Assessment of oral health in older adults by non-dental professional caregivers-development and validation of a photograph-supported oral health-related section for the interRAI suite of instruments.

OBJECTIVES: An optimized oral health-related section and a video training were developed and validated for the interRAI suite of instruments. The latter is completed by professional non-dental caregivers and used in more than 40 countries to assess care needs of older adults. METHODS: The optimized oral health-related section (ohr-interRAI) consists of nine items and a video training that were developed in consecutive phases. To evaluate psychometric properties, a study was conducted in 260 long-term care residents. Each resident was assessed by a dentist and by four caregivers (two who received the video training, two who did not). RESULTS: Mean kappa values and percent agreement between caregivers and dentist ranged between κ = 0.60 (80.2%) for dry mouth and κ = 0.13 (54.0%) for oral hygiene. The highest inter-caregiver agreement was found for dry mouth with κ = 0.63 [95% CI: 0.56-0.70] (81.6%), while for the item palate/lips/cheeks only κ = 0.27 [95% CI: 0.18-0.36] (76.7%) was achieved. Intra-caregiver agreement ranged between κ = 0.93 [95% CI: 0.79-1.00] (96.4%) for dry mouth and κ = 0.45 [95% CI: 0.06-0.84] (82.8%) for gums. Logistic regression analysis showed only small differences between caregivers who watched the video training and those who did not. CONCLUSIONS: Psychometric properties of the optimized ohr-interRAI section were improved compared to previous versions. Nevertheless, particularly the items based on inspection of the mouth require further refinement and caregiver training needs to be improved. CLINICAL RELEVANCE: Valid assessment of oral health by professional caregivers is essential due to the impaired accessibility of regular dental care for care-dependent older adults.

Development of practice guidelines for daily oral care in care-dependent older adults to complement the InterRAI suite of instruments using a modified Delphi approach.

AIM: To develop practice guidelines for nursing assistants who provide daily oral care to older adults. BACKGROUND: The interRAI suite of instruments is internationally used in professional health care to assess the needs of care-dependent older persons. An optimised oral health section was developed recently to identify care clients with poor oral health and hygiene. Internationally shared guidelines for daily oral care are needed to complement the optimised oral health section of the interRAI suite of instruments. MATERIAL AND METHODS: The modified Delphi approach started with the preparation of an initial draft. Subsequently, an online survey and a face-to-face discussion were conducted with international experts. Their feedback was used to revise the draft. Two additional online surveys were conducted with the experts to reach consensus agreement for each item of the revised version. The same group of experts was invited to the different study phases. RESULTS: The three surveys were completed by 26, 27 and 23 international experts, respectively. A group of 18 experts completed each survey, whereof a subgroup of 11 experts also took part in the face-to-face discussion. Experts were dental hygienists, dentists, nursing scientists, physicians and psychologists from 14 different countries. After the final survey, consensus agreement was reached for 54 of the 57 (94.7%) items, representing the final version of the guidelines. CONCLUSION: Available evidence was combined with practical feedback from international experts to develop clear and concise practice guidelines for daily oral care in older adults. IMPLICATIONS FOR PRACTICE: The guidelines will help to improve knowledge and reduce barriers of nursing assistants to provide daily oral care.

Assessment of oral health conditions presented in photographs - is there a difference between dentists and non-dental professional caregivers?

