Factors Associated With Perinatal Hepatitis C Screening Among Exposed Children: 2016-2020.

BACKGROUND AND OBJECTIVES: Children perinatally exposed to hepatitis C virus (HCV) should be screened for infection, yet testing rates are low. Clinical perinatal HCV testing recommendations vary and may contribute to poor completion. This study examines pediatric care factors associated with perinatal HCV testing completion. METHODS: A cohort of people living with HCV in Philadelphia, Pennsylvania, who delivered a live birth in 2016 to 2020 and their children were followed by the Philadelphia Department of Public Health. The association of completion of HCV screening with pregnant/postpartum person demographics, pediatric care factors, and testing policy were retrospectively explored. χ2 and multivariable logistic regressions were used. RESULTS: HCV-positive pregnant people gave birth to 457 children of whom 307 (67.2%) were tested for HCV according to recommendations and 79 (17.2%) were inadequately tested. Children were more likely to be tested if born to a pregnant person with HIV coinfection (P = .007), if they were always on schedule for vaccinations (P < .001), and if they attended the 18-month well visit (P < .001). Completion rates varied significantly by pediatrician's testing policy: 90.9% tested if the policy was for 2 months, 79.6% if 2 to 12 months, 61.9% if 12 months, and 58.5% if 18 months of age (P < .001). CONCLUSIONS: Timing of perinatal HCV testing policies was significantly associated with testing completion rates. Testing at 2 months was associated with far better HCV testing completion than other strategies, regardless of birthing person and pediatrician factors. These findings suggest routine HCV testing of children perinatally exposed to HCV is best achieved in the first year of life.

Integrating habits and practices data for soaps, cosmetics and air care products into an existing aggregate exposure model.

In order to accurately assess aggregate exposure to a fragrance material in consumers, data are needed on consumer habits and practices, as well as the concentration of the fragrance material in those products. The present study describes the development of Phase 2 Creme RIFM model by expanding the previously developed Phase 1 model to include an additional six product types. Using subject-matching algorithms, the subjects in the Phase 1 Creme RIFM database were paired with subjects in the SUPERB and BodyCare surveys based on age and gender. Consumption of the additional products was simulated to create a seven day diary allowing full data integration in a consistent format. The inhalation route was also included for air care and other products where a fraction of product used is inhaled, derived from the RIFM 2-box model. The expansion of the Phase 1 Creme RIFM model has resulted in a more extensive and refined model, which covers a broader range of product categories and now, includes all relevant routes of exposure. An evaluation of the performance of the model has been carried out in an accompanying publication to this one.

Capture-Recapture: Using Existing Data Sources to Improve Perinatal Hepatitis B Surveillance, Philadelphia, 2008-2014.

OBJECTIVE: The objective of this study was to describe the capture-recapture method used by the Philadelphia Department of Public Health to enhance surveillance of perinatal hepatitis B virus (HBV), report on results and limitations of the process, and determine why some HBV-positive mother-infant pairs were not initially identified by Philadelphia's Perinatal Hepatitis B Prevention Program (PHBPP). METHODS: We performed capture-recapture retrospectively for births in 2008 and 2009 in Philadelphia and prospectively for births from 2010 to 2014 by independently matching annual birth certificate data to PHBPP and HBV surveillance data. We compared the number of HBV-positive mother-infant pairs identified each year to the point estimates and lower-limit estimates calculated by the Centers for Disease Control and Prevention for the Philadelphia PHBPP. RESULTS: Of 156 605 pregnancy outcomes identified between 2008 and 2014, we found 1549 HBV-positive mother-infant pairs. Of 705 pairs that were initially determined, 358 (50.7%) were confirmed to be previously unidentified HBV-positive pairs. Reasons for failing to identify these mother-infant pairs prior to capture-recapture included internal administrative issues (n = 191, 53.4%), HBV testing and reporting issues (n = 92, 25.7%), and being lost to follow-up (n = 75, 20.9%). Each year that capture-recapture was used, the number of pairs identified by the Philadelphia PHBPP exceeded the Centers for Disease Control and Prevention's lower-limit estimates for HBV-positive mother-infant pairs. CONCLUSIONS: Capture-recapture was useful for identifying HBV-positive pregnant women for Philadelphia's PHBPP and for highlighting inadequacies in health department protocols and HBV testing during pregnancy. Other health departments with access to similar data sources and staff members with the necessary technical skills can adapt this method.

