of the mineral deposition occurred within 20 km from the coast, and 58% was within 50 km of the track. These results highlight an important link between tropical cyclone events and coastal wetland sedimentation, and are useful in identifying a more complete sediment budget for coastal wetland soils.
Campylobacters were sought in swabs taken from work surfaces, sinks and floors of four kitchens-i.e. hospital, university, cook-freeze and commercial, processing frozen or fresh chickens. Each kitchen was visited on four occasions. In the large commercial kitchen environmental contamination was found on each visit, whereas campylobacters were isolated on six of the twelve visits to the other kitchens. The hands of operatives were contaminated with campylobacters on only two of the 45 swabs taken during processing. Cleaning with detergent and hot water (or steam) and drying appears to be sufficient to remove the organism from the environment. Evidence of carriage of campylobacters by the birds was obtained on all 16 visits. In the three kitchens where only frozen birds were used the organism was isolated from 30% and 9.8% of swabs taken from the internal and external surfaces respectively, while 41% of giblets and 22.2% of thawed juices yielded campylobacters. The external surface of 30 (88%) of 34 fresh birds grew campylobacters.
The Journey Project, part of the Virginia Commonwealth University Libraries' Social Work Information Specialist in Context Fellowship, was designed to merge social work and consumer health librarianship skills in order to improve the provision of health information to patients. A resource notebook was created encompassing the many dimensions of cancer health information. A social work informationist distributed the notebooks and provided individualized consultations with respect to patients' health information needs. Areas of congruence as well as key differences between social work and consumer health librarianship emerged during the course of the project. Merging the two professions into the role of a social work informationist increased the ability to attend holistically to clients' health information needs.
During the past several years, Baylor College of Medicine has made a substantial commitment to the use of information technology in support of its corporate and academic programs. The concept of an Integrated Academic Information Management System (IAIMS) has proved central in our planning, and the IAIMS activities that we have undertaken with funding from the National Library of Medicine have proved to be important extensions of our technology development. Here we describe our Virtual Notebook system, a conceptual and technologic framework for task coordination and information management in biomedical work groups. When fully developed and deployed, the Virtual Notebook will improve the functioning of basic and clinical research groups in the college, and it currently serves as a model for the longer-term development of our entire information management environment.
eCAT is an electronic lab notebook (ELN) developed by Axiope Limited. It is the first online ELN, the first ELN to be developed in close collaboration with lab scientists, and the first ELN to be targeted at researchers in non-commercial institutions. eCAT was developed in response to feedback from users of a predecessor product. By late 2006 the basic concept had been clarified: a highly scalable web-based collaboration tool that possessed the basic capabilities of commercial ELNs, i.e. a permissions system, controlled sharing, an audit trail, electronic signature and search, and a front end that looked like the electronic counterpart to a paper notebook.
During the development of the beta version feedback was incorporated from many groups including the FDA's Center for Biologics Evaluation & Research, Uppsala University, Children's Hospital Boston, Alex Swarbrick's lab at the Garvan Institute in Sydney and Martin Spitaler at Imperial College. More than 100 individuals and groups worldwide then participated in the beta testing between September 2008 and June 2009. The generally positive response is reflected in the following quote about how one lab is making use of eCAT: "Everyone uses it as an electronic notebook, so they can compile the diverse collections of data that we generate as biologists, such as images and spreadsheets. We use to it to take minutes of meetings. We also use it to manage our common stocks of antibodies, plasmids and so on. Finally, perhaps the most important feature for us is the ability to link records, reagents and experiments."
By developing eCAT in close collaboration with lab scientists, Axiope has come up with a practical and easy-to-use product that meets the need of scientists to manage, store and share data online. eCAT is already being perceived as a product that labs can continue to use as their data management and sharing grows in scale and complexity.