BACKGROUND: Photographs can help non-dental professional caregivers to identify problems when inspecting the mouth of care-dependent older individuals. This study evaluated whether the assessment of oral health-related conditions presented in photographs differed between dentists and non-dental professional caregivers. MATERIALS AND METHODS: One-hundred-and-seventy-nine photographs were taken from long-term care facility residents and from patients at the Department of Dentistry of a University Hospital. The following oral health aspects were depicted: denture hygiene, oral hygiene, teeth, gums, tongue and palate/lips/cheeks. Collection continued until for each oral health aspect a pool of photographs was available that showed conditions from perfect health and hygiene to severe problems. A segmented Visual Analogue Scale was applied to assess the conditions presented in the photographs. Each photograph was assessed by each participant of this study. The benchmark was established by three dentists with academic-clinical expertise in gerodontology, special needs dentistry and periodontology. For each photograph, they provided a collective score after reaching consensus. Photographs were assessed individually by 32 general dentists and by 164 non-dental professional caregivers. Linear mixed effects models and generalized linear mixed effects models were fitted and mean squared errors were computed to quantify differences between both groups. RESULTS: For the different oral health aspects, absolute distances from the benchmark scores were 1.13 (95%CI:1.03-1.23) to 1.51 (95%CI:1.39-1.65) times higher for the caregivers than for the dentists. The odds to overestimate the condition were higher for the caregivers than the dentists for oral hygiene (OR = 0.72, 95%CI = 0.62-0.84) and teeth (OR = 0.74; 95%CI = 0.61-0.88). The odds to underestimate the condition were higher for the caregivers than the dentists for gums (OR = 1.39; 95%CI:1.22-1.59) and palate/lips/cheeks (OR = 1.22; 95%CI = 1.07-1.40). Over all assessments, the variance in caregiver scores was 1.9 (95%CI:1.62-2.23) times higher than that for the dentists. CONCLUSION: Small but significant differences were found between dentists and non-dental professional caregivers assessing oral health-related conditions presented in photographs. When photographs are used to aid non-dental professional caregivers with the oral health assessment, these visualizations should be complemented with comments to facilitate accurate interpretation.

Can the interRAI home care instrument be applied to the definition criteria of the Global Leadership Initiative on Malnutrition (GLIM)? A longitudinal study.

BACKGROUND & AIMS: As malnutrition is an important modifiable risk factor for poor clinical outcomes, it is important to target malnourished older people and older people at risk of malnourishment. The Global Leadership Initiative on Malnutrition (GLIM) recently reached a consensus for a global definition of malnutrition. The primary aim of this study was to apply the interRAI Home Care (interRAI HC) instrument to fit the GLIM definition criteria of malnutrition to the closest. A second goal was to identify potential risk factors associated with malnutrition using this comprehensive assessment and to quantify their association. METHODS: This is a case control study, which retrospectively determines the exposure to the risk of malnutrition and estimates its potential risk factors. The longitudinal data came from a larger study called Protocol 3. Eligibility criteria were a minimum age of 65 years old, a minimum score of 6 on the Edmonton Frail Scale or at least a moderate level of functional impairment measured by a Belgian version of the Katz scale. Older people with an official dementia diagnosis were also eligible. Bivariate analysis was performed and logistic regression models were developed in order to identify significant determinants of malnutrition. RESULTS: The data consisted of 6334 frail older people (mean age: 80.6 ± 6.9, 70.6% female). About 2.4% became malnourished within a follow-up period of one year after baseline. The adjusted logistic regression yielded significant odds ratios for dysphagia (OR 2.2), loss of appetite (OR 1.8), bladder incontinence (OR 1.5) and low fluid intake (OR 1.5). Diabetes (OR 0.5) and visits to the physician (OR 0.5) had both a significant reverse effect. CONCLUSIONS: This study was the first large longitudinal research to explore the risk factors of malnutrition with a comprehensive assessment instrument as the interRAI HC, applying it to the recent GLIM definition criteria. The worldwide use of the interRAI instruments makes these findings relevant for global clinical practice and research. Adapting the interRAI instruments to the GLIM definition improves accurate detection, prevention and early treatment of malnourishment, avoiding further health deterioration in older people.

The oral health-related section of the interRAI: Evaluation of test content validity by expert rating and assessment of potential reasons for inaccurate assessments based on focus group discussions with caregivers.

OBJECTIVES: To explore the failure of the oral health-related section of the interRAI (ohr-interRAI), this study investigated test content validity (A.) and reasons for inaccurate assessments (B.). BACKGROUND: Poor oral health negatively affects quality of life and is associated with a number of systemic diseases. The interRAI instruments, internationally used for geriatric assessment, should accurately detect oral conditions that require care. Previous research showed that the ohr-interRAI and related precursor versions do not achieve this goal. MATERIALS AND METHODS: (A.) A group of 12 experts rated completeness, relevance, clarity of wording and feasibility of the ohr-interRAI. Content validity indices were calculated per item (threshold 0.78). (B.) Focus group discussions with 23 caregivers were organized. A semi-structured question guide made sure that all topics of interest were covered. Qualitative content structuring analysis was applied after transcription. RESULTS: (A.) Experts agreed on the relevance of the items on chewing, pain, gingival inflammation and damaged teeth. They regarded none of the items as worded clearly and only prosthesis use and pain were considered to be assessable by untrained caregivers. All experts agreed that the ohr-interRAI was incomplete. (B.) Focus group discussions revealed that in the care environment oral health had low priority. Aspects related to the ohr-interRAI itself and aspects related to the assessment situation impeded the oral health assessment. The approach of the caregivers to complete the ohr-interRAI was inappropriate to accurately detect oral care needs. CONCLUSIONS: Findings challenge test content validity of the ohr-interRAI and reveal reasons for inaccurate assessments.

