Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

Functional abdominal complaints in pre-school children: parental reports of health-related quality of life

Purpose The aim of this study is to assess the influence of functional abdominal complaints (FAC) on health-related quality of life in a group of Dutch pre-school children. Methods Parents of children aged up to 6.0 visiting the outpatient pediatric department, Erasmus MC-Sophia, Rotterdam, The Netherlands in the period January 2005-December 2006 for functional abdominal complaints during at least 3 months were asked to complete the Infant/Toddler Quality of life Questionnaire (ITQOL), and questions of the abdominal pain index for use by parents to report pain symptoms in pre-school children. ITQOL scale scores of children with FAC were compared against with Dutch reference values. The abdominal pain index was tested for internal consistency and test-retest reliability. Correlations between ITQOL scale scores and abdominal pain index were assessed by Spearman's rank test. Results Results are based on 81 questionnaires completed by parents of children with FAC (response rate 61%). Children had a median age of 46 months (interquartile range 27-59), 48% girls. A significant impact was observed on most aspects of quality of life, particularly for physical functioning, general development, bodily pain, temperament and moods, general health perceptions and parental emotional impact. Parents of children with functional constipation tended to report lower scores than those of children with other FAC. The abdominal pain index appeared to be valid and was significantly correlated with ITQOL scales bodily pain and general health perceptions. Conclusions A substantial lower health-related quality of life is reported in pre-school children with functional abdominal complaints, with effects on physical, emotional and parental domains. The 5-question severity index of abdominal pain appeared a valid tool and may be helpful to quickly assess the severity of abdominal pain in clinical practice

Overweight, Obesity and Underweight Is Associated with Adverse Psychosocial and Physical Health Outcomes among 7-Year-Old Children: The 'Be Active, Eat Right' Study

Background:Limited studies have reported on associations between overweight, and physical and psychosocial health outcomes among younger children. This study evaluates associations between overweight, obesity and underweight in 5-year-old children, and parent-reported health outcomes at age 7 years.Methods:Data were used from the 'Be active, eat right' study. Height and weight were measured at 5 and 7 years. Parents reported on child physical and psychosocial health outcomes (e.g. respiratory symptoms, general health, happiness, insecurity and adverse treatment). Regression models, adjusted for potential confounders, were fitted to predict health outcomes at age 7 years.Results:The baseline study sample consisted of 2,372 children mean age 5.8 (SD 0.4) years; 6.2% overweight, 1.6% obese and 15.0% underweight. Based on parent-report, overweight, obese and underweight children had an odds ratio (OR) of 5.70 (95% CI: 4.10 to 7.92), 35.34 (95% CI: 19.16; 65.17) and 1.39 (95% CI: 1.05 to 1.84), respectively, for being treated adversely compared to normal weight children. Compared to children with a low stable body mass index (BMI), parents of children with a high stable BMI reported their child to have an OR of 3.87 (95% CI: 1.75 to 8.54) for visiting the general practitioner once or more, an OR of 15.94 (95% CI: 10.75 to 23.64) for being treated adversely, and an OR of 16.35 (95% CI: 11.08 to 24.36) for feeling insecure.Conclusion:This study shows that overweight, obesity and underweight at 5 years of age is associated with more parent-reported adverse treatment of the child. Qualitative research examining underlying mechanisms is recommended. Healthcare providers should be aware of the possible adverse effects of childhood overweight and also relative underweight, and provide parents and children with appropriate counseling

The role of a probiotics mixture in the treatment of childhood constipation: a pilot study

<p>Abstract</p> <p>Background</p> <p>Inconsistent data exist about the efficacy of probiotics in the treatment of constipation. Several studies in adults with constipation showed positive effects of probiotics on constipation. Inconsistent data exist regarding the effect of a single probiotic strain in constipated children. The aim of this pilot study was to determine the effect of a mixture of probiotics containing bifidobacteria and lactobacilli in the treatment of childhood constipation.</p> <p>Methods</p> <p>Children aged 4–16 years with constipation as defined by the Rome III criteria were eligible for the study. During a 4 week period, children received a daily mix of 4 × 10⁹colony forming units of a probiotic mixture (<it>Ecologic</it>^®<it>Relief</it>) containing Bifidobacteria (B.) bifidum, B. infantis, B. longum, Lactobacilli (L.) casei, L. plantarum and L. rhamnosus. Primary outcome measures were frequency of bowel movements (BMs) per week and stool consistency. Secondary outcome measures were number of faecal incontinence episodes per week, abdominal pain and side effects.</p> <p>Results</p> <p>Twenty children, 50% male, median age 8 (range 4–16) were included.</p> <p>The frequency of BMs per week increased from 2.0 (1.0–5.0) to 4.2 (0.0–16.0) in week 2 (p = 0.10) and 3.8 (2.1–7.0) in week 4 (p = 0.13). In 12 children presenting with <3 BMs/week, BMs per week increased significantly from 1.0 (0.0–2.0) to 3.0 (0.0–7.0) in week 2 (p = 0.01) and 3.0 (0.0–10.0) in week 4 (p = 0.01). The stool consistency was reported as hard in 7 children at baseline, in 4 children at week 2 (p = 0.23) and in 6 children after 4 weeks of treatment (p = 1.00). A significant decrease in number of faecal incontinence episodes per week was found in the entire group: 4.0 (0.0–35.0) to 1.5 (0.0–14.0) in week 2 (p = 0.01) and 0.3 (0.0–7.0) in week 4 (p = 0.001). The presence of abdominal pain decreased significantly from 45% to 25% in week 2 (p = 0.04) and 20% at week 4 (p = 0.006). No side effects were reported.</p> <p>Conclusion</p> <p>This pilot study shows that a mixture of probiotics, has positive effects on symptoms of constipation. To confirm these findings, a large randomised placebo controlled trial is required.</p

