Lifetime study in mice after acute low-dose ionizing radiation: a multifactorial study with special focus on cataract risk.

Because of the increasing application of ionizing radiation in medicine, quantitative data on effects of low-dose radiation are needed to optimize radiation protection, particularly with respect to cataract development. Using mice as mammalian animal model, we applied a single dose of 0, 0.063, 0.125 and 0.5 Gy at 10 weeks of age, determined lens opacities for up to 2 years and compared it with overall survival, cytogenetic alterations and cancer development. The highest dose was significantly associated with increased body weight and reduced survival rate. Chromosomal aberrations in bone marrow cells showed a dose-dependent increase 12 months after irradiation. Pathological screening indicated a dose-dependent risk for several types of tumors. Scheimpflug imaging of the lens revealed a significant dose-dependent effect of 1% of lens opacity. Comparison of different biological end points demonstrated long-term effects of low-dose irradiation for several biological end points.

An Experience-Based Value Set for the EQ-5D-5L in Germany.

OBJECTIVE: Valuation of health states provides a summary measure useful to health care decision makers. Results may depend on whether the currently experienced health state or a hypothetical health state is being evaluated. This study derives a value set for the EuroQoL Five-Dimensional Five-Level Questionnaire (EQ-5D-5L) by focusing on the individual's current experience. DATA AND METHODS: Data include four pooled population surveys of the general German population in 2012-2015 (N = 8114). For valuation, a visual analogue scale (VAS) was used. Six specifications of a generalized linear model with binomial error distribution and constraint parameter estimation were analyzed. In each 1000 simulation runs, models were cross-validated after splitting the sample into an estimation part and a validation part. Predictive accuracy was measured by mean absolute error and sum of squared errors. RESULTS: The models rendered a consistent set of parameters. With regard to predictive accuracy, the model considering all problem levels within the five dimensions and the highest problem level reached performed best overall. DISCUSSION: Estimation proved to be feasible. Predictive accuracy exceeded that of a similar, experience-based value set for the EQ-5D-3L. Compared with a Dutch value set for the EQ-5D-5L derived for hypothetical health states, experienced values tended to be slightly lower for mild health states and substantially higher for severe health states. Clinical relevance and usefulness of the value set remain to be determined in future studies. CONCLUSIONS: For decision makers who prioritize patient-relevant benefit, the experience-based value set provides a novel option to summarize health states, reflecting how health states experienced are valued in a population.

International comparison of experience-based health state values at the population level.

BACKGROUND: Decision makers need to know whether health state values, an important component of summary measures of health, are valid for their target population. A key outcome is the individuals' valuation of their current health. This experience-based perspective is increasingly used to derive health state values. This study is the first to compare such experience-based valuations at the population level across countries. METHODS: We examined the relationship between respondents' self-rated health as measured by the EQ-VAS, and the different dimensions and levels of the EQ-5D-3 L. The dataset included almost 32,000 survey respondents from 15 countries. We estimated generalized linear models with logit link function, including country-specific models and pooled-data models with country effects. RESULTS: The results showed significant and meaningful differences in the valuation of health states and individual health dimensions between countries, even though similarities were present too. Between countries, coefficients correlated positively for the values of mobility, self-care and usual activities, but not for the values of pain and anxiety, thus underlining structural differences. CONCLUSIONS: The findings indicate that, ideally, population-specific experience-based value sets are developed and used for the calculation of health outcomes. Otherwise, sensitivity analyses are needed. Furthermore, transferring the results of foreign studies into the national context should be performed with caution. We recommend future studies to investigate the causes of differences in experience-based health state values through a single international study possibly complemented with qualitative research on the determinants of valuation.

Longitudinal change in health-related quality of life in people with prevalent and incident type 2 diabetes compared to diabetes-free controls.

