Influences of sociodemographic characteristics and parental HPV vaccination hesitancy on HPV vaccination coverage in five US states.

BACKGROUND: In the United States (US), half of new human papillomavirus (HPV) infections occur among young people aged 15-24 years. Despite the effectiveness of HPV vaccination in protecting against HPV-associated cancers, its coverage among adolescents remains suboptimal. This study examined the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage in five US states with disproportionately low adolescent coverage rates compared to the national average. METHODS: Responses to an online Qualtrics survey from 926 parents of children aged 9-17 years in Arkansas, Mississippi, Missouri, Tennessee, and Southern Illinois in July 2021 were analyzed using multivariate logistic regression to estimate the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage. RESULTS: Of the parents, 78 % were female, 76 % were non-Hispanic White, 61.9 % lived in rural areas, 22 % were classified as HPV vaccine hesitant, and 42 % had vaccinated their oldest child between the ages of 9-17 years against HPV. Children of vaccine hesitant parents were less likely to have received any doses of the HPV vaccine than children of non-vaccine hesitant parents (AOR: 0.17, 95 % CI:0.11-0.27). Male children were less likely to have initiated the HPV vaccine series than female children (AOR: 0.70, 95 % CI:0.50-0.97). Older children (13-17 vs 9-12 years), receiving the meningococcal conjugate or most recent seasonal influenza vaccine were all associated with higher likelihoods of receiving any doses of the HPV vaccine (AOR: 6.01, 95 % CI:3.98-9.08; AOR: 2.24, 95 % CI:1.27-3.95; AOR: 2.41, 95 % CI:1.73-3.36, respectively). CONCLUSIONS: Adolescent HPV vaccination coverage remains low in our targeted states. Children's age, sex, and parental vaccine hesitancy were significantly associated with likelihood of HPV vaccination. These findings offer the opportunity for targeted interventions among parents in regions with low vaccine uptake and underscore the importance of developing and implementing strategies to address parental HPV vaccination hesitancy to improve uptake in the US.

[Treatment of tracheo(broncho)malacia in children]. / Comment je traite la trachéo(broncho)malacie de l'enfant ?

Tracheomalacia (TM) is characterized by tracheal collapse due to an intrinsic anomaly resulting in a lack of rigidity of the cartilaginous rings and/or the posterior membrane during expiration, coughing or crying. It may also be secondary to external compression or acquired during endobronchial diseases. TM is commonly associated with other syndromes or airway abnormalities. Tracheomalacia can be localized or diffused and if the main bronchi are involved, the term of tracheobronchomalacia (TBM) is used. The most common symptoms include expiratory stridor, barking cough and recurrent respiratory tract infections. If tracheal weakness is severe, Acute Life Threating Events (ALTE) or Brief Resolved Unexplained Event (BRUE) can occur. While mild forms usually do not require any treatment, severe TBM may require medical and/or surgical management. Amongst several possible treatments, including tracheostomy, noninvasive ventilation and airway stenting, the pexy surgical approach (posterior, anterior tracheopexy or aortopexy) is currently the favoured option.

La trachéomalacie (TM) est caractérisée par un collapsus trachéal plus ou moins important durant l'expiration, lors des efforts de toux ou des pleurs. Elle peut être due à une anomalie intrinsèque, par manque de rigidité des anneaux cartilagineux et/ou de la membrane postérieure. Elle peut aussi avoir une origine extrinsèque, soit secondaire à une compression externe, soit acquise dans le cadre de pathologies endo-bronchiques. Elle peut enfin être associée à certains syndromes ou malformations des voies respiratoires. La TM peut être localisée ou généralisée, et si les bronches principales sont atteintes, on parlera de trachéobronchomalacie (TBM). Les symptômes les plus courants sont : un stridor expiratoire, une toux aboyante, et des infections respiratoires récurrentes. Dans les cas les plus sévères, des événements menaçant la vie de l'enfant (Acute Life-Threatening Event «ALTE¼ ou Brief Resolved Unexplained Event «BRUE¼) peuvent survenir. Alors que les formes légères ne requièrent généralement pas de traitement, la TBM sévère peut nécessiter une prise en charge médicale et/ou chirurgicale. Parmi les divers choix thérapeutiques, incluant notamment la trachéostomie, la ventilation non invasive et les stents trachéaux, l'approche chirurgicale par pexie (aortopexie, trachéopexie postérieure ou antérieure) est actuellement l'option favorite.

