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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Efficacy of tacrolimus 0.1% ointment in cutaneous lupus erythematosus: a multicenter, randomized, double-blind, vehicle-controlled trial.

BACKGROUND: Topical calcineurin inhibitors are licensed for the treatment of atopic dermatitis; however, the efficacy of tacrolimus in cutaneous lupus erythematosus (CLE) has only been shown in single case reports. OBJECTIVE: In a multicenter, randomized, double-blind, vehicle-controlled trial, we sought to evaluate the efficacy of tacrolimus 0.1% ointment for skin lesions in CLE. METHODS: Thirty patients (18 female, 12 male) with different subtypes of CLE were included, and two selected skin lesions in each patient were treated either with tacrolimus 0.1% ointment or vehicle twice daily for 12 weeks. The evaluation included scoring of clinical features, such as erythema, hypertrophy/desquamation, edema, and dysesthesia. RESULTS: Significant improvement (P < .05) was seen in skin lesions of CLE patients treated with tacrolimus 0.1% ointment after 28 and 56 days, but not after 84 days, compared with skin lesions treated with vehicle. Edema responded most rapidly to tacrolimus 0.1% ointment and the effect was significant (P < .001) in comparison to treatment with vehicle after 28 days. Clinical score changes in erythema also showed remarkable improvement (P < .05) after 28 days, but not after 56 and 84 days. Moreover, patients with lupus erythematosus tumidus revealed the highest degree of improvement. None of the patients with CLE demonstrated any major side effects. LIMITATIONS: The study was limited by the small sample size. CONCLUSION: Explorative subgroup analyses revealed that topical application of tacrolimus 0.1% ointment may provide at least temporary benefit, especially in acute, edematous, non-hyperkeratotic lesions of CLE patients, suggesting that calcineurin inhibitors may represent an alternative treatment for the various disease subtypes.

Patient-related risk factors for tooth loss in aggressive periodontitis after active periodontal therapy.

OBJECTIVES: Evaluation of patient-related risk factors contributing to tooth loss and recurrence of periodontitis 10.5 years after initial therapy in patients with aggressive periodontitis (AgP). MATERIAL AND METHODS: Eighty-four of 174 patients were included. Re-examination consisted of patient's history, clinical examination and test for interleukin (IL)-1 composite genotype. Patients' charts were searched for regularity of maintenance and initial diagnosis. Statistical analysis was performed using Poisson and logistical regression analysis. RESULTS: The responder rate was 48%. Thirteen of 84 patients presented a localized AgP, 68 were females and 29 smoked. One hundred and thirteen teeth out of 2154 were lost after therapy (1.34 teeth/patient). Age (p=0.0018), absence of IL-1 composite genotype (p=0.0091) and educational status (p=0.0085) were identified as statistically significant risk factors for tooth loss. Twenty patients exhibited recurrence of periodontitis at re-examination. Smoking (p=0.0034) and mean Gingival Bleeding Index (GBI) (p=0.0239) contributed significantly to recurrence of disease. No patient participating regularly in supportive periodontal therapy (SPT) showed disease recurrence. CONCLUSION: Age, absence of IL-1 composite genotype and low social status are detected as risk factors for tooth loss. Smoking and high mean GBI are associated with an increased risk for recurrence of periodontitis, whereas regular SPT acts as a protective factor.

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.

The procoagulant effects of fine particulate matter in vivo.

Inhalation of fine particulate matter (<2.5 µm; fine PM) has been shown to increase the risk for cardiovascular events. In this letter, we reappraise the role of tissue factor (TF) antigen and we also summarize changes in measured coagulation proteins in humans and rodents by other studies with fine PM. By considering all studies including ours, we conclude that monitoring the overall coagulation state by measuring capacity assays such as thrombin generation, and quantification of TF activity would be more suitable than determining single coagulation proteins (such as TF antigen) in order to better assess the systemic prothrombotic effects of fine PM.

Cardiovascular and inflammatory effects of intratracheally instilled ambient dust from Augsburg, Germany, in spontaneously hypertensive rats (SHRs).

