Synthesis and antimicrobial studies of hydrazone derivatives of 4-[3-(2,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid and 4-[3-(3,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid.

Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78 µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.

Brain morphometry, T2-weighted hyperintensities, and IQ in children with neurofibromatosis type 1.

BACKGROUND: Larger gray matter (GM) volume in healthy children is correlated with higher IQ. Children with neurofibromatosis type 1 (NF1) have larger brains, their magnetic resonance images frequently show T2-weighted hyperintensities, and their IQs are lower. OBJECTIVES: To confirm the hypotheses that (1) children with NF1 have larger GM and white matter volumes, (2) the greatest volume differences are in the frontal and parietal regions and in children with NF1 with hyperintensities, and (3) GM volume is inversely related to IQ in children with NF1. DESIGN: Wechsler Intelligence Scale for Children-Third Edition IQ testing and measurement of cerebral volumes and hyperintensities in brain magnetic resonance images were performed on 36 children with NF1 and on 36 matched relatives who served as control subjects. RESULTS: Gray matter and white matter volumes were significantly larger in children with NF1. The greatest difference was observed in cerebral white matter volume, predominantly in the frontal lobes, whereas the greatest difference in GM volume was in the temporal, parietal, and occipital regions. In controls, IQ was significantly related to GM volume, but in children with NF1, IQ was not inversely associated with GM volume, although IQs of children with NF1 were significantly lower. CONCLUSIONS: Children with NF1 do not have the normal relationship between GM volume and IQ. Larger GM volume in the posterior brain regions and larger white matter volumes in the frontal brain regions contribute to the larger brain volume in children with NF1.

Examining the association between parenting stress and the development of early childhood caries.

OBJECTIVES: Numerous studies have explored the effects of pediatric health on parenting stress, but very little work has been carried out to explore the opposite and equally as compelling relationship of how parenting stress might affect child health, especially as it relates to oral health. This study examined the association between parenting stress and early childhood caries (ECC) in 97, 4- to 5-year-old Australian children attending preschools in the North Brisbane Health Region, Australia. METHODS: Using a cross-sectional study design, clinical examinations were conducted to evaluate the caries status of each child. Two caregiver questionnaires were completed -- one soliciting demographic and oral health behavior information, and the other, information on parenting stress. RESULTS: This study demonstrated a significant bivariate association between parenting stress and ECC experience as measured by dmft; however, the association did not persist in the two-part forward-selection logistic and linear regression models. A negative association between social desirability (defensive responding) and extent of caries was also determined. CONCLUSIONS: Our findings suggest the need to conduct longitudinal studies to give proper consideration to the temporal aspect of caries development and clarify the results obtained by on the relationship between parenting stress and oral health. Further study is also warranted to more clearly elucidate the association between social desirability (defensive responding) in parents and their children's ECC experience.

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Early childhood caries: analysis of psychosocial and biological factors in a high-risk population.

The influences that link social factors and caries development are not well understood, although mediation by stress has been suggested. The association between caregiver stress and early childhood caries (ECC), in particular, remains unclear. The purpose of this study was to examine the relationships between parenting stress and ECC while controlling for behavioral and biological factors in a high-risk population. One hundred and fifty healthy children aged 18-36 months were examined in a cross-sectional study design. Parental interviews were conducted to obtain demographic, oral health behavior and parenting stress data. Clinical data included parent and child bacterial measures, fingernail fluoride analyses, caries prevalence and presence of child enamel hypoplasia. Bivariate analyses revealed that parenting stress predicted caries. Multivariate analyses demonstrated that a combination of psychosocial, behavioral, temporal and biological variables predicted ECC outcomes. Total parenting stress did not contribute independently to the best prediction model. Our findings suggest the need for the development of a multidimensional stress model that considers the parent-child dyad to elucidate further the link between psychosocial factors and ECC.

Outcome in children with fetal mild ventriculomegaly: a case series.

