Better Social-emotional Behavior in Young Nepali Children is Associated with Household Wealth, Child Age, and Family Participation in a Community Development Intervention.

Background Mental health and behavior problems are under-recognized in low- and middleincome countries, especially in young children. Early identification of these problems could encourage governments to address the shortages of child mental health professionals and promote early intervention programs to help children achieve their full developmental potential. Objective Describe the social-emotional development of young rural Nepali children; explore risk factors for poor development. Method The study was embedded in a longitudinal intervention trial comparing control households with those who received training in family nutrition+livestock management (Partial Package) or family nutrition+livestock management+community mobilization (Full Package). At midline, enumerators completed a 145-item household questionnaire, child anthropometry, and Administered the Ages and Stages Questionnaire-Social-Emotional (ASQ-SE) to all enrolled children age 33-47 months (n=310). Bivariate and regression analyses examined the relationship of child and household risk factors to administered the Ages and Stages QuestionnaireSocial-Emotional scores. Result Administered the Ages and Stages Questionnaire-Social-Emotional scores were below age cutoffs in 24% of children, suggesting worse social-emotional development. In bivariate analyses and the adjusted linear regression model, older child age, greater household wealth, and Full Package Intervention status were all associated with better social-emotional development scores. Partial Package Intervention status was associated with worse scores. Conclusion The Administered the Ages and Stages Questionnaire-Social-Emotional is a potential tool to assess child social-emotional development in the context of household and community level interventions. Further work is necessary to validate the administered the Ages and Stages Questionnaire-Social-Emotional and similar tools in Nepal, and to better understand the prevalence of challenges to optimal socialemotional development in young children in order to use this information to design and monitor needed interventions.

Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia.

Upregulation of the immune response may be involved in the pathogenesis of schizophrenia with changes occurring in both peripheral blood and brain tissue. To date, microarray technology has provided a limited view of specific inflammatory transcripts in brain perhaps due to sensitivity issues. Here we used SOLiD Next Generation Sequencing to quantify neuroimmune mRNA expression levels in the dorsolateral prefrontal cortex of 20 individuals with schizophrenia and their matched controls. We detected 798 differentially regulated transcripts present in people with schizophrenia compared with controls. Ingenuity pathway analysis identified the inflammatory response as a key change. Using quantitative real-time PCR we confirmed the changes in candidate cytokines and immune modulators, including interleukin (IL)-6, IL-8, IL-1ß and SERPINA3. The density of major histocompatibility complex-II-positive cells morphologically resembling microglia was significantly increased in schizophrenia and correlated with IL-1ß expression. A group of individuals, most of whom had schizophrenia, were found to have increased inflammatory mRNA expression. In summary, we have demonstrated changes in an inflammatory response pathway that are present in ∼40% of people diagnosed with schizophrenia. This suggests that therapies aimed at immune system attenuation in schizophrenia may be of direct benefit in the brain.

Effect of porcine reproductive and respiratory syndrome virus on porcine alveolar macrophage function as determined using serial analysis of gene expression (SAGE).

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide and causes considerable economic loss. The main target of infection is the porcine alveolar macrophage (PAM). Infection of PAMs by PRRSV causes significant changes in their function by mechanisms that are not understood. We have employed Serial Analysis of Gene Expression (SAGE) to examine the global expression of genes in PRRSV-infected PAMs. Total cellular RNAwas prepared from in vitro mock-infected and PRRSV strain VR-2332-infected PAMs at 0, 6, 12, 16 and 24 hours after infection, and subjected to SAGE analysis to obtain > 100,000 tags per time point. These sequences were processed to account for sequencing error before generating tag:count lists. These lists were deposited into a modified Identitag database for mapping to porcine and PRRSV genes. Identified unique mRNAtags were analyzed for their identity and relative abundance. Examination of the SAGE data indicated that there were changes in gene expression occurring in the PRRSV-infected PAMs over time post-infection. More than 400 unique tags with significantly altered expression levels were identified (p < 0.01 with Bonferroni correction). The validity and kinetics of expression of SAGE identified genes were evaluated using real-time RT-PCR.

Time use in Russian Baby Homes.