OBJECTIVE: The objective of this analysis is to compare people with prevalent type 2 diabetes, incident type 2 diabetes and without diabetes with respect to longitudinal change in health-related quality of life (HRQOL) when adjusting for baseline determinants of HRQOL. RESEARCH DESIGN AND METHODS: Primary baseline and follow-up data from three regional and one national population-based cohort studies in Germany were pooled for analysis. HRQOL was measured using physical and mental health summary scores (PCS and MCS) from the German version of the Short Form Health Survey with 36 or 12 items. Mean score change per observation year was compared between the three groups (prevalent diabetes, incident diabetes, no diabetes) based on linear regression models. RESULTS: The analysis included pooled data from 5367 people aged 45-74 years at baseline. Of these, 85.5% reported no diabetes at baseline and follow-up, 6.3% reported diabetes at both baseline and follow-up (prevalent diabetes), and 8.2% reported diabetes only at follow-up (incident diabetes). Over a mean observation period of 8.7 years, annual decline in HRQOL scores is pronounced at 0.27-0.32 (PCS) and 0.34-0.38 (MCS) in the group with prevalent diabetes compared with people without diabetes. Those with incident diabetes showed intermediate values but did not differ significantly from people without diabetes after adjustment for covariates in the full model. CONCLUSION: Compared with data from cross-sectional analysis, the HRQOL loss associated with prevalent diabetes appears to be much larger than previously assumed.

Investigation of the predictive validity of laser-EPs in normal, UVB-inflamed and capsaicin-irritated skin with four analgesic compounds in healthy volunteers.

AIMS: The aim of the present study was to assess the predictivity of laser-(radiant-heat)-evoked potentials (LEPs) from the vertex electroencephalogram, using an algesimetric procedure, testing the anti-nociceptive/anti-hyperalgesic effects of single oral doses of four marketed analgesics (of different compound classes) vs. placebo, in healthy volunteers with three skin types. METHODS: This was a randomized, placebo-controlled, single-blind, five-way-crossover trial. Twenty-five healthy male/female Caucasians were included (receiving celecoxib 200 mg, pregabalin 150 mg, duloxetine 60 mg, lacosamide 100 mg or placebo) in a Williams design, with CO2 laser-induced painful stimuli to normal, ultraviolet (UV) B-inflamed and capsaicin-irritated skin. LEPs and visual analogue scale ratings were taken at baseline and hourly for 6 h postdose from all three skin types. RESULTS: In normal skin, the averaged postdose LEP peak-to-peak-(PtP)-amplitudes were reduced by pregabalin (-2.68 µV; 95% confidence interval (CI) -4.16, 1.19) and duloxetine (-1.73 µV; 95% CI -3.21, -0.26) but not by lacosamide and celecoxib vs. placebo. On UVB-irradiated skin, reflecting inflammatory pain, celecoxib induced a pronounced reduction in LEP PtP amplitudes vs. placebo (-6.2 µV; 95% CI -7.88, -4.51), with a smaller reduction by duloxetine (-4.54 µV; 95% CI -6.21, -2.87) and pregabalin (-3.72 µV; 95% CI -5.40, -2.04), whereas lacosamide was inactive. LEP PtP amplitudes on capsaicin-irritated skin, reflecting peripheral/spinal sensitization, as in neuropathic pain, were reduced by pregabalin (-3.78 µV; 95% CI -5.31, -2.25) and duloxetine (-2.32 µV; 95% CI -3.82, -0.82) but not by celecoxib or lacosamide vs. placebo, which was in agreement with known clinical profiles. Overall, PtP amplitude reductions were in agreement with subjective ratings. CONCLUSIONS: LEP algesimetry is sensitive to analgesics with different modes of action and may enable the effects of novel analgesics to be assessed during early clinical development.

Common eye diseases in older adults of southern Germany: results from the KORA-Age study.

