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BACKGROUND: To investigate the presence of different isotypes of anti-carbamylated protein (CarP) antibodies in systemic sclerosis (SSc) patients and its association with skin involvement. METHODS: Sera of 194 SSc patients from the Leiden CCISS cohort, fulfilling ACR/EULAR 2013 criteria and a clinical diagnosis of SSc, 83 patients with other connective tissue diseases/Raynaud's Phenomenon, 24 rheumatoid arthritis patients and 98 age and sex-matched healthy controls were tested for the presence of anti-CarP IgG, IgA and IgM, determined by ELISA. Clinical characteristics, that were evaluated in SSc patients, included age, anti-topoisomerase antibodies (ATA), anti-centromere antibodies (ACA) and modified Rodnan Skin Score (mRSS). RESULTS: The SSc patients were 55 (SD:13) years and 155 (80%) were female. Forty-four (23%) patients tested positive for ATA, and 80 (42%) ACA. The median mRSS was 2 (range: 0; 47). Prevalence of anti-CarP IgG was higher in SSc patients than in healthy controls (8% vs 3%, p = 0.007. Prevalence of anti-CarP IgA and IgM and levels of anti-CarP isotypes were comparable between SSc patients and healthy controls. Fifteen (8%) SSc patients tested positive for anti-CarP IgG, 16 (8%) for anti-CarP IgA, and 36 (19%) for anti-CarP IgM. There were no significant correlations between age and levels of anti-CarP isotypes. No correlation between anti-CarP IgG levels and mRSS was found (r = 0.141, p = 0.049), nor for anti-CarP IgM and IgA levels. Anti-CarP IgA levels were higher in ATA compared to ACA positive SSc patients (ATA: 616 aU/ml [359; 1103]; ACA: 424 aU/ml [300; 673], p = 0.015). CONCLUSION: SSc patients can test positive for Anti-CarP IgG, IgA and IgM. We do not observe a relevant clinical association between anti-CarP antibody response and skin involvement in SSc.

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Apc-driven tumor formation in patients and Apc-mutant mouse models is generally attributed to increased levels of ß-catenin signaling. We and others have proposed that a specific level of ß-catenin signaling is required to successfully initiate tumor formation, and that each tissue prefers different dosages of signaling. This is illustrated by APC genotype-tumor phenotype correlations in cancer patients, and by the different tumor phenotypes displayed by different Apc-mutant mouse models. Apc1638N mice, associated with intermediate ß-catenin signaling, characteristically develop intestinal tumors (<10) and extra-intestinal tumors, including cysts and desmoids. Apc1572T mice associated with lower levels of ß-catenin signaling are free of intestinal tumors, but instead develop mammary tumors. Although the concept of ß-catenin signaling dosage and its impact on tumor growth among tissues is gaining acceptance, it has not been formally proven. Additionally, alternative explanations for Apc-driven tumor formation have been proposed. To obtain direct evidence for the dominant role of ß-catenin dosage in tumor formation and tissue-specific tumor predisposition, we crossed Apc1638N mice with heterozygous ß-catenin knockout mice, thereby reducing ß-catenin levels. Whereas all the Apc1638N;Ctnnb1(+/+) mice developed gastrointestinal tumors, none were present in the Apc1638N;Ctnnb1(-/+) mice. Incidence of other Apc1638N-associated lesions, including desmoids and cysts, was strongly reduced as well. Interestingly, Apc1638N;Ctnnb1(-/+) females showed an increased incidence of mammary tumors, which are normally rarely observed in Apc1638N mice, and the histological composition of the tumors resembled that of Apc1572T-related tumors. Hereby, we provide in vivo genetic evidence confirming the dominant role of ß-catenin dosage in tumor formation and in dictating tumor predisposition among tissues in Apc-driven cancer.