BACKGROUND: We investigated time use of Russian children residing in Baby Homes to document their opportunities and experiences during institutional care. METHODS: Time use of 138 non-special needs, randomly selected children (65 female vs. 73 male, age 1 month to 4 years) in Baby Homes in Murmansk, Russia, was analysed. Baby Home specialists were trained in time-use spot observation methodology. Each child was observed every 10 min for 5 h (31 observations/child; >4000 data points). At each observation, we coded: who the child was with, adult role, what the child was doing, location and vocalizations. RESULTS: Children spent 50% of their time alone, 27% with a caregiver, 15% with another adult, and 7% with another child. Infants spent significantly more time alone (65%) than toddlers (43%) or pre-schoolers (46%) [F(2,133) = 13.05, P < 0.0001]. Caregivers supervised children (58%), led group activities (16%), cared for individuals (14%), or were absent from the room (12%). Children spent the most time (32%) in activities of daily living; remaining time was spent in meaningful play (27%), non-purposeful activity (16%) or sleep (18%). The percentage of time spent in meaningful play significantly increased across age groups [infants 10%, toddlers 25%, pre-schoolers 36%, F(2,133) = 26.9, P < 0.001]. Infants (23%) and toddlers (20%) spent significantly more time than the older group (10%) in non-purposeful activity [F(2,133) = 26.9, P < 0.001]. In 12% of observations, an adult was speaking to the child, in 10% to the group, and <1% to another adult. Child vocalizations varied by age: infants 42% of observations, toddlers 56%, and pre-schoolers 59%. Older children directed more vocalizations to adults than younger children [F(2,133) = 24.47, P < 0.001]. CONCLUSION: Time use of children residing in Baby Homes is limited by routinized schedules and care, at the expense of child-directed or interactive play with adults. Despite close proximity and living in group care, children's vocalizations and interactions with others are limited.

Management of Xiphinema americanum and Soybean Severe Stunt in Soybean Using Crop Rotation.

Soybean severe stunt (SSS), caused by the Soybean severe stunt virus (SSSV), is a soilborne virus disease affecting soybean (Glycine max) first described in Delaware in 1988. Lack of breeding programs directed at incorporating resistance to SSSV in new cultivar releases necessitated alternative methods of SSS control. The effect of crops in 2-year rotations on the dagger nematode (Xiphinema americanum), the putative nematode vector of SSSV, and SSS severity were examined. Two years of continuous corn or grain sorghum, wheat followed by 'HT-5203' soybean, or 2-year fallow, reduced both dagger nematode density in the soil and SSS severity. Crop rotation to the SSSV-tolerant HT-5203 soybean as a single crop for 2 years increased dagger ematode populations and SSS severity. Greenhouse studies indicated that corn, wheat, marigold, castor, and fallow treatments reduced dagger nematodes the most after 14 weeks compared with 'Essex' and HT 5203 soybean.

Norepinephrine transporter-deficient mice respond to anxiety producing and fearful environments with bradycardia and hypotension.

The study of anxiety and fear involves complex interrelationships between psychiatry and the autonomic nervous system. Altered noradrenergic signaling is linked to certain types of depression and anxiety disorders, and treatment often includes specific transporter blockade. The norepinephrine transporter is crucial in limiting catecholaminergic signaling. Norepinephrine transporter-deficient mice have increased circulating catecholamines and elevated heart rate and blood pressure. We hypothesized, therefore, that reduced norepinephrine clearance would heighten the autonomic cardiovascular response to anxiety and fear. In separate experiments, norepinephrine transporter-deficient (norepinephrine transporter-/-) mice underwent tactile startle and trace fear conditioning to measure hemodynamic responses. A dramatic tachycardia was observed in norepinephrine transporter-/- mice compared with controls following both airpuff or footshock stimuli, and pressure changes were also greater. Interestingly, in contrast to normally elevated home cage levels in norepinephrine transporter-deficient mice, prestimulus heart rate and blood pressure were actually higher in norepinephrine transporter+/+ animals throughout behavioral testing. Upon placement in the behavioral chamber, norepinephrine transporter-deficient mice demonstrated a notable bradycardia and depressor effect that was more pronounced in females. Power spectral analysis indicated an increase in low frequency oscillations of heart rate variability; in mice, suggesting increased parasympathetic tone. Finally, norepinephrine transporter-/- mice exhibited sexual dimorphism in freeze behavior, which was greatest in females. Therefore, while reduced catecholamine clearance amplifies immediate cardiovascular responses to anxiety- or fear-inducing stimuli in norepinephrine transporter-/- mice, norepinephrine transporter deficiency apparently prevents protracted hemodynamic escalation in a fearful environment. Conceivably, chronic norepinephrine transporter blockade with transporter-specific drugs might attenuate recognition of autonomic and somatic distress signals in individuals with anxiety disorders, possibly lessening their behavioral reactivity, and reducing the cardiovascular risk factors associated with persistent emotional arousal.

Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells.

Infection by porcine reproductive and respiratory syndrome virus (PRRSV) results in a weak induction of the innate immune response. There are many genes that collectively comprise this response and the extent to which each gene responds to PRRSV infection is unclear and warrants further investigation. To this end, we have utilized real-time PCR using SYBR Green I dye-based detection to quantify transcript abundance of the type I interferons (IFN-alpha and -beta) and IFN-beta transcriptional enhanceasome genes. In MARC-145 cells, both IFN-alpha and -beta transcript abundance were unaffected by PRRSV infection. However, stimulation of MARC-145 cells by exogenous double-stranded RNA, resulted in significant increases in transcript abundance of both IFN-alpha and -beta as well as IFN-beta enhanceasome components, indicating that a type I IFN response could be induced in these cells. The double-stranded RNA induction of type I IFN transcription was significantly inhibited by dual-exposure with PRRSV. These results suggest that PRRSV infection directly interferes with type I IFN transcriptional activation early in its pathway, at the level of IFN-beta gene transcription.

Preferences about the characteristics of future HIV prevention products among men who have sex with men.

This study of men who have sex with men (MSM) examined preferences about the characteristics of a potential product for preventing sexual transmission of HIV, such as a rectal microbicide. MSM were recruited in West Hollywood, California. They self-administered a questionnaire and rated 48 product characteristics representing seven dimensions. Overall, the ratings were highest for effectiveness in preventing HIV and other sexually transmitted diseases, followed by characteristics reflecting the physical or secondary effects of the product and logistics of use. Physical attributes, convenience/accessibility, and psychological aspects had intermediate ratings; interpersonal dynamics had the lowest rating. Men with negative attitudes about using condoms to prevent HIV infection were more likely than their counterparts to prefer a product that does not reduce sexual sensation or pleasure, does not break the mood, and can be used after a sexual encounter ends. A similar pattern was observed when participants were stratified by whether or not they had engaged in unprotected anal intercourse in the past 12 months. The findings inform the development, testing, and marketing of a future HIV prevention product for MSM.

Role of the cytoplasmic domain of the beta-subunit of integrin alpha(v)beta6 in infection by foot-and-mouth disease virus.

Field isolates of foot-and-mouth disease virus (FMDV) are believed to use RGD-dependent integrins as cellular receptors in vivo. Using SW480 cell transfectants, we have recently established that one such integrin, alpha(v)beta6, functions as a receptor for FMDV. This integrin was shown to function as a receptor for virus attachment. However, it was not known if the alpha(v)beta6 receptor itself participated in the events that follow virus binding to the host cell. In the present study, we investigated the effects of various deletion mutations in the beta6 cytoplasmic domain on infection. Our results show that although loss of the beta6 cytoplasmic domain has little effect on virus binding, this domain is essential for infection, indicating a critical role in postattachment events. The importance of endosomal acidification in alpha(v)beta6-mediated infection was confirmed by experiments showing that infection could be blocked by concanamycin A, a specific inhibitor of the vacuolar ATPase.

Age-related risk for HIV infection in men who have sex with men: examination of behavioral, relationship, and serostatus variables.

The study examined behavioral, relationship, and serostatus variables that potentially contribute to HIV infection risk in three age groups of men who have sex with men (MSM). MSM recruited in West Hollywood, California self-administered a questionnaire measuring unprotected insertive anal intercourse (UIAI) and unprotected receptive anal intercourse (URAI) with primary and nonprimary partners. The following relationship/serostatus variables were also assessed: recency of HIV testing, knowledge of own HIV serostatus, perception of partner's serostatus, seroconcordance (self and partner seronegative), and self-reported monogamy status. The prevalence of UIAI and URAI was higher with primary than nonprimary partners. These sexual risk behaviors with primary partners were substantially more prevalent among men younger than 25 years of age than among men aged 25 to 30 or over age 30. UIAI and URAI with nonprimary partners were uncommon in each age group, and there were no significant age differences on the serostatus and relationship variables. The findings suggest that young MSM may be at elevated risk for contracting HIV by virtue of their sexual risk behavior with primary partners. Targeted interventions for MSM need to address sexual risk in the context of primary relationships.

Preaching to the choir: preference for female-controlled methods of HIV and sexually transmitted disease prevention.

