Inhalation toxicity profiles of particulate matter: a comparison between brake wear with other sources of emission.

Objective: There is substantial evidence that exposure to airborne particulate matter (PM) from road traffic is associated with adverse health outcomes. Although it is often assumed to be caused by vehicle exhaust emissions such as soot, other components may also contribute to detrimental effects. The toxicity of fine PM (PM2.5; <2.5 µm mass median aerodynamic diameter) released from brake pads was compared to PM from other sources. Materials and methods: PM2.5 of different types of brake pads (low-metallic, semi-metallic, NAO and ECE-NAO hybrid), tires and road pavement, poultry as well as the combustion of diesel fuel and wood (modern and old-fashioned stove technologies) were collected as suspensions in water. These were subsequently aerosolized for inhalation exposures. Female BALB/cOlaHsd mice were exposed for 1.5, 3, or 6 hours by nose-only inhalation up to 9 mg/m3. Results: Neither cytotoxicity nor oxidative stress was observed after exposure to any of the re-aerosolized PM2.5 samples. Though, at similar PM mass concentrations the potency to induce inflammatory responses was strongly dependent on the emission source. Exposure to most examined PM2.5 sources provoked inflammation including those derived from the poultry farm, wear emissions of the NAO and ECE-NAO hybrid brake pads as well as diesel and wood combustion, as indicated by neutrophil chemoattractant, KC and MIP-2 and lung neutrophil influx. Discussion and conclusions: Our study revealed considerable variability in the toxic potency of brake wear particles. Understanding of sources that are most harmful to health can provide valuable information for risk management strategies and could help decision-makers to develop more targeted air pollution regulation.

Precore and core promoter mutants are associated with higher HBeAg seroconversion but low disease remission rates in HBV patients treated with nucleos(t)ide analogues.

HBeAg seroconversion in HBV patients is considered an important event. We determined precore (PC) and base core promoter (BCP) mutations in 137 HBeAg-positive nucleos(t)ide analogues (NA) treated patients by INNO-LiPA HBV PreCore assay (Innogenetics). The majority of patients with nongenotype A had PC/BCP mutants present at baseline (P = 0.02). During 29 months of therapy, 45 patients achieved HBeAg seroconversion. Probability of HBeAg seroconversion was higher in patients with PC and/or BCP mutants (P = 0.01). After HBeAg seroconversion, patients with BCP mutants had more HBeAg relapse (P = 0.07), and PC mutants less often achieved HBV DNA < 2000 IU/mL (P = 0.07).

[Diagnosis and assessment of psychopathological symptoms in Parkinson's disease]. / Diagnostiek en beoordeling van psychopathologische symptomen bij de ziekte van Parkinson.

BACKGROUND: Parkinson's disease(PD) is a multidimensional disorder characterized primarily by motor symptoms, but often accompanied by non-motor symptoms, including psychopathological and autonomic symptoms. AIM: To provide an overview of current knowledge concerning the diagnosis, assessment and epidemiology of a number of psychopathological syndromes in PD. METHODS: Relevant literature is discussed. RESULTS: Depressive disorders, apathy, anxiety, cognitive impairment and hallucinations are all common in PD . For most of these syndromes, there is consensus regarding diagnostic criteria, and reliable rating scales are available. In general, an inclusive approach is recommended, which means that without interpretation or attribution, all symptoms present contribute to a psychopathological diagnosis. All psychopathological syndromes are more common in the hypokinetic rigid subtype of the disease. CONCLUSION: The recognition and treatment of psychopathological symptoms in PD require specific expertise. In the treatment of pd patients, therefore, it is essential that there should be multidisciplinary collaboration between the neurologist, the neuropsychologist and the psychiatrist.

Adefovir serum levels do not differ between responders and nonresponders.

Primary or secondary failure of adefovir dipivoxil (ADV) therapy of chronic hepatitis B is not infrequent. The reasons for suboptimal responses are not well defined. In HIV and hepatitis C virus infection, failure of antiviral drug therapy has been linked with low blood drug levels. We have studied 20 well-defined patients with chronic hepatitis B who were treated with ADV for drug and virus kinetics. Importantly, neither Cmax levels (mean 26 ng/mL, range 14-59 ng/mL) nor the time to maximal drug levels (mean 4 h, range 2-8 h) differed between patients showing a complete virological response to adefovir (n = 10), patients with secondary treatment failure (n = 7) and patients with suboptimal primary response (hepatitis B virus-DNA >10,000 IU/mL after 6 months of treatment; n = 3). Thus, adefovir treatment failure is unlikely to be due to an inability to mount sufficient drug levels in the blood.

Frequency and clinical outcomes of flares related to nucleos(t)ide analogue therapy in patients with chronic hepatitis B.

Flares in chronic hepatitis B are often detrimental but sometimes lead to sustained immune control and disease remission. The aim of this study was to estimate the frequency of hepatitis flares which occur during and/or after cessation of nucleos(t)ide analogue (NA) therapy, and to assess their outcomes. In a single centre cohort study we investigated 227 patients who received a total of 351 NA treatment courses. NA therapy was discontinued after 149 treatment courses. In total, 27 flares were observed during 9779 on-treatment patient-months. The frequency was estimated as 3.2 per 100 person-years (95% CI 2.2-4.7). Lamivudine (LAM)-treated patients demonstrated the highest frequency (4.9/100 person-years, 95% CI 3.2-7.4). Twenty (74%) of 27 on-therapy flares were associated with development of genotypic resistance, which all occurred during LAM therapy. NA withdrawal flares occurred after a median post-treatment follow-up of 3.5 months in 17 (11%) of 149 treatment discontinuations. No flares were observed in patients who switched to another antiviral agent (n = 51). None of the on-therapy and withdrawal flares related to NA therapy were associated with sustained disease remission, and seven flares resulted in decompensated liver disease. In this study, flares related to NA therapy never led to immune control and sustained disease remission, and sometimes resulted in decompensated liver disease.

