Microbicides 2000 conference. Welcoming remarks. The role of the Office of AIDS Research, NIH, USA.
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Biomedical subjects
Publications and source records attributed to J Auerbach.
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The prevalence of developmental dyscalculia (DC) in the school population ranges from 3-6 %, a frequency similar to that of developmental dyslexia and ADHD. These studies fulfilled the criteria for an adequate prevalence study, i.e., were population based, using standardized measures to evaluate arithmetic function. Although the variation in prevalence is within a narrow range, the differences are probably due to which definition of dyscalculia was used, the age the diagnosis was made and the instrument chosen to test for DC. The relative predominance of girls with DC may reflect a greater vulnerability to environmental influences alone or in addition to a biological predisposition. DC is not only encountered as a specific learning disability but also in diverse neurological disorders, examples of which include ADHD, developmental language disorder, epilepsy, treated phenylketonuria and Fragile X syndrome. Although the long-term prognosis of DC is as yet unknown, current data indicate that DC is a stable learning disability persisting, at least for the short term, in about half of affected children. The long-term consequences of DC and its impact on education, employment and psychological well-being have yet to be determined.
OBJECTIVES: This study quantified AIDS incidence in Massachusetts in relation to economic deprivation. METHODS: Using 1990 census block-group data, 1990 census population counts, and AIDS surveillance registry data for the years 1988 through 1994, we generated yearly and cumulative AIDS incidence data for the state of Massachusetts stratified by sex and by neighborhood measures of economic position for the total, Black, Hispanic, and White populations. RESULTS: Incidence of AIDS increased with economic deprivation, with the magnitude of these trends varying by both race/ethnicity and sex. The cumulative incidence of AIDS in the total population was nearly 7 times higher among persons in block-groups where 40% or more of the population was below the poverty line (362 per 100,000) than among persons in block-groups where less than 2% of the population was below poverty (53 per 100,000). CONCLUSIONS: Observing patterns of disease burden in relation to neighborhood levels of economic well-being elucidates further the role of poverty as a population-level determinant of disease burden. Public health agencies and researchers can use readily available census data to describe neighborhood-level socioeconomic conditions. Such knowledge expands options for disease prevention and increases the visibility of economic inequality as an underlying cause of AIDS.
BACKGROUND: Stress exacerbates many neuropsychiatric disorders associated with prefrontal cortical (PFC) dysfunction. Stress also impairs the working memory functions of the PFC. Although stress research has focused on dopaminergic mechanisms, stress also increases norepinephrine (NE) release in PFC, and intra-PFC infusions of NE alpha-1-adrenoceptor agonists impair working memory. The current study examined whether NE alpha-1-adrenoceptor actions in PFC contribute to stress-induced deficits in working memory performance. METHODS: Rats were treated with a pharmacological stressor, FG7142 (30 mg/kg) or vehicle 30 min before testing on a test of spatial working memory, delayed alternation. The alpha-1-adrenoceptor antagonist, urapidil (0.1 microgram/0.5 microL), or saline vehicle, was infused into the PFC 15 min before delayed alternation testing. RESULTS: As observed previously, FG7142 significantly impaired the accuracy of delayed alternation performance, and induced a perseverative pattern of responding consistent with PFC dysfunction. FG7142 also slowed motor response times. Infusion of urapidil into the PFC completely reversed the FG7142-induced impairment in delayed alternation performance, but did not alter the slowed motor responding. CONCLUSIONS: These findings indicate that alpha-1-adrenoceptor stimulation in the PFC contributes to stress-induced impairments in PFC cognitive functions. These neurochemical actions may contribute to symptoms of working memory impairment, poor attention regulation, or disinhibited behaviors in neuropsychiatric disorders sensitive to stress exposure.
