[24] The well-established cognitive appraisal model of stress and coping developed by Lazarus[25] and the “sustained activation hypothesis”[26] can help to understand stress reactions to bullying. These models suggest that repeated bullying experiences in children’s life might cause a state of emotional distress that can lead to adverse health outcomes such as recurrent headache. To date, 2

meta-analyses[22, 23] have shown that bullied students can be affected by poor physical health and that these youths are about 2 times more likely than non-bullied agemates to report a variety of symptoms, such as headache, backache, abdominal pain, skin problems, vomiting, etc. However, both these meta-analytic reviews only reported an overall risk estimate this website for victims’ health problems and did not specifically focus MK-2206 supplier on headache. The current meta-analysis aims

at (1) estimating the risk for headache in children and adolescents who are bullied by peers (ie, victims) compared with non-bullied peers; (2) performing separate meta-analyses of longitudinal and cross-sectional studies; (3) testing for potential moderators of variation in the magnitude of effect sizes, that is, testing whether certain study features explain differences in the strength of the effect sizes. Several methods were used to identify relevant studies. First, electronic searches in PsychInfo, Pubmed, EMBASE, the Cochrane Library database, the Campbell Collaboration database, and Scopus were conducted in September 2013 with the following keywords: “bullying,” or “peer victimization” and “headache,” “somatic,” “psychosomatic,” and “physical health.” Second, the “cited by” function in Scopus was used to retrieve empirical articles that have cited the 2 meta-analyses[22, 23] on the association between bullying and health problems. Third, previous issues of the journal “Headache” were searched for relevant studies. Finally, review articles regarding consequences of bullying and the reference sections of the collected articles were reviewed

for possible relevant citations. If a study was not available in full-text, the corresponding author was contacted. This medchemexpress meta-analysis was planned, conducted, and reported in adherence to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines.[27] A study had to meet the following a priori criteria to be included. The most basic requirement was the inclusion of measures of bullying victimization at school in childhood or adolescence and of headache. Consistent with the international literature, bullying was defined as a deliberate, repeated exposure to aggressive acts performed by a peer or a group of peers with higher power or strength than the bullied schoolmate (ie, the “victim”).[17, 18] These measures could include (1) self-report questionnaires; (2) peer or adult reports; or (3) an interview that resulted in a quantitative rating of peer victimization and headache frequency.

8C). This may help explain a lack of correlation between inflammation and hepatocellular damage (serum ALT levels) observed in some patients with chronic liver diseases.8-13 In our study, injection with CCl4 induced much higher levels of systemic and hepatic inflammation in STAT3 mice than in wild-type mice, suggesting that STAT3 in myeloid cells plays an important role in inhibiting inflammation in a

model of CCl4-induced liver injury. This is consistent with previously well-documented studies showing the anti-inflammatory effects of STAT3 in 5-Fluoracil datasheet myeloid cells using various models of organ injury.26-28 Surprisingly, despite higher levels of inflammation in STAT3 mice, they had much lower serum ALT levels and less liver necrosis than wild-type mice after CCl4 administration.

The resistance of STAT3 mice to CCl4-induced liver necrosis may be attributable to either the impaired ability of STAT3-deficient neutrophils/macrophages to induce hepatocellular damage or the resistance of hepatocytes to CCl4-induced hepatocellular damage in STAT3 mice. Several lines of evidence suggest that it is the second mechanism that contributes to reducing liver necrosis in STAT3 mice because of enhanced STAT3 activation in the liver. The hepatotoxicity of CCl4 is mediated by the direct induction of hepatocyte damage U0126 in vivo and indirect activation of Kupffer cells/macrophages and neutrophils.14 Activated Kupffer cells/macrophages produce free radicals and proinflammatory cytokines such as TNF-α that further trigger hepatocellular damage and induce neutrophil accumulation and activation.2, 5 Activated neutrophils can cause hepatocyte damage by releasing oxygen species and proteases.2, 5 We have

previously shown that Kupffer cells from STAT3 mice produce much higher levels of reactive oxygen species and TNF-α compared with those from wild-type mice.27 By using four different assays, Lee et al.29 previously demonstrated that STAT3-deficient neutrophils mature normally and are functional. In the 上海皓元 current study we also confirmed that STAT3-deficient neutrophils from STAT3 mice are functional in vitro because they produced a similar respiratory burst after phorbol 12-myristate 13-acetate stimulation compared with phorbol 12-myristate 13-acetate–stimulated wild-type mouse neutrophils (Supporting Fig. S1c). Moreover, an additional deletion of STAT3 in hepatocytes restored liver necrosis in STAT3 mice after CCl4 administration, suggesting that neutrophils from STAT3 mice are functional in vivo. Collectively, these findings suggest that STAT3-deficient macrophages and neutrophils in STAT3 mice have normal ability to induce inflammatory responses and hepatocellular damage, and that the reduced liver necrosis observed in STAT3 mice is not attributable to a defect in STAT3-deficient macrophages and neutrophils to induce hepatocellular damage.