Purpose: a population-based study in the region of Augsburg (Germany, KORA) was used to identify the prevalence of eye diseases and their risk factors in a sample of aged individuals. Methods: data originated from the KORA-Age study collected in 2012 and 822 participants (49.6% women, 50.4% men, aged 68-96 years) were asked standardised questions about eye diseases. Positive answers were validated and specified by treating ophthalmologists. Additional information came from laboratory data. Polymorphic markers were tested for candidate genes. Results: we received validations and specifications for 339 participants. The most frequent eye diseases were cataracts (299 cases, 36%), dry eyes (120 cases, 15%), glaucoma (72 cases, 9%) and age-related macular degeneration (AMD) (68 cases, 8%). Almost all participants suffering from glaucoma or from AMD also had cataracts. Cataract surgery was associated with diabetes (in men; OR = 2.24; 95% confidence interval [CI] 1.11-4.53; P = 0.025) and smoking (in women; OR = 6.77; CI 1.62-28.35; P = 0.009). In men, treatments in airway diseases was associated with cataracts (glucocorticoids: OR = 5.29, CI 1.20-23.37; P = 0.028; sympathomimetics: OR = 4.57, CI 1.39-15.00; P = 0.012). Polymorphisms in two genes were associated with AMD (ARMS2: OR = 2.28, CI 1.48-3.51; P = 0.005; CFH: OR = 2.03, CI 1.35-3.06; P = 0.010). Conclusion: combinations of eye diseases were frequent at old age. The importance of classical risk factors like diabetes, hypertension and airway diseases decreased either due to a survivor bias leaving healthier survivors in the older age group, or due to an increased influence of other up to now unknown risk factors.

EQ-5D-5L in the General German Population: Comparison and Evaluation of Three Yearly Cross-Section Surveys.

Health-related quality of life (HRQoL) is a key measure for evaluating health status in populations. Using the recent EQ-5D-5L for measurement, this study analyzed quality of life results and their stability over consecutive population surveys. Three cross-section surveys for representative samples of the general German population from 2012, 2013, and 2014 were evaluated using the EQ-5D-5L descriptive system and valuation by the Visual Analog Scale (VAS). Aggregated sample size reached 6074. The dimension with the highest prevalence of problems was pain/discomfort (31.7%). Compared with 2012 (59.3%), the percentage of participants in the best health state increased slightly in 2013 (63.4%) and 2014 (62%). Over the 3-year period, diabetes and heart disease had the strongest negative influence on mean VAS result. The number of reported chronic diseases cumulatively reduced mean VAS. Extreme problems in one or more dimensions were stated by only 0.1%-0.2% of patients. Of the potential 247 health states with a problem score ≥ 20, only six were observed in the aggregated sample. HRQoL results were fairly stable over the 3 years, but the share of the population with no problems was not. Results from the aggregated sample may serve as updated reference values for the general German population.

Assessing quality of life in a clinical study on heart rehabilitation patients: how well do value sets based on given or experienced health states reflect patients' valuations?

BACKGROUND: Quality of life as an endpoint in a clinical study may be sensitive to the value set used to derive a single score. Focusing on patients' actual valuations in a clinical study, we compare different value sets for the EQ-5D-3L and assess how well they reproduce patients' reported results. METHODS: A clinical study comparing inpatient (n = 98) and outpatient (n = 47) rehabilitation of patients after an acute coronary event is re-analyzed. Value sets include: 1. Given health states and time-trade-off valuation (GHS-TTO) rendering economic utilities; 2. Experienced health states and valuation by visual analog scale (EHS-VAS). Valuations are compared with patient-reported VAS rating. Accuracy is assessed by mean absolute error (MAE) and by Pearson's correlation ρ. External validity is tested by correlation with established MacNew global scores. Drivers of differences between value sets and VAS are analyzed using repeated measures regression. RESULTS: EHS-VAS had smaller MAEs and higher ρ in all patients and in the inpatient group, and correlated best with MacNew global score. Quality-adjusted survival was more accurately reflected by EHS-VAS. Younger, better educated patients reported lower VAS at admission than the EHS-based value set. EHS-based estimates were mostly able to reproduce patient-reported valuation. Economic utility measurement is conceptually different, produced results less strongly related to patients' reports, and resulted in about 20 % longer quality-adjusted survival. CONCLUSION: Decision makers should take into account the impact of choosing value sets on effectiveness results. For transferring the results of heart rehabilitation patients from another country or from another valuation method, the EHS-based value set offers a promising estimation option for those decision makers who prioritize patient-reported valuation. Yet, EHS-based estimates may not fully reflect patient-reported VAS in all situations.

Exploration of Energy Metabolism in the Mouse Using Indirect Calorimetry: Measurement of Daily Energy Expenditure (DEE) and Basal Metabolic Rate (BMR).

