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Rationale: Disparities in pediatric asthma exist in that Latino children have higher prevalence and greater morbidity from asthma than non-Latino white children. The factors behind these disparities are poorly understood, but ethnic-related variations in children's ability to accurately recognize and report their pulmonary functioning may be a contributing process.Objectives: To determine (1) if differences exist between Latino and non-Latino white children's perceptual accuracy and (2) whether these differences are related to asthma outcomes.Methods: Five hundred and twelve children, aged 7-16 years (290 island Puerto Ricans, 115 Rhode Island Latinos, and 107 Rhode Island non-Latino white children) participated in a 5-week home-based protocol in which twice daily they entered subjective estimates of their peak expiratory flow rate into a hand-held, programmable spirometer and then performed spirometry. Their accuracy was summarized as three perceptual accuracy scores. Demographic data, asthma severity, intelligence, emotional expression, and general symptom-reporting tendencies were assessed and covaried in analyses of the relationship of perceptual accuracy to asthma morbidity and health care use.Measurements and Main Results: Younger age, female sex, lower intelligence, and poverty were associated with lower pulmonary function perception scores. Island Puerto Rican children had the lowest accuracy and highest magnification scores, followed by Rhode Island Latinos; both differed significantly from non-Latino white children. Perceptual accuracy scores were associated with most indices of asthma morbidity.Conclusions: Controlling for other predictive variables, ethnicity was related to pulmonary function perception ability, as Latino children were less accurate than non-Latino white children. This difference in perceptual ability may contribute to recognized asthma disparities. [ABSTRACT FROM AUTHOR]

The effect of problem-focused and avoidant coping on social withdrawal was investigated among a sample of 31 urban children with asthma experiencing varied levels of illness-related stress. Two main and two moderating effects were examined. Neither problem-focused nor avoidant coping was significantly associated with withdrawal when the child's asthma symptoms and stressors were controlled. However, a pattern emerged in analyses of the interaction between coping and stress level. Higher levels of both problem-focused and avoidant coping were associated with lower levels of social withdrawal, but only for children with low levels of asthma-related stress. [ABSTRACT FROM AUTHOR]

This paper presents a conceptual model including examples of risk and resource factors associated with indices of school-related asthma morbidity (eg, missed sleep, participation in activities, school absences) in a group of urban, school-aged children with asthma from ethnic minority backgrounds. Specifically, the current longitudinal study examines relations between a contextual risk factor (ie, family life stressors), an asthma-related risk factor (ie, asthma symptoms), individual resources (ie, attention, children's problem-solving beliefs, and self-esteem), and aspects of asthma morbidity that have been shown to have an impact on children's academic performance. Participants of the study included 31 mother-child dyads from low-income, inner-city neighborhoods. Results of hierarchical regression analyses revealed that after controlling for risk factors (ie, asthma symptoms and family life stressors) at baseline, children's individual characteristics (ie, children's problem-solving beliefs and self-esteem) functioned as resource factors for some indices of asthma-related functioning (school absences, participation in activities, and missed sleep) at follow-up (1 year later). Results suggest that contextual and individual risk and resource factors should be further explored in studies including larger samples of urban children with asthma in order to help guide the development of preventive interventions in school-based and health care settings. [ABSTRACT FROM AUTHOR]

In this article we present (a) a definition and conceptual model of asthma-related resilience for urban children with asthma and (b) a study testing an example of such a model. Preliminary analyses explored associations between risk factors (neighborhood disadvantage and asthma symptoms), children's individual characteristics (adaptability and perceived control), and asthma management behaviors across 2 years of middle childhood. Higher levels of adaptability at baseline were significantly associated with more optimal asthma management strategies at follow-up despite the presence of neighborhood disadvantage and asthma symptoms. Statistical support did not emerge for the relation between perceptions of self-control abilities and asthma management behaviors. Results suggest that individual, familial, and contextual risk and protective factors should be further explored in studies including larger samples of urban children with asthma, to help guide the development of preventive interventions. [ABSTRACT FROM AUTHOR]

This study examines associations among self-competence, asthma coping strategies, and asthma-related functioning in school-aged children with asthma. Thirty 8- to 10-year-old children and their mothers from inner-city neighborhoods were interviewed. Hierarchical multiple regression analyses revealed that higher levels of children's self-competence were significantly related to more accurate asthma knowledge. Higher levels of active and avoidance asthma coping strategies were significantly related to higher levels of participation in activities and recommended asthma management behaviors. Implications for future research and culturally sensitive clinical supports for urban families are discussed. [ABSTRACT FROM AUTHOR]

This study assessed the role of human astrovirus (HAstV) in outbreaks and sporadic cases of diarrhea among children attending child care centers (CCCs) and determined the infecting astrovirus antigenic types by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence analysis. Eight astrovirus outbreaks occurred in 6 CCCs. Of 179 children with diarrhea, 36 (20%) had astrovirus-associated diarrhea. Diarrhea stools obtained during diarrhea outbreaks were more likely to contain astrovirus (40/476) than were samples not associated with a diarrhea outbreak (14/452) (P<.001). Type-specific RT-PCR and DNA sequencing identified 5 outbreaks associated with HAstV-1 and 3 outbreaks with HAstV-2. Sequential outbreaks in 2 CCCs occurred with a different type in the same year. Phylogenetic analysis identified 6 clades of HAstV-1 and 2 clades of HAstV-2 during this 1-year surveillance. Astrovirus was a significant cause of diarrhea outbreaks, and 2 antigenic types were present in the community during 1 diarrhea season. Copyright © 1999 The University of Chicago [ABSTRACT FROM AUTHOR]

Astroviruses cause outbreaks of diarrhea in children attending day care centers (DCCs). Reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with EIA detection of astrovirus in stool specimens to characterize further the molecular epidemiology of an outbreak of astrovirus-associated gastroenteritis. Three hundred sixty-eight stool specimens collected prospectively from 36 children enrolled in a DCC during an 11-week outbreak of diarrhea were evaluated by EIA and RT-PCR. Astrovirus was detected in 32% of specimens by RT-PCR versus 10% by EIA (P < .001) and in 89% of children by RT-PCR versus 50% by EIA. The median duration of astrovirus excretion episodes detected by EIA was 1.5 days versus 4 days by RT-PCR (P = .06). Astrovirus was excreted for prolonged periods by immunocompetent children during this outbreak. RT-PCR was more sensitive than EIA for detection of astrovirus in stool specimens and redefined the epidemiology of astrovirus infection in this setting. [ABSTRACT FROM AUTHOR]

