Based on this analysis, a drug having a positive

effect on the HCC group and a negative effect on the non-HCC group should be assumed to have a mode of action with beneficial impact mainly targeting HCC. This could be the case for a drug holding anticancer properties. Conversely, a drug associated with improved survivals on both HCC and non-HCC patients should be assumed to act on the outcome of liver transplantation in general. When looking at the non-HCC group and performing a univariate analysis, tacrolimus-based therapy was associated with improved survivals, whereas cyclosporine-based treatment was linked to decreased survivals (Table 2). On multivariate analysis, only the use of cyclosporine-based maintenance protocols remained associated with decreased outcomes (HR 1.3, 95% CI: 1–1.7, P ≤ 0.05). In order to better understand the effects of the various studied drugs on patient survival, www.selleckchem.com/products/MLN-2238.html we plotted the HR (±95% CIs) found in the HCC and non-HCC groups (Fig. 2). Of the significant variables in the multivariate analyses, both anti-CD25 antibodies and cyclosporine demonstrated trends in similar directions in both groups, suggesting that their effect was primarily directed toward liver transplant in general (and not specifically toward HCC). Conversely, sirolimus-based immunosuppression

had a trend toward a protective effect in the HCC group and a negative impact in the non-HCC group, thus suggesting that the significant effect of this drug was primarily directed toward HCC. Of all the studied protocols, selleck inhibitor sirolimus-based immunosuppression was the only one showing such a pattern. As described earlier, the SRTR does not include data on HCC recurrence. In order to approximate these data we performed an assessment of patients dying of malignancy, and have shown that twice as many patients not on sirolimus died from cancer (HCC or other) compared to those on sirolimus (11% versus 5%, respectively, at 5 years). Although this observation did not

reach significance (P = 0.15, log-rank), possibly due to the low report rate of this variable, the observed trend further supports the message of the study. According to the present SRTR registry data, 上海皓元 the use of sirolimus-based immunosuppression protocols has unique beneficial posttransplant effects on HCC patients, leading to significantly improved survival. Our analysis of the SRTR dataset also suggests that anti-CD25 antibody induction is associated with a longer posttransplant life expectancy (significant for HCC and with a trend for non-HCC). Although the anticancer effect of sirolimus has been suggested by previous animal and single-center studies,7–12 the present data are the first to be adequately powered. It highlights a key potential role for this agent in patients undergoing liver transplantation for HCC.

Over the last 10 years, there has been significant scientific advancement in the field of 90Y. Standardization of the practice and assessment of indications has transformed radioembolization from a procedure relying on local expertise to a routine procedure yielding predictable results

in properly trained centers. Early series were limited by sample size, with a 43- and 24-patient series describing outcomes in small cohorts.[6, 8, 28] Since then, seven well-controlled investigations establishing the safety Tyrosine Kinase Inhibitor Library nmr and antitumoral effect of 90Y have been published; these will be presented temporally (Table 1). One of the common indications for 90Y that has emerged is HCC with portal venous thrombosis (PVT). Because 90Y is a microembolic procedure causing minimal occlusion of hepatic arteries, it may be safely used in the setting of PVT.[34] This is a relevant clinical scenario, because PVT significantly increases the chances of extrahepatic spread.[9] Given this interest,

the first large-series analysis was a phase II study by Kulik et al. analyzing 90Y in 108 HCC patients with (34%) and without PVT (66%). Partial response rates of 42.2% (size) and 70% (necrosis) were reported.[34] Survival varied by location of PVT and presence of cirrhosis. This study was important given its multicenter nature, challenging preconceived notions that embolotherapy could

