Candida dubliniensis in Japanese Oral Microbiota: A Cross-Sectional Study of Six Geographic Regions in Japan.

INTRODUCTION: Candida dubliniensis was reclassified from the C. albicans genotype D, and reports show its frequent detection in HIV-positive individuals and easy acquisition of antifungal drug resistance. However, the oral carriage rate in healthy people and contribution to candidiasis in Japan is unclear. METHODS: We conducted a cross-sectional survey of the C. dubliniensis carriage rate, performed genotyping and tested antifungal drug susceptibility and protease productivity. Specimens from 2432 Japanese subjects in six regions (1902 healthy individuals, 423 with candidiasis individuals, 107 HIV-positive individuals) were cultured using CHROMagarTMCandida, and the species was confirmed via 25S rDNA amplification and ITS sequences analyzed for genotyping. RESULTS: The C. dubliniensis carriage rate in healthy Japanese was low in the central mainland (0-15%) but high in the most northerly and southerly areas (30-40%). The distribution of these frequencies did not differ depending on age or disease (HIV-infection, candidiasis). Genotype I, previously identified in other countries, was most frequent in Japan, but novel genotypes were also observed. Six antifungal drugs showed higher susceptibility against C. albicans, but protease productivity was low. CONCLUSIONS: Oral C. dubliniensis has low pathogenicity with distribution properties attributed to geography and not dependent on age or disease status.

Defining the Middle Corona.

The middle corona, the region roughly spanning heliocentric distances from 1.5 to 6 solar radii, encompasses almost all of the influential physical transitions and processes that govern the behavior of coronal outflow into the heliosphere. The solar wind, eruptions, and flows pass through the region, and they are shaped by it. Importantly, the region also modulates inflow from above that can drive dynamic changes at lower heights in the inner corona. Consequently, the middle corona is essential for comprehensively connecting the corona to the heliosphere and for developing corresponding global models. Nonetheless, because it is challenging to observe, the region has been poorly studied by both major solar remote-sensing and in-situ missions and instruments, extending back to the Solar and Heliospheric Observatory (SOHO) era. Thanks to recent advances in instrumentation, observational processing techniques, and a realization of the importance of the region, interest in the middle corona has increased. Although the region cannot be intrinsically separated from other regions of the solar atmosphere, there has emerged a need to define the region in terms of its location and extension in the solar atmosphere, its composition, the physical transitions that it covers, and the underlying physics believed to shape the region. This article aims to define the middle corona, its physical characteristics, and give an overview of the processes that occur there.

A Statistical Comparison of EUV Brightenings Observed by SO/EUI with Simulated Brightenings in Nonpotential Simulations.

The High Resolution Imager (HRIEUV) telescope of the Extreme Ultraviolet Imager (EUI) instrument onboard Solar Orbiter has observed EUV brightenings, so-called campfires, as fine-scale structures at coronal temperatures. The goal of this paper is to compare the basic geometrical (size, orientation) and physical (intensity, lifetime) properties of the EUV brightenings with regions of energy dissipation in a nonpotential coronal magnetic-field simulation. In the simulation, HMI line-of-sight magnetograms are used as input to drive the evolution of solar coronal magnetic fields and energy dissipation. We applied an automatic EUV-brightening detection method to EUV images obtained on 30 May 2020 by the HRIEUV telescope. We applied the same detection method to the simulated energy dissipation maps from the nonpotential simulation to detect simulated brightenings. We detected EUV brightenings with a density of 1.41 × 10 - 3 brightenings/Mm2 in the EUI observations and simulated brightenings between 2.76 × 10 - 2 - 4.14 × 10 - 2 brightenings/Mm2 in the simulation, for the same time range. Although significantly more brightenings were produced in the simulations, the results show similar distributions of the key geometrical and physical properties of the observed and simulated brightenings. We conclude that the nonpotential simulation can successfully reproduce statistically the characteristic properties of the EUV brightenings (typically with more than 85% similarity); only the duration of the events is significantly different between observations and simulation. Further investigations based on high-cadence and high-resolution magnetograms from Solar Orbiter are under consideration to improve the agreement between observation and simulation.