Mild enlargement of the lateral ventricles is associated with schizophrenia and other neurodevelopmental disorders. While it has been hypothesized that ventricle abnormalities associated with neurodevelopmental disorders arise during fetal brain development, there is little direct evidence to support this hypothesis. Using ultrasound, it is possible to image the fetal ventricles in utero. Fetal mild ventriculomegaly (MVM) has been associated with developmental delays in early childhood, though longer-term neurodevelopmental outcome has not been studied. Follow-up of five children (aged 4--9 years) with mild enlargement of the lateral ventricles on prenatal ultrasound and two unaffected co-twins is reported: one child had attention deficit hyperactivity disorder (ADHD), one had autism, and two had evidence of learning disorders. These cases suggest that the mild enlargement of the lateral ventricles associated with these neurodevelopmental disorders arises during fetal brain development and can be detected with prenatal ultrasound. In addition, the presence of mildly enlarged, asymmetric ventricles in two children on prenatal ultrasound and on follow-up MRI at age 6 years indicates that ventricle structure present in utero can persist well into childhood brain development. The study of fetal ventricle development with ultrasound may provide important insights into neurodevelopmental disorders and allow the identification of children at high risk.

A "labor from the heart".

SUMMARY While it is true that publications targeted to gay males historically were glossier, had more consistent advertising income, and claimed higher circulations than lesbian periodicals, the number of lesbian newsletters, newspapers, and magazines grew significantly during the nearly 50 years covered in this study. This study chronicles that origin, growth and disappearance of four significant lesbian publications-Vice Versa, The Ladder, Focus: A Journal for Lesbians, and Sinister Wisdom-from 1947 to 1994. These magazines illustrate varied genre in lesbian publishing history and represent three distinctly different geographical areas. They also span almost five decades during the inauspicious beginning and rapid growth of the lesbian press. This study argues that lesbian publications, although often tied to politically active organizations, existed primarily to help individual lesbians come to terms with a homophobic world and to provide social connections and essential support systems. Less financially secure than their counterparts in the gay male magazine industry, lesbian publications were labors of love and rarely survived.

Social skills and psychological adjustment of child and adolescent cancer survivors.

Social skills and psychological adjustment for survivors of childhood cancer were investigated. Cancer survivors included 42 children and adolescents ranging in age at evaluation from 6 to 18 years with a mean age of 13.1 years. Measures included teacher and parent ratings of social skills and adjustment and parent ratings of family functioning. The findings showed that social skills and psychological adjustment as rated by both parents and teachers were primarily associated with academic functioning. In addition, family cohesiveness was found to account for nearly one third of the variance in survivors' adjustment when rated by teachers, and length of time off treatment accounted for a significant percentage of the variance in children's adjustment when rated by parents. The findings underscore the importance of a multi-informant approach to the assessment of psychological adjustment of pediatric cancer survivors and demonstrate the role of learning difficulties and family functioning in influencing social skills and adjustment for these children and adolescents.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and polymerase chain reaction for differentiation of Prevotella intermedia and Prevotella nigrescens.

Isolates previously thought to be Prevotella intermedia have been shown to be a closely related species now known as Prevotella nigrescens. The purpose of this study was to determine the efficacy of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and polymerase chain reaction (PCR) to differentiate endodontic isolates of P. nigrescens from P. intermedia. Fifty-six strains of black-pigmented bacteria isolated from endodontic infections and conventionally identified as P. intermedia were used in this study. Using SDS-PAGE, novel polypeptide bands were used to differentiate P. nigrescens from P. intermedia. PCR was accomplished with specific primers for the 16S ribosomal RNA gene of both strains. Of 56 endodontic isolates, 41 (73%) strains were identified by SDS-PAGE as P. nigrescens and 15 (27%) strains as P. intermedia. Of the 41 strains of P. nigrescens identified by SDS-PAGE, PCR identified 37 strains as P. nigrescens. Restriction endonuclease digestion of amplified 16S ribosomal RNA genes indicated that the remaining four strains originally identified by SDS-PAGE as P. nigrescens were actually strains of Prevotella distinct from P. nigrescens and P. intermedia. Of 15 strains of P. intermedia identified by SDS-PAGE, PCR identified 14 strains as P. intermedia; but, one strain was identified as P. nigrescens. The results indicated that PCR was a more precise method than SDS-PAGE to differentiate P. intermedia from P. nigrescens. This study confirms that P. nigrescens is more commonly isolated in pure culture from endodontic infections than P. intermedia.