not be applied Trametinib cell line in the setting of PVT (ischemic hepatitis). Because 90Y is microembolic, this study reintroduced the idea of embolotherapy in the context of vascular invasion.[14] Recently, mature long-term outcomes for PVT patients treated with 90Y in the sorafenib era were updated.[35] It is unknown whether treating patients with PVT has any effect on metastatic dissemination, regardless of the response in the tumor thrombus. In 2010, a detailed review of the pathologic findings 上海皓元医药股份有限公司 subsequent to 90Y treatment was presented by Riaz et al. in patients bridged or downstaged to transplantation.[26] The intent was to examine the antitumoral effect of 90Y, a pathological proof of concept. This analysis demonstrated a very high rate (89%) of complete pathologic necrosis (CPN) in smaller lesions (1-3 cm) and a promising rate of CPN in larger lesions (65%; 3-5 cm) (independent pathology review). These data were compared to the CPN achieved in an identical pathology review of HCC after conventional TACE,[36] confirming that 90Y could achieve better antitumoral effect (pathology), when compared with the standard of care (TACE), thereby introducing a new tool to the armamentarium of downstaging strategies. In 2010, the seminal experience from Northwestern University confirmed the positive outcomes of 291 patients with HCC treated with 90Y.

However,

on the other hand, the fact that the patient is aged and had a solid tumour (stomach cancer) may have created a higher risk of an autoantibody development. Therefore, we cannot deny the possibility that the patient’s haemophilia is acquired. The novel factor VIII mutation identified here provides potential insight into the genetic contribution to haemophilia A pathogenesis and inhibitor development. Although the FVIII antibody developed in this patient is interesting, further analysis and knowledge are necessary to judge whether the inhibitor is an Decitabine mouse alloantibody or an autoantibody. This study was partially supported by Health and Labor Sciences Research Grants for Research on HIV/AIDS from the Japanese Ministry of Health,

Labor and Welfare. K. Fukutake has received speaking fees and honoraria from Baxter Healthcare, Bayer HealthCare and Pfizer Inc. K. Shinozawa is an employee of an endowed chair at the Department of Molecular Genetics of Coagulation Disorders of Tokyo Medical University, which received funding from Baxter Healthcare. The other authors declare that they have no interests that might be perceived as posing a conflict of interest. “
“Summary.  Although body adiposity and disease severity in haemophilia have been found in selleck kinase inhibitor cross-sectional studies to be negatively associated with joint mobility, it is not clear how these two factors affect the rate of joint mobility loss over time. Over a 10-year period, repeated measures of joint range of motion (ROM) were collected annually using universal goniometers on bilateral

hip, knee, ankle, shoulder and elbow joints in 6131 young males with haemophilia A aged ≤20 years. Body mass index (BMI) was calculated using data on weight and height during follow up. The effect of body adiposity, adjusted for disease severity, on the rate of joint mobility loss over time was assessed using a longitudinal model. Compared with haemophilia males with normal BMI, those who were obese had lower ROM at initial visit and a faster rate of joint mobility loss in the lower limbs. Overweight subjects experienced similar loss in ROM, although to a lesser degree. A decline in ROM with age was also observed in upper 上海皓元 limb joints but the rate was not significantly affected by body adiposity. Haemophilia severity, joint bleeding and the presence of an inhibitor were other significant contributors to joint mobility loss in both upper and lower limb joints. Excess body adiposity accelerates joint mobility loss in weight bearing joints particularly among those with severe haemophilia. Our findings suggest that body weight control and effective treatment of bleeds should be implemented together to achieve better joint ROM outcomes in males with haemophilia. “
“Summary.

ROC curves were made and cut-off values calculated. Results: The ELF-test results were compared with the outcome of TE. AUROC for severe fibrosis