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

Introduction: Approximately 50% of melanomas harbor an activating BRAFV600E mutation. Standard of care involves a combination of inhibitors targeting mutant BRAF and MEK1/2, the substrate for BRAF in the MAPK pathway. PTEN loss-of-function mutations occur in ~40% of BRAFV600E melanomas, resulting in increased PI3K/AKT activity that enhances resistance to BRAF/MEK combination inhibitor therapy., Methods: To compare the response of PTEN null to PTEN wild-type cells in an isogenic background, CRISPR/Cas9 was used to knock out PTEN in a melanoma cell line that harbors a BRAFV600E mutation. RNA sequencing, functional kinome analysis, and drug synergy screening were employed in the context of BRAF/MEK inhibition., Results: RNA sequencing and functional kinome analysis revealed that the loss of PTEN led to an induction of FOXD3 and an increase in expression of the FOXD3 target gene, ERBB3/HER3 . Inhibition of BRAF and MEK1/2 in PTEN null, BRAFV600E cells dramatically induced the expression of ERBB3/HER3 relative to wild-type cells. A synergy screen of epigenetic modifiers and kinase inhibitors in combination with BRAFi/MEKi revealed that the pan ERBB/HER inhibitor, neratinib, could reverse the resistance observed in PTEN null, BRAFV600E cells., Conclusions: The findings indicate that PTEN null BRAFV600E melanoma exhibits increased reliance on ERBB/HER signaling when treated with clinically approved BRAFi/MEKi combinations. Future studies are warranted to test neratinib reversal of BRAFi/MEKi resistance in patient melanomas expressing ERBB3/HER3 in combination with its dimerization partner ERBB2/HER2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 DuBose, Bevill, Mitchell, Sciaky, Golitz, Dixon, Rhodes, Bear, Johnson and Angus.)

Purpose: Plexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) associated with neurofibromatosis type 1 (NF1). Despite similar histologic appearance, these neoplasms exhibit diverse evolutionary trajectories, with a subset progressing to malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through the development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathologic features and CDKN2A copy-number loss. Although genomic studies have uncovered key driver events promoting tumor progression, the transcriptional changes preceding malignant transformation remain poorly defined., Experimental Design: Here we resolve gene-expression profiles in PNST across the neurofibroma-to-MPNST continuum in NF1 patients and mouse models, revealing early molecular features associated with neurofibroma evolution and transformation., Results: Our findings demonstrate that ANF exhibit enhanced signatures of antigen presentation and immune response, which are suppressed as malignant transformation ensues. MPNST further displayed deregulated survival and mitotic fidelity pathways, and targeting key mediators of these pathways, CENPF and BIRC5, disrupted the growth and viability of human MPNST cell lines and primary murine Nf1-Cdkn2a-mutant Schwann cell precursors. Finally, neurofibromas contiguous with MPNST manifested distinct alterations in core oncogenic and immune surveillance programs, suggesting that early molecular events driving disease progression may precede histopathologic evidence of malignancy., Conclusions: If validated prospectively in future studies, these signatures may serve as molecular diagnostic tools to augment conventional histopathologic diagnosis by identifying neurofibromas at high risk of undergoing malignant transformation, facilitating risk-adapted care., (©2023 American Association for Cancer Research.)

AP endonuclease-1/Redox factor-1 (APE1/Ref-1 or Ref-1) is a multifunctional protein that is overexpressed in most aggressive cancers and impacts various cancer cell signaling pathways. Ref-1's redox activity plays a significant role in activating transcription factors (TFs) such as NFκB, HIF1α, STAT3 and AP-1, which are crucial contributors to the development of tumors and metastatic growth. Therefore, development of potent, selective inhibitors to target Ref-1 redox function is an appealing approach for therapeutic intervention. A first-generation compound, APX3330 successfully completed phase I clinical trial in adults with progressing solid tumors with favorable response rate, pharmacokinetics (PK), and minimal toxicity. These positive results prompted us to develop more potent analogs of APX3330 to effectively target Ref-1 in solid tumors. In this study, we present structure-activity relationship (SAR) identification and validation of lead compounds that exhibit a greater potency and a similar or better safety profile to APX3330. In order to triage and characterize the most potent and on-target second-generation Ref-1 redox inhibitors, we assayed for PK, mouse and human S9 fraction metabolic stability, in silico ADMET properties, ligand-based WaterLOGSY NMR measurements, pharmacodynamic markers, cell viability in multiple cancer cell types, and two distinct 3-dimensional (3D) cell killing assays (Tumor-Microenvironment on a Chip and 3D spheroid). To characterize the effects of Ref-1 inhibition in vivo, global proteomics was used following treatment with the top four analogs. This study identified and characterized more potent inhibitors of Ref-1 redox function (that outperformed APX3330 by 5-10-fold) with PK studies demonstrating efficacious doses for translation to clinic., Competing Interests: Declaration of Competing Interest None. Mark R. Kelley has licensed APX3330 through Indiana University Research and Technology Corporation to Apexian Pharmaceuticals LLC. Second generation compounds also licensed to Apexian Pharmaceuticals. Apexian has licensed some compounds to Ocuphire Parma. Neither Apexian Pharmaceuticals nor Ocuphire Pharma had control nor oversight of the studies, interpretation, or presentation of the data in this manuscript. Authors do not have any conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A growing body of literature has documented high rates of adverse childhood experiences (ACEs) and their effects on behavioral health among adolescents impacted by the juvenile legal system. Most research with justice-impacted youth assesses the ten standard ACEs, encompassing abuse, neglect, and household dysfunction. This body of work has largely ignored the five expanded ACEs which assess social and community level adversity. Justice-impacted youth commonly experience expanded ACEs (racial discrimination, placement in foster care, living in a disadvantaged neighborhood, witnessing violence, bullying), and inclusion of these adversities may enhance predictive utility of the commonly used ACEs score. The current study examined the prospective impact of total ACEs (standard and expanded) on alcohol and cannabis use, substance-related consequences, and psychiatric symptoms during the year following first ever contact with the juvenile court. Results indicate justice-impacted youth experience multiple expanded ACEs prior to first court contact. The expanded ACEs did not predict any of the behavioral health outcomes assessed, over and above the standard ACEs. Inclusion of expanded ACEs in the standard ACEs score may not increase utility in identifying prospective behavioral health outcomes among youth in first time contact with the juvenile legal system., (© 2022. The Author(s).)