Application of the expanded Creme RIFM consumer exposure model to fragrance ingredients in cosmetic, personal care and air care products.

As part of a joint project between the Research Institute for Fragrance Materials (RIFM) and Creme Global, a Monte Carlo model (here named the Creme RIFM model) has been developed to estimate consumer exposure to ingredients in personal care products. Details of the model produced in Phase 1 of the project have already been published. Further data on habits and practises have been collected which enable the model to estimate consumer exposure from dermal, oral and inhalation routes for 25 product types. . In addition, more accurate concentration data have been obtained which allow levels of fragrance ingredients in these product types to be modelled. Described is the use of this expanded model to estimate aggregate systemic exposure for eight fragrance ingredients. Results are shown for simulated systemic exposure (expressed as µg/kg bw/day) for each fragrance ingredient in each product type, along with simulated aggregate exposure. Highest fragrance exposure generally occurred from use of body lotions, body sprays and hydroalcoholic products. For the fragrances investigated, aggregate exposure calculated using this model was 11.5-25 fold lower than that calculated using deterministic methodology. The Creme RIFM model offers a very comprehensive and powerful tool for estimating aggregate exposure to fragrance ingredients.

Use of an aggregate exposure model to estimate consumer exposure to fragrance ingredients in personal care and cosmetic products.

Ensuring the toxicological safety of fragrance ingredients used in personal care and cosmetic products is essential in product development and design, as well as in the regulatory compliance of the products. This requires an accurate estimation of consumer exposure which, in turn, requires an understanding of consumer habits and use of products. Where ingredients are used in multiple product types, it is important to take account of aggregate exposure in consumers using these products. This publication investigates the use of a newly developed probabilistic model, the Creme RIFM model, to estimate aggregate exposure to fragrance ingredients using the example of 2-phenylethanol (PEA). The output shown demonstrates the utility of the model in determining systemic and dermal exposure to fragrances from individual products, and aggregate exposure. The model provides valuable information not only for risk assessment, but also for risk management. It should be noted that data on the concentrations of PEA in products used in this article were obtained from limited sources and not the standard, industry wide surveys typically employed by the fragrance industry and are thus presented here to illustrate the output and utility of the newly developed model. They should not be considered an accurate representation of actual exposure to PEA.

Novel database for exposure to fragrance ingredients in cosmetics and personal care products.

Exposure of fragrance ingredients in cosmetics and personal care products to the population can be determined by way of a detailed and robust survey. The frequency and combinations of products used at specific times during the day will allow the estimation of aggregate exposure for an individual consumer, and to the sample population. In the present study, habits and practices of personal care and cosmetic products have been obtained from market research data for 36,446 subjects across European countries and the United States in order to determine the exposure to fragrance ingredients. Each subject logged their product uses, time of day and body application sites in an online diary for seven consecutive days. The survey data did not contain information on the amount of product used per occasion or body measurements, such as weight and skin surface area. Nevertheless, this was found from the literature where the likely amount of product used per occasion or body measurement could be probabilistically chosen from distributions of data based on subject demographics. The daily aggregate applied consumer product exposure was estimated based on each subject's frequency of product use, and Monte Carlo simulations of their likely product amount per use and body measurements. Statistical analyses of the habits and practices and consumer product exposure are presented, which show the robustness of the data and the ability to estimate aggregate consumer product exposure. Consequently, the data and modelling methods presented show potential as a means of performing ingredient safety assessments for personal care and cosmetics products.