(>F3) was 0.876 (95% C. l.0.757-0.995). AUROC for significant fibrosis (>F2) was 0.732 (95% C. I. 0.597-0.866). The cut-off value of 10.3 of the ELF-score based on ROC curve predicted severe fibrosis with a sensitivity of 66.7%, a specificity of 95.3%, NPV of 89.1% and PPV of 83.3%. For exclusion of fibrosis, a cut-off value of 7.7 yielded an NPV of 88.9%. For diagnosing significant fibrosis, a cut-off CT99021 value of 10.2 yielded a PPV of 85.7%. Conclusion: The ELF test is a good discriminator for severe fibrosis and can exclude fibrosis with a high certainty in haemophilia patients with hepatitis C. Disclosures: Karel J. van Erpecum – Grant/Research Support: Bristol Meyers Squibb, MSD The following people have nothing to disclose: Greet Boland, Lisa Manen van, Evelien Mauser-Bunschoten, Dietje Fransen-van de Putte Background: The emergence of direct acting antiviral agents(DAAs) had brought about great changes to the treatment

of chronic hepatitis C. However, gene polymorphism of HCV and high viral variability would naturally cause resistance to the DAAs. In this study, we tried to detect natural polymorphisms and illustrate the prevalence of such mutations in Chinese treatment-naīve patients. Methods: A total of 184 treatment-naīve chronic hepatitis C patients from the third affiliated hospital of Rucaparib datasheet Sun Yat-sen University were enrolled. HCV genotypes were determined by direct sequencing and phylogenetic tree analysis based on HCV core and NS5B conserved regions sequence. Several nested PCR assays with genotypespecific primers were performed to amplify the HCV viral regions of NS3, NS5A and NS5B. Results: The genotyping result showed that 1 84 patients were classified into 3 categories: genotype 1b, 2a and 6a at frequencies of 40.2%(74/184), 8.2%(15/184), 51.6%(95/184). We also successfully amplified

88.04%(162/184) in NS3, 86.96%(160/184) in NS5A as well as 84.24%(155/184) in NS5B. For NS3 sequences, a total of 266 amino acid substitutions were detected in 125 (77.16%) patients. Major resistant-mutation A156S was found in 18.33% of patients with HCV 1b and 64.28% MCE公司 of patients with HCV 2a, while Q80K and V170I variability were detected in 95.45% and 100% of HCV 6a. None of the 162 individuals had the substitution V55A and R155K/T/Q. The proportion of these 3 resistance mutations (Q80K, A156S, V170I) in different groups were obviously different(p<0.05). For NS5A sequences, resistant-mutations Q30R was detected in 116 cases of HCV 1b and 6a, while L31M was found 12 of HCV 2a and 4 of HCV 6a, H58P was discovered in 42.5%(68/160) patients with the above genotypes, Y93C was showed in 9 individuals only with genotype 2a. For NS5B sequences, C316N were detected among all HCV 1b patients, while s282T was found in 20.73% (17/82) of HCV 6a.

2D). More important, HCC cells overexpressing Cryab had a mesenchymal phenotype in HCC tissues (Fig. 2E). Thus, we conclude

that the Cryab overexpression promotes HCC progression by inducing cancer cell EMT. We employed a multivariate approach for integrating genome-wide expression data and biological knowledge23 to search for pathways that are dysregulated as a consequence of Cryab overexpression. We used this method to search through functional pathways defined by KEGG MK-8669 mw and BioCarta in Hep3B-Mock versus Hep3B-Cryab cells. Pathways with significant P values at 0.01 are shown. We identified 28 gene sets in the BioCarta database and 67 gene sets in the KEGG database, with false discovery rates (Q values) < 0.05 by paired t tests between these populations (Table S5). The magnitudes of MEK, FAK, Src, p38, ERK1/2, p65, and Akt phosphorylation

in Hep3B-Mock and HCCLM3-Mock cells were compared to their corresponding control cells. As shown in Fig. 3A, markedly elevated levels of MEK, ERK1/2, and p38 phosphorylation were detected in HCCLM3-Mock and Hep3B-Cryab cells compared with the corresponding control cells, while consistent changes in Src, FAK, and p65 phosphorylation were not observed in the Hep3B-Cryab/Hep3B-Mock Buparlisib mouse and HCCLM3-Mock/HCCLM3-vshCryab cells. Immunofluorescent staining showed that expression of Cryab in Hep3B-Cryab and HCCLM3-Mock cells correlated with high ERK1/2 phosphorylation (Fig. 3B). To identify the signaling pathways that might contribute to the observed phenotypic changes, we blocked MEK/ERK signaling using U0126 or P38 signal using SD203580. Upon ERK1/2 inhibition, the Hep3B-Cryab and HCCLM3-Mock cells presented an epithelial phenotype based on mRNA and protein expression (Fig. 3C)