Currently most biomedical labs in universities and government funded research institutions use paper lab notebooks for recording experimental data and spreadsheets for managing sample data. One consequence is that sample management and documenting experiments are viewed as separate and distinct activities, notwithstanding that samples and aliquots are an integral part of a majority of the experiments carried out by these labs.
Various drivers are pushing labs towards integrated management of sample data and experimental data. These include the ever increasing amounts of both kinds of data, the increasing adoption of online collaborative tools, changing expectations about online communication, and the increasing affordability of electronic lab notebooks and sample management software. There is now an opportunity for smaller labs, which have been slow to move from paper to electronic record keeping, to leapfrog better resourced commercial labs and lead the way in adopting the new generation of tools which permit integrated management of samples and experimental data and a range of tangible benefits to conducting research, including:
1. Fewer lost and mislabelled samples
2. Clearer visualization of relationships between samples and experiments
3. Reduction of experimental error
4. More effective search
5. Productivity gains
6. More efficient use of freezers, leading to cost reduction and enhanced sustainability
7. Improved archiving and enhanced memory at the lab and institutional levels
A study was made of the extent to which frozen broilers, contaminated with indicator organisms, can cause cross-contamination in the kitchen. In 60 kitchens a number of relevant objects were sampled during the preparation of contaminated frozen broilers. The results show that cross-contamination occurred in a high proportion of the kitchens examined. In many instances the indicator organism was still present on various objects even after rinsing, 'clearing' or washing up. In view of the possible risk of a cross-contamination with Salmonella spp. the importance of instructing food preparers is emphasized. No salmonellas could be found in the sinks of the 60 kitchens examined.
Cooked chicken was allowed to spoil in a normal kitchen refrigerator (variable temperature) and at a standard 4C. After 10 days' storage, bacteria were isolated from the chicken. It was found that the numbers of organisms at variable refrigeration temperature were tenfold higher than those at a uniform 4C. In an attempt to find the sources of contamination, swabs were made of different areas of the kitchen. Many of the bacteria isolated from the spoiled chicken, were also isolated from the kitchen environment. When pure cultures of organisms isolated from spoiled chicken were inoculated into sterile cooked chicken and held at 4C, the main spoilage organisms were found to be Pseudomonas putida and Aeromonas hydrophila, which were also isolated from the refrigerator where the chickens were stored in the kitchen. Aeromonas hydrophila was found in significantly high numbers on plates, cutting knives, chopping boards and cold water taps.
To describe key determinants for residents’ selection of a new community-based, interprofessional site for their family medicine training, and to evaluate residents’ satisfaction with their programs.
Combined qualitative and quantitative methods using in-depth interviews and a survey.
McMaster University, including the new site of the Centre for Family Medicine in Kitchener-Waterloo, Ont, and a long-established site in Hamilton, Ont.
Eleven first-year and second-year family medicine residents from the Kitchener-Waterloo site participated in in-depth interviews. Forty-four first-year and second-year family medicine residents completed the survey, 22 in Kitchener-Waterloo and 22 in Hamilton.
Kitchener-Waterloo residents participated in in-depth interviews during their residency programs in 2008 to 2009 using a semistructured format to explore their choice of site and the effect of an interprofessional environment on their education. Common themes were established using qualitative analysis techniques; based on these themes, a survey was developed and distributed to residents from both sites to further explore factors influencing site selection, satisfaction, and effects of interprofessional education.
Residents identified several reasons for selecting a new community-based, interprofessional family medicine residency program. Reasons included preference for the location and opportunities to learn in an interprofessional teaching environment. A less hierarchical structure and greater opportunities for one-on-one teaching also influenced their choices. Perception of poor communication from the well established site was identified as a challenge. Residents at both sites indicated similarly high levels of program satisfaction.
Residents selected the new community-based family medicine site for reasons of geographic location and the potential for clinical learning experiences and interprofessional education. High program satisfaction was achieved at both the new and well established sites. Family medicine residency programs developing community-based networks might consider and encourage the positive influence of interprofessional care and education. Good communication between distributed sites remains a challenge.
purpose of this article is to look at how prepared people in communities outside the main areas devastated by Hurricanes Katrina and Rita thought they were for those storms and for major hurricanes in the near future, what factors were related to why people did not evacuate, and what concerns people had in communities that took in evacuees from the hurricanes.