Purpose: Plexiform neurofibromas (PNF) are peripheral nerve sheath tumors that cause significant morbidity in persons with neurofibromatosis type 1 (NF1), yet treatment options remain limited. To identify novel therapeutic targets for PNF, we applied an integrated multi-omic approach to quantitatively profile kinome enrichment in a mouse model that has predicted therapeutic responses in clinical trials for NF1-associated PNF with high fidelity., Experimental Design: Utilizing RNA sequencing combined with chemical proteomic profiling of the functionally enriched kinome using multiplexed inhibitor beads coupled with mass spectrometry, we identified molecular signatures predictive of response to CDK4/6 and RAS/MAPK pathway inhibition in PNF. Informed by these results, we evaluated the efficacy of the CDK4/6 inhibitor, abemaciclib, and the ERK1/2 inhibitor, LY3214996, alone and in combination in reducing PNF tumor burden in Nf1flox/flox;PostnCre mice., Results: Converging signatures of CDK4/6 and RAS/MAPK pathway activation were identified within the transcriptome and kinome that were conserved in both murine and human PNF. We observed robust additivity of the CDK4/6 inhibitor, abemaciclib, in combination with the ERK1/2 inhibitor, LY3214996, in murine and human NF1(Nf1) mutant Schwann cells. Consistent with these findings, the combination of abemaciclib (CDK4/6i) and LY3214996 (ERK1/2i) synergized to suppress molecular signatures of MAPK activation and exhibited enhanced antitumor activity in Nf1flox/flox;PostnCre mice in vivo., Conclusions: These findings provide rationale for the clinical translation of CDK4/6 inhibitors alone and in combination with therapies targeting the RAS/MAPK pathway for the treatment of PNF and other peripheral nerve sheath tumors in persons with NF1., (©2023 American Association for Cancer Research.)

Objective: To evaluate genetic evaluation practices in newborns with the most common birth defect, congenital heart defects (CHD), we determined the prevalence and the yield of genetic evaluation across time and across patient subtypes, before and after implementation of institutional genetic testing guidelines., Study Design: This was a retrospective, cross-sectional study of 664 hospitalized newborns with CHD using multivariate analyses of genetic evaluation practices across time and patient subtypes., Results: Genetic testing guidelines for hospitalized newborns with CHD were implemented in 2014, and subsequently genetic testing increased (40% in 2013 and 75% in 2018, OR 5.02, 95% CI 2.84-8.88, P < .001) as did medical geneticists' involvement (24% in 2013 and 64% in 2018, P < .001). In 2018, there was an increased use of chromosomal microarray (P < .001), gene panels (P = .016), and exome sequencing (P = .001). The testing yield was high (42%) and consistent across years and patient subtypes analyzed. Increased testing prevalence (P < .001) concomitant with consistent testing yield (P = .139) added an estimated 10 additional genetic diagnoses per year, reflecting a 29% increase., Conclusions: In patients with CHD, yield of genetic testing was high. After implementing guidelines, genetic testing increased significantly and shifted to newer sequence-based methods. Increased use of genetic testing identified more patients with clinically important results with potential to impact patient care., Competing Interests: Declaration of Competing Interest This work was supported by the American Heart Association Transformational Award (grant number 19TPA34850054 [to [S.W.]), the Indiana University Health-Indiana University School of Medicine (Strategic Research Initiative and Physician Scientist Initiative [to [S.W.]), and National Institutes of Health (grant number 2P01HL134599 [to S.W. and M.D.] and grant number K08HL148508 [to M.D.]). The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Fanconi anemia (FA) pathway safeguards genomic stability through cell cycle regulation and DNA damage repair. The canonical tumor suppressive role of FA proteins in the repair of DNA damage during interphase is well established, but their function in mitosis is incompletely understood. Here, we performed a kinome-wide synthetic lethality screen in FANCA -/- fibroblasts, which revealed multiple mitotic kinases as necessary for survival of FANCA-deficient cells. Among these kinases, we identified the depletion of the centrosome kinase SIK2 as synthetic lethal upon loss of FANCA. We found that FANCA colocalizes with SIK2 at multiple mitotic structures and regulates the activity of SIK2 at centrosomes. Furthermore, we found that loss of FANCA exacerbates cell cycle defects induced by pharmacological inhibition of SIK2, including impaired G2-M transition, delayed mitotic progression, and cytokinesis failure. In addition, we showed that inhibition of SIK2 abrogates nocodazole-induced prometaphase arrest, suggesting a novel role for SIK2 in the spindle assembly checkpoint. Together, these findings demonstrate that FANCA-deficient cells are dependent upon SIK2 for survival, supporting a preclinical rationale for targeting of SIK2 in FA-disrupted cancers., (© 2021 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Importance: Brain metastasis (BM) is the most common malignant intracranial neoplasm in adults with over 100,000 new cases annually in the United States and outnumbering primary brain tumors 10:1., Observations: The incidence of BM in adult cancer patients ranges from 10-40%, and is increasing with improved surveillance, effective systemic therapy, and an aging population. The overall prognosis of cancer patients is largely dependent on the presence or absence of brain metastasis, and therefore, a timely and accurate diagnosis is crucial for improving long-term outcomes, especially in the current era of significantly improved systemic therapy for many common cancers. BM should be suspected in any cancer patient who develops new neurological deficits or behavioral abnormalities. Gadolinium enhanced MRI is the preferred imaging technique and BM must be distinguished from other pathologies. Large, symptomatic lesion(s) in patients with good functional status are best treated with surgery and stereotactic radiosurgery (SRS). Due to neurocognitive side effects and improved overall survival of cancer patients, whole brain radiotherapy (WBRT) is reserved as salvage therapy for patients with multiple lesions or as palliation. Newer approaches including multi-lesion stereotactic surgery, targeted therapy, and immunotherapy are also being investigated to improve outcomes while preserving quality of life., Conclusion: With the significant advancements in the systemic treatment for cancer patients, addressing BM effectively is critical for overall survival. In addition to patient's performance status, therapeutic approach should be based on the type of primary tumor and associated molecular profile as well as the size, number, and location of metastatic lesion(s)., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Fanconi anemia (FA) is a disease of genomic instability and cancer. In addition to DNA damage repair, FA pathway proteins are now known to be critical for maintaining faithful chromosome segregation during mitosis. While impaired DNA damage repair has been studied extensively in FA-associated carcinogenesis in vivo , the oncogenic contribution of mitotic abnormalities secondary to FA pathway deficiency remains incompletely understood. To examine the role of mitotic dysregulation in FA pathway deficient malignancies, we genetically exacerbated the baseline mitotic defect in Fancc-/- mice by introducing heterozygosity of the key spindle assembly checkpoint regulator Mad2 . Fancc-/-;Mad2+/- mice were viable, but died from acute myeloid leukemia (AML), thus recapitulating the high risk of myeloid malignancies in FA patients better than Fancc-/- mice. We utilized hematopoietic stem cell transplantation to propagate Fancc-/-; Mad2+/- AML in irradiated healthy mice to model FANCC -deficient AMLs arising in the non-FA population. Compared to cells from Fancc-/- mice, those from Fancc-/-;Mad2+/- mice demonstrated an increase in mitotic errors but equivalent DNA cross-linker hypersensitivity, indicating that the cancer phenotype of Fancc-/-;Mad2+/- mice results from error-prone cell division and not exacerbation of the DNA damage repair defect. We found that FANCC enhances targeting of endogenous MAD2 to prometaphase kinetochores, suggesting a mechanism for how FANCC-dependent regulation of the spindle assembly checkpoint prevents chromosome mis-segregation. Whole-exome sequencing revealed similarities between human FA-associated myelodysplastic syndrome (MDS)/AML and the AML that developed in Fancc-/-; Mad2+/- mice. Together, these data illuminate the role of mitotic dysregulation in FA-pathway deficient malignancies in vivo , show how FANCC adjusts the spindle assembly checkpoint rheostat by regulating MAD2 kinetochore targeting in cell cycle-dependent manner, and establish two new mouse models for preclinical studies of AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Edwards, Mitchell, Abdul-Sater, Chan, Sun, Sheth, He, Jiang, Yuan, Sharma, Czader, Chin, Liu, de Cárcer, Nalepa, Broxmeyer, Clapp and Sierra Potchanant.)