Proteome analysis of high affinity mouse saliva proteins to hydroxyapatite.

Caries sensitivity varies between the two strains of inbred mice, BALB/cA has high sensitivity and C3H/HeN has low sensitivity. One potential reason seems to be a difference in pellicle-forming saliva protein composition. Here, we performed a proteomic analysis in order to identify differences of hydroxyapatite (HAP) adsorbed saliva proteins between these two mouse strains. HAP column chromatography revealed twice the quantity of high-affinity saliva proteins in C3H/HeN compared to BALB/cA. One- and two-dimensional electrophoresis showed 2 bands/spots with deviating migration. They were identified as murine carbonic anhydrase VI (CAVI) by peptide mass fingerprinting and confirmed with western blotting using a specific polyclonal antibody. Total RNA from the salivary glands of both mouse strains, PCR amplification of cDNA with a CAVI specific primer, and sequence analysis revealed one different base in codon 96, resulting in one different amino acid. Glyco-chains of CAVI deviate in one N-glycan, confirmed by mass analysis. CAVI activity was estimated from distinct circular dichroism spectra of the molecules and found higher in C3H/HeN mice. In summary, the CAVI composition of BALB/cA and C3H/HeN differs in one amino acid and a glyco-chain modification. Further, saliva from caries resistant C3H/HeN mice displayed higher CAVI activity and also overall hydroxyapatite adsorption, suggesting a relationship with caries susceptibility.

Limosilactobacillus (Lactobacillus) fermentum ALAL020, a Probiotic Candidate Bacterium, Produces a Cyclic Dipeptide That Suppresses the Periodontal Pathogens Porphyromonas gingivalis and Prevotella intermedia.

Periodontal disease develops as a result of oral microbiota in dysbiosis, followed by the growth of periodontal pathogens such as Porphyromonas gingivalis and Prevotella intermedia. In case of acute symptoms, antibacterial agents and disinfectants are administered, however the appearance of drug-resistant bacteria and allergies cause problems. In recent years, studies on the effects of probiotics have been conducted as an alternative therapy for periodontitis. However, the basic mechanism of the inhibitory effect of probiotic bacteria on periodontal disease has not been clearly elucidated. To clarify the antibacterial mechanism of probiotics against periodontal pathogens, we used Limosilactobacillus (Lactobacillus) fermentum ALAL020, which showed the strongest antibacterial activity against P. gingivalis and P. intermedia among 50 screened lactic acid bacteria strains. The antibacterial substances produced were identified and structurally analyzed. After neutralizing the MRS liquid culture supernatant of ALAL020 strain, the molecular weight (m/z) of the main antibacterial substance separated by gel filtration column chromatography and reverse phase HPLC was 226.131. This low molecular weight compound was analyzed by LC-MS and disclosed the composition formula C11H18O3N2, however the molecular structure remained unknown. Then, structural analysis by NMR revealed C11H18O3N2 as the cyclic dipeptide, "hexahydro-7-hydroxy-3- (2-methylpropyl) pyrrolo [1,2-a] pyrazine-1,4-dion cyclo (Hyp-Leu) ". Based on the results of this analysis, cyclo (Hyp-Leu) was chemically synthesized and the antibacterial activity against P. gingivalis and P. intermedia was measured. The minimum inhibitory concentration (MIC) was 2.5 g/L and the minimum bactericidal concentration (MBC) was shown to be less than 5 g/L. In addition, an in vitro epithelial tissue irritation test at 10 g/L showed no tissue toxicity. So far there are no reports of this peptide being produced by probiotic bacteria. Furthermore, antibacterial activity of this cyclic dipeptide against periodontal disease bacteria has not been confirmed. The results of this study might lead to a comprehensive understanding of the antibacterial mechanism against periodontal disease bacteria in future, and are considered applicable for the prevention of periodontal disease.