RATIONALE: Several epidemiological studies associated exposure to increased levels of particulate matter in Augsburg, Germany with cardiovascular mortality and morbidity. To elucidate the mechanisms of cardiovascular impairments we investigated the cardiopulmonary responses in spontaneously hypertensive rats (SHR), a model for human cardiovascular diseases, following intratracheal instillation of dust samples from Augsburg. METHODS: 250 µg, 500 µg and 1000 µg of fine ambient particles (aerodynamic diameter <2.5 µm, PM2(.)5-AB) collected from an urban background site in Augsburg during September and October 2006 (PM2(.)5 18.2 µg/m³, 10,802 particles/cm3) were instilled in 12 months old SHRs to assess the inflammatory response in bronchoalveolar lavage fluid (BALF), blood, lung and heart tissues 1 and 3 days post instillation. Radio-telemetric analysis was performed to investigate the cardiovascular responses following instillation of particles at the highest dosage based on the inflammatory response observed. RESULTS: Exposure to 1000 µg of PM2(.)5-AB was associated with a delayed increase in delta mean blood pressure (ΔmBP) during 2(nd)-4(th) day after instillation (10.0 ± 4.0 vs. -3.9 ± 2.6 mmHg) and reduced heart rate (HR) on the 3rd day post instillation (325.1 ± 8.8 vs. 348.9 ± 12.5 bpm). BALF cell differential and inflammatory markers (osteopontin, interleukin-6, C-reactive protein, and macrophage inflammatory protein-2) from pulmonary and systemic level were significantly induced, mostly in a dose-dependent way. Protein analysis of various markers indicate that PM2(.)5-AB instillation results in an activation of endothelin system (endothelin1), renin-angiotensin system (angiotensin converting enzyme) and also coagulation system (tissue factor, plasminogen activator inhibitor-1) in pulmonary and cardiac tissues during the same time period when alternation in ΔmBP and HR have been detected. CONCLUSIONS: Our data suggests that high concentrations of PM2(.)5-AB exposure triggers low grade PM mediated inflammatory effects in the lungs but disturbs vascular homeostasis in pulmonary tissues and on a systemic level by affecting the renin angiotensin system, the endothelin system and the coagulation cascade. These findings are indicative for promotion of endothelial dysfunction, atherosclerotic lesions, and thrombogeneis and, thus, provide plausible evidence that susceptible-predisposed individuals may develop acute cardiac events like myocardial infarction when repeatedly exposed to high pollution episodes as observed in epidemiological studies in Augsburg, Germany.

Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma are associated with nonprogressive HIV-1 infection.

BACKGROUND: Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease. RESULTS: We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease. CONCLUSION: The novel antigen-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.

Tooth loss after active periodontal therapy. 1: patient-related factors for risk, prognosis, and quality of outcome.

OBJECTIVES: Assessment of patient-related factors contributing (1) to tooth loss and (2) to the quality of treatment outcome 10 years after initiation of anti-infective therapy. MATERIAL AND METHODS: All patients who had received active periodontal treatment 10 years ago by the same examiner were recruited consecutively until a total of 100 patients were re-examined. Re-examination was performed by a second examiner and included clinical examination, test for interleukin-1 (IL-1) polymorphism, smoking history, review of patients' files (e.g. regularity of supportive periodontal therapy: SPT). Statistical analysis included Poisson and logistic regressions. RESULTS: Fifty-three patients attended SPT regularly, 59 were females, 38 were IL-1 positive. Poisson regressions identified mean plaque index during SPT (p<0.0001), irregular attendance of SPT (p<0.0001), age (p<0.0001), initial diagnosis (p=0.0005), IL-1 polymorphism (p=0.0007), smoking (p=0.0053), and sex (p=0.0487) as factors significantly contributing to tooth loss. Additionally, mean plaque index during SPT (p=0.011) and irregular SPT (p=0.002) were associated with a worse periodontal status 10 years after initiation of therapy. CONCLUSION: The following risk factors for tooth loss were identified: ineffective oral hygiene, irregular SPT, IL-1 polymorphism, initial diagnosis, smoking, age and sex.

Tooth loss after active periodontal therapy. 2: tooth-related factors.

OBJECTIVE: To assess tooth-related factors contributing to tooth loss over a period of 10 years after completion of active periodontal therapy (APT). MATERIAL AND METHODS: All patients who had received APT by the same experienced periodontist, 10 years before beginning the research, were recruited until 100 patients were re-examined. Examinations included, at the patient level: test for interleukin-1 polymorphism, compliance to supportive periodontal therapy (SPT), mean plaque scores during SPT; at the tooth level: assessment of baseline bone loss (type, amount), tooth type, furcation status and abutment status. Logistic multilevel regression was performed for statistical analysis. RESULTS: Hundred patients with 2301 teeth at the baseline (completion of APT) were retrospectively examined. One hundred fifty-five teeth were lost over 10 years after APT. Logistic multilevel regression identified high plaque scores, irregular attendance of SPT and age as patient-related factors significantly accounting for tooth loss. Tooth-related factors significantly contributing to tooth loss were baseline bone loss, furcation involvement and use as an abutment tooth. However, in patients with regular SPT, 93% of teeth with 60-80% bone loss at the baseline, survived 10 years. CONCLUSION: The following tooth-related risk factors for tooth loss were identified: baseline bone loss, furcation involvement, and use as an abutment tooth.

Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats.

BACKGROUND: Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 mug.m-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY). METHODS: Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF). RESULTS: Increased BP and heart rate (HR) by about 5% with a lag of 1-3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors - except hemeoxygenase-1 - were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma. CONCLUSION: Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.