Neurofibromatosis type 1 (NF1) is a common cancer predisposition syndrome caused by mutations in the NF1 tumor suppressor gene. NF1 encodes neurofibromin, a GTPase-activating protein for RAS proto-oncogene GTPase (RAS). Plexiform neurofibromas are a hallmark of NF1 and result from loss of heterozygosity of NF1 in Schwann cells, leading to constitutively activated p21RAS. Given the inability to target p21RAS directly, here we performed an shRNA library screen of all human kinases and Rho-GTPases in a patient-derived NF1 -/- Schwann cell line to identify novel therapeutic targets to disrupt PN formation and progression. Rho family members, including Rac family small GTPase 1 (RAC1), were identified as candidates. Corroborating these findings, we observed that shRNA-mediated knockdown of RAC1 reduces cell proliferation and phosphorylation of extracellular signal-regulated kinase (ERK) in NF1 -/- Schwann cells. Genetically engineered Nf1 flox/flox ;PostnCre + mice, which develop multiple PNs, also exhibited increased RAC1-GTP and phospho-ERK levels compared with Nf1 flox/flox ;PostnCre - littermates. Notably, mice in which both Nf1 and Rac1 loci were disrupted ( Nf1 flox/flox Rac1 flox/flox ;PostnCre + ) were completely free of tumors and had normal phospho-ERK activity compared with Nf1 flox/flox ; PostnCre + mice. We conclude that the RAC1-GTPase is a key downstream node of RAS and that genetic disruption of the Rac1 allele completely prevents PN tumor formation in vivo in mice., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Mund et al.)

Objective: Latino children of Caribbean descent remain at high risk for poorly controlled asthma. Controller medications improve asthma control; however, medication adherence remains suboptimal, particularly among minorities. This study assessed socioeconomic, family-based, and parent factors in medication adherence among children with asthma from Rhode Island (RI; Latino and non-Latino white [NLW]) and Puerto Rico., Methods: Data collection occurred as part of a multicenter study of asthma disparities. Our sample included children (ages 7-16) prescribed objectively monitored controller medications (n = 277; 80 island Puerto Rico, 114 RI Latino, 83 RI NLW). Parents completed questionnaires regarding family background and beliefs about medications. Families participated in an interview regarding asthma management. Multilevel analyses (maximum likelihood estimates) accounting for children being nested within site and ethnic group assessed the contribution of social context, family, and parent variables to medication adherence., Results: Medication adherence differed by ethnic group (F(2, 271) = 7.46, P < .01), with NLW families demonstrating the highest levels of adherence. Multilevel models indicated that parental beliefs about medication necessity and family organization regarding medication use were significant predictors of adherence, even for families below the poverty threshold. With family factors in the model, a substantial improvement in model fit occurred (Akaike Information Criterion change of 103.45)., Conclusions: Adherence to controller medications was lower among Latino children in our sample. Targeted interventions that capitalize on existing family resources, emphasize structure, and address parental beliefs about the importance of medications may be of benefit to families from different cultural backgrounds.

Background: Epidemiologic studies have documented higher rates of asthma prevalence and morbidity in minority children compared to non-Latino white (NLW) children. Few studies focus on the mechanisms involved in explaining this disparity, and fewer still on the methodological challenges involved in rigorous disparities research., Objectives and Methods: This article provides an overview of challenges and potential solutions to research design for studies of health disparities. The methodological issues described in this article were framed on an empirical model of asthma health disparities that views disparities as resulting from several factors related to the healthcare system and the individual/community system. The methods used in the Rhode Island-Puerto Rico Asthma Center are provided as examples, illustrating the challenges in executing disparities research., Results: Several methods are described: distinguishing ethnic/racial differences from methodological artifacts, identifying and adapting culturally sensitive measures to explain disparities, and addressing the challenges involved in determining asthma and its severity in Latino and other minority children. The measures employed are framed within each of the components of the conceptual model presented., Conclusions: Understanding ethnic and/or cultural disparities in asthma morbidity is a complicated process. Methodologic approaches to studying the problem must reflect this complexity, allowing us to move from documenting disparities to understanding them, and ultimately to reducing them., (Copyright 2009 Wiley-Liss, Inc.)