Molecular mechanism of SHP2 activation by PD-1 stimulation.

In cancer, the programmed death-1 (PD-1) pathway suppresses T cell stimulation and mediates immune escape. Upon stimulation, PD-1 becomes phosphorylated at its immune receptor tyrosine-based inhibitory motif (ITIM) and immune receptor tyrosine-based switch motif (ITSM), which then bind the Src homology 2 (SH2) domains of SH2-containing phosphatase 2 (SHP2), initiating T cell inactivation. The SHP2-PD-1 complex structure and the exact functions of the two SH2 domains and phosphorylated motifs remain unknown. Here, we explain the structural basis and provide functional evidence for the mechanism of PD-1-mediated SHP2 activation. We demonstrate that full activation is obtained only upon phosphorylation of both ITIM and ITSM: ITSM binds C-SH2 with strong affinity, recruiting SHP2 to PD-1, while ITIM binds N-SH2, displacing it from the catalytic pocket and activating SHP2. This binding event requires the formation of a new inter-domain interface, offering opportunities for the development of novel immunotherapeutic approaches.

Genetic and environmental factors influencing tooth and jaw malformations in rabbits.

Tooth alterations of 281 rabbits from 10 different breeds were evaluated, starting at the age of three weeks until they were fully grown. All rabbits were kept in an outdoor facility, fed with a pelleted diet and had free access to water and hay. The most common finding in 3182 clinical examinations was a gap between the mandibular incisors (38 per cent). Skull X-rays from 4 adult breeding rabbits, 15 offspring with clinical signs of dental disease and 12 clinically healthy siblings were assessed by two different methods using cephalometric distances and anatomical reference lines. Repeatabilities of cephalometric distances were mostly low and no significant associations to tooth health were found. The anatomical reference lines revealed dental findings even in rabbits that were graded as tooth healthy in previous clinical examinations. On the basis of the demonstrated age-dependent development of tooth and jaw malformations a first examination and selection at the age of 12 weeks can be recommended. Also genetic aspects for tooth and jaw malformations were considered. The estimated heritability for brachygnathia superior was 0.254 ± 0.169 for all examinations and 0.105 ± 0.092 comprising the last examination of each rabbit when fully grown.

HPV Vaccine Awareness and Knowledge Among Women Living with HIV.

Cervical cancer risk is increased among women living with HIV (WLH). Human papillomavirus (HPV) vaccination has been shown to be safe and immunogenic among WLH. We examined HPV vaccine awareness and HPV knowledge among WLH. This cross-sectional study collected data from 145 WLH between March 2011 and April 2012. An interviewer-administered survey assessed HPV vaccine awareness and knowledge. Stata/IC 13 was used to perform chi-square tests and multivariate logistic regression analyses. Our sample was 90 % non-Hispanic black and 64 % earned <$10,000/year. Few (38 %) had heard of the HPV vaccine. Half (50 %) knew that HPV caused cervical cancer. HPV vaccine awareness was ten times higher among WLH who knew HPV caused cervical cancer (OR = 10.17; 95 % CI 3.82-27.06). HPV vaccine awareness is low among WLH. Cancer prevention efforts aimed at raising awareness about the HPV vaccine and increasing knowledge about HPV are necessary first steps in reducing cervical cancer disparities among WLH.

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

Methanobactin and MmoD work in concert to act as the 'copper-switch' in methanotrophs.