We and others have previously shown that the dopamine D4 exon III repeat (D4DR) and the serotonin-transporter promoter region (5-HTTLPR) polymorphisms are not only associated with adult personality traits1-7 but also with temperament in 2-week-old neonates.8 We now report the results of a second study of these infants and their temperament at 2 months using Rothbart's Infant Behavior Questionnaire (IBQ).9 There were significant negative correlations between neonatal orientation and motor organization as measured by the Neonatal Behavioral Assessment Scale (NBAS)10 at 2 weeks and negative emotionality, especially distress in daily situations, at 2 months of age. There were significant main effects for negative emotionality and distress when the infants were grouped by the D4DR and the 5-HTTLPR polymorphisms. Infants with long D4DR alleles had significantly lower scores on Negative Emotionality (F[1, 72] = 8.50, P = 0.005) and Distress to Limitations (F[1,72] = 4.93, P = 0.03) than infants with short D4DR alleles. In contrast, infants with the short homozygous (s/s) 5-HTTLPR genotype had higher scores on Negative Emotionality (F[1,72] = 3.88, P = 0.053) and Distress to Limitations (F[1,72] = 4.94, P = 0.029) than infants with the I/s or I/I genotypes. The strongest effects occurred in those infants with the s/s 5-HTTLPR polymorphism who also were lacking long D4DR alleles which in some studies has been linked to adult novelty seeking.1,6 These infants showed most negative emotionality and most distress to daily situations, temperament traits that are perhaps the underpinning of adult neuroticism.
The construct representation of the cross-informant model of the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF) was evaluated using confirmatory factor analysis. Samples were collected in seven different countries. The results are based on 13,226 parent ratings and 8893 teacher ratings. The adequacy of fit for the cross-informant model was established on the basis of three approaches: conventional rules of fit, simulation, and comparison with other models. The results indicated that the cross-informant model fits these data poorly. These results were consistent across countries, informants, and both clinical and population samples. Since inadequate empirical support for the cross-informant syndromes and their differentiation was found, the construct validity of these syndrome dimensions is questioned.
OBJECTIVE: To study the natural history of developmental dyscalculia (DC), a specific learning disability affecting approximately 5% of the normal school age population and to identify factors that contribute to persistence. STUDY DESIGN: Of a cohort of 3029 fourth-grade students, 185 children were classified as having DC; 140 participated in phase 1 in which they underwent IQ testing; arithmetic, reading, and writing evaluations; and an assessment for attention-deficit/hyperactivity disorder over a 3-year period. Three years later (phase 2), 88% of the children (123 of 140) were retested. RESULTS: The arithmetic scores of 95% of the 123 children with DC fell within the lowest quartile for their class. At phase 2, 47% (57 of 123) of the children were reclassified as having persistent DC, scoring in the lowest 5% for their age group (13 to 14 years old). Factors significantly associated with persistence of DC in a multivariate model were severity of the arithmetic disorder and arithmetic problems in siblings of the probands. Factors that were not associated with persistence included socioeconomic status, gender, the presence of another learning disability, and educational interventions. CONCLUSIONS: The outcome of DC is similar to that of other learning disabilities, with a persisting course in almost half of affected children; the remainder continue to perform poorly in arithmetic. The ultimate outcome of children with dyscalculia and the effect on education, employment, and psychologic well-being have yet to be determined.
Genetic effects on behavior were evaluated at a time in early development when we hypothesized that environmental influences are minimal and least likely to confound associations between temperament and genes. The behavioral effects of two common polymorphisms linked respectively in some, but not all, studies to novelty seeking (dopamine D4 receptor-D4DR) and neuroticism and harm avoidance (serotonin transporter promoter region-STPR) were examined in a group of 81 two-week-old neonates. Neonate temperament was evaluated using the Brazelton neonatal assessment scale (NBAS). Multivariate tests of significance showed a significant association of D4DR across four behavioral clusters pertinent to temperament including orientation, motor organization, range of state and regulation of state. A significant multivariate interaction was also observed between D4DR and STPR. The effect of the homozygous short STPR genotype (s/s) was to lower the orientation score for the group of neonates lacking the long form (L) of D4DR. When adult subjects were grouped by the STPR polymorphism there is no significant effect of L-D4DR in those subjects homozygous for the STPR short form (s/s) whereas in the group without the homozygous genotype the effect of L-D4DR is significant and accounts for 13% of the variance in novelty seeking scores between groups.