Investigation of the Middle Corona with SWAP and a Data-Driven Non-Potential Coronal Magnetic Field Model.

The large field-of-view of the Sun Watcher using Active Pixel System detector and Image Processing (SWAP) instrument onboard the PRoject for Onboard Autonomy 2 (PROBA2) spacecraft provides a unique opportunity to study extended coronal structures observed in the EUV in conjunction with global coronal magnetic field simulations. A global non-potential magnetic field model is used to simulate the evolution of the global corona from 1 September 2014 to 31 March 2015, driven by newly emerging bipolar active regions determined from Helioseismic and Magnetic Imager (HMI) magnetograms. We compare the large-scale structure of the simulated magnetic field with structures seen off-limb in SWAP EUV observations. In particular, we investigate how successful the model is in reproducing regions of closed and open structures, the scale of structures, and compare the evolution of a coronal fan observed over several rotations. The model is found to accurately reproduce observed large-scale, off-limb structures. When discrepancies do arise they mainly occur off the east solar limb due to active regions emerging on the far side of the Sun, which cannot be incorporated into the model until they are observed on the Earth-facing side. When such "late" active region emergences are incorporated into the model, we find that the simulated corona self-corrects within a few days, so that simulated structures off the west limb more closely match what is observed. Where the model is less successful, we consider how this may be addressed, through model developments or additional observational products. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11207-020-01668-2) contains supplementary material, which is available to authorized users.

Identifying community priorities for neighborhood livability: Engaging neighborhood residents to facilitate community assessment.

Identifying community-driven priorities to improve health outcomes is crucial toward achieving health equity. Seldom are communities experiencing health disparities included in community health assessment (CHA) and health improvement planning efforts (Pennel, McLeroy, Burdine, Matarrita-Cascante, & Wang, 2017). The purpose of this project was to conduct a CHA using a socio-ecological framework and community engagement (CE) process. In this paper we describe an exemplar engaging local residents as community facilitators to assess indicators of neighborhood livability, challenges and lessons learned, and implications for public health and community/public health nursing. Community residents were trained to facilitate focus groups and participated in analyzing these data. Data analysis yielded five neighborhood livability indicators and priorities reflecting the social determinants of health. Engaging community residents as stakeholders in CHA and health improvement planning is critical for identifying structural factors affecting neighborhood livability and priorities to improve health and well-being. Public health and health care system partnerships employing inclusive CE practices are necessary to improve overall population health outcomes. Public health nursing's role as strategy and system leaders can contribute toward the success of these cross-sector partnerships with diverse communities and populations.

The crystal structure and oligomeric form of Escherichia colil,d-carboxypeptidase A.

Bacterial peptidoglycan is constructed by cross-linking sugar chains carrying pentapeptide building blocks with two d-alanine residues at the C-terminus. Incorporation into the polymer and subsequent breakdown of peptidoglycan releases a tetrapeptide with a single d-alanine residue. Removal of this residue is necessary for the tripeptide to receive a new D-Ala-D-Ala dipeptide in the synthetic pathway, but proteases are generally unable to work with substrates having residues of unusual chirality close to the scissile bond. Processing of the tetrapeptide is carried out by a dedicated ld-carboxypeptidase, which is of interest as a novel drug target. We describe the high resolution crystal structure of the enzyme from E. coli, and demonstrate the dimeric structure is highly conserved.

Realistic Sunscreen Durability: A Randomized, Double-blinded, Controlled Clinical Study.