Health-related quality of life in preschool children in five health conditions

Objective: To test the responsiveness of the Infant/Toddler Quality of Life Questionnaire (ITQOL) to five health conditions. In addition, to evaluate the impact of the child's age and gender on the ITQOL domain scores. Methods: Observational study of 494 Dutch preschool-aged children with five clinical conditions and 410 healthy preschool children randomly sampled from the general population. The clinical conditions included neurofibromatosis type 1, wheezing illness, bronchiolitis, functional abdominal complaints, and burns. Health-related quality of life (HRQoL) was assessed by a mailed parent-completed ITQOL. Mean ITQOL scale scores for all conditions were compared with scores obtained from the reference sample. The effect of patient's age and gender on ITQOL scores was assessed using multi-variable regression analysis. Results: In all health conditions, substantially lower scores were found for several ITQOL scales. The conditions had a variable effect on the type of ITQOL domains and a different magnitude of effect. Scores for 'physical functioning', 'bodily pain', and 'general health perceptions' showed the greatest range. Parental impact scales were equally affected by all conditions. In addition to disease type, the child's age and gender had an impact on HRQoL. Conclusions: The five health conditions (each with a distinct clinical profile) affected the ITQOL scales differently. These results indicate that the ITQOL is sensitive to specific characteristics and symptom expression of the childhood health conditions investigated. This insight into the sensitivity of the ITQOL to health conditions with different symptom expression may help in the interpretation of HRQoL results in future applications

Overweight and constipation in adolescents

Background: the association between overweight and gastrointestinal symptoms has been recently studied in the literature; however, few studies have evaluated the association between overweight and constipation in adolescents in a community-based sample. the aim of this study was to analyze the prevalence of constipation and its association with being overweight in a community-based survey with adolescents.Methods: This cross-sectional study included 1,077 adolescents who were enrolled in five schools in the city of Sao Jose dos Campos, Brazil. Constipation was defined according to modified and combined Rome III criteria for adolescents and adults. Being overweight was defined as a body mass index (BMI) that was equal to or greater than that of the 85(th) percentile for age and gender.Results: Constipation was diagnosed in 18.2% (196/1077) of the included adolescents. There was no significant difference in the prevalence of constipation in males and females who were both younger and older than 14 years. Fecal incontinence was observed in 25 adolescents, 22 (88.0%) of whom were diagnosed as being constipated. the prevalence of being overweight was found in 13.5% (145/1077) of the study population. the prevalence of constipation was observed to be similar in adolescents who were (19.4%; 28/144) and were not (18.0%; 168/933) overweight (p = 0.764; OR = 1.10). Fecal incontinence that was associated with constipation was more frequent in adolescents who were overweight (37.0%; 8/28) than in adolescents who were not overweight (8.5%; 14/168; p = 0.005; OR = 4.40).Conclusions: the prevalence of constipation was high among the investigated adolescents. There was no association between being overweight and constipation; however, an association between being overweight and fecal incontinence in constipated adolescents was confirmed.Universidade Federal de São Paulo, Div Pediat Gastroenterol, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Pediat Gastroenterol, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Aerobic nonylphenol degradation and nitro-nonylphenol formation by microbial cultures from sediments

