Advances Using Single-Particle Trajectories to Reconstruct Chromatin Organization and Dynamics.

Chromatin organization remains complex and far from understood. In this article, we review recent statistical methods of extracting biophysical parameters from in vivo single-particle trajectories of loci to reconstruct chromatin reorganization in response to cellular stress such as DNA damage. We look at methods for analyzing both single locus and multiple loci tracked simultaneously and explain how to quantify and describe chromatin motion using a combination of extractable parameters. These parameters can be converted into information about chromatin dynamics and function. Furthermore, we discuss how the timescale of recurrent encounter between loci can be extracted and interpreted. We also discuss the effect of sampling rate on the estimated parameters. Finally, we review a polymer method to reconstruct chromatin structure using crosslinkers between chromatin sites. We list and refer to some software packages that are now publicly available to simulate polymer motion. To conclude, chromatin organization and dynamics can be reconstructed from locus trajectories and predicted based on polymer models.

Feasibility of a multdisciplinary lung cancer videoconference between a peripheral hospital and a comprehensive cancer centre.

OBJECTIVE: Treatment of lung cancer patients is changing rapidly and new treatment options have emerged in recent years. In 2007, to guarantee the best treatment procedure for lung cancer patients being treated in our peripheral hospital, we decided to introduce an interdisciplinary tumour videoconference between the Haemato-Oncological Day Hospital in Merano and the Comprehensive Cancer Centre Innsbruck. This retrospective analysis aims to describe the feasibility of such a conference. PATIENTS AND METHODS: Two hundred and three patients with lung cancer treated at the peripheral hospital of Merano between May 2003 until May 2011 were retrospectively analysed. After introduction of the tumour videoconference in 2007, 54% (n = 110) of the patients in this cohort were discussed in the conference. RESULTS: One hundred and four videoconferences were performed. Videoconference was feasible for 110 patients. Radiotherapeutic treatments were prescribed more frequently in patients from the conference group. Overall, major and minor treatment changes were undertaken in 7% (n = 8) and 18% (n = 20), respectively. CONCLUSION: Interdisciplinary tumour videoconference is feasible between a peripheral hospital and a comprehensive cancer centre. Radiotherapeutic treatment was prescribed more frequently, suggesting that such a conference facilitates the access to cancer-centre-specific treatment modalities. Accordingly, tumour videoconference between a peripheral hospital and a cancer centre is to be recommend.

Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.

Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

[PIMS-a new pediatric challenge]. / PIMS ­ eine neue pädiatrische Herausforderung: 9-Jahre alter Knabe mit SARS-CoV-2 assoziiertem hyperinflammatorischem Schocksyndrom.

The boy of Egyptian origin was previously healthy. After a history of fever for 7 days, abdominal pain, vomiting and dry cough resistant to treatment with oral antibiotics, he was admitted to hospital. The clinical examination showed a slightly red throat, a tense abdomen and erythema. The blood tests revealed leukocytosis and significantly increased inflammatory parameters. The abdominal ultrasound showed thickened intestinal loops in the left lower abdomen and the echocardiography showed minimal mitral regurgitation, a narrow pericardial effusion lamella over both ventricles and normal coronary arteries. Accordingly, cardiac enzymes were elevated. The day after admission, the boy developed an increasing rash and was transferred to the PICU because of septic shock refractory to high volume resuscitation, requiring hemodynamic support with noradrenaline and noninvasive respiratory assistance. The initial testing for SARS-CoV­2 on nasopharyngeal aspirates was negative twice; however, serum IgG antibodies were positive. Other viral and bacterial infections were excluded as the cause of the symptoms.The patient received IVIG, ASS, furosemide and methylprednisolone and the antibiotic treatment was continued. The dosage of the catecholamine could be reduced according to the patient's condition and the serially performed echocardiographic findings. The patient recovered in his general condition and was discharged from the PICU after 8 days. With the help of a detailed family history, we were able to figure out that the whole family, including the patient himself, had symptoms of a cold about 1 month earlier. Hence, SARS-CoV­2 antibody tests carried out showed a positive result for all of them.Pediatric inflammatory multisystem syndrome (PIMS) can quickly lead to manifest shock symptoms, necessitating close monitoring. A PICU background is crucial to treat possibly occurring symptoms and complications. High-dose steroids are used therapeutically alongside supportive therapies.

Effect of sex, age and transmission category on the progression to AIDS and survival of zidovudine-treated symptomatic patients.