Temperament and parenting: implications for understanding developmental pathways to conduct disorder.

This article reviews research linking a number of temperamental vulnerabilities that can place a child at risk for developing severe conduct problems. One primary focus of this article is on how certain temperamental vulnerabilities can disrupt normal developmental processes during early childhood, such as the development of emotional regulatory abilities and the development of the affective components of conscience, to place a child at risk for acting in an antisocial and aggressive manner. A second focus of the paper is on how the quality of parenting that a child experiences interacts with the child's temperament to either increase or decrease the child's risk for problem behavior. Identifying those parent factors that can enhance the development of children at risk for conduct problems due to temperamental vulnerabilities could be very important for enhancing interventions for children with severe behavior problems.

Capillary electrophoretic application of 1-alkyl-3-methylimidazolium-based ionic liquids.

Ionic substances with melting points at or close to room temperature are referred to as ionic liquids. Interest in ionic liquids for their potential in different chemical processes is increasing, because they are environmentally benign and are good solvents for a wide range of both organic and inorganic materials. In this study, a capillary electrophoretic method for resolving phenolic compounds found in grape seed extracts is reported. The method, in which 1-alkyl-3-methylimidazolium-based ionic liquids are used as the running electrolytes, is simple and reproducible. The separation mechanism seems to involve association between the imidazolium cations and the polyphenols. The role of the alkyl substituents on the imidazolium cations was investigated and will be discussed.

Quantitative 3D maxillary arch evaluation of two different infant managements for unilateral cleft lip and palate.

OBJECTIVE: A two-institution retrospective study was undertaken to determine whether two different prepalatoplasty protocols quantitatively affect maxillary arch morphology in infants with complete unilateral cleft lip and palate (UCLP). DESIGN: Serial maxillary dental casts, obtained at regular intervals through the first 18 months of life from preintervention until palatoplasty were evaluated quantitatively using computer-assisted three-dimensional digitization and analysis for three populations: institution 1 (protocol 1), institution 2 (protocol 2), and unaffected individuals (neither cleft nor treatment). Sequential UCLP patients from institution 1 were matched for age and initial alveolar cleft width, sex and cleft side having been demonstrated to be nonsignificant, with UCLP patients from institution 2 and to unaffected individuals for age for the analysis. SETTING: Both treatment institutions are well-established regional interdisciplinary cleft centers. Institution 1 is located in a tertiary, academic children's hospital in a metropolis within a primarily agrarian region of the Midwest; institution 2 is a freestanding private clinic located in a small city within a primarily agrarian region of an eastern state; the unaffected population is a historic archive acquired in the 1930s. Data acquisition (model digitization) and computer processing were performed at institution 1. PATIENTS: Eighty-five casts of 28 infants from institution 1, 106 casts of 31 infants from institution 2, and 68 casts of 29 unaffected infants were analyzed. All infants had alginate impressions taken prior to intervention and at several additional 6-month intervals after that, consistent with each institution's treatment protocol. INTERVENTIONS: At institution 1, patients with UCLP underwent lip adhesion and placement of a passive alveolar molding plate at 7 weeks of age, definitive cheiloplasty at 7 months of age, and one-stage palatoplasty at 14 months of age. At institution 2, patients with UCLP underwent definitive cheiloplasty at 3 months of age, had no maxillary orthopedics, and had vomer flap hard palate repair at 12 months of age and soft palate repair at 18 months of age. MAIN OUTCOME MEASURES: The outcome measures included directly digitized (cleft segment and hemialveolar ridge lengths) and derived (alveolar base width, alveolar cleft gap, maxillary frenum-alveolar base perpendicular angle, and rates of change over time of digitized cleft segment and hemialveolar ridge lengths) features. The data were assessed by comparing simple linear regression lines and an unpaired, two-tailed t test. RESULTS: Prior to initiating therapy, there were no statistically significant differences between the two populations with clefts. However, both populations with clefts differed significantly from unaffected individuals (p < .001), with increased maxillary base widths and larger perpendicular/frenum angles. At the time of palatoplasty, the two populations with clefts had statistically significant differences between them in the maxillary base width (p < .01) and the cleft gap distance (p < .05). The base width of institution 1 did not differ significantly from that of widths of unaffected children, and that of institution 2 was significantly less, although the latter had already received first-stage palate repair. Alveolar segment growth rates were similar for the greater and lesser segments, respectively, and the left side hemialveolus of both groups. The growth rate for the noncleft side hemialveolus of institution 2 exceeded (p < .05) that of both institution 1 and unaffected patients. CONCLUSION: Two different regimens for the initial management of UCLP can significantly affect maxillary alveolar arch growth with respect to the treatment used and in comparison with unaffected controls.