Cross-Country Validation of the Association Between Oral Health and General Health in Community-Dwelling Older Adults.

OBJECTIVE: Oral health is known to be associated with general health, but longitudinal relationships between oral health and general health indicators have not yet been fully explored in international research. SETTING AND PARTICIPANTS: The sample consisted of 3 longitudinal databases: a sample from Belgium from the Protocol 3 project (n = 8359), a combined sample from 6 European countries (n = 2501) from the IBenC study (Belgium, Finland, Iceland, Germany, Italy, and the Netherlands), and a sample from New Zealand (n = 15,012). All clients were 65 years or older and received long-term home care services. METHODS: Bayesian models were used to analyze the associations between 3 oral health indicators (chewing difficulty, nonintact teeth, and dry mouth) and 4 aspects of general health (activities of daily living functioning, cognition, depression, and health instability). In addition, the models explored the associations between current oral health and general health status and future oral health and general health status. RESULTS: Clients who had poorer oral health had a higher risk of suffering from poor general health. Especially chewing difficulty was associated with all general health indicators in all data sets (odds ratios > 1). Dry mouth and nonintact teeth showed significant associations with almost all general health indicators. Additionally, having poor oral health (respectively general health) was predictive of poor general health (respectively oral health) at future assessments (significant cross-lagged parameters). CONCLUSIONS/IMPLICATIONS: The results point out the need of the inclusion of oral health assessment and advice from dentists or oral health practitioners into the multidisciplinary conversation. In addition, identifying older people with oral health problems is essential in order to provide treatment and monitoring. Raising awareness for oral health is important, and policy makers should foster oral health promotion and care for older adults in order to keep them in good health.

Association between oral health and general health indicators in older adults.

Oral health (OH) and general health (GH) indicators are representations of the health status of the body. The OH indicators provide information about the oral health status while the GH indicators are used to assess the functional, cognitive, and mental conditions. OH is reported to be associated with GH. However, some specific associations, especially longitudinal relationships between OH and GH indicators, have not been fully explored. We examined the prediction ability from OH to GH and vice versa using a Belgian registry. We collected information from 8359 elderly participants, who were older than 65, lived at home, and received home care. The demographic and clinical information including three binary OH indicators and four ordinal GH indicators were collected. The participants were recorded at baseline and every six months afterwards. We opted for a generalization of a vector autoregressive model to ordinal responses. This model allows to estimate autocorrelations and cross-lagged correlations, addressing the prediction of GH from OH in a cross-sectional and longitudinal manner. We showed that individuals who had poorer OH had a higher risk of suffering from poor GH status. The percentages of correct or close prediction for GH indicators from OH indicators are high, being around 80% for all GH indicators. Additionally, having a poor OH (resp. GH) status was additionally predictive of a poor GH (resp. OH) status at following assessments. Our finding suggests using historical records of OH as well as GH indicators to draw better health care plan for geriatrics population.

Predictors of Patient Satisfaction with Removable Denture Renewal: A Pilot Study.