OBJECTIVES: This study assessed interest in female-controlled methods of HIV and sexually transmitted disease (STD) prevention. METHODS: Surveys were conducted with 168 African American women, aged 18 to 32 years, who had had unprotected sex and at least 3 sexual partners in the last 2 years. RESULTS: Of 44 potential features, "female control" (where women control the method by either wearing or applying it) ranked 22nd in average importance. Women who rated female control as highly important had fewer sex partners and fewer STDs and were more likely to use existing prevention methods frequently. CONCLUSIONS: Female control may be of less interest to women most at risk for HIV and other STDs. This underscores the need to take the priorities and preferences of women into consideration when developing new prevention methods.

Health of children adopted from China.

OBJECTIVE: Since 1989, American parents have adopted 18 846 Chinese children. This study assesses the health and developmental status of these children after their arrival in the United States. PATIENTS AND METHODS: A total of 452 children (443 girls) in 2 groups were evaluated. The clinic group children (n = 192) included all Chinese adoptees seen in an international adoption clinic between 1991 and 1998. The travel group comprised 260 of 325 Chinese children placed by a single Massachusetts adoption agency between 1991 and 1996 whose adoptive parents and American physicians responded to mailed questionnaires. One hundred ninety-one of the travel group children were cared for by 1 of us (N.W.H.) during the adoption process in China. RESULTS: Growth and developmental delays were frequent in the clinic group. Z scores

Soluble adhesion molecules in juvenile rheumatoid arthritis.

OBJECTIVE: To determine serum levels of soluble (s) adhesion molecules in patients with juvenile rheumatoid arthritis (JRA), and to determine whether differences exist in these levels among the 3 subtypes of JRA, and whether levels of these molecules correlate with other measures of disease activity. METHODS: Serum levels of soluble forms of intercellular adhesion molecule-1 (ICAM-1), ICAM-3, vascular (V) CAM-1, L-selectin, and E-selectin were determined by sandwich ELISA in 16 patients with JRA (6 systemic, 6 polyarticular, 4 pauciarticular). Differences in levels among JRA subtypes were determined by ANOVA, and correlations between levels and the following clinical variables were assessed by linear regression analysis: erythrocyte sedimentation rate (ESR), total white blood cell count (WBC), hematocrit (HCT), platelet count (PLT), and total swollen joint count (JC). RESULTS: sE-selectin levels were significantly higher in patients with systemic disease compared to other subtypes (p<0.04). Furthermore, there was a trend toward higher levels of sICAM-1 in systemic disease, which did not reach statistical significance. Significant correlations were found between sE-selectin and ESR (r = 0.68, p<0.006), WBC (r = 0.70, p<0.003), and PLT (r = 0.54, p<0.05) and between sL-selectin and WBC (r = 0.55, p<0.03). CONCLUSION: Because of the small number of patients studied, and the lack of age matched control data, our results must be interpreted with caution. Nonetheless, levels of sE-selectin, and possibly ICAM-1 appear to be relatively elevated in systemic JRA, and may indicate cytokine induction and endothelial cell activation in that subtype. Several molecules, especially sE-selectin, correlate with hematologic variables in JRA. These results suggest that serum levels of these molecules may provide a useful additional marker for disease activity in certain patients.

Racial differences in hormone replacement therapy prescriptions.

OBJECTIVE: To examine racial differences in hormone replacement therapy (HRT) use by analyzing the relative risks and rates of HRT prescriptions for black and white women. METHODS: Data on visits to hospital outpatient departments and office-based physicians by black and white women aged 45-64 years were obtained from 25,203 visits sampled in the 1993-1995 National Ambulatory Medical Care Surveys and National Hospital Ambulatory Medical Care Surveys. The relative effect of race on the provision of an HRT prescription at an ambulatory visit was estimated by controlling confounders using logistic regression. Population-based rates of physician visits and visits with HRT prescriptions were also calculated to address issues involving access to care. RESULTS: Approximately 98,787,000 annual visits were made by black and white women 45-64 years of age, 9.2% of which involved prescriptions for HRT. The percentage of visits by black women in which prescriptions for HRT were reported (4.5%) was roughly half that of white women (9.7%). The association persisted after controlling for type of physician, practice type, geographic region, payment source, and non-HRT prescription(s) (odds ratio 2.1; 95% confidence interval 1.5, 2.9). The rate of ambulatory care among black women (3.82 visits per year per woman) was virtually identical to that of white women (3.94 visits per year), whereas the rate of visits with HRT prescriptions for white women was twice as high as for black women (0.38 and 0.17 visits per year, respectively). CONCLUSION: Apparent racial differences in HRT use persist after controlling for physician and visit factors not explored in previous studies.