Current comprehensive mouse metabolic phenotyping involves studying energy balance in cohorts of mice via indirect calorimetry, which determines heat release from changes in respiratory air composition. Here, we describe the measurement of daily energy expenditure (DEE) and basal metabolic rate (BMR) in mice. These well-defined metabolic descriptors serve as meaningful first-line read-outs for metabolic phenotyping and should be reported when exploring energy expenditure in mice. For further guidance, the issue of appropriate sample sizes and the frequency of sampling of metabolic measurements is also discussed.

Towards patient-oriented diabetes care: results from two KORA surveys in southern Germany.

OBJECTIVE: This study aims to examine the relationship of diabetes care processes and patient outcomes with an expanded set of indicators regarding patient-oriented care delivery, such as treatment satisfaction, the quality of patient-physician relationship, and a wider range of patient outcomes such as self-management, health behaviour, disease-related burden, and health-related quality of life (HRQL). METHODS: The study population consisted of 486 participants with type 2 diabetes in two population-based follow-up surveys, conducted in 2003 to 2005 and 2006 to 2008 in Southern Germany. Data were self-reported and questionnaire-based, including the SF-12 for HRQL. Multiple regression models were used to identify associations between care processes and outcomes with adjustment for confounders. RESULTS: Frequent medical examinations increased the likelihood of self-monitoring activities, such as foot care. A positive patient experienced relationship with their physician is associated with higher adherence to medical recommendations, such as medication intake, and the score of the SF-12 mental component. Participants with diabetes-related complications reported higher levels of medical examinations and multiprofessional care. CONCLUSIONS: Indicators of patient-oriented care should become an indispensable part of diabetes clinical practice guidelines with the aim of striving for more effective support of patients.

The impact of differences between patient and general population EQ-5D-3L values on the mean tariff scores of different patient groups.

BACKGROUND: Health states can be valued by those who currently experience a health state (experienced health states [EHS]) or by the general public, who value a set of given health states (GHS) described to them. There has been debate over which method is more appropriate when making resource allocation decisions. OBJECTIVE: This article informs this debate by assessing whether differences between these methods have an effect on the mean EQ-5D-3L tariff scores of different patient groups. METHODS: The European tariff based on GHS valuations was compared with a German EHS tariff. Comparison was made in the context of EQ-5D-3L health states describing a number of diagnosed chronic diseases (stroke, diabetes, myocardial infarction, and cancer) taken from the Cooperative Health Research in the Augsburg Region population surveys. Comparison was made of both the difference in weighting of the dimensions of the EQ-5D-3L and differences in mean tariff scores for patient groups. RESULTS: Weighting of the dimensions of the EQ-5D-3L were found to be systematically different. The EHS tariff gave significantly lower mean scores for most, but not all, patient groups despite tariff scores being lower for 213 of 243 EQ-5D-3L health states using the GHS tariff. Differences were found to vary between groups, with the largest change in difference being 5.45 in the multiple stoke group. CONCLUSIONS: The two tariffs have systematic differences that in certain patient groups could drive the results of an economic evaluation. Therefore, the choice as to which is used may be critical when making resource allocation decisions.

Enamel matrix derivative in propylene glycol alginate for treatment of infrabony defects with or without systemic doxycycline: 12- and 24-month results.

BACKGROUND: This aim of this study is to compare regenerative therapy of infrabony defects with and without administration of post-surgical systemic doxycycline (DOXY) 12 and 24 months after therapy. METHODS: In each of 57 patients, one infrabony defect (depth ≥ 4 mm) was treated regeneratively using enamel matrix derivative at two centers (Frankfurt am Main and Heidelberg). By random assignment, patients received either 200 mg DOXY per day or placebo (PLAC) for 7 days after surgery. Twelve and 24 months after surgery, clinical parameters (probing depths [PDs] and vertical clinical attachment level [CAL-V]) and standardized radiographs were obtained. Missing data were managed according to the last observation carried forward. RESULTS: Data of 57 patients (DOXY: 28; PLAC: 29) were analyzed (26 males and 31 females; mean age: 52 ± 10.2 years; 13 smokers). In both groups, significant (P <0.01) PD reduction (DOXY: 3.7 ± 2.2 mm; PLAC: 3.4 ± 1.7 mm), CAL-V gain (DOXY: 2.7 ± 1.9 mm; PLAC: 3.0 ± 1.9 mm), and bone fill (DOXY: 1.6 ± 2.7 mm; PLAC: 1.8 ± 3.0 mm) were observed 24 months after surgery. However, the differences between both groups failed to be statistically significant (PD: P = 0.574; CAL-V: P = 0.696; bone fill: P = 0.318). CONCLUSIONS: Systemic DOXY, 200 mg/day for 7 days, after regenerative therapy of infrabony defects did not result in better PD reduction, CAL-V gain, or radiographic bone fill compared with PLAC 12 and 24 months after surgery, which may be attributable to low power and, thus, random chance.