PURPOSE: Conventional removable dentures still play an important role in the treatment of lost teeth. A thorough understanding of the parameters that influence patient satisfaction is useful for deciding whether denture replacement is meaningful. From a clinical perspective, factors that can be measured before starting treatment are relevant. This pilot study investigated whether patient satisfaction after denture renewal was affected by aspects related to the old prostheses, type of jaw, and patient motivation for denture renewal. MATERIALS AND METHODS: Fifty subjects (mean age 68.2 ± 8.4) were provided with 74 removable dentures (partial n = 20, complete n = 54). Satisfaction was assessed before treatment and 3 months after new prosthesis insertion. Total satisfaction 3-month post-insertion (TSP3) merged 6 individual satisfaction items measured after treatment. Change of total satisfaction 3-month post-insertion (CTS3) represented the difference of total satisfaction when old and new prostheses were compared. The effect of the following independent variables was investigated: reason patients requested new dentures (fit, esthetics, broken denture, wear, advice of dentist, extractions), satisfaction with the old prosthesis (general, retention, stability, comfort, pronunciation, chewing, esthetics), and technical quality of the old prostheses as assessed by a dentist (stability, retention, fit, border, wear, esthetics). Gender, age, and a cognitive screening test were included as confounding variables. Mann-Whitney-U tests and linear mixed model analysis were performed. RESULTS: All individual satisfaction items significantly improved with new prostheses for maxillary and mandibular jaws. TSP3 was higher for maxillary prostheses, if retention satisfaction with the old prosthesis was good, and if the dentist assessed the esthetics of the old prosthesis as deficient. CTS3 was associated with male gender, dissatisfaction with chewing before treatment, and dissatisfaction with esthetics before treatment. CONCLUSIONS: This pilot study showed that satisfaction 3 months after new denture insertion was associated with aspects of satisfaction and quality related to the old prosthesis, type of jaw, and gender. These factors may help dentists predict therapeutic benefits when deciding on the need for denture replacement. Further research should be done with a greater number of subjects and should include balanced quantities of the different types of dentures.

Risk Factors for Malnutrition in Older Adults: A Systematic Review of the Literature Based on Longitudinal Data.

The present systematic review critically examines the available scientific literature on risk factors for malnutrition in the older population (aged ≥65 y). A systematic search was conducted in MEDLINE, reviewing reference lists from 2000 until March 2015. The 2499 papers identified were subjected to inclusion criteria that evaluated the study quality according to items from validated guidelines. Only papers that provided information on a variable's effect on the development of malnutrition, which requires longitudinal data, were included. A total of 6 longitudinal studies met the inclusion criteria and were included in the systematic review. These studies reported the following significant risk factors for malnutrition: age (OR: 1.038; P = 0.045), frailty in institutionalized persons (ß: 0.22; P = 0.036), excessive polypharmacy (ß: -0.62; P = 0.001), general health decline including physical function (OR: 1.793; P = 0.008), Parkinson disease (OR: 2.450; P = 0.047), constipation (OR: 2.490; P = 0.015), poor (OR: 3.30; P value not given) or moderate (ß: -0.27; P = 0.016) self-reported health status, cognitive decline (OR: 1.844; P = 0.001), dementia (OR: 2.139; P = 0.001), eating dependencies (OR: 2.257; P = 0.001), loss of interest in life (ß: -0.58; P = 0.017), poor appetite (ß: -1.52; P = 0.000), basal oral dysphagia (OR: 2.72; P = 0.010), signs of impaired efficacy of swallowing (OR: 2.73; P = 0.015), and institutionalization (ß: -1.89; P < 0.001). These risk factors for malnutrition in older adults may be considered by health care professionals when developing new integrated assessment instruments to identify older adults' risk of malnutrition and to support the development of preventive and treatment strategies.

Impact of Denture Cleaning Method and Overnight Storage Condition on Denture Biofilm Mass and Composition: A Cross-Over Randomized Clinical Trial.

BACKGROUND: Appropriate oral hygiene is required to maintain oral health in denture wearers. This study aims to compare the role of denture cleaning methods in combination with overnight storage conditions on biofilm mass and composition on acrylic removable dentures. METHODS: In a cross-over randomized controlled trial in 13 older people, 4 conditions with 2 different mechanical cleaning methods and 2 overnight storage conditions were considered: (i) brushing and immersion in water without a cleansing tablet, (ii) brushing and immersion in water with a cleansing tablet, (iii) ultrasonic cleaning and immersion in water without a cleansing tablet, and (iv) ultrasonic cleaning and immersion in water with a cleansing tablet. Each test condition was performed for 5 consecutive days, preceded by a 2-days wash-out period. Biofilm samples were taken at baseline (control) and at the end of each test period from a standardized region. Total and individual levels of selected oral bacteria (n = 20), and of Candida albicans were identified using the Polymerase Chain Reaction (PCR) technique. Denture biofilm coverage was scored using an analogue denture plaque score. Paired t-tests and Wilcoxon-signed rank tests were used to compare the test conditions. The level of significance was set at α< 5%. RESULTS: Overnight denture storage in water with a cleansing tablet significantly reduced the total bacterial count (p<0.01). The difference in total bacterial level between the two mechanical cleaning methods was not statistically significant. No significant effect was observed on the amount of Candida albicans nor on the analogue plaque scores. CONCLUSIONS: The use of cleansing tablets during overnight denture storage in addition to mechanical denture cleaning did not affect Candida albicans count, but reduced the total bacterial count on acrylic removable dentures compared to overnight storage in water. This effect was more pronounced when combined with ultrasonic cleaning compared to brushing. TRIAL REGISTRATION: ClinicalTrials.gov NCT02454413.