BACKGROUND: Studies show that sunscreen under real-life conditions is often not reapplied and/or applied insufficiently. This study investigated the durability of 2 current sunscreens with different SPF protection over an 8-hour period under simulated real-life conditions. METHODS: Participants (n=24) were randomized into two study groups utilizing either 2 mg/cm2 (FDA testing concentration) or 1 mg/cm2 (real-life application levels) of sunscreen. Two current SPF 15 and 70 sunscreens were applied to test spots on each participant's back. SPF values were obtained at baseline, 3.5, and 8 hours after initial application, during which subjects completed 30 minutes of moderate exercise followed by 80 minutes of water exposure. RESULTS: Participants in both dose study groups revealed only a 15-40% overall decrease in their SPF protection 8 hours after application. The study group that received half the FDA test concentration of sunscreen achieved approximately half or less the labeled SPF. At 8 hours, the test sites that received SPF 70 maintained an average SPF greater than 64 (2 mg/cm2 application) and 26 (1 mg/cm2 application). Similarly, the SPF 15 product test sites revealed an in vivo protection of 13 (2 mg/cm2) and 7 (1 mg/cm2). CONCLUSION: This study demonstrates that current sunscreens may be durable on skin even following significant exercise and water exposure, suggesting that reapplication intervals may be longer than currently recommended. In addition, the higher SPF sunscreen maintained a skin cancer-protective level of SPF following extended use.

J Drugs Dermatol. 2018;17(1):116-117.

Sun Protection by Beach Umbrella vs Sunscreen With a High Sun Protection Factor: A Randomized Clinical Trial.

Importance: Sun-protective behavior affects skin cancer prevention. Shade works by physically shielding skin from direct harmful UV rays; however, skin may still remain exposed to reflected and indirect UV rays. There is no current standard metric to evaluate shade for its effectiveness in sun protection, and there is insufficient clinical evidence that a beach umbrella alone can provide adequate sun protection. Objective: To directly measure sunburn protection offered by a standard beach umbrella compared with that provided by sunscreen with a high sun protection factor under actual use conditions. Design, Setting, and Participants: A single-center, evaluator-blinded, randomized clinical study was conducted from August 13 to 15, 2014, in Lake Lewisville, Texas (elevation, 159 m above sea level), among 81 participants with Fitzpatrick skin types I (n = 1), II (n = 42), and III (n = 38). Participants were randomly assigned to 2 groups: 1 using only a beach umbrella, and the other using only sunscreen with a sun protection factor of 100. All participants remained at a sunny beach for 3½ hours at midday. Clinical sunburn evaluation of each individual for all exposed body sites was conducted 22 to 24 hours after sun exposure. Interventions: The shade provided by a beach umbrella or protection provided by sunscreen with a sun protection factor of 100. Main Outcomes and Measures: Sunburn on all exposed body sites 22 to 24 hours after sun exposure. Results: Among the 81 participants (25 male and 56 female; mean [SD] age, 41 [16] years) for all body sites evaluated (face, back of neck, upper chest, arms, and legs), the umbrella group showed a statistically significant increase in clinical sunburn scores compared with baseline and had higher postexposure global scores than the sunscreen group (0.75 vs 0.05; P < .001). There was a total of 142 sunburn incidences in the umbrella group vs 17 in the sunscreen group. Thirty-two of the 41 participants (78%) in the umbrella group showed erythema in 1 or more sites vs 10 of the 40 participants (25%) in the sunscreen group (P < .001). Neither umbrella nor sunscreen alone completely prevented sunburn. Conclusions and Relevance: A beach umbrella alone may not provide sufficient protection for extended UV exposure. It is important to educate the public that combining multiple sun protection measures may be needed to achieve optimal protection. Trial Registration: isrctn.org Identifier: ISRCTN19177299.

Community Health Needs Assessments: Expanding the Boundaries of Nursing Education in Population Health.