The effect of case management on the costs of health care for enrollees in Medicare Plus Choice plans: a randomized trial.

OBJECTIVE: To measure the effects of case management on an older population's costs of health care. DESIGN: A 1-year randomized controlled trial. SETTING: Multiple sites of care in San Francisco, California. PARTICIPANTS: Patients aged 65 or older of primary care physicians in a large provider organization bearing financial risk for their care (n = 6409). INTERVENTION: Screening for high risk and provision of social work-based case management. OUTCOME MEASURES: Volume and cost of hospital, physician, case management, and other health-related services. RESULTS: The experimental group used more case management services than the control group (0.09 vs. 0.02 months per person, P<.001). The experimental group's average total payments for health care were slightly lower ($3148 vs $3277, P = .40). CONCLUSIONS: This study provides no statistically significant evidence that social work-oriented case management reduces the use or the cost of health care for high-risk older people. Other potentially favorable effects of this type of case management need to be evaluated, as do the effects of other types of case management.

Hand-eye dominance in a population with mental handicaps: prevalence and a comparison of methods.

BACKGROUND: The primary purpose of this study was to investigate hand-eye dominance in a population with mental handicaps and how the distribution compared with the general population. In addition, this study investigated the correlation between two methods of hand-eye dominance testing. METHODS: Two methods were used to determine eye dominance: the hole-in-the-hand method and the eye dominance wand. Hand dominance was determined by the subject's choice of accepting hand. The sample was comprised of a population of 421 athletes participating in the 1997 Special Olympic Games in Toronto. All subjects unable to give a dominant hand or unable to perform either of the ocular dominance tests were eliminated from analysis. Athletes who demonstrated strabismus or a difference in visual acuity between the two eyes of greater than 1 line were separated in the analysis, reducing the sample population to 191. RESULTS: The hole-in-the-hand method of eye dominance showed that 40.3% of this population exhibited crossed dominance. The eye dominance wand found crossed dominance in 36.6% of this population. The eye dominance wand demonstrated moderate agreement with the hole-in-the-hand method; however, there was some crossover of eye dominance between tests, when the tests were compared on a case-by-case basis. CONCLUSIONS: The prevalence rate of this population of persons with mental handicaps agrees with the prevalence rates found by Robison et al., in which 41% of a general nonhandicapped population demonstrated crossed dominance. The results suggest that persons with mental handicaps have prevalence rates of crossed dominance similar to those found in the general population.

Evaluation of subchronic (13 week), reproductive, and in vitro genetic toxicity potential of 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Octocrylene).