OBJECTIVE: To examine the characteristics of infants suffering from failure to thrive in a community based cohort in Israel and to ascertain the effect of failure to thrive on their cognitive development. METHODS: By review of records maintained at maternal and child health clinics in Jerusalem and the two of Beit Shemesh, epidemiological data were obtained at age 15 months on a cohort of all babies born in 1991. For each case of failure to thrive, a matched control was selected from the same maternal and child health clinic. At age 20 months, cognitive development was measured, and at 25 months a home visit was carried out to assess maternal psychiatric status by questionnaire, and the HOME assessment was performed to assess the home environment. RESULTS: 3.9% of infants were found to have fallen below the third centile in weight for at least three months during the first year of life. Infants with failure to thrive did not differ from the general population in terms of obstetric or neonatal complications, birth order, or parents' ethnic origin, age, or years of education. The infants with failure to thrive did have lower birthweights and marginally smaller head circumferences at birth. Developmental assessment at 20 months of age showed a DQ of 99.7 v 107.2 in the matched controls, with 11.5% having a DQ below 80, as opposed to only 4.6% of the controls. No differences were found in maternal psychiatric problems as measured by a self report questionnaire. There were, however, significant differences in subscales of the HOME scale. CONCLUSIONS: (1) Infants who suffered from failure to thrive had some physiological predispositions that put them at risk; (2) failure to thrive may be an early marker of families providing suboptimal developmental stimulation.
This article observes that, despite the clear potential benefits of health care reform's expanding health insurance coverage for people with human immunodeficiency virus (HIV) disease, there is a real danger of losing existing acquired immunodeficiency syndrome (AIDS) services if federal categorical public health programs are cut. It discusses the considerable accomplishments of the Ryan White CARE Act and of Centers for Disease Control and Prevention (CDC) prevention funding. The funding for these current efforts will not be assumed by near universal insurance coverage for a variety of reasons, including the need to care for populations who are neglected by health care reform, to continue services unlikely to be reimbursable, and to offer care in a range of locations other than licensed health care facilities.
Behavioral characteristics of 140 children with developmental dyscalculia (DC) were evaluated using the Child Behavior Checklist. DC children demonstrated more behavior problems than normal children but significantly fewer problems than children psychiatrically referred. DC children had significantly more attentional problems although they had normal levels of anxiety/depression. Significantly higher scores on all syndrome scales were found for DC children who had attentional problems in the clinical range. When associated with dyslexia and a low verbal IQ, DC children had more attentional problems and externalizing syndromes. The implications of the behavioral characteristics of DC are discussed.
Porcine enteroviruses (PEV) types 1-11 were assigned to three serologic groups by indirect immunofluorescence (IIF). Serotype group I consists of PEV types 1-7 and 11 and is correlated with CPE-type I. Serotype group II is represented by PEV type 8, producing CPE-type II, while PEV types 9 and 10 are classified as serotype group III and cause CPE-type III. Three PEV isolates from the central nervous system of pigs with polioencephalomyelitis were assigned to serotype group I by IIF but to none of the established 11 serotypes by cross-neutralization. It is concluded that these isolates are representatives of two new PEV types for which the designation PEV12 and 13 is suggested.