Biological oxidation of methane to methanol by aerobic bacteria is catalysed by two different enzymes, the cytoplasmic or soluble methane monooxygenase (sMMO) and the membrane-bound or particulate methane monooxygenase (pMMO). Expression of MMOs is controlled by a 'copper-switch', i.e. sMMO is only expressed at very low copper : biomass ratios, while pMMO expression increases as this ratio increases. Methanotrophs synthesize a chalkophore, methanobactin, for the binding and import of copper. Previous work suggested that methanobactin was formed from a polypeptide precursor. Here we report that deletion of the gene suspected to encode for this precursor, mbnA, in Methylosinus trichosporium OB3b, abolishes methanobactin production. Further, gene expression assays indicate that methanobactin, together with another polypeptide of previously unknown function, MmoD, play key roles in regulating expression of MMOs. Based on these data, we propose a general model explaining how expression of the MMO operons is regulated by copper, methanobactin and MmoD. The basis of the 'copper-switch' is MmoD, and methanobactin amplifies the magnitude of the switch. Bioinformatic analysis of bacterial genomes indicates that the production of methanobactin-like compounds is not confined to methanotrophs, suggesting that its use as a metal-binding agent and/or role in gene regulation may be widespread in nature.

Malformations of the index nails.

We report a 52-year-old woman with micronychia of the index fingers. Radiographic examination revealed a Y-shaped bifurcation of the distal phalanx of both index fingers. She was diagnosed with congenital onychodysplasia of the index fingers (COIF) or Iso-Kikuchi syndrome. COIF is a rare condition characterized by a variety of nail dysplasia of the index fingers. Five criteria characterize COIF: congenital occurrence, unilateral or bilateral index finger involvement, variability in nail appearance, hereditary involvement and frequently associated bone abnormalities. Micronychia, polyonychia, anonychia, hemionychrogryphosis and malalignment are the observed index finger defects. Most cases have been described in Japan, and to our knowledge, this is the first case of COIF reported in South America.

CYLD mutations in familial skin appendage tumours.

BACKGROUND: Germ-line mutations in CYLD are found in patients with familial skin appendage tumours. The protein product functions as a deubiquitinase enzyme, which negatively regulates NF-kappaB and c-Jun N-terminal kinase signalling. Brooke-Spiegler syndrome (BSS) is characterised by cylindromas, trichoepitheliomas and spiradenomas, whereas in familial cylindromatosis (FC) patients present with cylindromas and in multiple familial trichoepitheliomas (MFT) with trichoepitheliomas as the only skin tumour type. Although described as distinct entities, recent studies suggest that they are within the spectrum of a single entity. OBJECTIVE: To investigate the mutation spectrum of CYLD and possible genotype-phenotype correlations. METHODS: 25 families including 13 BSS, 3 FC, and 9 MFT families were examined and evaluated for mutations in the CYLD gene. RESULTS: In total, 18 mutations in CYLD, including 6 novel mutations, were identified in 25 probands (72%). The mutation frequencies among distinct phenotypes were 85% for BSS, 100% for FC, and 44% for MFT. The majority of the mutations were insertions, deletions or nonsense mutations leading to formation of truncated proteins. All mutations were located between exons 9 to 20, encoding the NEMO binding site and the catalytic domain. Genotype-phenotype analysis failed to reveal a correlation between the types of mutations and their location within the gene and the patients' phenotypes and disease severity. CONCLUSIONS: This study provides further evidence on the role of CYLD in the pathogenesis of skin appendage tumours characterised by cylindromas, trichoepitheliomas and/or spiradenomas, but the molecular mechanisms of CYLD in skin tumorigenesis and the reasons for phenotypic variability remain to be explored.

[The end of life in Dutch nursing homes]. / Het levenseinde in Nederlandse verpleeghuizen.

BACKGROUND: Nursing homes (NH) are less well studied than hospices or hospitals as a setting for terminal care. The aim of this study is to identify the direct causes and underlying diseases of the terminal phase in Dutch nursing homes. METHODS: A prospective study of terminally ill patients with a maximum life-expectancy of (less than) 6 weeks in 16 NHs in the Netherlands. 544 long-term care patients were enrolled in the study. RESULTS: The terminal phase was marked with symptoms of low fluid and food intake, general weakness and respiratory problems/dyspnea. Direct causes of these conditions were diseases of the respiratory system (mainly pneumonia), and general disorders, e.g., cachexia. Mental and behavioral disorders and diseases of the circulatory system were the two main underlying diseases of the terminal phase. Per 100 beds per year, 34 NH patients entered a terminal phase. Most patients (82.9%) died within seven days of inclusion. End-of-life decisions occurred in 70% of all deceased patients, most often made on the psycho-geriatric wards. CONCLUSIONS: Providing good and timely palliative care to elderly patients in Dutch nursing homes is a major medical and societal challenge. In this study, the terminal phase of the mainly non-cancer patients is difficult to predict, and once diagnosed, little time is left.