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Taxa of the Talaromyces purpurogenus complex were studied using a polyphasic approach. ITS barcodes were used to show relationships between species of the T. purpurogenus complex and other Talaromyces species. RPB1, RPB2, ß-tubulin and calmodulin sequences were used to delimit phylogenetic species in the complex. These data, combined with phenotypic characters, showed that the complex contains four species: T. purpurogenus, T. ruber comb. nov. and two new species T. amestolkiae sp. nov. and T. stollii sp. nov. The latter three species belong to the same clade and T. purpurogenus is located in a phylogenetic distant clade. The four species all share similar conidiophore morphologies, but can be distinguished by macromorphological characters. Talaromyces ruber has a very distinct colony texture on malt extract agar (MEA), produces bright yellow and red mycelium on yeast extract sucrose agar (YES) and does not produce acid on creatine sucrose agar (CREA). In contrast, T. amestolkiae and T. stollii produce acid on CREA. These two species can be differentiated by the slower growth rate of T. amestolkiae on CYA incubated at 36 °C. Furthermore, T. stollii produces soft synnemata-like structures in the centre of colonies on most media. Extrolite analysis confirms the distinction of four species in the T. purpurogenus complex. The red diffusing pigment in T. purpurogenus is a mixture of the azaphilone extrolites also found in Monascus species, including N-glutarylrubropunctamine and rubropunctatin. Talaromyces purpurogenus produced four different kinds of mycotoxins: rubratoxins, luteoskyrin, spiculisporic acid and rugulovasins and these mycotoxins were not detected in the other three species.

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In co-ordination with the Umweltbundesamt Berlin, the Landesgesundheitsamt Baden-Wurttemberg (LGA) initiated external quality assurance in the diagnosis of indoor fungi in autumn 2001. Four of six fungal strains commonly found indoors have to be fully identified (on the genus and species level). There are two distributions per year; the six distributions hitherto carried out resulted in correct identification by 46-89% of laboratories (40-71 participants, total 148). It is clear from the results that repeat participants were more successful. In addition to the pure cultures sent out we offered actual samples (two air samples, one wood material, one sample of house dust, hitherto); 43- 69% of participating laboratories also took part in this facultative investigation of actual samples and 29-62% were successful. Results that differed considerably revealed problems while treating and evaluating actual samples. Therefore, activities in this field should be enhanced. In conclusion, external quality assurance in the diagnosis of indoor fungi is a useful management aid in the maintenance and improvement of laboratory performance.

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We report a case of invasive pulmonary aspergillosis caused by Neosartorya pseudofischeri S. W. Peterson [anamorph Aspergillus thermomutatus (Paden) S. W. Peterson]. The diagnosis was initially based on a positive blood culture for a strain isolated from a neutropenic patient by means of a BACTEC 9050 blood culture system. The final diagnosis was established based on X-ray and computer tomography scan results as well as the detection of Aspergillus antigen in the patient's serum.

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In Afghanistan health services have been disrupted by 23 years of conflict and 1 of 4 children die before age 5 years. Measles accounts for an estimated 35,000 deaths annually. Surveillance data show a high proportion of measles cases (38%) among those >/=5 years old. In areas with complex emergencies, measles vaccination is recommended for those aged 6 months to 12-15 years. From December 2001 to May 2002, Afghan authorities and national and international organizations targeted 1,748,829 children aged 6 months to 12 years in five provinces in central Afghanistan for measles vaccinations. Two provinces reported coverage of >90% and two >80%. Coverage in Kabul city was 62%. A subsequent cluster survey in the city found 91% coverage (95% confidence interval [CI], 0.85-0.91) among children 6-59 months and 88% (95% CI, 0.87-0.95) among those 5-12 years old. Thus, this campaign achieved acceptable coverage despite considerable obstacles.

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OBJECTIVE: To investigate whether children and adolescents can recall prior headache complaints accurately and to study whether age, gender, headache severity, preferred coping strategies, depression, somatization, and trait anxiety are related to recall errors, causing recall bias. METHODS: A retrospective headache questionnaire and a prospective 4-week headache diary were filled out by 181 children aged 9 to 16 years who experienced headache at least weekly. In addition, several other questionnaires were administered, measuring coping strategies, depression, somatization, and trait anxiety. Headache frequency, intensity, and duration, as scored on the questionnaire and the diary, were compared using Wilcoxon tests. Regression analyses were performed to study whether age, gender, headache severity, preferred coping strategies, depression, somatization, and trait anxiety can predict the size of differences between the diary and the questionnaire. RESULTS: Compared with the diary, headache intensity and headache duration were overestimated on the questionnaire. At group level, median headache frequency as measured by the diary and the questionnaire was equal. Regarding headache frequency and headache intensity, age and headache severity were statistically related to errors in recall. For headache frequency, depression was also predictive of the size of recall error. CONCLUSIONS: Recall errors occur when children are asked to report their headaches on a retrospective questionnaire. As compared to a prospective diary, pain complaints are evaluated more negatively on a questionnaire. Other factors such as age, depression, and headache severity influence the way children and adolescents recall their headaches. To minimize bias, the use of a diary when studying recurrent headache complaints in children is recommended.