BACKGROUND: Conducting federally mandated community health needs assessments through academic-practice partnerships provides new opportunities for developing population health nursing competencies. OBJECTIVES: The purpose of this article was to describe how a baccalaureate practicum experience within such an assessment process, involving health care system partners, re-affirms the importance of community and population health assessment in the development of future nursing leaders. RESULTS: Student evaluations indicated an emerging appreciation for the social determinants of health, the power of partnerships, and the importance of diversity. Integrating health care and public health system perspectives on assessment meets both public health and nursing accreditation standards and extends student leadership experiences. Such integration also improves regional capacity for improving population health. CONCLUSIONS: Federal mandates for community health needs assessments provide opportunities to advance leadership roles for nursing graduates throughout the health care system, and for confirming the importance of community assessment as an essential nursing competency.

Standardized Infection Ratio for Surgical Site Infection after Colon Surgery: Discord in Models Measuring Healthcare Quality.

The government publishes 3 different public report surgical site infection (SSI) metrics, all called standardized infection ratios (SIRs), that impact perceived hospital quality. We conducted a non-random cross-sectional observational pilot study of 20 California hospitals that voluntarily submitted colon surgery and SSI data. Discordant SIR values, leading to contradictory conclusions, occurred in 35% of these hospitals. Infect Control Hosp Epidemiol 2016;1-5.

Evaluation of Seasonal Changes in Facial Skin With and Without Acne.

The objective of this study was to compare facial skin of adolescent males with (acne) and without acne (non-acne) over the course of 1 year. At study entry, presence of acne was determined by clinical image analysis (acne n=7, non-acne n=10). Monthly evaluations of skin condition were made using standard and fluorescent imaging, fluorescence spectroscopic analysis, sebum analysis, skin high frequency conductivity (moisture content), transepidermal water loss (TEWL), and sampling of skin bacteria (aerobic and anaerobic). Data were evaluated seasonally. Over the course of the study, subjects in the acne and non-acne groups had no significant increase in their clinical acne score. Sebum production was significantly greater in subjects with acne than in those without for each season examined (P<0.019) and was lowest in the winter and highest in the fall. TEWL was higher in those with acne than without acne across all seasons (P=0.001). Skin moisture in both groups was increased during summer and fall compared with winter (P≤0.016 for both seasons). Subjects with acne had a higher recovery of both aerobic and anaerobic bacteria compared with subjects without acne (P≤0.015). Analysis of cheek skin in the nasal area revealed significantly higher fluorescence (500-800 nm) in image-based and spectroscopic analysis from subjects with acne, suggesting the greater presence of the bacterial metabolite porphyrin in those with acne. In these cohorts of adolescent males, significant differences in sebum production, skin barrier function, moisture content, and microbial load (anaerobic and aerobic) were noted between those with and without acne. Evidence for seasonality was observed, with lower lipid production and reduced barrier function during the winter. More studies to quantify differences in skin lipid components and bacterial species among these cohorts are planned.

An early oral health care program starting during pregnancy--a long-term study--phase V.

OBJECTIVES: Objective was to analyze the effects of a long-term prevention program on dental and oral health of adolescents. MATERIALS AND METHODS: The entire study was subdivided into five phases. Phase I comprised an individual preventive care during pregnancy, phase II assessed mothers and their children until the age of 3, and in phase III until the age of 6. In phase IV, 13- to 14-year-old teenagers were investigated. In phase V, 18-19-year-old adolescents were examined (18.4 ± 0.4 years, n = 26). All phases consisted of an examination, education, and treatment based on the concept of an "early oral health care promotion." The control group consisted of randomly selected adolescents of the same age (n = 35). The following clinical parameters were assessed: DMF-T/DMF-S, HI, PBI, PSI, and Streptococcus mutans/lactobacilli concentration in saliva. RESULTS: The adolescents of the prevention group revealed a share of 92.3 % caries-free dentition. Mean DMF-T was 1.4 ± 2.6. The control group showed a significantly higher mean DMF-T of 3.8 ± 3.2 (p < 0.05) and revealed 71.4 % of caries-free dentition. The prevention group showed a significant lower PSI of 1.2 ± 0.8 compared to the control group (2.1 ± 0.4) (p < 0.05). CONCLUSION: An "early oral health care promotion" starting during pregnancy may cause a sustained and long-term improvement of the oral health of young adults. CLINICAL RELEVANCE: Prevention programs starting during pregnancy may establish an improved health behavior. Caries, periodontitis, and dietary complications in mother and child can be avoided by improving maternal oral health and by a tooth-friendly diet.