Nonylphenol (NP) is an estrogenic pollutant which is widely present in the aquatic environment. Biodegradation of NP can reduce the toxicological risk. In this study, aerobic biodegradation of NP in river sediment was investigated. The sediment used for the microcosm experiments was aged polluted with NP. The biodegradation of NP in the sediment occurred within 8 days with a lag phase of 2 days at 30°C. During the biodegradation, nitro-nonylphenol metabolites were formed, which were further degraded to unknown compounds. The attached nitro-group originated from the ammonium in the medium. Five subsequent transfers were performed from original sediment and yielded a final stable population. In this NP-degrading culture, the microorganisms possibly involved in the biotransformation of NP to nitro-nonylphenol were related to ammonium-oxidizing bacteria. Besides the degradation of NP via nitro-nonylphenol, bacteria related to phenol-degrading species, which degrade phenol via ring cleavage, are abundantly present

Role of IKK/NF-κB Signaling in Extinction of Conditioned Place Aversion Memory in Rats

The inhibitor κB protein kinase/nuclear factor κB (IKK/NF-κB) signaling pathway is critical for synaptic plasticity. However, the role of IKK/NF-κB in drug withdrawal-associated conditioned place aversion (CPA) memory is unknown. Here, we showed that inhibition of IKK/NF-κB by sulphasalazine (SSZ; 10 mM, i.c.v.) selectively blocked the extinction but not acquisition or expression of morphine-induced CPA in rats. The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase. Thus, the IKK/NF-κB signaling pathway might play a critical role in the extinction of morphine-induced CPA in rats and might be a potential pharmacotherapy target for opiate addiction

Seroprevalence of 13 common pathogens in a rapidly growing U.S. minority population: Mexican Americans from San Antonio, TX

<p>Abstract</p> <p>Background</p> <p>Infection risks vary among individuals and between populations. Here we present information on the seroprevalence of 13 common infectious agents in a San Antonio-based sample of Mexican Americans. Mexican Americans represent the largest and most rapidly growing minority population in the U.S., and they are also considered a health disparities population.</p> <p>Methods</p> <p>We analyzed 1227 individuals for antibody titer to <it>Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii</it>, cytomegalovirus, Epstein-Barr virus, herpes simplex virus-1, herpes simplex virus-2 (HSV-2), human herpesvirus-6 (HHV-6), varicella zoster virus (VZV), adenovirus-36, hepatitis A virus, and influenza A and B. Seroprevalence was examined as a function of sex, age, household income, and education.</p> <p>Results</p> <p>Seroprevalence estimates ranged from 9% for <it>T. gondii</it> to 92% for VZV, and were similar in both sexes except for HSV-2, which was more prevalent in women. Many pathogens exhibited a significant seroprevalence change over the examined age range (15-94 years), with 7 pathogens increasing and HHV-6 decreasing with age. Socioeconomic status significantly correlated with serostatus for some pathogens.</p> <p>Conclusions</p> <p>Our findings demonstrate substantial seroprevalence rates of these common infections in this sample of Mexican Americans from San Antonio, Texas that suffers from high rates of chronic diseases including obesity and type-2 diabetes.</p

Connecting Network Properties of Rapidly Disseminating Epizoonotics

To effectively control the geographical dissemination of infectious diseases, their properties need to be determined. To test that rapid microbial dispersal requires not only susceptible hosts but also a pre-existing, connecting network, we explored constructs meant to reveal the network properties associated with disease spread, which included the road structure.Using geo-temporal data collected from epizoonotics in which all hosts were susceptible (mammals infected by Foot-and-mouth disease virus, Uruguay, 2001; birds infected by Avian Influenza virus H5N1, Nigeria, 2006), two models were compared: 1) 'connectivity', a model that integrated bio-physical concepts (the agent's transmission cycle, road topology) into indicators designed to measure networks ('nodes' or infected sites with short- and long-range links), and 2) 'contacts', which focused on infected individuals but did not assess connectivity.THE CONNECTIVITY MODEL SHOWED FIVE NETWORK PROPERTIES: 1) spatial aggregation of cases (disease clusters), 2) links among similar 'nodes' (assortativity), 3) simultaneous activation of similar nodes (synchronicity), 4) disease flows moving from highly to poorly connected nodes (directionality), and 5) a few nodes accounting for most cases (a "20:80" pattern). In both epizoonotics, 1) not all primary cases were connected but at least one primary case was connected, 2) highly connected, small areas (nodes) accounted for most cases, 3) several classes of nodes were distinguished, and 4) the contact model, which assumed all primary cases were identical, captured half the number of cases identified by the connectivity model. When assessed together, the synchronicity and directionality properties explained when and where an infectious disease spreads.Geo-temporal constructs of Network Theory's nodes and links were retrospectively validated in rapidly disseminating infectious diseases. They distinguished classes of cases, nodes, and networks, generating information usable to revise theory and optimize control measures. Prospective studies that consider pre-outbreak predictors, such as connecting networks, are recommended