Neurodevelopmental outcome of infants with acute lymphoblastic leukemia: a Children's Cancer Group report.

BACKGROUND: Infants diagnosed with acute lymphoblastic leukemia (ALL) are considered the patient subgroup at the highest risk for central nervous system (CNS) disease, both at presentation and as an isolated extramedullary relapse. In addition, they are highly vulnerable to adverse developmental sequelae from CNS-directed therapy. METHODS: Thirty patients younger than 12 months at diagnosis (12 males, 18 females) in first hematologic remission were evaluated after completion of ALL therapy (mean age = 62.1 months; standard deviation = 17.2 months; range = 38-102 months). CNS-directed treatment included very high dose infusions of methotrexate (MTX) and intrathecal cytarabine and MTX. Three patients had meningeal leukemia that required additional therapy. Children were administered the McCarthy Scales of Children's Abilities, and parents completed a sociodemographic questionnaire to obtain information about occupation and education. RESULTS: Mean scores on all 6 cognitive and motor indices of the McCarthy Scales were in the average range (Verbal = 52.0; Perceptual = 53.6; Quantitative = 49.6; General Cognitive Index [GCI] = 102.1; Memory = 49.2; Motor = 51.0). Score distributions for each neurodevelopmental index were comparable to age-based population standards. One patient obtained a GCI that exceeded 2 standard deviations above the mean; none scored more than 2 standard deviations below. There was no report of developmental disabilities or neurologic disorders for any of the patients. Risk factors, including age at diagnosis, gender, additional CNS-directed treatment, and family socioeconomic status, were not associated with developmental outcome. CONCLUSIONS: Test findings indicated a generally positive neurodevelopmental outcome for ALL patients diagnosed in infancy who were treated with very high dose MTX as CNS-directed therapy. Combined with the reduction in the isolated CNS relapse rate achieved by the Children's Cancer Group (CCG) clinical trial CCG-107, the results of this study represent a substantial improvement in neurodevelopmental outcome for very young patients compared with infants treated for ALL in the past.

The "we of me": Carson McCullers as lesbian novelist.

Although Carson McCullers camouflaged her love for women in her fiction, gay and lesbian themes are inarguably present in her work. The loneliness that her characters face takes on allegorical intensity, and it is even more potent due to her own sexual confusion and alienation. Married twice to the same man and falling in love repeatedly with both women and men, McCullers wrestled with bisexuality throughout her personal and literary life. Her deepest attachments were to her husband Reeves McCullers; David Diamond, a musician-composer in love with both McCullers and her husband; and Anne-marie Clarac-Schwarzenbach, a Swiss writer. All three of these love interests required that McCullers deal with complicated and ultimately destructive triangles. Given that fact, it is no surprise that she created fictional worlds peopled with characters engaged in three-way relationships. In her novels, Mick (The Heart Is a Lonely Hunter), Frankie (The Member of the Wedding), Miss Amelia (The Ballad of the Sad Cafe) and Weldon Penderton (Reflections in a Golden Eye) also reflect the author's sexual ambivalence and inability to fit into the prescribed social structures of the South.

HIV-infected children with hemophilia: one- and two-year follow-up of neuropsychological functioning.

This report describes the absence of neuropsychologic change observed over a 2-year period for 25 HIV-seropositive (HIV+) children and adolescents with hemophilia and 33 HIV-seronegative (HIV-) controls. Efforts were made to match the groups on the basis of chronological age, race, and hemophilia severity. The baseline evaluation included blinded neuropsychologic measurement of motor, attention, language, visual processing, memory, and general intelligence. HIV+ and HIV-group means did not differ at baseline on any neuropsychologic domain, and this trend continued at the 2-year follow-up. Mixed models analyses did not indicate that the HIV+ group performed more poorly than the HIV- group on any of the neuropsychological domains, nor did they show different patterns of change over time on these variables for the HIV+ group. Consistent with emergent findings, it continues to be premature to attribute subtle neuropsychologic deficits in seropositive children with hemophilia directly to the central nervous system (CNS) effects of HIV infection.

Behavioral adjustment and social functioning of long-term survivors of childhood leukemia: parent and teacher reports.