Missing Oral Health-Related Data in the interRAI-HC - Associations with Selected Variables of General Health and the Effect of Multiple Imputation on the Relationship between Oral and General Health.

BACKGROUND: Missing data within the comprehensive geriatric assessment of the interRAI suite of assessment instruments potentially imply the under-detection of conditions that require care as well as the risk of biased statistical results. Impaired oral health in older individuals has to be registered accurately as it causes pain and discomfort and is related to the general health status. OBJECTIVE: This study was based on interRAI-Home Care (HC) baseline data from 7590 subjects (mean age 81.2 years, SD 6.9) in Belgium. It was investigated if missingness of the oral health-related items was associated with selected variables of general health. It was also determined if multiple imputation of missing data affected the associations between oral and general health. MATERIALS AND METHODS: Multivariable logistic regression was used to determine if the prevalence of missingness in the oral health-related variables was associated with activities of daily life (ADLH), cognitive performance (CPS2) and depression (DRS). Associations between oral health and ADLH, CPS2 and DRS were determined, with missing data treated by 1. the complete-case technique and 2. by multiple imputation, and results were compared. RESULTS: The individual oral health-related variables had a similar proportion of missing values, ranging from 16.3% to 17.2%. The prevalence of missing data in all oral health-related variables was significantly associated with symptoms of depression (dental prosthesis use OR 1.66, CI 1.41-1.95; damaged teeth OR 1.74, CI 1.48-2.04; chewing problems OR 1.74, CI 1.47-2.05; dry mouth OR 1.65, CI 1.40-1.94). Missingness in damaged teeth (OR 1.27, CI 1.08-1.48), chewing problems (OR 1.22, CI 1.04-1.44) and dry mouth (OR 1.23, CI 1.05-1.44) occurred more frequently in cognitively impaired subjects. ADLH was not associated with the prevalence of missing data. When comparing the complete-case technique with the multiple imputation approach, nearly identical odds ratios characterized the associations between oral and general health. CONCLUSION: Cognitively impaired and depressive individuals had a higher risk of missing oral health-related information. Associations between oral health and ADLH, CPS2 and DRS were not influenced by multiple imputation of missing data. Further research should concentrate on the mechanisms that mediate the occurrence of missingness to develop preventative strategies.

Human B cells differentiate into granzyme B-secreting cytotoxic B lymphocytes upon incomplete T-cell help.

Recently, CD4(+) T helper cells were shown to induce differentiation of human B cells into plasma cells by expressing interleukin (IL-)21 and CD40 ligand (CD40L). In the present study we show, that in the absence of CD40L, CD4(+) T cell-derived IL-21 induces differentiation of B cells into granzyme B (GzmB)-secreting cytotoxic cells. Using fluorescence-activated cell sorting (FACS) analysis, ELISpot and confocal microscopy, we demonstrate that CD4(+) T cells, activated via their T-cell receptor without co-stimulation, can produce IL-21, but do not express CD40L and rapidly induce GzmB in co-cultured B cells in an IL-21 receptor-dependent manner. Of note, we confirmed these results with recombinant reagents, highlighting that CD40L suppresses IL-21-induced GzmB induction in B cells in a dose-dependent manner. Surprisingly, although GzmB-secreting B cells did not express perforin, they were able to transfer active GzmB to tumor cell lines, thereby effectively inducing apoptosis. In contrast, no cytotoxic effects were found when effector B cells were activated with IL-2 instead of IL-21 or when target cells were cultured with IL-21 alone. Our findings suggest GzmB(+) cytotoxic B cells may have a role in early cellular immune responses including tumor immunosurveillance, before fully activated, antigen-specific cytotoxic T cells are on the spot. CD40 ligand determines whether IL-21 induces differentiation of B cells into plasma cells or into granzyme B-secreting cytotoxic cells.

Molecular signatures classify astrocytic gliomas by IDH1 mutation status.