Scarce resources and competing land-use goals necessitate efficient biodiversity conservation. Combining multicriteria analysis with conservation decision-support tools improves efficiency of conservation planning by maximizing outcomes for biodiversity while minimizing opportunity costs to society. An opportunity cost is the benefit that could have been received by taking an alternative course of action (i.e., costs to society of protecting an area for biodiversity rather than developing it for some other use). Although different ways of integrating multiple opportunity costs into conservation planning have been suggested, there have been no tests as to which method is most efficient. We compared the relative efficiency of 3 such procedures(Faith & Walker [1996], Sarkar et al. [2004], and a procedure of our own design) in a systematic conservation-planning framework for the Milne Bay Province of Papua New Guinea. We devised 14 opportunity costs and assigned these to 3 scenarios representing different conservation planning concerns: food security, macro-economic development, and biodiversity persistence. For each scenario, we compared the efficiency of the 3 methods in terms of amount of biodiversity protected relative to total expenditure for each opportunity cost. All 3 methods captured similar amounts of biodiversity, but differed in total cost. Our method had the least overall cost and was therefore most efficient. Nevertheless, there was a high correlation and geographical concordance among all 3 methods, indicating a high degree of spatial overlap. This suggests that choosing an appropriate approach may often depend on contextual factors related to the design of the planning question, rather than efficiency alone.

RATIONALE: This study assesses the relationships between ADHD symptoms, specific family asthma management domains, and pediatric asthma morbidity. METHODS: Participants were 110 children with asthma and a respective parent (ages 7-17, X = 11.6 years, 25% ethnic/racial minority). Parents completed measures of asthma morbidity and report of child ADHD symptoms. Children completed measures of attention, concentration, and impulsivity. Families participated in the Family Asthma Management System Scale (FAMSS) interview to assess the effectiveness of eight features of asthma management. RESULTS: Parent report of ADHD symptoms and poor child performance on a computerized task of sustained visual attention were associated with asthma morbidity. Paper and pencil tasks of visual attention, and an index of auditory attention, were not related to asthma morbidity. Modest associations were found between parent report of ADHD symptoms, child performance-based indicators of attention and concentration, and features of family asthma management, although not across all measures. The family response to asthma partially mediated the relationship between ADHD symptoms and morbidity. CONCLUSIONS: ADHD symptoms are modestly associated with difficulties in family asthma management.

The purpose of this study was to examine the association between asthma symptom perception measured during a 5-6 week baseline and functional morbidity measured prospectively across a 1-year follow-up. Symptom perception was measured by comparing subjective ratings with peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV(1)). We hypothesized that accurate symptom perception (ASP) would be associated with less functional morbidity. Participants consisted of 198 children with asthma ages 7-17 recruited from three sites. The children used a programmable electronic spirometer in the home setting to guess their PEFR prior to exhalation. Each "subjective" guess was classified as being in an ASP, dangerous symptom perception (DSP; underestimation of symptoms), or symptom magnification (SM; overestimation) zone based upon the corresponding measurement of PEFR or FEV(1). An index of functional morbidity was collected by parent report at baseline and across 1-year follow-up. A greater proportion of ASP blows and a lower proportion of DSP blows based on PEFR predicted less functional morbidity reported at baseline, independent of asthma severity and race/ethnicity. A greater proportion of ASP blows (using PEFR and FEV(1)) and a lower proportion of SM blows (using FEV(1)) predicted less functional morbidity across 1-year follow-up. Symptom perception was not associated with emergency department visits for asthma at baseline or across follow-up. In comparison to PEFR, FEV(1) more frequently detected a decline in pulmonary function that children did not report. Symptom perception measured in naturalistic settings was associated with functional morbidity at baseline and prospectively across 1-year follow-up. Support was found for including multiple measures of pulmonary function in the assessment of asthma symptom perception., ((c) 2007 Wiley-Liss, Inc.)

Human astroviruses (HAstVs) cause gastroenteritis. Real-time, reverse-transcription-polymerase chain reaction (RT2-PCR) was developed to quantitate HAstV RNA. An 88 bp amplicon from the conserved 3' genomic region was detected by binding of SYBR Green. RT2-PCR was reproducible, with a correlation coefficient of 0.998-1.00 and PCR efficiency of 94.4-100% (mean 97%). The coefficient of variation was 0.6-2.5%, dynamic range with RNA standard up to 5 x 10(8) RNA copies (RNACN) and sensitivity 5 RNACN. Of 54 blinded, archived stool samples from children hospitalized because of gastroenteritis tested by RT-PCR, 49 (91%) agreed by RT2-PCR for HAstV-positivity (Cohen kappa=0.81, 95%CI 0.66-0.97). HAstV RNACN in stools ranged from 7.6 x 10(1) to 3.6 x 10(14)copies/0.1g. Children coinfected with rotavirus had lower RNACN (mean log 4.22/standard deviation=2.26) than those without coinfection (7.57/3.06; p=.019). Children taking infant formula also had lower RNACN (5.96/2.98) than breast-fed or weaned children (8.73/2.92; p=.027). Higher RNACN tended to occur with longer duration of diarrhea for the episode (r=0.49, p=.064), but was not associated with change in age, gender, illness day, severity or breast-feeding. RT2-PCR quantitated HAstV RNA and RNACN in stool correlates with features of clinical illness.

This study assessed the safety and immunogenicity of a pediatric formulation of the 2003-2004 inactivated, trivalent, split virion influenza vaccine, administered in a 2-dose schedule in healthy children ages 6-36 months, of whom 94% had protective titers (> or =1/40) to at least 1 antigen. The 2003-2004 split virion influenza vaccine was safe and immunogenic in young children.