and cellular characteristics, such as decreased E-cadherin and increased Fn 1, vimentin, and F-actin when compared with the parental cells (Fig. 3D). These results indicate that hyperactivation of ERK1/2 appears to be crucial for the observed Cryab-mediated phenotypic characteristics of HCC cells. Sorafenib, an oral multikinase 上海皓元 inhibitor, offers hope for the clinical treatment of several advanced solid cancers by inhibiting intracellular signals in the ERK cascade and blocking receptor tyrosine kinases.17, 24 Here, we tried to assess whether sorafenib inhibited the activity of the ERK cascade induced by Cryab overexpression. As shown in Fig. S3, Hep3B-Mock cells were evidently inhibited compared with Hep3B-Cryab cells when the sorafenib concentration reached 10 or 20 μM (P < 0.05). We further evaluated the changes in the phosphorylation levels of ERK1/2 by western blot in both Hep3B-Mock/Hep3B-Cryab and HCCLM3-Mock/HCCLM3-vshCryab cells after treatment with sorafenib in a dose-dependent or time-dependent manner at the concentration of 10 μM.

2D). More important, HCC cells overexpressing Cryab had a mesenchymal phenotype in HCC tissues (Fig. 2E). Thus, we conclude

that the Cryab overexpression promotes HCC progression by inducing cancer cell EMT. We employed a multivariate approach for integrating genome-wide expression data and biological knowledge23 to search for pathways that are dysregulated as a consequence of Cryab overexpression. We used this method to search through functional pathways defined by KEGG Aloxistatin solubility dmso and BioCarta in Hep3B-Mock versus Hep3B-Cryab cells. Pathways with significant P values at 0.01 are shown. We identified 28 gene sets in the BioCarta database and 67 gene sets in the KEGG database, with false discovery rates (Q values) < 0.05 by paired t tests between these populations (Table S5). The magnitudes of MEK, FAK, Src, p38, ERK1/2, p65, and Akt phosphorylation

in Hep3B-Mock and HCCLM3-Mock cells were compared to their corresponding control cells. As shown in Fig. 3A, markedly elevated levels of MEK, ERK1/2, and p38 phosphorylation were detected in HCCLM3-Mock and Hep3B-Cryab cells compared with the corresponding control cells, while consistent changes in Src, FAK, and p65 phosphorylation were not observed in the Hep3B-Cryab/Hep3B-Mock U0126 order and HCCLM3-Mock/HCCLM3-vshCryab cells. Immunofluorescent staining showed that expression of Cryab in Hep3B-Cryab and HCCLM3-Mock cells correlated with high ERK1/2 phosphorylation (Fig. 3B). To identify the signaling pathways that might contribute to the observed phenotypic changes, we blocked MEK/ERK signaling using U0126 or P38 signal using SD203580. Upon ERK1/2 inhibition, the Hep3B-Cryab and HCCLM3-Mock cells presented an epithelial phenotype based on mRNA and protein expression (Fig. 3C)

and cellular characteristics, such as decreased E-cadherin and increased Fn 1, vimentin, and F-actin when compared with the parental cells (Fig. 3D). These results indicate that hyperactivation of ERK1/2 appears to be crucial for the observed Cryab-mediated phenotypic characteristics of HCC cells. Sorafenib, an oral multikinase 上海皓元 inhibitor, offers hope for the clinical treatment of several advanced solid cancers by inhibiting intracellular signals in the ERK cascade and blocking receptor tyrosine kinases.17, 24 Here, we tried to assess whether sorafenib inhibited the activity of the ERK cascade induced by Cryab overexpression. As shown in Fig. S3, Hep3B-Mock cells were evidently inhibited compared with Hep3B-Cryab cells when the sorafenib concentration reached 10 or 20 μM (P < 0.05). We further evaluated the changes in the phosphorylation levels of ERK1/2 by western blot in both Hep3B-Mock/Hep3B-Cryab and HCCLM3-Mock/HCCLM3-vshCryab cells after treatment with sorafenib in a dose-dependent or time-dependent manner at the concentration of 10 μM.

