Nuclear factor κB (NF-κB) suppresses food intake and energy expenditure in mice by directly activating the Pomc promoter.

AIMS/HYPOTHESIS: While chronic low-grade inflammation is associated with obesity, acute inflammation reduces food intake and leads to negative energy balance. Although both types of inflammation activate nuclear factor κB (NF-κB) signalling, it remains unclear how NF-κB activation results in opposite physiological responses in the two types of inflammation. The goal of this study was to address this question, and to understand the link between inflammation and leptin signalling. METHODS: We studied the ability of NF-κB to modulate Pomc transcription, and how it impinges on signal transducer and activator of transcription 3 (STAT3)-mediated leptin signalling by using a combination of animal models, biochemical assays and molecular biology. RESULTS: We report that suppression of food intake and physical movement with acute inflammation is not dependent on STAT3 activation in pro-opiomelanocortin (POMC) neurons. Under these conditions, activated NF-κB independently leads to increased Pomc transcription. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) experiments reveal that NF-κB v-rel reticuloendotheliosis viral oncogene homologue A (avian) (RELA [also known as p65]) binds to the Pomc promoter region between -138 and -88 bp, which also harbours the trans-acting transcription factor 1 (SP1) binding site. We found significant changes in the methylation pattern at this region and reduced Pomc activation under chronic inflammation induced by a high-fat diet. Furthermore, RELA is unable to bind and activate transcription when the Pomc promoter is methylated. Finally, RELA binds to STAT3 and inhibits STAT3-mediated promoter activity, suggesting that RELA, possibly together with forkhead box-containing protein 1 (FOXO1), may prevent STAT3-mediated leptin activation of the Pomc promoter. CONCLUSIONS/INTERPRETATION: Our study provides a mechanism for the involvement of RELA in the divergent regulation of energy homeostasis in acute and chronic inflammation.

Establishment and evaluation of a model of a community health service in an underdeveloped area of China.

OBJECTIVES: To develop and evaluate an applicable model for a community health service (CHS) in an underdeveloped area of China that ensures efficient, convenient and affordable primary healthcare access for all residents. STUDY DESIGN: The current study was carried out in Puyang, a typical medium-sized city in central-eastern China. Based on the healthcare requirements of the residents in Puyang, a CHS network was set up and its operation was evaluated from 1999 to 2006. The system is characterized by its focus on community health education (CHE). METHODS: Firstly, 8231 residents, selected at random, were surveyed to investigate the healthcare requirements of the local residents. Meanwhile, the operation of the pre-existing healthcare resources was investigated in Puyang. Based on the information gained, a network-based CHS system was proposed and established, with CHE as the major focus. This study compared CHS operation prior to and after establishment of the network. Finally, an analytic hierarchy process based evaluation model was applied to evaluate the operation of the CHS network. RESULTS: There was a high prevalence (86.98 per thousand) of chronic diseases among the residents who participated in this investigation. The majority (84.39%) of the residents who had healthcare requirements resorted to professional health care; the other residents did not have access to health services. Among those residents who sought professional treatment, 71.3% visited primary healthcare institutions. This information reflects the enormous requirement for a CHS in primary health care but the lack of accessibility among the residents; this motivated the authors to establish a system to solve the problem. The improvement in CHS operation after the network was established suggests the importance of a network for optimizing the primary healthcare system. The improvement was indicated by better understanding of the residents regarding the CHS, and enhanced capability of self-monitoring for chronic diseases such as hypertension after the network was established. Moreover, the residents' knowledge of health care was significantly increased and, accordingly, the incidence of health risk behaviour was reduced after the network was established. Furthermore, the CHE index between 1999 and 2006 showed good correlation (r=0.988, p<0.005) with the CHS index, suggesting the important role of CHE in CHS development. CONCLUSIONS: A network-characterized CHS system was established in Puyang, and improved the primary healthcare situation. This study provides a feasible model for the development of a CHS in medium and small cities in underdeveloped parts of China.

Biostabilization assessment of MSW co-disposed with MSWI fly ash in anaerobic bioreactors.

Municipal solid waste incinerator (MSWI) fly ash has been examined for possible use as landfill interim cover. For this aim, three anaerobic bioreactors, 1.2m high and 0.2m in diameter, were used to assess the co-digestion or co-disposal performance of MSW and MSWI fly ash. Two bioreactors contained ratios of 10 and 20 g fly ash per liter of MSW (or 0.2 and 0.4 g g(-1) VS, that is, 0.2 and 0.4 g fly ash per gram volatile solids (VS) of MSW). The remaining bioreactor was used as control, without fly ash addition. The results showed that gas production rate was enhanced by the appropriate addition of MSWI fly ash, with a rate of approximately 6.5l day(-1)kg(-1)VS at peak production in the ash-added bioreactors, compared to approximately 4l day(-1)kg(-1)VS in control. Conductivity, alkali metals and VS in leachate were higher in the fly ash-added bioreactors compared to control. The results show that MSW decomposition was maintained throughout at near-neutral pH and might be improved by release of alkali and trace metals from fly ash. Heavy metals exerted no inhibitory effect on MSW digestion in all three bioreactors. These phenomena indicate that proper amounts of MSWI fly ash, co-disposed or co-digested with MSW, could facilitate bacterial activity, digestion efficiency and gas production rates.