Short communication: Association analysis of microsatellites and Mycobacterium avium subspecies paratuberculosis antibody response in German Holsteins.

Paratuberculosis in ruminants is characterized by chronic granulomatous enteritis, resulting in persistent diarrhea and progressive wasting of cattle infected with Mycobacterium avium ssp. paratuberculosis (MAP). The disease occurs worldwide with high frequency, leading to growing economic losses in beef and dairy industries. The objective of this study was to investigate associations of microsatellites (BMC9006, BB704, BB705, BB717, BB719, BMS1617, BB702, and BOBT24) located near or within candidate genes involved in response mechanisms to paratuberculosis. Pedigree information existed for 4,686 German Holstein cows that had routinely been screened for MAP status using commercially available serum antibody ELISA test. The immunoglobulin G cutoff level was used to classify all animals as positive or negative for paratuberculosis. A total of 594 (12.7%) cows tested positive for paratuberculosis. The control group comprised 585 animals testing negative for MAP. Microsatellite BMC9006 had only 3 alleles (2 of which occurred at very low frequencies in the present data set) and was therefore not informative; the remaining microsatellites showed 3 to 12 alleles. Fisher's exact and chi2 tests revealed no significant differences in microsatellite allele frequencies between the 2 groups of German Holstein cows testing positive or negative for paratuberculosis.

PAF-receptor in inflammatory versus non inflammatory human epidermis, cell cultures and embryonal cells.

OBJECTIVE: PAF-R (platelet activating factor-receptor) has been found on human keratinocytes to bind PAF, a proinflammatory phospholipid. We aimed to study PAF-R in a range of dermal cell lines and in samples of normal and psoriatic human skin to learn about its further role in humans. METHODS: PAF-R was labeled immunocytochemically, histochemically and additionally studied with western blotting in human keratinocytes, human fibroblasts, embryonal keratinocytes, tumor cell lines and samples of normal and psoriatic human skin. RESULTS: Keratinocytes from adult and embryonal epidermis of the 20th week of pregnancy showed a low level of labeling for PAF-R, but 3 +/- 0.05% of plantar keratinocytes from adults were positive as were 4.2 +/- 0.05% of embryonal plantar keratinocytes from the 21st week of pregnancy. In fibroblasts from adult and embryonal epidermis the protein was expressed at low levels. Western blotting revealed PAF-R positive bands at 67 k.Da in normal human skin and psoriasis, in psoriasis additionally at 45 k.Da. A 68 k.Da band was found in the colon cancer line HT 29 (control), and HaCaT cells, in embryonal keratinocytes additionally at 116 k.Da. CONCLUSIONS: PAF-R seems not to be important for embryonal or adult fibroblasts. In embryonal keratinocytes it is turned on after the 21st pregnancy week in a few cells seen as a band of 67 k.Da and at 116 k.Da, the latter is not found in adult keratinocytes. An additional 45 k.Da band of PAF-R was found in psoriasis that might stand for a truncated receptor. In the epithelial tumor cell line HaCaT and the HT29 colon cancer cell line PAF-R characterizes the anti-apoptotic effect of this receptor propagating tumor proliferation.

Bitumen fumes: review of work on the potential risk to workers and the present knowledge on its origin.