Telephone interviews were conducted with randomly selected adults in Baton Rouge, Houston, Dallas, and Mississippi/Alabama (excluding the immediate Gulf Coast) to assess respondents' knowledge, attitudes, and behaviors about hurricane preparedness and response to Hurricanes Katrina and Rita.
The surveys found a sizeable proportion of respondents who might not, for a number of reasons, comply with future orders to evacuate. A substantial proportion reported that they were not prepared for another major hurricane and indicated a desire for more information about how to prepare for future hurricanes. In communities that reported taking in large numbers of evacuees, residents expressed concern about the impact of the evacuees on their community.
Evacuating communities involves a number of concrete problems that were not adequately addressed in the cases of Hurricanes Katrina and Rita. Responses to these surveys indicate a need for more comprehensive hurricane disaster planning.
The p53 tumor suppressor protein negatively regulates hypoxia-inducible factor 1α (HIF-1α). Here, we show that induction of p53 by the small-molecule RITA (reactivation of p53 and induction of tumor cell apoptosis) [2,5-bis(5-hydroxymethyl-2-thienyl) furan] (NSC-652287) inhibits HIF-1α and vascular endothelial growth factor expression in vivo and induces significant tumor cell apoptosis in normoxia and hypoxia in p53-positive cells. RITA has been proposed to stabilize p53 by inhibiting the p53-HDM2 interaction. However, induction of p53 alone was insufficient to block HIF-1α induced in hypoxia and has previously been shown to require additional stimuli, such as DNA damage. Here, we identify a new mechanism of action for RITA: RITA activates a DNA damage response, resulting in phosphorylation of p53 and γH2AX in vivo. Unlike other DNA damage response-inducing agents, RITA treatment of cells induced a p53-dependent increase in phosphorylation of the α subunit of eukaryotic initiation factor 2, requiring PKR-like endoplasmic reticulum kinase activity, and led to the subsequent downregulation of HIF-1α and p53 target proteins, including HDM2 and p21. Through the identification of a new mechanism of action for RITA, our study uncovers a novel link between the DNA damage response-p53 pathway and the protein translational machinery.
A patient presented with severe triple-vessel coronary artery disease, including multiple lesions on the left anterior descending coronary artery (LAD), which supplied a well-contracting myocardium. In approaching our patient, we judged that a pedicled left internal thoracic artery (LITA) would not provide enough length for sequential grafting of the multisegment-diseased LAD. We also considered that a pedicled right internal thoracic artery (RITA) conduit would not be long enough to provide a free segment that would form a tandem graft with a LITA and then arrive at the marginal branch, unless it was detached at its origin. Consequently, we decided to form a composite graft that would connect a free, short segment (6–7 cm) of pedicled LITA to the in situ pedicled RITA, in an end-to-end fashion. This new composite conduit enabled us to perform sequential grafting (3 sequential anastomoses, 2 with the LITA segment) of the multisegment-diseased LAD, following the route anterior to the aorta. The in situ remnant of the LITA was grafted to the marginal branch. Although many large series have reported resourceful solutions, to the best of our knowledge, tandem arterial sequential grafting (an in situ pedicled RITA plus a free, short segment of a pedicled LITA) has not heretofore been reported in application to the multisegmented-diseased LAD artery.
We strongly believe that this technique is an attractive variation on bilateral pedicled ITA left-sided revascularization in cases of multivessel coronary artery disease, including LADs with multiple lesions.
Coronary arteriosclerosis, diffuse; coronary artery bypass/methods; grafting, sequential; internal mammary-coronary artery anastomosis/methods; mammary arteries/transplantation; myocardial re-vascularization/methods; vascular patency