Seventeen strains of porcine enteroviruses (PEV) were isolated from organs of 119 pigs with symptoms of polioencephalomyelitis submitted to the State Veterinary Institute Arnsberg/Westphalia between 1983 and 1991. 15 isolates originated from the central nervous system and 2 from organ suspensions made up of a brain-spleen-pool and a lung-spleen-lymph node-pool, respectively. Isolates were assigned to 7 PEV types which were present at the following frequencies: PEV1: 2x; PEV2: 6x; PEV4: 3x; PEV5: 1x; PEV6: 2x; PEV 12: 1x; PEV 13: 2x. Mortality rates of affected groups exhibited an age-dependent curvilinear relationship suggesting that the PEV involved possessed a rather similar low to medium grade neurovirulence, irrespective of type. Exceptions were 1 herd with 100% mortality at the age of 10-18 weeks from which PEV2 strain 6793/83 was isolated (described earlier) and a second herd with 18% mortality at the age of 14-18 weeks from which PEV types 1, 2 and 4 were recovered. Sensitivity of 5 cell lines for the isolation of PEV was compared. Rates of isolation from organ suspensions which had proved positive in any of the cell lines tested were as follows: PS-EK: 77%; IB-RS-2: 63%; ST: 56%; PK-15: 47%; BHK21 (CT): 10%.
This paper presents the Israeli norms for the Achenbach Child Behavior Checklist. Questionnaire data were collected on a clinically-referred sample (N = 2227) and a non-referred sample (N = 1275) of children between the ages of 4-16. Basic descriptive data for total behavior scores and scores for broad-band and narrow-band syndromes by sex, age group, and clinical status are presented. The mean total behavior score in the non-referred sample is similar to that reported for American and Dutch samples. For the Israeli referred sample, the mean total behavior score was considerably lower than that reported for the American and Dutch samples. Issues involved in selecting an optimal cutoff point to discriminate between clinically-referred and non-referred populations are discussed.
Maternal and environmental characteristics as predictors of behavioral problems and cognitive competence in 505 Israeli kindergarten children were investigated. Events in closer temporal proximity to assessments of functioning appeared more predictive than those in early infancy. Findings support the need to include variables reflecting maternal characteristics in any prediction of child outcome and to consider the sex of the child in selection of variables.
Increased platelet membrane fluidity is a stable familial trait that identifies a prominent subgroup of patients with Alzheimer's disease. Patients in this subgroup have distinct clinical features, including an early age at symptomatic onset and a rapidly progressive course. The morbid risk of Alzheimer's-type dementia was studied in 421 first-degree relatives of 43 patients who met current consensus criteria for probable Alzheimer's disease and 47 healthy controls. Relatives of patients showed an approximate 50% (90- to 95-year) lifetime risk of dementia, regardless of the platelet membrane phenotype of the respective proband, which was over four times the control value. However, relatives of patients with increased platelet membrane fluidity who developed dementia exhibited symptoms significantly earlier than relatives of patients with normal platelet membrane fluidity. Alternative genetic models that describe the relationship of platelet membrane fluidity and Alzheimer's disease are discussed.
Using a family history questionnaire, we investigated the occurrence of dementia among relatives of patients with a clinical diagnosis of Alzheimer's disease (AD) and among the relatives of age-matched control subjects. Cumulative lifetime risk of developing AD-type dementia was greater among relatives of AD probands and was consistent with an autosomal dominant genetic mode of transmission. Although the lifetime risk of AD-type dementia was similar among relatives of early-onset and late-onset AD probands, relatives of early-onset probands tended to have an earlier onset of dementia than did relatives of late-onset AD probands. This result raises the possibility that age at onset of dementia in AD may be genetically determined.
Phage lambda controls its integration and excision by differential catalysis of the forward and reverse reactions. The lambda Int protein is required for both directions, but Xis for excision only. Previous electron microscopic observations have shown that Int protein forms a stable, condensed protein-DNA complex with the phage (attP) and prophage left (attL) substrate sites, but not with the host (attB) or prophage right (attR) sites. We have found that Int and Xis together produce a stable, condensed complex with attR. The attR complex involves the P region DNA to the left of the crossover point (O site). In contrast, the attP complex includes DNA on both sides of the crossover point (P and P'), and the attL structure involves the P' DNA to the right of O. In the presence of Int and Xis, the attL and attR sites form a paired structure. We conclude that the role of Xis is to provide a distinct reactive structure at attR, allowing attL and attR to pair efficiently.