Bitumens fumes contain polycyclic aromatic compounds (PAC). There is a possibility of long-term health effects following chronic exposure by inhalation or skin contamination in asphalt road pavers and highway maintenance workers. Epidemiological and experimental studies on this topic are reviewed and the possible causes of cancer discussed with a primary focus on heterocyclic polyaromatic compounds. In 2001, the results of the IARC epidemiological study confirmed an excess of lung cancer despite a lower cancer mortality. In vitro genotoxicity and mechanistic studies demonstrated a mutagenic effect of bitumen fume condensates (BFC) and some data suggested that the polycyclic aromatic hydrocarbons (PAH) analysed were not the major genotoxic compounds in bitumen fume condensates. Other compounds such as nitrogen-, sulfur- and/or oxygen-containing PAH or their alkyl substituted analogues, mutagenic in the Ames mutation assay, may be involved in the genotoxic effect of BFC. After skin painting with BFC, DNA adducts were found in skin, lung and lymphocytes of all the treated animals. Differences in the adduct patterns were also observed, but a more polar adduct was common to the three tissues and not observed in those from rats treated with coal-tar fume condensates (CTFC). Rat inhalation experiments with bitumen fumes confirmed the presence of a DNA-adduct in the lungs with the same Rf as the previous polar adduct. This adduct therefore merits further investigation as a potential biomarker in lymphocyte DNA to follow exposed workers. All the analytical data and the mechanistic data are complementary and suggest the potential role of thiophenes in the genotoxicity of bitumen fumes. Some thiophenes have lower mutagenic activity than their isosteric PAH, whereas others are very potent carcinogens. Generally, the sulfur analogues of PAH (SPAH) in bitumen fumes have a higher concentration than the PAH of similar molecular weight, whereas the SPAH in coal-tar fumes have a much lower concentration than the corresponding PAH. This may explain why the more polar adducts have been detected only in animals exposed to bitumen fume. In a skin carcinogenicity study of condensed asphalt roofing fumes, it has been demonstrated that the most active fractions were those containing a variety of aromatic SPAH. In conclusion to this review, there is an interest in determining the chemical identity of the major DNA adducts induced by BFC. This would allow experimental studies on the carcinogenic potency of these compounds and their validation as potential biomarkers. These compounds could thus merit further analytical investigation in preference to the PAH included in the list of the US Environmental Protection Agency that are currently being analysed by the industry in field studies.

Serum DNA and urine DNA alterations of urinary transitional cell bladder carcinoma detected by fluorescent microsatellite analysis.

There are no reliable serologic tumor markers for transitional cell carcinoma (TCC) of the urinary bladder and noninvasive urine investigations are inadequate. We used fluorescent microsatellite analysis (MSA) to detect serum DNA and urine-sediment DNA alterations in patients with bladder cancer and prospectively collected fresh tumor, peripheral blood, serum and spontaneous urine specimens from 39 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA. Fluorescent MSA was performed with 17 polymorphic markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q and 20q in the 39 cancer patients and in 10 healthy controls. Serum DNA alterations were identified in 84.5% (33 of 39 patients) and tumor-specific urine DNA alterations indicating the diagnosis were present in 72% (27 of 39 patients) of cases. None of the healthy controls displayed serum DNA alterations. The highest frequency of serum DNA aberrations (56%) was detected for chromosomal region 8p. The most frequent alterations in urine-sediment DNA, 36% and 26%, were detected in chromosomal regions 8p and 9p, respectively. Identification of serum DNA and urine-sediment DNA alterations was not related to stage of disease or grade of tumor (p > 0.05). Thus, MSA offers a highly sensitive and specific method for serum- and urine-bound diagnosis of bladder TCC.

Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro.

Neuregulin 1 (Nrg-1) isoforms have been shown to influence the emergence and growth of oligodendrocytes, the CNS myelin-forming cells. We have investigated how Nrg-1 signaling of ErbB receptors specifically controls the early stages of oligodendrocyte generation from multipotential neural precursors (NPs). We show here that embryonic striatal NPs express multiple Nrg-1 transcripts and proteins as well as their specific receptors, ErbB2 and ErbB4, but not ErbB3. The major isoform synthesized by striatal NPs is a transmembrane type III isoform called cysteine-rich domain Nrg-1. To examine the biological effect of Nrg-1, we added soluble ErbB3 (sErbB3) to growing neurospheres. This inhibitor of Nrg-1 bioactivity decreased mitosis of NPs and increased their apoptosis, resulting in a significant reduction in neurosphere size and number. When NPs were induced to migrate and differentiate by adhesion of neurospheres to the substratum, the level of type III isoforms detected by RT-PCR and Western blot decreased in parallel with a reduction in Nrg-1 fluorescence intensity in differentiating astrocytes, neurons, and oligodendrocytes. Pretreatment of growing neurospheres with sErbB3 induced a threefold increase in the proportion of oligodendrocytes generated from NPs migrating out of the neurosphere. This effect was not observed with an unrelated soluble receptor. Addition of sErbB3 during NP growth and differentiation enhanced oligodendrocyte maturation as shown by expression of galactocerebroside and myelin basic protein. We propose that both type III Nrg-1 signaling and soluble ErbB receptors modulate oligodendrocyte development from NPs.