For stimulation, we used a vertically rotating optokinetic drum with complex colored figures. Group analysis of migraineurs with aura vs controls revealed different activation patterns in functional magnetic resonance imaging: attenuation of the physiological right lateralization with a significantly increased activation in the left V5 complex, the left area V3, and the right V5 complex. Analysis of the visually evoked flow response of the cerebral blood flow velocity in the posterior cerebral artery showed a larger side-difference of the offset latency (P < .05) and a reduced steepness of the decreasing slope on the left

side (P < .05). Combining Autophagy inhibitor library examinations with a good structural (functional magnetic resonance imaging) and temporal (functional transcranial Doppler) resolution is a novel approach to migraine pathophysiology. Our findings of an altered pattern of activation by optokinetic visual stimulation with hyperresponsiveness in visual areas activated by motion perception (V5 and V3) further strengthen the concept of an interictal motion-processing deficit in migraine. This is complemented by the slower restitution of the visually evoked

flow response after stimulus offset in migraine with aura patients. Migraine is a highly prevalent, periodic, and chronic neurological disorder. Substantial Ibrutinib price research into the pathophysiology has focused on visual processing in migraine patients owing to the fact that typical visual disturbances can occur before and during migraine headache and due to the observation that visual stimuli can trigger an attack of migraine. Experimental data have suggested that

the preceding aura symptoms may reflect a cortical spreading depression (CSD) associated with local blood flow changes and transient clinical signs.[1] 上海皓元医药股份有限公司 Assuming that underlying abnormalities are not limited to the attacks, different features of visual processing have been investigated in migraine patients during the interictal phase using transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI),[2] and functional transcranial Doppler (fTCD).[3] Several of these studies have suggested either a reduced cortical inhibition or an increased neuronal excitability and responsiveness of the primary visual cortical areas, possibly precipitating migraine aura.4-6 In addition, analysis of the dynamic pattern of the cerebrovascular response in migraineurs has led to the assumption that a lack of habituation of the cerebrovascular response might contribute to a disturbance of the metabolic homeostasis of the brain and thereby promote migraine attacks, and may even lead to stroke.

4, 5 SSeCKS, the rodent ortholog of AKAP12, has been demonstrated to act as tumor suppressor in vitro and in vivo.6, 7 This function was also described in human solid neoplasms, such as prostate and gastric cancer,7, 8 but data concerning the role of AKAP12 in human hepatocarcinogenesis are scarce. The AKAP12 gene locus in human and rodents encodes three major transcripts under the control of three independent promoters, designated α, β, and γ (Fig. 1). The two major protein isoforms of AKAP12, α and β, are expressed ubiquitously in most cell and tissue types, whereas the expression of isoform γ is restricted to testes.9 The proteins translated from each transcript are

encoded by Panobinostat datasheet a single large exon and share >95% amino acid sequence homology; however, they differ in their N-terminal domains. These isoforms are frequently posttranslationally modified; for example, only the α isoform is myristoylated at the N-terminus, a modification that facilitates AKAP12α association with plasma membranes and vesicles of the endoplasmic reticulum.9 In one of our recent learn more studies analyzing 63 HCCs by aCGH, the AKAP12 gene locus on chromosome 6q24-25.2 showed chromosomal losses in 36% (23/63) of all analyzed cases, whereas gains were observed