On-treatment monitoring of adefovir therapy in chronic hepatitis B: virologic response can be assessed at 24 weeks.

Patients with chronic hepatitis B (CHB) who will and those who will not respond to adefovir (ADV) monotherapy need to be identified at an early stage in order to adjust treatment and prevent future development of antiviral resistance. In a single-centre cohort study, we investigated 76 CHB patients [50% hepatitis B e antigen (HBeAg)-positive] treated with long-term ADV monotherapy. During a median follow-up of 122 (24-185) weeks, 42 (55%) patients achieved virologic response (VR), defined as HBV-DNA levels <10(3) copies/mL, and 10 patients (13%) developed genotypic ADV resistance. Independent baseline predictors of VR were HBeAg negativity [hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.24-7.19; P = 0.02], high alanine aminotransferase (ALT) levels (HR 1.11; 95% CI 1.05-1.18; P = 0.001), and low HBV-DNA levels (HR 0.56; 95% CI 0.41-0.75; P < 0.001). HBV-DNA at week 24 demonstrated a higher predictive value for VR than HBV-DNA at week 48. Important predictors of genotypic resistance were presence of cirrhosis (HR 6.54; 95% CI 1.39-30.9; P = 0.018), and not achieving VR during treatment (HR 6.60; 95% CI 1.35-32.4; P = 0.008). Patients without VR at week 24 already demonstrated a trend towards the emergence of ADV resistance (P = 0.07). HBV-DNA at week 24 was a better on-treatment predictor of VR than HBV-DNA at week 48, and ADV-resistant mutations developed more frequently in patients without VR at week 24. Therefore, our study suggests that virologic response to ADV therapy can be assessed at 24 weeks, instead of the generally recommended 48 weeks.

The association between motor subtypes and psychopathology in Parkinson's disease.

BACKGROUND: In Parkinson's disease (PD) it has been suggested that various motor subtypes are also characterized by a different prevalence and severity of specific non-motor symptoms such as cognitive deterioration, depression, apathy and hallucinations. The aim of this study was to investigate the association between motor subtypes and psychopathology in PD. METHODS: An exploratory and confirmatory cluster analysis of motor and psychopathological symptoms was performed with a randomized sample of 173 patients each, stemming from two research databases: one from Stavanger University Hospital and one from Maastricht University Hospital. These databases contained data of standardized assessments of patients with the Unified Parkinson's Disease Rating Scale, the Montgomery-Asberg Depression Rating Scale, and the Mini-Mental State Examination. RESULTS: PD patients can be accurately and reliably classified into four different subtypes: rapid disease progression subtype, young-onset subtype, non-tremor-dominant subtype with psychopathology and a tremor-dominant subtype. Cognitive deterioration, depressive and apathetic symptoms, and hallucinations all cluster within the non-tremor-dominant motor subtype, that is characterized by hypokinesia, rigidity, postural instability and gait disorder. CONCLUSIONS: This study shows that non-tremor-dominant PD is associated with cognitive deterioration, depression, apathy, and hallucinations, which has implications for future research into the pathophysiology of psychopathology in PD.

Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis.

BACKGROUND: Inherited thrombophilia is only weakly associated with recurrence in patients with a first venous thrombosis (VT). In spite of this, thrombophilia testing is often performed in these patients. Positive results may influence patient management such as prolonged anticoagulant treatment or intensified prophylaxis in high-risk situations. OBJECTIVE: To investigate whether thrombophilia testing reduces the risk of recurrent VT by virtue of these management alterations. METHODS: From a large case-control study of patients (MEGA study), aged 18-70 years, with a first VT between 1999 and 2004, we selected 197 patients who had had a recurrence during follow-up. We compared the incidence of thrombophilia testing to that of a control cohort of 324 patients. We calculated the odds ratio (OR) for recurrent thrombosis in tested vs. non-tested patients. Only patients who were tested before recurrence were regarded as tested. All first and recurrent thrombotic events were objectively confirmed. RESULTS: Thrombophilia tests were performed in 35% of cases and in 30% of controls. The OR for recurrence was 1.2 [95% confidence interval (CI) 0.9-1.8] for tested vs. non-tested patients. After correction for age, sex, family history, geographic region, presence of clinical risk factors, and year of first VT, the OR remained unchanged. DISCUSSION: Thrombophilia testing in patients with a first VT does not reduce the incidence of recurrence in clinical practice.

Pinning of vortices in a Bose-Einstein condensate by an optical lattice.

We consider the ground state of vortices in a Bose-Einstein condensate. We show that turning on a weak optical periodic potential leads to a transition from the triangular Abrikosov vortex lattice to phases where the vortices are pinned by the optical potential. We discuss the phase diagram of the system for a two-dimensional optical periodic potential with one vortex per optical lattice cell. We also discuss the influence of a one-dimensional optical periodic potential on the vortex ground state. The latter situation has no analog in other condensed-matter systems.

Quantum hall states and boson triplet condensate for rotating spin-1 bosons.

We propose and analyze two series of clustered quantum Hall states for rotating systems of spin-1 bosons. The first series [labeled SU(4)(k)] includes the exact ground states of a model Hamiltonian at large angular momentum L, and also for N=3k particles at L=N. The latter is a spin-singlet boson-triplet condensate. The second series, labeled SO(5)(k), includes exact ground states at large L for different parameter values.