Inhalation study on exposure to bitumen fumes. Part 1: Development and validation of the equipment.

Bitumen fumes emitted during road paving or roofing contain polycyclic aromatic hydrocarbons (PAHs). Experimental studies have been previously performed to test the carcinogenic potency of bitumen fumes. Some of them have been criticised either on the grounds that the fume condensates were not representative of fumes to which humans are exposed or because the fumes were never characterised in terms of particle size and poorly in terms of composition and concentration in the chambers. For a nose-only inhalation study, we have evaluated the ability of a new fume generation system to deliver stable and reproducible atmospheres of bitumen fumes to an inhalation chamber and investigated the representativity of the fumes generated at a concentration level of 5 mg/m3. The fume generator comprises: (1) an insulated 20 l heated kettle (200 degrees C for bitumen); (2) an insulated inlet pipe with a needle valve to adjust the flow of the test compound from the kettle; (3) a fume generation chamber equipped with a series of interchangeable channels of different width. The fume concentration in the exposure chamber can be controlled by changing the channel width or by restricting the evaporation surface with aluminium foil, and/or by changing the flow rate. Samples of the atmosphere in the chamber were collected and analysed for quantitative determination of total particulate matter (TPM), soluble matter, benzo[a]pyrene (B[a]P) content of the fumes and other PAHs, and evaluation of the particle size distribution. The representativeness of the fumes has been tested by comparison with fumes generated in the Shell small-scale fume rig, which was previously validated against field fumes collected during paving operations. Evaporative losses from the filters during sampling, transport and storage have been also assessed. At 5 mg/m3 TPM, the agreement between laboratories was quite good for the TPM analyses and was good for the soluble matter and B[a]P. Evaporative losses may lead to underestimation of the true exposure level in the inhalation chambers but the use of an XAD-2 cartridge backup is one approach to partially recover losses which occur on the filter. The particle size distributions are somewhat different from those reported for fumes associated with roofing and indoor mastic laying works, in that we found more than 85% of particles to be smaller than 1 micron, compared with 40% particles in the previous analyses. In conclusion, this equipment allows reproducible generation of fumes at the 5 mg/m3 TPM that are fairly representative of those produced in the field with the same bitumen.

Development of an on-line coupling of liquid-liquid extraction, normal-phase liquid chromatography and high-resolution gas chromatography producing an analytical marker for the prediction of mutagenicity and carcinogenicity of bitumen and bitumen fumes.

A fast and fully automated system for the determination of polycyclic aromatic compounds (PACs) is described. The system has been developed to produce an analytical 'marker', correlating chemical characteristics (including PAC analysis) with mutagenicity and carcinogenicity. The products of interest are bitumen fumes, bitumen and other (heavy or even residual) oil products, regardless of their boiling range. Dimethyl sulphoxide (DMSO) extractables obtained from a flow-injection analysis (FIA) system are introduced on-line in a normal-phase liquid chromatographic (NPLC) system. Here, the PACs are separated from the DMSO and possible co-extracted heavy residual species. The final step incorporates on-line gas chromatographic analysis of the three-to-six-ring PAC fraction, followed by flame-ionisation detection for quantification. It was demonstrated that data obtained from samples in the distillate lubrication-oil range correlate well with data obtained from the manual DMSO-extraction method standardised by the Institute of Petroleum as IP346.