Obtained parent and teacher reports of behavior and social competence for children who were survivors of acute lymphoblastic leukemia (ALL). At follow-up, children were 5-18 years of age, 48 months postdiagnosis, in first continuous remission, and off chemotherapy. Each child had been randomized to receive either 1,800 cGy whole brain radiation therapy (WBRT) plus intrathecal methotrexate (IT MTX), or IT MTX alone as central nervous system prophylaxis, and one of four chemotherapy regimens that varied in treatment intensity. Scores on standardized measures (CBCL-P/T and PIC) were generally similar to instrument norms. Parents, but not teachers, reported heightened child somatic concerns. There was no effect of WBRT or chemotherapy regimen on ratings of behavioral adjustment. Results indicate minimal psychosocial morbidity among long-term survivors of ALL and suggest that the stressful life events associated with cancer and its treatment do not cause significant behavioral or emotional difficulties.

Plasma flow and net nutrient flux across gut and liver of cattle fed twice daily.

The objectives of this study were 1) to quantify daily patterns of plasma flow and metabolite flux through portal-drained viscera (PDV) and liver in cattle fed twice daily and 2) to identify an interval for blood sampling that would approximate the average daily plasma flow and nutrient flux values. Data are from three experiments in which multicatheterized cattle were fed at or near ad libitum intake twice daily. Five lactating primiparous Holstein cows (506 kg, fed at 0730 and 1930) ate 17.3 kg DM/d as chopped alfalfa hay:corn grain plus supplement (urea and minerals) 50:50 (Exp 1). Five beef steers (474 kg, fed at 0900 and 2100) ate 8.3 kg DM/d as chopped switchgrass hay:corn grain plus supplement 37:63 (Exp 2). Six beef steers (306 kg fed at 0900 and 2100) ate 6.9 kg DM/d as chopped alfalfa hay (Exp 3). Plasma flow (by dilution of para-aminohippurate) was measured hourly for 24 h. Plasma flows (mean +/- SE) through PDV were 1,264 +/- 147, 538 +/- 56, and 499 +/- 26 L/h for Exp. 1, 2, and 3, respectively. Corresponding liver flows were 1,662 +/- 216, 642 +/- 41, and 591 +/- 30 L/h. The within-animal differences from their respective daily means were estimated as a function of time of day using nonparametric smoothing. Across experiments, PDV and liver flows were above the daily mean from 1200 to 1400, were not different from the daily mean from 1600 to 1700, and were below the daily mean from 1930 to 2130. Metabolites measured were ammonia, urea, alpha-amino N, and glucose. In general, metabolite flux was not different from the average daily mean values between 1200 and 1600. Blood sampling over 12 h or one 12-h feeding cycle is sufficient for daily plasma flow and metabolite flux estimation in cattle fed twice daily.

MRI morphometric analysis and neuropsychological function in patients with neurofibromatosis.

Volumes of cerebral gray and white matter were measured in 22 children with neurofibromatosis type 1 (NF1) and in 20 controls. Judgment of Line Orientation (JLO) and the Developmental Test of Visual-Motor Integration (DTVMI) were administered to 16 of the NF1 patients. General linear models analysis of covariance revealed significantly larger brain volumes in NF1 children than in controls, particularly in white matter, and particularly in girls. JLO and DTVMI performance were positively related to right-hemisphere gray-matter volume. The results implicate a failure of growth control in NF1, leading to aberrant neurodevelopment. Our findings also suggest a basis for refined understanding of learning disabilities, which are a prominent feature of NF1.

Effects of dietary concentrate level on nutrient absorption, liver metabolism, and urea kinetics of beef steers fed isonitrogenous and isoenergetic diets.