Positive-sense single-stranded RNA (+ssRNA) viruses replicate by uncoating the RNA genome for translation to provide viral proteins essential for genome replication and the production of new viral particles. The viral proteins are synthesized from a polyprotein precursor, which is cleaved nascently. The synthesized proteins include viral RNA-dependent RNA polymerase (RdRP), viral genome-linked protein (VPg), and a helicase. VPg is covalently attached to the genomic form of +ssRNA viruses. Helicases and NTPase unwind the RNA before replication. VPg and helicases have been identified in +ssRNA families, however, the presence of VPg and helicase in the Astroviridae, another +ssRNA family, has not been fully elucidated. Computational tools were utilized to provide sequence analysis evidence for the presence and genomic location of astrovirus VPg and helicase. HMMER program v2.1.1 was used to build Hidden Markov Model (HMM) profile for calicivirus VPg to search for conserved motifs in the astrovirus genome. We performed phylogenetic analysis of two genomic regions of astroviruses and caliciviruses (encoding the RdRP and VPg). We identified a putative VPg coding region in astrovirus. This region was located in open reading frame 1a (ORF1 a) and included sites with high sequence similarity to the VPg coding regions of Caliciviridae, Piconaviridae, and Potyviridae. A region encoding a putative astrovirus helicase identified conserved motifs only with pestivirus helicase sequences. Sequence analysis and comparison to other +ssRNA viruses supports the presence of VPg in the Astroviridae. Further laboratory analysis will be necessary to confirm these findings.

Aim: To determine the severity and clinical characteristics of human astrovirus (HAstV) infections among hospitalized children and compare them with children infected by rotavirus., Methods: Retrospective, case-control study of astrovirus-infected and rotavirus-infected children. Astroviruses were detected in stool samples by enzyme immunoassay and/or reverse transcriptase-polymerase chain reaction. All stool samples were tested for rotavirus and bacterial pathogens, and all negative samples were further tested for human astrovirus. Children with astrovirus-positive stool samples and complete clinical data were included in this study., Results: Astrovirus was detected in 29 (1.8%) children, and 63 rotavirus-infected children were included as controls. Astrovirus-infected children had shorter duration of diarrhea than rotavirus-infected children (median 4 and 6 d, respectively; p<0.05), and 79% of the astrovirus infections were associated with a short duration of vomiting (median 1 and 4 d, respectively; p<0.0001). Rotavirus-infected children had longer hospitalization (p<0.050) than astrovirus-infected children., Conclusion: HAstV-infected children had similar symptoms to those occurring in rotavirus infection. However, astrovirus-infected patients had a significantly shorter duration of diarrhea and vomiting, and they required a shorter hospitalization. On the basis of the clinical data and severity scores, children with rotavirus infection had more severe illness.

Background: Human milk components, including oligosaccharides, affect the gastrointestinal flora of infants. Previous studies in adults have demonstrated that fructo-oligosaccharides increase potentially beneficial fecal bacteria, including bifidobacteria. The purpose of this study was to determine the prebiotic effect of infant formula supplemented with fructo-oligosaccharides., Methods: Healthy term infants 2 to 6 weeks of age were enrolled in a 5-week, prospective, randomized, crossover, single-site study with a nonrandomized human milk comparator group. Washout weeks preceded and followed a week of feeding with fructo-oligosaccharide-supplemented formula (1.5 or 3.0 g/L). Stool specimens were quantitatively cultured weekly for bacteroides, lactobacilli, bifidobacteria, clostridia and enterococci and were tested for Clostridium difficile toxin., Results: Seventy-two of 87 infants completed the trial; 58 were formula fed and 14 were human milk fed. Mean counts of bifidobacteria and lactobacilli were similar in all groups at entry and no group experienced a significant change in counts with fructo-oligosaccharide supplementation. After 7 days of fructo-oligosaccharide supplementation the bifidobacteria counts were greater in the 1.5 g/L fructo-oligosaccharide formula group than in the human milk fed or 3.0 g/L fructo-oligosaccharide formula groups. Formula-fed infants had higher counts of enterococci and bacteroides before fructo-oligosaccharide supplementation, and these counts did not change after supplementation. Clostridium counts increased 7 days after supplementation in the 1.5 g/L fructo-oligosaccharide formula group (P = 0.0356). No human milk fed infants had C. difficile toxin in stools. Fructo-oligosaccharide (3.0 g/L) supplementation resulted in more frequent and significantly softer stools., Conclusions: Infant formula supplemented with 1.5 or 3.0 g/L fructo-oligosaccharides was safe but had minimal effect on fecal flora and C. difficile toxin.

Human astroviruses (HAstVs) are major pathogens in viral gastroenteritis worldwide. Twenty-five HAstV strains were detected from stool specimens of children hospitalized for acute gastroenteritis in Budapest, Hungary, between 1995 and 1999. Sequence analysis was performed at the 3' end of the capsid gene to determine genotypic diversity of HAstVs circulating in Hungary. Five different genotypes of HAstVs were identified: HAstV-1 was predominant, followed by types 5, 8, 3 and 4. Two different subtypes of HAstV-1 were detected, but only one at a time in the community. This is the first report on the genetic diversity of HAstVs in Hungary and Central/Eastern Europe.

Purpose of Review: Public health concerns related to enteric viral agents, such as astroviruses and caliciviruses, include their ability to cause sporadic diarrhea, large outbreaks of gastroenteritis, and hospitalizations or deaths resulting from vomiting, diarrhea, and dehydration. Improved surveillance and application of sensitive molecular assays has increased awareness of these enteric pathogens and reduced the 'diagnostic gap' or unknown causes of non-bacterial gastroenteritis., Recent Findings: Molecular assays have been applied to further describe the epidemiology of human astroviruses from a variety of geographic areas. The burden of astrovirus infections compared with other enteric viral agents, including rotaviruses, caliciviruses, and enteric adenoviruses have been reported. New methods for detection of astroviruses such as reverse transcription-polymerase chain reaction and molecular typing methods have advanced the understanding of the epidemiology. Additional molecular studies have described the protein processing mechanisms of this single-stranded RNA virus., Summary: Astroviruses are increasingly recognized as significant gastrointestinal pathogens. The understanding of molecular epidemiology and molecular processing of the virus may lead to specific prevention strategies.