Use of 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Octocrylene) in commercial sunscreen products has increased considerably in recent years. To support larger scale human exposure to this compound, additional toxicological information was needed in several key areas. The present studies evaluated subchronic toxicity, developmental toxicity, and in vitro genotoxic potential of Octocrylene. In the subchronic study, male and female New Zealand white (NZW) rabbits treated topically with concentrations of octocrylene up to 534 mg/kg/day for 13 weeks showed slight to moderate dose-dependent skin irritation that correlated positively with a mild depression in body weight gain. Lack of associated histopathologic or clinical hematology abnormalities suggested that the body weight effect probably reflected a nonspecific response to topical irritation. In percutaneous developmental toxicity studies, NZW does were treated topically with Octocrylene at levels up to 267 mg/kg/day on Days 6 through 18 of gestation. Body weight gain, food consumption, and all maternal, reproductive, and offspring parameters evaluated were comparable between Octocrylene-treated and control animals. In the oral developmental toxicity assay, female CD-1 mice received oral doses of Octocrylene up to 1000 mg/kg/day on Days 8-12 of gestation. No evidence of maternal or developmental toxicity was seen at any dose tested. Genotoxicity was evaluated in vitro using the Chinese hamster ovary cell assay to assess clastogenicity and the mouse lymphoma cell assay to assess forward gene mutations. Octocrylene did not induce any significant increase in genotoxicity. This evaluation of toxicological potential supports the use of Octocrylene as a human photoprotectant.

Assessment of the in vivo genotoxicity of 2-hydroxy 4-methoxybenzophenone.

The genotoxic potential of 2-hydroxy 4-methoxy-benzophenone (benzophenone-3, Bz-3), a commonly used sunscreen, has been evaluated previously with in vitro systems. Data from Salmonella studies (with and without activation) have been predominantly negative, but two reports have shown weakly positive results in a single bacterial strain under conditions of metabolic activation. In addition, Bz-3 has been reported to induce chromosome aberrations and equivocal results for sister chromatid exchange in Chinese hamster ovary (CHO) cells. We used the Drosophila somatic mutation and recombination test (SMART) and in vivo cytogenetics in rat bone marrow to define the potential for in vivo expression of this in vitro activity. For the SMART assay, larva from a mating of "multiple wing hair" (mwh) females with heterozygous "flare" (flr) males were exposed to 0, 3000, or 3500 ppm Bz-3 or 25 ppm dimethylnitrosamine (DMN, positive control) for 72 hr. A recombination between the mwh and flr genes produces twin wing spots, while events such as deletions produce single spots. None of the Bz-3-treated larva produced flies with significantly more single or multiple wing spots than controls. In contrast, DMN-treated larva produced flies with significantly more single or multiple wing spots than controls. The in vivo cytogenetic assay in rat bone marrow cells was conducted to evaluate the clastogenicity of Bz-3. Sprague-Dawley rats were treated by oral gavage with a single administration of 0.0, 0.5, 1.67, or 5 gm/kg Bz-3 or a single dose of 5 gm/kg/day Bz-3 for 5 consecutive days. Cyclophosphamide (CP) was the positive control and was administered at 20 mg/kg with both treatment regimens. Colchicine growth-arrested bone marrow cells were collected 8 and 12 hr after the single treatment and 12hr after the last daily treatment. Under either treatment protocol none of the Bz-3 concentrations caused any significant increase in chromosomal aberrations. Results from these two studies strongly support the conclusion that Bz-3 is not genotoxic in vivo.

Repair of N-methylpurines in DNA from lymphocytes of patients with amyotrophic lateral sclerosis.

We have previously reported reduced ability of ALS fibroblasts to repair genomic DNA damage produced by alkylating agents. This report presents our experience of studying DNA repair in lymphocytes from ALS patients. The repair of N-methylpurines produced by treatment with the alkylating agent, methyl methanesulfonate, was studied in T-lymphocytes from patients with sporadic and familial ALS, and appropriate controls. Repair of damage was quantitated by using alkaline elution for genomic DNA repair, and methoxyamine protection of abasic sites in DNA fragments for gene-specific repair in the dihydrofolate reductase (dhfr) gene, at time points 0, 6 h and 24 h. No significant repair rate differences were observed between ALS and control lymphocytes in either genomic or gene-specific DNA repair. The possible reasons for the discrepancy with our earlier results in lymphocytes and fibroblasts are discussed.