Caries experience after periodontal treatment in aggressive and chronic periodontitis: results of a 10-year follow-up.

OBJECTIVE: To compare the increase of DMF-T and DMF-S in patients with aggressive periodontitis (AgP) and chronic periodontitis (ChP) after active periodontal therapy. MATERIALS AND METHODS: One hundred and thirty-six periodontally treated patients were re-examined after 10 years. Dental and periodontal status was assessed and patients' charts were screened for diagnosis, compliance to supportive periodontal treatment (SPT) and DMF-T/-S at baseline and re-examination. δDMF-T/-S was calculated and multi-level regression analyses were performed to identify factors contributing to increase of DMF-T/-S. RESULTS: Thirty patients with AgP, 37 with moderate ChP and 69 with severe ChP could be included. δDMF-T between first visit and re-examination was 2.07 (SD = 2.51, range = 0-14 teeth), mean δDMF-S = 14.66 (SD = 14.54, range = 0-83 surfaces). Patients with AgP showed a similar increase in DMF-T/-S to those with ChP. Regression analysis identified compliance as the only factor significantly accounting for preventing an increase of DMF-S (p = 0.017). No factor had a significant impact on DMF-T. CONCLUSIONS: DMF-T and DMF-S developed similarly in periodontally-treated patients with AgP and ChP during a follow-up of 10 years. SPT showed a positive influence on avoiding decline in DMF-S in periodontally compromised patients. No significant impact was detected for all other studied factors.

Impact of educational level on health-related quality of life (HRQL): results from Germany based on the EuroQol 5D (EQ-5D).

BACKGROUND: To date, there is hardly any study focussing on the question how the concept of HRQL could deepen our understanding of health inequalities. The study aims at describing this potential by analysing data for adults from Germany. METHODS: The analyses are based on three national, representative surveys conducted from 2006 to 2008. HRQL was assessed by the EuroQol-5D (EQ-5D), the descriptive part (problems in five dimensions) and the valuation of health by visual analogue scale (VAS) rendering a value between '0' (worst) and '100' (best imaginable). The major independent variable is educational level (high vs. low). Four other variables were included (i.e. age, sex, per capita income and chronic disease). Multivariate analyses were performed by logistic and linear regression. RESULTS: Data were available for 5676 persons aged ≥ 20 years (response rate 73%). The prevalence of 'moderate or severe problems' is especially high in the dimension 'pain/discomfort' (low resp. high educational level: 46.3% resp. 25.0%). The mean VAS-value is 79.8 (low resp. high educational level: 75.3 resp. 83.6). Bivariate and multivariate analyses show that similar differences in VAS-values can be seen even after restricting the analyses to participants with a chronic disease. CONCLUSION: Empirical analyses concerning HRQL could further our understanding of health inequalities. They indicate that low status groups are faced with a double burden, first by increased levels of health impairments, and second by lower levels of HRQL once health is impaired. Thus, the extent of health inequalities could be underestimated if measures of HRQL are not taken into account.

Dose-response relationship after single oral dose administrations of morphine and oxycodone using laser-evoked potentials on UVB- and capsaicin-irritated skin in healthy male subjects.