A comparative analysis was performed with 25 isolates of astroviruses (AstVs) detected in sewage sources and 22 concurrently identified clinical AstV isolates from the Tshwane (Pretoria) Metropolitan Area in South Africa. The samples and specimens were screened for AstVs by using an enzyme immunoassay and/or a reverse transcriptase PCR (RT-PCR) for the highly conserved untranslated region (3' end) of the genome. The RT-PCR results were confirmed by oligonucleotide probe dot blot hybridization. Viable viruses were propagated in cell cultures for amplification when a minimal specimen was available or indeterminate sequences were obtained. AstV strains were characterized by RT-PCR and partial sequence analysis of the capsid region. The presence of multiple human AstV (HAstV) types in a single sewage sample complicated identification of individual strains, and additional type-specific RT-PCR and sequence analyses of the capsid region were required for characterization. Amplification and characterization of one genotype from a sample, therefore, did not preclude the possibility that a sample harbored additional different genotypes. Genotype and sequence information obtained from AstVs in wastewater samples were compared to information obtained from AstV strains from human stools. HAstV type 1 (HAstV-1), as well as HAstV-3, -5, -6, and -8, were identified among the clinical isolates, and HAstV-1, -2, -3, -4, -5, -7, and -8 were identified among the environmental samples. Phylogenetic analysis demonstrated that HAstV-1, -3, -5, and -8, which were present in human stool and sewage samples, clustered together, indicating that these viruses are closely related. The concurrent presence of identical HAstV strains in wastewater samples and in hospitalized patients suggests that AstVs present in the environment pose a potential risk to communities in which fecally contaminated water is used for recreational and domestic purposes.

Background: Immunization of young children against cytomegalovirus (CMV) might decrease child-to-child and child-to-adult transmission of CMV and thereby reduce maternal infection during pregnancy. We conducted a Phase I trial in CMV-seronegative toddlers to evaluate the reactogenicity and immunogenicity of a CMV gB vaccine administered with MF59, an oil and water adjuvant., Methods: Eighteen children between 12 and 35 months of age received either 20 microg of CMV gB/MF59 (n = 15) or a control hepatitis A vaccine (n = 3) at 0, 1 and 6 months. The study was open-label for the first six children and then observer-blinded and randomized. Children were monitored for local and systemic reactions and for the development of antibodies to the envelope protein gB and CMV-neutralizing antibodies., Results: Adverse reactions were uncommon and mild. Two children were excluded from the immunogenicity analysis because they had serologic evidence of CMV infection. Reciprocal geometric mean neutralizing titers were: 0 preimmunization (n = 18); 90 (range, 53 to 188) after Dose 2 (n = 6); and 638 (range, 210 to 1645) 1 month after Dose 3 (n = 13). The reciprocal geometric mean neutralizing titers of antibody to gB by EIA were: 0 preimmunization (n = 18); 857 (range, 307 to 2073) after Dose 1 (n = 12); 27 457 (range, 9312 to 55,080) after Dose 2 (n = 6); and 98,264 (range, 35,480 to 228,780) 1 month after Dose 3 (n = 5). After Dose 3 antibody responses of toddlers were greater than those of naturally infected adults and were notably higher than among 149 adults given 3 doses of the same vaccine in other trials., Conclusion: The CMV gB vaccine is well-tolerated and highly immunogenic in toddlers.

We report a naturally occurring human astrovirus (HAstV) strain detected in two different geographic locations. We identified two isolates of this strain in a diarrhea outbreak at a child care center in Houston, Texas; and two isolates in diarrhea stool samples from two children in Mexico City. All four isolates were detected in stool samples by enzyme immunoassay (EIA). One of the Mexican isolates was typed by EIA and all four isolates were HAstV-5 by typing RT-PCR. The four isolates were >97% nucleotide-identical in two different genomic regions: ORF1a (246 nt), and the 3' end of the genome (471 nt). One isolate from each geographic location was further sequenced in the transition region from ORF1b to ORF2 (1255 nt) and this region of the two isolates showed > or = 99% nt identity. Phylogenetic analyses of sequences of eight HAstV antigenic types and the novel strain in the transition region demonstrated the new strain being closely related to HAstV-3 in ORF1b, but closest to HAstV-5 in ORF2. These results and high sequence identity among all HAstV antigenic types in the transition region and RNA structural predictions supported a potential recombination site at the ORF1b/ORF2 junction. This is the first evidence that recombination occurs among human astroviruses.

Human astroviruses (HAstV) can, on the basis of immunoassays using type-specific rabbit antisera, be classified into eight serotypes that correlate with genotypes. Very few isolates of HAstV type 8 have been described and there is a paucity of data available with regard to the antigenic and genetic relationships between HAstV type 8 (HAstV-8) and HAstV types 1 (HAstV-1) to 7 (HAstV-7). A wild-type HAstV from a South African paediatric patient with diarrhoea was analysed antigenically, by immune electron microscopy and enzyme immunoassay, and genetically in selected regions of the ORF1a, ORF1b and ORF2 and characterised as a HAstV-8. This HAstV-8 strain exhibited greatest homology with HAstV-4 in the 5' end of the capsid gene and ORF1a and 1b, and greatest homology with HAstV-5 in the 3' end of the capsid region. This study confirms, by both antigenic and genetic analyses, that HAstV-8 represents a distinct antigenic and genotype and is the first report of a HAstV-8 from a hospitalised paediatric patient with diarrhoea in southern Africa., (Copyright 2001 Wiley-Liss, Inc.)

Human astroviruses (HAstVs) were detected in 23 stool samples from 365 diarrhea episodes among 214 children (<18 months old) prospectively monitored for diarrhea in Mexico City. Stool samples were tested by EIA and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. EIA was less sensitive (74%) and equally specific, compared with RT-PCR analysis using type-common primers for HAstV detection. Of 31 HAstV isolates, EIA typed 18 (69%) of 26 EIA-positive samples, and RT-PCR analysis typed 26 (84%) of 31 RT-PCR-positive samples. Phylogenetic analysis of the 3' end of the capsid region (363 nucleotides) confirmed the type assignment by EIA and RT-PCR analysis and determined the type for 5 previously untyped samples. Six HAstV antigenic types cocirculated in the community: HAstV-2 (42%), HAstV-4 (23%), HAstV-3 (13%), HAstV-1 (10%), HAstV-5 (6%), and HAstV-7 (6%). RT-PCR and sequence analysis provided more detailed epidemiology of HAstV in the community than did antigenic detection methods.

