Mitogen‐activated protein kinases (MAPKs) regulate normal brain functioning, and their dysfunction is implicated in a number of brain disorders. Thus, there is great interest in understanding the signalling systems that control MAPK functioning. One family of proteins that contribute to this process, the mitogen‐activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in foetal development, the immune system, cancer and synaptic plasticity and memory. In the present study, we performed an unbiased investigation using MKP‐2?/? mice to assess whether MKP‐2 plays a global role in modulating brain function. Local cerebral glucose utilization is significantly increased in the ventral tegmental area (VTA) of MKP‐2?/? mice, with connectivity analysis revealing alterations in VTA functional connectivity, including a significant reduction in connectivity to the nucleus accumbens and hippocampus. In addition, spontaneous excitatory postsynaptic current frequency, but not amplitude, onto putative dopamine neurons in the VTA is increased in MKP‐2?/? mice, which indicates that increased excitatory drive may account for the increased VTA glucose utilization. Consistent with modified VTA function and connectivity, in behavioural tests MKP‐2?/? mice exhibited increased sucrose preference and impaired amphetamine‐induced hyperlocomotion. Overall, these data reveal that MKP‐2 plays a role in modulating VTA function and that its dysfunction may contribute to brain disorders in which altered reward processing is present. 相似文献
Objective: Iron deficiency is the most common nutrient deficiency in the world. While deficiency can often be resolved through dietary supplementation with iron, adverse events are common and frequently preclude compliance. The objective of this study was to determine whether a food-derived dietary supplement containing a low dose of iron and nutrients that increase iron absorption could resolve iron deficiency with fewer adverse events than reported at higher doses.
Methods: A pilot clinical trial (NCT02683369) was conducted among premenopausal women with nonanemic iron deficiency that was verified by blood screening. Participants consumed a dietary supplement (Blood Builder®/Iron Response®) once daily for 8 weeks containing 26 mg of iron, vitamin C, folate, and other food-derived nutrients. Primary outcomes were markers of iron status (serum ferritin, hemoglobin, soluble transferrin receptor, total body iron stores) and secondary outcomes were self-reported fatigue and energy. All outcomes were assessed at baseline and 8 weeks. Adverse events were monitored with questionnaires, daily diaries, and contact with a physician. Dependent samples t test and Wilcoxon signed-rank test were used to analyze outcomes.
Results: Twenty-three participants enrolled in the study. Iron deficiency was resolved in the sample (mean serum ferritin: baseline = 13.9 μg/L, 8 weeks = 21.1 μg/L, p < 0.001). All other markers of iron status, fatigue, and energy also improved during the study (p < 0.04). No adverse events were reported. Conclusions: While larger and controlled studies are needed to confirm these findings, a food-derived dietary supplement with a low dose of iron and absorption-enhancing nutrients resolved iron deficiency and improved all other markers of iron status without any adverse events. 相似文献
Objective: Recent studies have used Bayesian methods to predict timing of influenza epidemics many weeks in advance, but there is no documented evaluation of how such forecasts might support the day‐to‐day operations of public health staff. Methods: During the 2015 influenza season in Melbourne, Australia, weekly forecasts were presented at Health Department surveillance unit meetings, where they were evaluated and updated in light of expert opinion to improve their accuracy and usefulness. Results: Predictive capacity of the model was substantially limited by delays in reporting and processing arising from an unprecedented number of notifications, disproportionate to seasonal intensity. Adjustment of the predictive algorithm to account for these delays and increased reporting propensity improved both current situational awareness and forecasting accuracy. Conclusions: Collaborative engagement with public health practitioners in model development improved understanding of the context and limitations of emerging surveillance data. Incorporation of these insights in a quantitative model resulted in more robust estimates of disease activity for public health use. Implications for public health: In addition to predicting future disease trends, forecasting methods can quantify the impact of delays in data availability and variable reporting practice on the accuracy of current epidemic assessment. Such evidence supports investment in systems capacity. 相似文献
OBJECTIVES: The purposes of this study were to investigate factors related to utilization of dental services during pregnancy and to assess the extent of mothers' knowledge regarding oral health during pregnancy and its effect on pregnancy outcomes. MATERIALS AND METHODS: Cross-sectional data were collected from 625 women using a structured questionnaire mailed to mothers who had given birth in Johnson County, Iowa from August 2001 to March 2002. The survey assessed knowledge, behaviours, attitudes toward dental care during pregnancy, and personal, demographic and pregnancy-related factors. Variables which showed associations in bivariate analysis (p< or =0.1) were considered as candidates for building logistic regression models separately by domain (demographics, dental health care behaviours, lifestyle, financial variables, pregnancy-related variables, and knowledge of the possible association between oral health and pregnancy). Significant domain-specific regression results (p< or =0.05) were used to develop a final model using forward stepwise logistic regression analyses. RESULTS: The overall response rate was 69%. Dental visits during pregnancy were reported by 49% of respondents. Forty-three percent were aware of the possible connection between oral health and pregnancy outcomes. In the final logistic regression analysis, factors significantly associated with reporting dental visits during pregnancy were: (1) personal factors (being married, greater frequency of visiting the dentist when not pregnant and use of inter-proximal cleaning aids); (2) financial factors (dental insurance); and (3) knowledge of the possible connection between oral health and pregnancy outcomes. CONCLUSIONS: There was limited knowledge of the possible relationships between oral health and pregnancy outcomes in a fairly homogeneous population of women who were of relatively high socioeconomic standing. This study suggests that better education of the importance of dental care before and during pregnancy is needed. 相似文献