Use of elaborate feedback and an audience-response-system in dental education.

INTRODUCTION: The aim of the study was to examine the effect of an elaborate feedback and an audience response system (ARS) on learning success. METHODS: Students of the 1st clinical semester were randomly assigned to a study and a control group. The randomization was carried out considering the factors of age, gender and power spectrum during preliminary dental examination. Within 10 lectures 5 multiple-choice questions were asked about the learning objectives and answered by the students using an ARS. Only the study group received an immediate comprehensive feedback on the results. A final exam at the end was carried out in order to evaluate whether the elaborate feedback leads to a successful learning. Furthermore the effect of the ARS on the lecture atmosphere was investigated. RESULT: The results of the final exams showed no significant difference between the study and the control group regarding the learning success. CONCLUSION: Although no significant effect on learning success was found, the ARS creates a more interactive, positive learning environment.

Herbal mixtures in traditional medicine in Northern Peru.

The investigation of plant mixtures used in traditional medicine in Northern Peru yielded a total of 974 herbal preparations used to treat 164 different afflictions. Psychosomatic disorders were, with almost 30% of all recipes applied, the most important afflictions treated. In most cases, healers used only one or two mixtures to treat an illness. However, up to 49 different preparations were used to treat the same disease. This indicates a high degree of experimentation. Altogether 330 plant species, representing almost 65% of the medicinal flora used in the region were applied in mixtures. The overwhelming number of plant mixtures contained 2-7 different plant species, although in the most extreme case 27 distinct species were included. The cluster analysis confirmed that mixtures used for applications like inflammations, infections and blood purification, as well as cough, cold, bronchitis or other respiratory disorders, or urinary infection and kidney problems had similar floristic compositions. Mixtures used for nervous system disorders, anxiety and heart problems often had a similar composition.

An early oral health care program starting during pregnancy: results of a prospective clinical long-term study.

This study covers phase IV of a prospective clinical long-term study. Objective of this clinical investigation was to analyze the effects of a long-term prevention program on dental and oral health of teenagers at the age of 13 to 14 years. The entire study was subdivided into four phases. Phase I comprised an individual preventive care during pregnancy ("primary-primary prevention"); phase II assessed mothers and their young children until the age of 3 years ("primary prevention"); and in phase III, mothers and children at the age of 6 years were investigated. In phase IV of the study, the oral health of 13- to 14-year-old teenagers was examined (13.4 +/- 0.5 years; n = 29). All phases consisted of an examination, education about oral health care, and treatment based on the concept of an early oral health care promotion. The control group consisted of randomly selected adolescents at the same age (n = 30). The following clinical parameters were assessed: decayed/missing/filled teeth (DMF-T)/decayed, missing, and filled surface teeth index, hygiene index, papilla bleeding index, Periodontal Screening Index, and Streptococcus mutans/Lactobacillus concentration in saliva. The teenagers of the "prevention" group of phase IV of our prospective study revealed a share of 89.7% caries-free dentitions (65.5% sound; 24.2% caries-free with fillings). Mean DMF-T was 0.55 +/- 1.0. The control group showed a significantly higher mean DMF-T of 1.5 +/- 1.5 (p < 0.05) and revealed 56.7% of caries-free dentitions (30% sound, 26.7% caries-free with restorations). Our data clearly document that an early oral health care promotion starting during pregnancy may cause a sustained and long-term improvement of the oral health of children.