OBJECTIVE: To evaluate the effect of transmission category and demographic, clinical and immunological characteristics on the progression to AIDS and survival of zidovudine-treated patients. DESIGN: Prospective multicentre cohort study of symptomatic non-AIDS patients. SETTING: Eighty-three clinical centres reporting data to the National Zidovudine Registry. PATIENTS: A total of 1468 patients enrolled between July 1987 and January 1991 were analysed. MAIN OUTCOME MEASURES: Three-year AIDS-free survival probability estimates since therapy start. Cox proportional hazards regression analysis was used to identify independent predictors of progression to AIDS and survival. RESULTS: Faster progression was associated with increasing age (8% risk increase for a 5-year increase), low baseline CD4+ count (39% risk increase for 100 x 10(6)/l cells decrease), and zidovudine > 1000 mg/day (20% risk increase compared with < or = 1000 mg/day). Homosexual men had a 33% risk increase compared with other risk groups. The presence of fever and oral candidiasis at enrolment were also independently associated with a higher risk of progression. Differences in the risk of progression were not significant between men and women. Older age, baseline CD4+ count, homosexual behaviour, fever and oral candidiasis were independently associated with a shorter survival. CONCLUSIONS: Our results confirm that age and baseline CD4+ count are independent predictors of progression, but do not provide evidence for differences in clinical outcome between the sexes. The higher risk of progression to AIDS and shorter survival for homosexual men appears to be correlated with the higher risk of developing Kaposi's sarcoma.

Phase II controlled trial of post-exposure immunization with recombinant gp160 versus antiretroviral therapy in asymptomatic HIV-1-infected adults. VaxSyn Protocol Team.

OBJECTIVE: To alter the natural course of HIV-1 infection by inducing or potentiating immune responses to HIV-1 envelope glycoprotein. DESIGN: Multicentre, double-blind, three-arm, placebo-controlled study. SETTING: Outpatients attending clinics in two University Hospitals. PATIENTS: Ninety-nine asymptomatic HIV-1-infected adults with CD4+ T-cell counts > 400 and < 600 x 10(6)/l and no previous antiretroviral therapy were included. INTERVENTIONS: Patients were randomly assigned to three groups treated with: (i) gp160 in alum over a 2-year period in combination with placebo for the full study duration (n = 32); (ii) gp160 in alum over a 2-year period in combination with zidovudine for the full study duration (n = 34); and (iii) alum over a 2-year period in combination with zidovudine for the full study duration (n = 33). RESULTS: Immunotherapy was well tolerated and no significant differences in disease progression were seen in the treatment groups. The majority of patients (85%) receiving gp160 showed persistent lymphoproliferative responses to the immunogen and to a different Env antigen preparation. CD4+ cell count changes in patients receiving zidovudine alone were significantly higher than those seen in patients receiving immunotherapy alone after 1 year of treatment. Zidovudine administration was associated with initial transient reduction of plasma viraemia. CONCLUSIONS: Prolonged immunization with a soluble HIV-1 subunit provided no benefit to asymptomatic HIV-1-infected patients and was inferior to zidovudine monotherapy. Furthermore, immunization with gp160 shortened the duration of the transient viral load reduction induced by zidovudine.

Treatment of metastatic malignant melanoma with dacarbazine plus fotemustine.

Despite the poor prognosis of metastatic malignant melanoma, polychemotherapy with dacarbazine and fotemustine has shown promising results in several studies. We report on the clinical efficacy of a new sequential administration regimen with dacarbazine at a dose of 200 mg/m2 followed 24 h later by fotemustine 100 mg/m2 every 4 weeks in 63 patients with metastatic melanoma. A complete response was noted in 3 patients (5%), a partial response in 4 patients (6%), stable disease in 33 patients (5%) and progressive disease in 23 patients (37%). The duration of the 3 complete responses was 5, 14+ and 60+ months, for the 4 partial responses, 3, 4, 6 and 13 months. The median duration for stable disease was 4 months. The best response rates were obtained for lung and lymph node metastases. Toxicity was mild and mainly limited to haematological without pulmonary side-effects. Although there was a relatively low objective response rate, this chemotherapy regimen as a palliative treatment, is potentially valuable for patients with progressive stage IV melanoma.

The mechanism of renin release from the ischaemic kidney.

The re-establishment of blood flow to an ischaemic kidney produced an elevation of blood pressure in the rat. This response did not occur in animals with a pithed spinal cord or in rats with low blood pressure produced by haemorrhage. When the blood pressure was raised in rats with pithed spinal cords, by the intravenous infusion of noradrenaline, the response was restored. Occlusion of the subclavian arteries did not prevent the response. It is considered that the increase in blood pressure, produced by renin release, after re-establishment of the blood flow in an ischaemic kidney is a 'washout' phenomenon independent of the integrity of the nervous system.