Human astrovirus (HAstV) is a significant cause of acute diarrhea among children, resulting in outbreaks of diarrhea and occasionally in hospitalization. Improved detection methods for eight antigenic types of HAstV and studies assessing the frequency and severity of HAstV diarrhea have further defined the impact of HAstV infections in children. These studies have shown that HAstV infections are clinically milder (diarrhea, vomiting, fever) than rotavirus infections. However, frequent coinfection of HAstV with rotavirus and caliciviruses in childhood diarrhea complicates the epidemiology. Seroprevalence studies have provided evidence that the majority of children are infected by HAstV by 6 years of age. The route of transmission is probably fecal-oral from food or water sources. Recent and planned studies will help to define the epidemiology and in the future lead to prevention strategies, which could include vaccination.

This study assessed the role of human astrovirus (HAstV) in outbreaks and sporadic cases of diarrhea among children attending child care centers (CCCs) and determined the infecting astrovirus antigenic types by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence analysis. Eight astrovirus outbreaks occurred in 6 CCCs. Of 179 children with diarrhea, 36 (20%) had astrovirus-associated diarrhea. Diarrhea stools obtained during diarrhea outbreaks were more likely to contain astrovirus (40/476) than were samples not associated with a diarrhea outbreak (14/452) (P<.001). Type-specific RT-PCR and DNA sequencing identified 5 outbreaks associated with HAstV-1 and 3 outbreaks with HAstV-2. Sequential outbreaks in 2 CCCs occurred with a different type in the same year. Phylogenetic analysis identified 6 clades of HAstV-1 and 2 clades of HAstV-2 during this 1-year surveillance. Astrovirus was a significant cause of diarrhea outbreaks, and 2 antigenic types were present in the community during 1 diarrhea season.

During 1997, an extensive outbreak of astrovirus occurred in a unit where paediatric patients were being treated for leukaemias and inherited immune deficiency disorders. Prolonged shedding of virus for many months following infection was demonstrated in three patients who had undergone bone marrow transplantation. Comparison of reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay (EIA), and electronmicroscopy (EM) to monitor the outbreak showed that many subclinical infections, mainly in children aged > 3 years could only be detected by RT-PCR. Use of RT-PCR revealed that several patients were infected earlier and shed virus for longer than by using EM or EIA. The virus responsible for the outbreak was identified as HAstV-1 and was shown to have a sequence that differed from a strain obtained in 1988.

Objective: To determine the prevalence of antibody to human astrovirus types 1 (HAstV-1) and 3 (HAstV-3) in children., Methods: Sera from children hospitalized in Norfolk, VA, for noninfectious conditions were collected for a 1-month period every 6 months from 1993 to 1996 and tested by enzyme immunoassay for antibody to HAstV-1 and HAstV-3 with the use of baculovirus-expressed recombinant capsid proteins as antigens., Results: The seroprevalence of 393 infants and children to HAstV-1 decreased from 67% in infants <3 months of age to 7% by 6 to 8 months of age, consistent with loss of transplacental antibodies. Children acquired HAstV-1 antibody with a peak prevalence of 94% at 6 to 9 years of age (P < 0.001). Antibodies to HAstV-3 exhibited a lower prevalence, with 26% positive at <3 months, 0% at 6 to 11 months and 42% by 6 to 9 years of age. HAstV-1 seroprevalence in children O to 2 months of age decreased from 89% in November, 1993, to 40% in November, 1996 (P = 0.009)., Conclusions: Astrovirus type-specific antibody prevalence can be measured by baculovirus-expressed capsid antigens in an enzyme immunoassay. Children developed antibody to HAstV-1 (94%) and to HAstV-3 (42%) by 6 to 9 years of age indicating frequent exposure to these enteric viruses in infancy and early childhood.

Aim: To describe the epidemiologic and clinical characteristics of astrovirus-associated diarrhea in a cohort of young children from a periurban community in Mexico City., Methods: From November, 1988, through December, 1991, a total of 214 children were enrolled in a longitudinal study of diarrhea and monitored from birth to 18 months of age. A stool specimen was collected during each episode of diarrhea. Specimens from a total of 510 diarrhea episodes were tested for astrovirus by enzyme immunoassay and examined for other enteric pathogens. The antigenic types of astrovirus were determined by a typing enzyme immunoassay., Results: Astrovirus was detected in 26 (5%) of 510 diarrhea episodes, with an incidence rate of 0.1 episode/child year; the highest rate was in children 13 to 18 months of age. Astrovirus-associated diarrhea was characterized by a median of 4 stools (range, 2 to 10) during the first 24 h, a median duration of 3 days (range, 1 to 21), vomiting (20%), and fever (7%). No cases of dehydration or repeat symptomatic infections were observed. Coinfection with another pathogen was detected in 11 of the 26 episodes (42%). Serotype 2 (35%) was most common, followed by serotypes 4 (15%), 3 (11%), and 1 and 5 (4% each); 31% were nontypable. Astrovirus-associated diarrhea was less severe, as measured by the number of stools (4.3 +/- 1.9), than diarrhea caused by rotavirus (7.1 +/- 2.8) or when coinfections occurred (5.5 +/- 1.6; P = 0.008)., Conclusions: Astrovirus was associated with 5% of the episodes of diarrhea in this cohort of young Mexican children and presented as a mild secretory diarrhea. Five predominant antigenic types were detected with type 2 being the most common.

Objective: Evaluate antibiotic-associated diarrhea and toxigenic Clostridium difficile in stool specimens obtained from children before and after 10 days of amoxicillin/clavulanate for otitis media., Design: Children, 12 to 47 months of age, treated with amoxicillin/clavulanate for otitis media in an outpatient setting were enrolled. Stool specimens were obtained at enrollment, when diarrhea occurred and at the end of therapy. All stool specimens were tested for C. difficile toxins A and B by enzyme immunoassay., Results: Seventy-six children who had stool specimens collected at enrollment and after therapy were included in the analysis. None had C. difficile toxin in stool specimens at enrollment. Six (27%) of 22 children with diarrhea, and 4 (7%) of 54 children without diarrhea had C. difficile toxin present at completion of therapy (P = 0.03)., Conclusion: Toxigenic C. difficile was identified in 13% of children at the conclusion of amoxicillin/clavulanate therapy with a significantly higher frequency in children with diarrhea.