Pulp vitality in teeth suffering trauma during orthodontic therapy.

OBJECTIVE: To examine pulpal vitality in teeth suffering dental trauma during orthodontic therapy with fixed appliances. MATERIALS AND METHODS: Pulpal condition was evaluated in 59 teeth that had suffered dental trauma during orthodontic treatment (TO-group), in 800 orthodontically treated teeth without previous dental trauma (O-group), and in 193 orthodontically untreated teeth with previous dental trauma (T-group). Pulpal vitality was examined clinically and with radiographs. Degree of pulp obliteration was rated as absent, partial, or total. All teeth in the TO-group showed a positive sensibility test prior to resumption of orthodontic therapy. RESULTS: Teeth in the TO-group revealed a significantly higher frequency of pulp necrosis than teeth in the O-group or teeth in the T-group (P < .001, respectively). In the TO-group, teeth with extrusive or lateral luxation (P = .031) and teeth with intrusive luxation (P = .015) injuries showed a significantly higher rate of pulp necrosis than teeth with fracture of enamel. In addition, teeth with total pulp obliteration showed a significantly higher frequency of pulp necrosis than teeth without pulp obliteration (P = .013). CONCLUSION: Teeth with severe periodontal injury during orthodontic therapy and subsequent total pulp obliteration have an increased risk of pulp necrosis during additional orthodontic treatment stages.

Combined treatment of dendritoma vaccine and low-dose interleukin-2 in stage IV renal cell carcinoma patients induced clinical response: A pilot study.

Vaccination using dendritic/tumor cell hybrids represents a novel and promising cancer immunotherapy. We have developed a technology that can instantly purify the hybrids (dendritomas) from the fusion mixture of dendritic cells (DCs) and tumor cells. Our animal studies and a phase I study of stage IV melanoma patients demonstrated that dendritoma vaccination could be conducted without major toxicity and induced tumor cell-specific immunological and clinical responses. In this pilot study, ten stage IV renal cell carcinoma patients were studied. Dendritomas were made from autologous DCs and tumor cells and administered by subcutaneous injection. After initial vaccination, three escalating doses of IL-2 (3, 6, and 9 million units each) were followed within five days. This treatment regimen was tolerated well without severe adverse events directly related to the dendritoma vaccine. Most adverse events were related to IL-2 administration or pre-existing disease. Patient-specific immune responses were evaluated by flow cytometric measurement of interferon-gamma-producing T-cells before and after vaccination in response to stimulation with tumor antigens. Nine out of nine patients eligible for the analysis showed an increase of IFN-gamma-expressing CD4+ T cells after vaccination(s); while five out of eight patients eligible for the analysis showed an increase of IFN-gamma-expressing CD8+ T cells. Clinical responses were documented in 40% of the patients, three with stabilization of disease and one with a partial response documented by a reduction in tumor size. This pilot study demonstrated that dendritoma vaccines could be administered safely to patients with metastatic renal cell carcinoma, while producing both clinical and immunologic evidence of response.

Optimizing the acceptance of medication-based alerts by physicians during CPOE implementation in a community hospital environment.

There are significant challenges surrounding the implementation of CPOE systems in community hospitals without a mandate for system use. One of these is to incorporate clinical decision support such as medication-based alerts, which are key to benefit realization, but can be perceived adversely by busy physicians trying to learn a new system, without negatively affecting usability and adoption. We describe a phased, iterative approach to incorporating medical-based alerts into a successful CPOE deployment. During the first 8 months after system activation, we continuously monitored the frequency of alert presentation, the frequency of "positive" responses to the alerts and physician satisfaction with each of these. Responses included alterations in filtering strategies, changes in individual drug profiles; changes in user display options; and the addition or withdrawal of entire alert categories in order to decrease maximize value and acceptance. With this strategy we were able to document order removal or modification rates of 21-66% for 6 alert categories while still achieving CPOE adoption of 75-78% during this period.