To identify novel glioma-associated pathomechanisms and molecular markers, we performed an array-based comparative genomic hybridization analysis of 131 diffuse astrocytic gliomas, including 87 primary glioblastomas (pGBIV), 13 secondary glioblastomas (sGBIV), 19 anaplastic astrocytomas (AAIII) and 12 diffuse astrocytomas (AII). All tumors were additionally screened for IDH1 and IDH2 mutations. Expression profiling was performed for 74 tumors (42 pGBIV, 11 sGBIV, 13 AAIII, 8 AII). Unsupervised and supervised bioinformatic analyses revealed distinct genomic and expression profiles separating pGBIV from the other entities. Classifier expression signatures were strongly associated with the IDH1 gene mutation status. Within pGBIV, the rare subtype of IDH1 mutant tumors shared expression profiles with IDH1 mutant sGBIV and was associated with longer overall survival compared with IDH1 wild-type tumors. In patients with IDH1 wild-type pGBIV, PDGFRA gain or amplification as well as 19q gain were associated with patient outcome. Array-CGH analysis additionally revealed homozygous deletions of the FGFR2 gene at 10q26.13 in 2 pGBIV, with reduced FGFR2 mRNA levels being frequent in pGBIV and linked to poor outcome. In conclusion, we report that diffuse astrocytic gliomas can be separated into 2 major molecular groups with distinct genomic and mRNA profiles as well as IDH1 gene mutation status. In addition, our results suggest FGFR2 as a novel glioma-associated candidate tumor suppressor gene on the long arm of chromosome 10.

Elimination of a cis-proline-containing loop and turn optimization stabilizes a protein and accelerates its folding.

In the N2 domain of the gene-3-protein of phage fd, two consecutive beta-strands are connected by a mobile loop of seven residues (157-163). The stability of this loop is low, and the Asp160-Pro161 bond at its tip shows conformational heterogeneity with 90% being in the cis and 10% in the trans form. The refolding kinetics of N2 are complex because the molecules with cis or trans isomers at Pro161 both fold to native-like conformations, albeit with different rates. We employed consensus design to shorten the seven-residue irregular loop around Pro161 to a four-residue type I' turn without a proline. This increased the conformational stability of N2 by almost 10 kJ mol(-1) and abolished the complexity of the folding kinetics. Turn sequences obtained from in vitro selections for increased stability strongly resembled those derived from the consensus design. Two other type I' turns of N2 could also be stabilized by consensus design. For all three turns, the gain in stability originates from an increase in the rate of refolding. The turns form native-like structures early during refolding and thus stabilize the folding transition state. The crystal structure of the variant with all three stabilized turns confirms that the 157-163 loop was in fact shortened to a type I' turn and that the other turns maintained their type I' conformation after sequence optimization.

Genomic and expression profiling of glioblastoma stem cell-like spheroid cultures identifies novel tumor-relevant genes associated with survival.

PURPOSE: Glioblastoma spheroid cultures are enriched in tumor stem-like cells and therefore may be more representative of the respective primary tumors than conventional monolayer cultures. We exploited the glioma spheroid culture model to find novel tumor-relevant genes. EXPERIMENTAL DESIGN: We carried out array-based comparative genomic hybridization of spheroid cultures derived from 20 glioblastomas. Microarray-based gene expression analysis was applied to determine genes with differential expression compared with normal brain tissue and to nonneoplastic brain spheroids in glioma spheroid cultures. The protein expression levels of three candidates were determined by immunohistochemistry on tissue microarrays and correlated with clinical outcome. Functional analysis of PDPN was done. RESULTS: Genomic changes in spheroid cultures closely resembled those detected in primary tumors of the corresponding patients. In contrast, genomic changes in serum-grown monolayer cultures established from the same patients did not match well with the respective primary tumors. Microarray-based gene expression analysis of glioblastoma spheroid cultures identified a set of novel candidate genes being upregulated or downregulated relative to normal brain. Quantitative real-time PCR analyses of 8 selected candidate genes in 20 clinical glioblastoma samples validated the microarray findings. Immunohistochemistry on tissue microarrays revealed that expression of AJAP1, EMP3, and PDPN was significantly associated with overall survival of astrocytic glioma patients. Invasive capacity and RhoA activity were decreased in PDPN-silenced spheroids. CONCLUSION: We identified a set of novel candidate genes that likely play a role in glioblastoma pathogenesis and implicate AJAP1, EMP3, and PDPN as molecular markers associated with the clinical outcome of glioma patients.