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

Alpha1 antichymotrypsin signal peptide polymorphism in sporadic Creutzfeldt-Jakob disease.

In Creutzfeldt-Jakob disease (CJD), a transmissible spongiform encephalopathy, the deposition of the pathological prion protein (PrP-res) in the brain of affected individuals is the key event that triggers the appearance of the disease. Since a polymorphism in the signal peptide of the serine-protease inhibitor alpha1 antichymotrypsin (ACT) is one of the factors that may enhance amyloid formation, we studied this polymorphism in 63 CJD patients and 103 control subjects. No difference in allele frequencies and genotype distribution was found between CJD cases and controls, nor any difference was found between the ACT genotype and the age at onset and disease duration. Interestingly, there was a significantly different (P = 0.04) ACT distribution between CJD patients and controls in apolipoprotein E (ApoE) E4, and the interaction between ACT and ApoE was almost significant (P = 0.053). Further studies on a larger number of patients will clarify whether this association can identify a possible risk factor for CJD.

Apolipoprotein E in sporadic and familial Creutzfeldt-Jakob disease.

We assessed the apolipoprotein E (ApoE) genotype in 49 sporadic and ten familial Creutzfeldt-Jakob disease (CJD) patients, in seven healthy siblings with a PRNP mutation and in 84 controls. In sporadic CJD, ApoE genotypes and allelic frequencies do not significantly differ from that of controls. No influence of ApoE genotypes on age at onset was found. In familial cases, the disease appeared in mutated subjects showing the same ApoE genotype as members who have not yet developed CJD. Our results provide further evidence that ApoE is not a risk factor for CJD.

AIDS dementia complex in the Italian National AIDS Registry: temporal trends (1987-93) and differential incidence according to mode of transmission of HIV-1 infection.

OBJECTIVES: To investigate the occurrence of AIDS dementia complex (ADC) in Italy and its incidence over time, examining possible correlations between this condition and some demographic and immunological variables. DESIGN: Inception cohort. Data collected from the case notification forms of the Italian National AIDS Registry. SUBJECTS: 16813 consecutive AIDS cases reported to the National AIDS Registry from August 1, 1987 through October 31, 1993 were included. STATISTICAL METHODS: All data refer to the time of AIDS diagnosis as reported on the case notification forms. Main analyses of the monthly proportion of ADC cases were by multiple logistic regression. RESULTS: 1364 subjects (8.1%) were reported with a diagnosis of ADC as the first AIDS defining disease, either as the only manifestation or associated with other AIDS defining conditions. At the time of AIDS diagnosis, the observed ADC/AIDS proportion was significantly higher among intravenous drug users (IVDU), 9.1%, compared to heterosexuals, 6.3%, and homo-bisexual men, 5.2%. Simple logistic regression analysis showed a significant (p < 0.0001) quadratic trend in the monthly ADC/AIDS proportion, peaking in March 1990 and decreasing thereafter. Multiple logistic regression, adjusting for month of diagnosis, showed that IVDUs have consistently the highest risk and homo-bisexual men the lowest, although differences tended to decrease with increasing age. Older age, in fact, was highly associated with an increased risk, especially within the homo-bisexual and heterosexual transmission categories. CD4 + cells counts proved to have no significant effect on the risk of progressing to AIDS with ADC rather than with any other AIDS indicative disease. CONCLUSIONS: ADC is a relatively frequent manifestation at diagnosis of AIDS among Italian patients, and particularly in IVDUs. Differences in its occurrence were found according to time of diagnosis, transmission category and age.