The aim of the study was to evaluate the analgesic/antihyperalgesic efficacy and to establish the dose-response relationship of morphine immediate release (IR) and oxycodone IR in a human experimental algesimetric model. Calculated effect ratios for peak-to-peak (PtP) amplitudes of laser-evoked potentials (LEPs) and visual analog scales (VAS) postlaser pain on UVB-irradiated skin (main target variables) were 1.68 and 1.18 respectively for oxycodone 10mg/morphine 20mg, 3.00 and 1.63 respectively for oxycodone 15 mg/morphine 30 mg, and 1.12 and 1.25 respectively for oxycodone 20mg/morphine 40 mg. The effect on the laser-PtP amplitude of morphine at the highest dose (40 mg) and of oxycodone at all doses (10, 15, 20mg) was considered to be clinically relevant based on a difference from placebo of ≥ 2.5 µV. For both compounds, a statistically significant linear trend was observed between dose groups in at least 1 of the 2 main target variables (adjusted P value for both end points <.001 at all doses). Hyperalgesia developed over time vs baseline due to acute exposure to UVB irradiation and to topical/occlusive 1% capsaicin solution. For both compounds, the principal onset of analgesic/antihyperalgesic drug effects was around 0.5 hours with an average peak at about 1 to 2 hours and the effect lasting for more than 3 hours (morphine 20 and 30 mg) or 6 hours (morphine 40 mg and oxycodone all doses). In conclusion, the study demonstrated a solid outcome of a mixed objective/subjective human experimental algesimetric model to approach dose-response relationships and analgesic/antihyperalgesic effects of 2 opioids.

Regenerative therapy of infrabony defects with or without systemic doxycycline. A randomized placebo-controlled trial.

AIM: Comparison of regenerative therapy of infrabony defects with and without administration of postsurgical systemic doxycycline (DOXY). METHODS: In each of 61 patients one infrabony defect was treated with enamel matrix derivative (EMD), EMD plus filler or membrane at two centres. By random assignment patients received either 200 mg DOXY per day or placebo (PLAC) for 7 days after surgery. Prior to and 6 months after surgery probing pocket depths (PPD) and vertical attachment level (PAL-V) were obtained. RESULTS: Fifty-four patients (DOXY: 27; PLAC: 27) were re-examined after 6 months and had been treated exclusively with EMD. Seven to 8 days after surgery 81% of defects in both groups showed complete flap closure. In both groups significant (p < 0.001) PPD reduction (DOXY: 3.87 ± 1.44 mm; PLAC: 3.67 ± 1.30 mm) and PAL-V gain (DOXY: 3.11 ± 1.50 mm; PLAC: 3.32 ± 1.83 mm) were observed. However, the differences failed to be statistically significant (PPD: 0.20; p = 0.588; PAL-V: 0.21; p = 0.657). CONCLUSIONS: Two hundred milligram systemic DOXY administered for 7 days after therapy of infrabony defects with EMD failed to result in better PPD reduction and PAL-V gain compared with PLAC which may be due to low power (50%) and, thus, random chance.

The performance of a value set for the EQ-5D based on experienced health states in patients with inflammatory bowel disease.

OBJECTIVES: To compare in patients with inflammatory bowel disease the performance of a value set for the EQ-5D based on experienced health states (EHSs) with value sets based on given health states (GHSs). METHODS: A value set based on EHSs and valuation by the visual analogue scale (VAS) in the German general population was compared with a German and a U.K. value set, both based on GHSs and time-trade off valuation. Accuracy in the prediction of actual VAS ratings by patients was assessed using correlation and mean absolute error. Construct validity was tested by correlation with established disease activity indices and test-retest reliability by intraclass correlation between two measurements. Data originated from a survey of 270 patients with Crohn's disease and 232 patients with ulcerative colitis. RESULTS: EHS-VAS correlates best with actual VAS ratings for all patients but not for all subgroups. EHS-VAS has the lowest mean absolute error for almost all analyzed groups except for measured differences between two time points. Regarding test-retest reliability in all patients, EHS-VAS correlations were closest to those of actual VAS ratings. CONCLUSION: EHS-VAS renders experience-based valuations but not decision utilities. GHS-based approaches cover severe health states more extensively, but study patients reported health states similar to those of a general population. Compared to GHS time-trade off value sets, the EHS-VAS value set predicted EQ-5D VAS valuations by patients with inflammatory bowel disease equally well and partly better. It performed partly better with respect to test-retest reliability and the same with respect to construct validity.

A new antigen scanning strategy for monitoring HIV-1 specific T-cell immune responses.