Six multicatheterized beef steers (421 +/- 21 kg BW) were used to predict the effect of dietary concentrate level on blood flow and net flux of urea and other metabolites across splanchnic tissues. Diets ranged from 0% (switchgrass hay) to 90% concentrate (10% switchgrass hay, 89% cracked corn, 1% urea). Daily DMI varied from 8.01 to 5.34 kg/d. Nitrogen intake (99 g/d) and calculated ME intake (16.8 Mcal/d) were equal among diets. As dietary concentrate increased from 0 to 90%, liver blood flow decreased from 850 to 795 L/h, portal-drained visceral (PDV) blood flow decreased from 750 to 620 L/h, and mesenteric-drained visceral (MDV) blood flow decreased from 270 to 250 L/h. Liver release of urea N was 94 mmol/h when dietary concentrate was less than 20%, then increased to 146 mmol/h at 55% concentrate. Urinary excretion of urea N was 13 mmol/h or less when dietary concentrate was 20% or less, increased to 53 mmol/h at 55% concentrate, then continued to increase to 76 mmol/h at 90% concentrate. Transfer of urea N to PDV ranged from 71 to 91 mmol/h and transfer to MDV ranged from 0 to 10 mmol/h among diets. As dietary concentrate increased from 27 to 63%, VFA release by PDV decreased, net MDV and splanchnic release of glucose increased, and splanchnic tissues switched from net uptake to net release of L-lactate. Net PDV release or liver removal of ammonia or alpha-amino N and net liver release of glucose were not affected. We conclude that the liver responded to changes in the percentage of dietary concentrate by altering urea production and by altering the role of lactate in intermediary metabolism.

Neuropsychological effects of cranial irradiation in young children with acute lymphoblastic leukemia 9 months after diagnosis. The Children's Cancer Group.

STUDY OBJECTIVE: To determine the effects of cranial irradiation on neuropsychological test performance evident 9 months after diagnosis. DESIGN: A companion study to a randomized clinical trial (CCG-105). SETTING: Institutions participating in Childrens Cancer Group cooperative treatment trials. PATIENTS: Seventy-four children aged 3.0 to 6.5 years with average-risk acute lymphoblastic leukemia. Children with central nervous system leukemia at the time of diagnosis, preexisting mental retardation, or Down's syndrome or for whom English was not the primary language were not eligible for study. INTERVENTIONS: Children were randomized to receive treatment with one of four systemic chemotherapy regimens and either intrathecal methotrexate sodium during induction and consolidation plus 18 Gy of cranial irradiation or intrathecal methotrexate during induction, consolidation, and maintenance as central nervous system prophylaxis. MEASUREMENT AND RESULTS: The groups were comparable with regard to chronologic age, sex, and family socioeconomic status. Children who received cranial irradiation plus intrathecal methotrexate scored significantly lower on the McCarthy Motor Scale (P < .05) and the Token Test (P < .05) than children who received intrathecal methotrexate alone. The groups did not differ significantly on the McCarthy General Cognitive Index, Developmental Test of Visual Motor Integration, or Peabody Picture Vocabulary Test-Revised. CONCLUSIONS: Findings suggest that the combined effects of cranial irradiation and intrathecal methotrexate therapy on neuropsychological performance may be evident in young children as early as 9 months after diagnosis. Follow-up assessment of these children will reveal whether these effects remain constant, intensify, or resolve.

Behavioral adaptation to human immunodeficiency virus-seropositive status in children and adolescents with hemophilia.

OBJECTIVE: To examine the behavioral adaptation to human immunodeficiency virus (HIV)-seropositive status, as defined by parental report, in children and adolescents with hemophilia. RESEARCH DESIGN: A clinical descriptive study of two groups of patients as part of a longitudinal design. SETTING: A university-based comprehensive hemophilia center and department of neurology acquired immunodeficiency syndrome dementia center. PATIENTS: Forty-six male children with hemophilia divided into two groups based on HIV-seropositive (n = 18) or -seronegative (n = 28) status. None of the patients were symptomatic for acquired immunodeficiency syndrome. SELECTION PROCEDURES: All pediatric patients with documented factor VII or IX deficiency aged between 4 and 19 years at study onset and their families were eligible to participate. All subjects were recruited without regard to human immunodeficiency virus status. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Profiles of behavioral adjustment were obtained from parents' reports on the Child Behavior Checklist for the HIV-seropositive and HIV-seronegative groups. The two groups did not differ on any of the major indexes of the Child Behavior Checklist, even after adjusting for maternal education and severity of hemophilia. There also was no difference between the groups when individual cases were examined for the number of child behavior checklist scales falling within a clinically significant range. CONCLUSIONS: The current findings fail to confirm any clear evidence of behavioral problems in an asymptomatic group of HIV-seropositive children and adolescents with hemophilia.