Kinetics of two pathways in peroxyoxalate chemiluminescence

It has been shown that 1,1'-oxalyldiimidazole (ODI) is formed as an intermediate in the imidazole-catalyzed reaction of oxalate esters with hydrogen peroxide. Therefore, the kinetics of the chemiluminescence reaction of 1,1'-oxalyldiimidazole (ODI) with hydrogen peroxide in the presence of a fluorophore was investigated in order to further elucidate the mechanism of the peroxyoxalate chemiluminescence reaction. The effects of concentrations of ODI, hydrogen peroxide, imidazole (ImH), the general-base catalysts lutidine and collidine, and temperature on the chemiluminescence profile and relative quantum efficiency in the solvent acetonitrile were determined using the stopped-flow technique. Pseudo-first-order rate constant measurements were made for concentrations of either H2O2 or ODI in large excess. All of the reaction kinetics are consistent with a mechanism in which the reaction is initiated by a base-catalyzed substitution of hydrogen peroxide for imidazole in ODI to form an imidazoyl peracid (Im(CO)2OOH). In the presence of a large excess of H2O2, this intermediate rapidly decays with both a zero- and first-order dependence on the H2O2 concentration. It is proposed that the zero-order process reflects a cyclization of this intermediate to form a species capable of exciting a fluorophore via the "chemically initiated electron exchange mechanism" (CIEEL), while the first-order process results from the substitution of an additional molecule of hydrogen peroxide to the imidazoyl peracid to form dihydroperoxyoxalate, reducing the observed quantum yield. Under conditions of a large excess of ODI, the reaction is more than 1 order of magnitude more efficient at producing light, and the quantum yield increases linearly with increasing ODI concentration. Again, it is proposed that the slow initiating step of the reaction involves the substitution of H2O2 for imidazole to form the imidazoyl peracid. This intermediate may decay by either cyclization or by reaction with another ODI molecule to form a cyclic peroxide that is much more efficient at energy transfer with the fluorophore. The reaction kinetics clearly distinguishes two separate pathways for the chemiluminescent reaction.

Epiluminescence microscopy-based classification of pigmented skin lesions using computerized image analysis and an artificial neural network.

Epiluminescence microscopy (ELM) is a non-invasive technique for in vivo examination which can provide additional criteria for the clinical diagnosis of pigmented skin lesions (PSLs). In the present study we attempt to determine whether PSLs can be automatically diagnosed by an integrated computerized system. This system should recognize the PSL, automatically extract features and use these features in training an artificial neural network, which should--if sufficiently trained--be capable of recognizing and classifying a new PSL without human aid. One hundred and twenty images of randomly selected histologically proven PSLs (33 common naevi, 48 dysplastic naevi and 39 malignant melanomas) were used in this study. The images were digitally obtained and the morphological features of the PSLs were extracted electronically without human assistance. The numerical data were then divided into learning and testing cases and linked to an artificial neural network for training and for further classification of lesions that the system had not been trained on. Our results show that the computerized system was able to automatically identify 95% of the PSLs presented. The sensitivity and specificity of the computerized system were 90% and 74% respectively. In contrast, when differentiating between individual types of lesions, the system performed at true positive rates of only 38% for malignant melanoma, 62% for dysplastic naevi and 33% for common naevi. Our data indicate that (1) ELM images of PSLs provide an excellent source for digital image analysis; (2) the vast majority of PSLs can be correctly identified by a relatively simple (and thus not "intelligent") application of digital image analysis; (3) automatic feature extraction based mainly on ABCD rules provides reliable data on the distinction between benign and malignant PSLs; and (4) there is evidence that artificial neural networks can be trained to adequately discriminate between benign and malignant PSLs.

Correlations between subjective disturbances due to acute exposure to organic solvents and internal dose.

A general tendency to minor subjective disturbances ("susceptibility") were measured by questionnaire scores of psycho-/neurovegetative lability in 32 subjects independent of any experience with solvents. In series of experiments interrelations between subjective and biological variables during experimental exposures for 4 or 8 hr to acetone (1000 ppm), ethyl acetate (400 ppm), acetone/ethyl acetate mixture (500/200 ppm), or filtered air were investigated. Every two hr ratings of "tension", "tiredness", "complaints" and "annoyance" were reported and samples of urine were collected in order to analyse the internal dose of the substances. In exposures to ethyl acetate and to the mixture, the mean levels of urinary excretions of the substances show significant cross-correlations to rated complaints and annoyance, but not to rated tension and tiredness. Those subjects who showed higher susceptibility reported higher ratings of complaints and annoyance in those exposure conditions containing ethyl acetate. In exposures to acetone these relations were not found. Both, the quality of the substances and the individual tendency to report slight health impairments influence the variability of subjective reactions on exposure to solvents.

Repeated neurobehavioral investigations in workers exposed to mercury in a chloralkali plant.