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Due to the inability of most Penicillium species to grow at 37 degrees C, systemic non-marneffei infections are very rare in the human host. We describe a case of fungemia due to Penicillium piceum in a female patient, who died a few days after repeated isolation of this fungus from blood cultures. The species is a member of the section Biverticillata of Penicillium, as was confirmed by rDNA Internal Transcribed Spacer (ITS) sequence data, and hence may share virulence factors with P. marneffei.

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In 1996, China adopted a virological classification of acute flaccid paralysis (AFP) cases for its surveillance system. Only AFP cases with wild poliovirus in stool specimens are confirmed as polio. Cases with adequate stool specimens that are negative for wild poliovirus are not counted. This paper describes a methodology to rule out poliomyelitis in AFP cases with inadequate stool specimens. National surveillance data were analysed using dot maps to detect clusters of AFP cases with high-risk factors for poliomyelitis. The surveillance system and vaccine coverage were assessed during field investigations. Four clusters of AFP cases were identified, but no poliomyelitis cases. Programmatic failures in the identified high-risk areas included low vaccination rates, poor stool specimen collection and inadequate AFP surveillance. Programme strategies were implemented to correct the identified failures. Use of this methodology provides strong evidence consistent with the absence of wild poliovirus in China.

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OBJECTIVES: This study sought to compare the cost-effectiveness of a school-based hepatitis B vaccine delivery program with that of a vaccine delivery program associated with a network health maintenance organization (HMO). METHODS: The vaccination program enrolled 3359 sixth-grade students from 18 middle schools in Denver, Colo. Immunization status and direct and indirect program costs were compiled. The sensitivity of the outcomes was assessed by simulation methods. RESULTS: The per-dose cost-effectiveness ratio for the school-based delivery system was $31. This cost-effectiveness ratio remained stable when the model was simulated with costs that were underestimated or overestimated by 20%. In the network HMO, the direct cost per dose was $68 and the societal cost was $118 when the child's father worked full-time and the mother worked part-time. There is less than a 5% chance that the network HMO-based vaccination program could be more cost-effective than the school-based program. CONCLUSIONS: The cost per dose of the school-based program was significantly less than that of the network HMO-based program, because in the school program government-purchased vaccine was available at a lower cost and parents did not incur work-loss costs.

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Inner-city infants (n = 565) enrolled in the WIC program were randomly assigned at 6 months of age to either of 2 groups: (1) voucher incentive (frequency of issuance of food vouchers based on immunization status) plus reminder-recall (calls and/or letters to families of under-vaccinated children) or (2) voucher incentive alone. At 12 months, both groups' immunization levels were high and not significantly different: 80% +/- 4% versus 79% +/- 5% (P =.749).

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CONTEXT: Inner-city immunization rates have lagged behind those in other areas of the country. OBJECTIVE: To evaluate the impact of an initiative linking immunization with distribution of food vouchers in the inner city. DESIGN: Retrospective analysis of immunization data gathered in 1996 and 1997. SETTING: Nineteen Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) sites serving 30% of the Chicago, III, birth cohort. PARTICIPANTS: A total of 16581 children 24 months old or younger. INTERVENTIONS: Voucher incentives (varying frequency of food voucher issuance based on immunization status) and assessment of immunization status and referral to immunization provider. MAIN OUTCOME MEASURES: Age-appropriate immunization rates and WIC enrollment rates. RESULTS: During the 15-month period of evaluation, immunization rates increased from 56% to 89% at sites performing voucher incentives. The proportion of children needing voucher incentives declined from 51% to 12%. Sites performing assessment and referral, but not providing voucher incentives, showed no evidence of improvement in immunization coverage. No difference was observed in enrollment rates between sites performing voucher incentives and those that did not. CONCLUSION: Applied in a large-scale, programmatic fashion, voucher incentives in WIC can rapidly increase and sustain high childhood immunization rates in an inner-city population.