Delineation of the immune correlates of protection in natural infection or after vaccination is a mandatory step for vaccine development. Although the most recent techniques allow a sensitive and specific detection of the cellular immune response, a consensus on the best strategy to assess their magnitude and breadth is yet to be reached. Within the AIDS Vaccine Integrated Project (AVIP http://www.avip-eu.org) we developed an antigen scanning strategy combining the empirical-based approach of overlapping peptides with a vast array of database information. This new system, termed Variable Overlapping Peptide Scanning Design (VOPSD), was used for preparing two peptide sets encompassing the candidate HIV-1 vaccine antigens Tat and Nef. Validation of the VOPSD strategy was obtained by direct comparison with 15mer or 20mer peptide sets in a trial involving six laboratories of the AVIP consortium. Cross-reactive background responses were measured in 80 HIV seronegative donors (HIV-), while sensitivity and magnitude of Tat and Nef-specific T-cell responses were assessed on 90 HIV+ individuals. In HIV-, VOPSD peptides generated background responses comparable with those of the standard sets. In HIV-1+ individuals the VOPSD pools showed a higher sensitivity in detecting individual responses (Tat VOPSD vs. Tat 15mers or 20mers: p≤0.01) as well as in generating stronger responses (Nef VOPSD vs. Nef 20mers: p<0.001) than standard sets, enhancing both CD4 and CD8 T-cell responses. Moreover, this peptide design allowed a marked reduction of the peptides number, representing a powerful tool for investigating novel HIV-1 candidate vaccine antigens in cohorts of HIV-seronegative and seropositive individuals.

Langendorff heart: a model system to study cardiovascular effects of engineered nanoparticles.

Engineered nanoparticles (ENPs) are produced and used in increasing quantities for industrial products, food, and drugs. The fate of ENPs after usage and impact on health is less known. Especially as air pollution, suspended nanoparticles have raised some attention, causing diseases of the lung and cardiovascular system. Human health risks may arise from inhalation of ENPs with associated inflammation, dispersion in the body, and exposure of vulnerable organs (e.g., heart, brain) and tissues with associated toxicity. However, underlying mechanisms are largely unknown. Furthermore future use of ENPs in therapeutic applications is being researched. Therefore knowledge about potential cardiovascular risks due to exposure to ENPs is highly demanded, but there are no established biological testing models yet. Therefore, we established the isolated beating heart (Langendorff heart) as a model system to study cardiovascular effects of ENPs. This model enables observation and analysis of electrophysiological parameters over a minimal time period of 4 h without influence by systemic effects and allows the determination of stimulated release of substances under influence of ENPs. We found a significant dose and material dependent increase in heart rate accompanied by arrhythmia evoked by ENPs made of flame soot (Printex 90), spark discharge generated soot, anatas (TiO(2)), and silicon dioxide (SiO(2)). However, flame derived SiO(2) (Aerosil) and monodisperse polystyrene lattices exhibited no effects. The increase in heart rate is assigned to catecholamine release from adrenergic nerve endings within the heart. We propose the isolated Langendorff heart and its electrophysiological characterization as a suitable test model for studying cardiovascular ENP toxicity.

Tooth loss in aggressive periodontitis after active periodontal therapy: patient-related and tooth-related prognostic factors.

OBJECTIVES: To assess prognostic factors for tooth loss after active periodontal therapy (APT) in patients with aggressive periodontitis (AgP) at tooth level. MATERIAL AND METHODS: Eighty-four patients with AgP were re-evaluated after a mean period of 10.5 years of supportive periodontal therapy (SPT). Two thousand and fifty-four teeth were entered into the model. The tooth-related factors including baseline bone loss, tooth location and type, furcation involvement (FI), regenerative therapy, and abutment status, as well as time of follow-up and other patient-related factors were tested for their prognostic value at tooth level. Multilevel regression analysis was performed for statistical analysis to identify factors contributing to tooth loss. RESULTS: During SPT, 113 teeth (1.34 teeth per patient) were lost. Baseline bone loss, use as abutment tooth, tooth type, and maxillary location contributed significantly to tooth loss during SPT. Molars showed the highest risk for tooth loss after APT. Moreover, time of follow-up and the patient-related factor "educational status" significantly accounted for tooth loss at tooth level. CONCLUSION: Baseline bone loss, abutment status, tooth location, and type as well as time of follow-up and educational status were detected as prognostic factors for tooth loss during SPT in patients with AgP at tooth level.