Mercury exposed workers of a chloralkali electrolysis plant were investigated with neurobehavioral methods. At the beginning of the investigation an average exposure of 12 years was stated. Four periods of investigations were carried out over the course of 7 years. A low exposed group (n = 34-50, 21-26 micrograms Hg/l Urine) and a high exposed group (n = 14-21, 111-152 micrograms/l Urine) were defined for each of the time periods using 53 micrograms/l Urine as discriminating level. Controls (n = 37-43) were recruited from non-exposed departments of the factory. Age, verbal intelligence and gender were controlled statistically to reduce potential confounding. Symptoms and personality traits did not covary significantly with the exposure. Finger dexterity, tapping, and aiming were variables out of 13 performance measurements, which showed repeatedly a lower level of performance corresponding with increasing current exposure. However, dose-response relations could not be demonstrated by partial correlations to the concentration of mercury in Urine. Subgroups of 30 controls, 37 low exposed and 14 high exposed workers were examined in a follow-up study with repeated measurements. Significant exposure effects were shown for finger dexterity and aiming.

Neurobehavioral study on the interactive effects of age and solvent exposure.

Initial research revealed interaction effects on health measures between exposure to neurotoxicants and age. Symptom reports of workers were conspicuously increased if high-concentration occupational exposure (e.g. to organic solvents, lead) was combined with age above 54 years. The symptom increase in elderly workers was interpreted as a possible indicator of a biological vulnerable phase or delayed response of former high exposure. A second study of the hypothesized age-exposure interaction was performed with a group of workers who had homogenous exposure to a single organic solvent using a neurobehavioral performance evaluation (the EURO-NES). Workers in the rotogravure printing industry who were exposed to toluene were examined two times with an interval of one year (n =333/278). The sample was stratified by workers with significantly different toluene exposure, printers and end-processing operators, and four age classes (< 31, 31-40, 41-50, > 50). The mean lifetime weighted average exposure (LWAE) varied depending on age classes and years of employment with exposure between 7 and 17 ppm in the operators and between 35 to 62 ppm toluene in the printers. Multivariate analyses revealed a significant performance decrease with age (simple reaction time, symbol digit, switching attention, digit span). Again an interaction between age and exposure was found depending on diverging psychometric performance trends with older age. However, contrary to the hypothesis the group with higher exposures (printers) and older age revealed better performance and less symptoms than the group with lower exposure (end-processing operators). The paradoxical results are explained by differences in the intellectual capability in the oldest strata and a possible reversibility of neurobehavioral effects of former high toluene exposure under the condition of later low exposure. There are no hints of adverse delayed effects of former toluene exposure in a possible vulnerable phase in age over 50 years. The different interaction findings of the initial and present study seem to depend mainly on exposure differences in quality and quantity.

Switching attention--additional aspects for the analysis.

Problems related to attentional functions have often been reported within the neurotoxicology of long-term exposure to solvents, but knowledge about neuroanatomical sites involved in this degenerative process is still rare. However, some studies have emphasized the frontal cortex as a region of structural or functional changes in long-term exposed patients or accidental intoxications. Neurobehavioral tests using active switching tasks are widely used to detect frontal lobe dysfunction. Test batteries used in neurotoxicology provide such tasks but standard test interpretations often neglect these aspects. Rotogravure printing workers exclusively exposed to toluene were investigated in a longitudinal study with cross-sectional design. Data from two examination periods are presented. In the first sample 333 male workers were investigated. In the second examination period 278 workers could be retested. The workers differed with respect to level and duration of lifetime exposure to toluene. All subjects completed a neurobehavioral test battery including the task switching attention (EURONES). Different parameters were computed for consecutive trials with constant vs. shifted tasks and repetitions vs. changes of the response direction. In general the expected interaction between the two sequence factors could not be observed. In both examination periods the alternative strategy revealed no marked differences between task/response shifts. Considering the result of previous studies on task/response shifts, the results were highly unexpected. One explanation might be the strong deviations from equality for the relative frequencies of the four sequence conditions, resulting in biased expectancies. These may have superimposed on the basic effects of task shifts. However, in both examination periods weak effects of task shift could be revealed in the subgroup of the long-term exposed workers. In further studies it is necessary to balance conditions more carefully in order to exploit the sensitivity that the measurement of shift costs promises to provide. The exposure-related results of this study support this aspect.

Neurobehavioral effects of solvents and circadian rhythms.

Two studies on the combined neurobehavioral effects of shiftwork and solvent exposure were performed: two-shift work/mixed solvent exposure and three-shift work/single solvent exposure (acetone). Repeated measurements of exposure, body temperature, well-being, complaints, and performance were taken during each shift and during several shift cycles. The air concentrations of the solvent mixture were clearly below and of acetone were near the occupational exposure limit values. Both the exposure quality and the circadian factor contributed to the stronger adverse effects under the three-shift condition. The results support the view that exposure effects should be studied and evaluated in relation to shift and time.