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We compared urinary levels of the metabolite methyl-5-hydroxy-2-benzimidazole carbamate (5-HBC) among nursery workers exposed to the fungicide benomyl (specifically Benlate 50 DF [DuPont, Wilmington, DE]) and workers not exposed to benomyl. Environmental exposures were quantitated from gloves, body patches, and air samples collected with area and personal monitors. The median concentration of 5-HBC in the urine of benomyl-exposed workers was 23.8 mumol of 5-HBC per mole of creatinine. No 5-HBC was detected in the reference group. Industrial hygiene results and biological monitoring findings indicate that use of Benlate 50 DF in the ornamental industry can lead to absorption of the active ingredient, benomyl. Weighing, mixing, and application activities involved the highest exposures. Dermal contact appeared to be the primary route of exposure.

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In the European coastal dunes, marram grass (Ammophila arenaria) is planted in order to control sand erosion. In the years 1986 to 1991, workers on the Wadden islands in the Netherlands planting marram grass showed lesions of skin and mucous membranes, suggesting a toxic reaction. Fusarium culmorum dominated the mycoflora of those marram grass culms that were used for planting. This plant material had been cut and stored for more than one week in the open. The Fusarium toxin deoxynivalenol (DON) was detected in the suspect marram grass culms. Isolated F. culmorum strains were able to produce DON in vitro in liquid culture as well as in experimentally inoculated wheat heads. Pathogenicity tests, toxin test as well as RAPD analysis showed that the F. culmorum strains were not specialized for marram grass but may form part of the West-European F. culmorum population infecting cereals and grasses. Storage on old sand-dunes with plant debris may have led to the high occurrence of F. culmorum and contamination with DON. Marram grass culms should be obtained from young plantings on dunes on the seaward slopes and cut culms should not be stored.

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The presence of viable mold propagules in house dust was investigated by 10 different analytic methods, in order to determine to what extent different results are obtained when different analytic methods are used. Moreover, the value of this measurement as an estimator of the potential exposure to fungi in epidemiologic studies was assessed. Floor and mattress dust was sampled in 60 homes in The Netherlands during autumn 1990. For investigation of the variability in time, sampling was repeated in 20 homes after 6 weeks. Each analytic method is characterized by a unique combination of culture medium, suspension medium, and dilution step. The highest mean number of colony-forming units (CFU)/g dust was obtained by suspension of at least 100 mg dust in a peptone or sucrose solution in a ratio of 1:50 (w/w), followed by 10-fold dilution and plating on DG18 agar (geometric mean (GM) approximately 60,000 CFU/g dust). The lowest mean number of CFU/g dust was obtained by direct plating of 30 mg dust on V8 agar (GM approximately 5300 CFU/g dust). The mean coefficient of variation of duplicate analyses varied from 11%, for suspension in sucrose and plating on DG18 agar, to 27%, for suspension and dilution in sucrose in combination with V8 agar. The highest mean number of species isolated was obtained by direct plating of 30 mg dust on DG18 agar (mean number of species: 17). Suspension and dilution on DG18 or V8 agars yielded an average of approximately six species. In duplicate analyses, the mean percentage of agreement for the species isolated varied from approximately 35%, for suspension and dilution, to 60%, for direct plating.(ABSTRACT TRUNCATED AT 250 WORDS)

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As part of a case-control study on the relation between home dampness and respiratory symptoms of children, house-dust samples were collected from bedroom floors and mattresses in 60 homes in The Netherlands. The house-dust samples were analyzed for the presence of fungal propagules by plating 30 mg of dust directly onto DG18 agar. A checklist and questionnaire were used to obtain information on the home characteristics and occupant behavior that may have an effect on the presence of fungal propagules in house dust. The geometric mean (GM) numbers of colony-forming units (CFU)/g dust collected from the floors was 8990. The number of CFU/g dust was significantly higher in dust from carpeted floors than in dust from smooth floors (GM, respectively, 12,880 CFU/g dust and 3530 CFU/g dust). The GM number of CFU/g dust collected from mattresses was 6760. Overall, the mean numbers of CFU/g dust collected from floors and mattresses were higher in bedrooms where damp spots mold growth, or both were observed. However, these differences were not statistically significant. The relation between home characteristics and the number of CFU/g dust of the most frequently isolated mold species (n = 17), including Alternaria alternata, Cladosporium cladosporioides, Penicillium brevicompactum, and Scopulariopsis brevicaulis, was also investigated. Only the type of flooring had a significant and consistent effect on the number of CFU/g floor dust of the different mold species.(ABSTRACT TRUNCATED AT 250 WORDS)

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