Mapping residents' perceptions of neighborhood boundaries: a methodological note.

Neighborhood influences on children and youth are the subjects of increasing numbers of studies, but there is concern that these investigations may be biased, because they typically rely on census-based units as proxies for neighborhoods. This pilot study tested several methods of defining neighborhood units based on maps drawn by residents, and compared the results with census definitions of neighborhoods. When residents' maps were used to create neighborhood boundary definitions, the resulting units covered different space and produced different social indicator values than did census-defined units. Residents' agreement about their neighborhoods' boundaries differed among the neighborhoods studied. This pilot study suggests that discrepancies between researcher and resident-defined neighborhoods are a possible source of bias in studies of neighborhood effects.

The effect of a rapid change in availability of epidural analgesia on the cesarean delivery rate: a meta-analysis.

OBJECTIVE: This study was undertaken to quantitatively estimate the effect of a rapid introduction or withdrawal of on-demand epidural analgesia on the cesarean delivery rate. STUDY DESIGN: MEDLINE and meeting abstracts were searched for studies reporting the cesarean delivery rate immediately before and after a rapid change in the availability of epidural analgesia. Nine studies reporting data on 37,753 patients were selected. Meta-analysis was performed to estimate the means and 95% confidence intervals for the changes in rates of total cesarean deliveries, cesarean deliveries among nulliparous women, cesarean deliveries for dystocia, and operative vaginal deliveries. RESULTS: There was no significant change in the overall cesarean delivery rate with an increase in the availability of epidural analgesia. Similarly, the rates of cesarean deliveries among nulliparous patients, of cesarean deliveries for dystocia, and of operative vaginal deliveries did not significantly differ between periods of high and low epidural analgesia availability. CONCLUSION: A rapid change in the availability of epidural analgesia is not associated with any increase in the cesarean delivery rate.

Impoverishment and child maltreatment in African American and European American neighborhoods.

Although it is well documented that child maltreatment exerts a deleterious impact on child adaptation, much less is known about the precise etiological pathways that eventuate in child abuse and neglect. This paper reports on a multimethod ecological study of the relationship between neighborhood structural factors and child maltreatment reports in African American and European American census tracts. The study had two major components. First, in an aggregate analysis, the effects of four measures of community structure (impoverishment, child care burden, instability, and geographic isolation) on child maltreatment report rates were examined separately for predominantly African American (n = 94) and predominantly European American (n = 189) census tracts. Impoverishment in particular had a significantly weaker effect on maltreatment rates in African American than in European American neighborhoods. Second, focused ethnographies were conducted in four selected census tracts with child maltreatment report rates in the highest and lowest quartiles. Ethnographic data point to the importance of the social fabric in accounting for differences in child maltreatment report rates by predominant neighborhood ethnicity.

Community level factors and child maltreatment rates.

Using census and administrative agency data for 177 urban census tracts, variation in rates of officially reported child maltreatment is found to be related to structural determinants of community social organization: economic and family resources, residential instability, household and age structure, and geographic proximity of neighborhoods to concentrated poverty. Furthermore, child maltreatment rates are found to be intercorrelated with other indicators of the breakdown of community social control and organization. These other indicators are similarly affected by the structural dimensions of neighborhood context. Children who live in neighborhoods that are characterized by poverty, excessive numbers of children per adult resident, populations turnover, and the concentration of female-headed families are at highest risk of maltreatment. This analysis suggests that child maltreatment is but one manifestation of community social organization and that its occurrence is related to some of the same underlying macro-social conditions that foster other urban problems.

Statistical description of microcirculatory flow as measured with an MR method.

Quantification of microcirculatory flow is important for the functional assessment of biologic systems. The authors describe a method of analyzing the dependence of the magnetic resonance (MR) signal intensity on microcirculatory flow. A gel bead phantom was used to simulate the randomly oriented flow capillaries, and the MR signal intensity of the phantom was studied at different flow velocities by using velocity-sensitized and -compensated spin-echo pulse sequences. A theoretical model based on the spin-phase phenomenon is proposed to elucidate the effect of flow on signal intensity. The velocity phase of a spin depends on its path and the corresponding velocity-encoding gradients. A Monte Carlo simulation was used to generate the path of a spin on the basis of a statistical model for flow through a random capillary network. From the velocity-phase distribution of a group of spins within a voxel, the signal attenuation due to flow can be calculated. The results of the statistical model and experimental measurements agreed well. Also, T1 and T2 effects in MR flow measurements were investigated. The current study provides a theoretical framework for understanding MR measurements of microcirculatory flow.