DNA repair and mutant frequency in schizophrenia.

The in vivo frequency of mutants resulting from mutation at the hprt locus in human T-lymphocytes was determined with a cloning assay. T-lymphocytes were obtained from 14 individuals diagnosed with schizophrenia and 5 controls. No significant difference in mutant frequency was observed between the 2 groups. In addition, DNA-repair capacity was measured with the unscheduled DNA synthesis technique in lymphocytes from 7 individuals diagnosed with schizophrenia and 7 controls. Repair capacity was determined following treatment with MMS, MNNG, and 20 J/m2 ultraviolet light. No significant differences in DNA repair were observed between the patient and control groups in response to any of the 3 DNA-damaging agents. These results argue against differences between normal and schizophrenic individuals with respect to in vivo mutant frequency or their capacity to repair DNA lesions induced by MMS, MNNG, or ultraviolet radiation.

Two expressed human genes sustain slightly more DNA damage after alkylating agent treatment than an inactive gene.

Alkylating agent damage was quantified in human T-lymphocytes by calculating gene-specific lesion frequencies and repair rates. At 3 time points after exposure to methyl methanesulfonate (0, 6, and 24 h), T-lymphocyte DNA was extracted, digested with HindIII, and divided into 2 aliquots. Apurinic sites were formed in the DNA fragments of both aliquots by heat-induced liberation of the N-methylpurines. The methoxyamine-treated aliquot provided gene fragments which were refractory to alkaline hydrolysis (full-length fragments), while the fragments in the untreated aliquot were cleaved at apurinic sites by hydroxide. After Southern blotting, lesion frequencies were calculated by comparing the band intensity of the full-length fragment to its unprotected counterpart. The restriction fragments analyzed were from the constitutively active dihydrofolate reductase (dhfr) plus hypoxanthine phosphoribosyltransferase (hprt) genes and from the transcriptionally inactive Duchenne muscular dystrophy gene (dmd). In decreasing order, the fragments containing the most lesions per kb of DNA were: hprt greater than dhfr greater than dmd. T-Lymphocytes from 2 females had 30% more heat-labile N-methylpurines in the active X-linked hprt gene than in the inactive X-linked dmd gene. The lesion frequency found in the male's lone hprt allele was the highest observed. These lesion frequency differences are discussed in terms of chromatin structure. After 6 and 24 h, no significant repair rate differences were observed among the 3 genes.

The relationship between DNA repair after alkylation damage and in vitro aging in human T-lymphocytes.

In vitro cultures of human peripheral blood lymphocytes, both unstimulated G0 cells as well as phytohemagglutinin (PHA) stimulated cells, have been used in the investigation of DNA repair following different types of damage, including that induced by ultraviolet light, ionizing radiation, and chemical agents. We report here repair of DNA damage in cultured normal human T-lymphocytes after treatment with the alkylating agents, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or methanesulfonate (MMS), as measured by the alkaline elution technique. T-lymphocytes cultured with different sources of T-cell growth factors (TCGFs) were shown to have similar repair levels, as measured by loss of single-strand breaks. However, diminished repair was observed with in vitro culture age when T-cells were cultured with PHA and TCGF for a 3-week period. Cell-cycle analysis performed on asynchronously growing cultures indicated that differential repair with in vitro aging was not cell-cycle-related. Fluorescence Activated Cell Sorting (FACS) was used to determine the percentages of CD4+ and CD8+ T-cell subsets present during the in vitro culture periods. Cultures consisted primarily of CD4+ cells until day 20 when the percentage of CD8+ cells increased to approximately 50% of the T-cell population. Neither the absolute percentages of CD4+ and CD8+ cells not the CD4+/CD8+ ratios correlated with repair rates of cultured T-cells. Therefore, the observed decreases in the repair of alkylating agent-induced damage are not due solely to the change in the CD4+/CD8+ ratio.