only in 5% (3/63).10 Yet this is an incomplete explanation of the observed AKAP12 down-regulation in HCC. Here, we show protein expression data of the tumor suppressor AKAP12 in a large series of human liver specimens, containing typical pathohistological features of hepatocarcinogenesis. In order to elucidate mechanisms

of AKAP12 down-regulation, we have analyzed genetic, epigenetic, and posttranscriptional mechanisms. In summary, we here propose three different mechanisms of AKAP12 down-regulation in hepatocarcinogenesis: microRNA (miRNA) interference in preneoplastic lesions, genetic alterations, and AKAP12α promoter hypermethylation in HCCs. aCGH, array-based comparative genomic hybridization; AKAP12, a kinase anchor protein 12; 5-aza-dC, 5-aza-2′deoxycytidine; CL, cirrhotic liver; DN, dysplastic nodule; FFPE, formalin-fixed paraffin-embedded; HCC, hepatocellular carcinoma; HBV, hepatitis B virus; HCV, hepatitis C virus; miRNA, microRNA; NL, normal liver; PCR, polymerase chain reaction; PHH, primary 上海皓元 human hepatocytes; PT, noncirrhotic peritumorous tissue; SSeCKS, Src-suppressed C kinase substrate; TMA, tissue microarray; UTR, untranslated region. A total of 388 human liver tissue samples were evaluated by tissue microarrays (TMAs). TMA#1 (n = 225) contained two representative areas (diameter: 0.6 mm) of 14 histologically normal liver (NL), 38 dysplastic nodule (DN), 135 hepatocellular carcinoma (HCC; grading: 29 × G1, 76 × G2, 30 × G3), 14 cirrhotic (CL), and 24 noncirrhotic peritumorous (PT) liver tissue samples. The independently designed, processed, and evaluated TMA#2 (n = 163) contained two representative areas (diameter: 0.

Reproductive tract metrics vary across species in relation to mating strategy, and have been used to infer mating ecology. Reproductive tracts from beluga and narwhal were collected between 1997 and 2008 from five beluga stocks and two narwhal stocks across the Canadian Arctic. Tract length for males and females, relative testes mass for males, and tusk length for male narwhal were measured. We assessed variation relative to species, body size, stock, maturity, and season. Significant variation was found in testes mass across month and stock for beluga, and no significant difference between stock or

date of harvest for narwhal. Beluga had buy Ku-0059436 significantly larger testes relative to body size than narwhal, suggesting they were more promiscuous than narwhal. A significant relationship was found between narwhal tusk length and testes mass, indicating the tusk may be GSI-IX important in female mate choice. No significant differences were found between narwhal and beluga reproductive tract length for males or females. The mating systems suggested for narwhal and belugas by our results mean the two species may respond differently to climate change. “
“In this quantitative study of locational

and social dispersal at the individual level, we show that bottlenose dolphins (Tursiops sp.) continued to use their natal home ranges well into adulthood. Despite substantial home range overlap, mother–offspring associations decreased after weaning, particularly for sons. These data provide strong evidence for bisexual locational philopatry and mother–son

avoidance in bottlenose dolphins. While bisexual locational philopatry offers the benefits of familiar social networks and foraging habitats, the costs of philopatry may be mitigated by reduced mother–offspring association, in which the risk of mother–daughter resource competition and mother–son mating is reduced. Our study highlights the advantages of high fission–fusion dynamics and longitudinal studies, and emphasizes the need for clarity when describing dispersal in this and other species. “
“Long-term social structure this website data on small delphinids is lacking for most species except the bottlenose dolphin. This study describes the long-term social structure of one community of Atlantic spotted dolphins, Stenella frontalis, divided into three social clusters. Data from 12 yr were analyzed using SOCPROG 2.3. Coefficients of association (CoA) were calculated using the half-weight index. The overall mean community CoA ranged from 0.09 to 0.12. Temporal analyses and mantel tests revealed significant differences between sex class associations due to high male-male CoA (0.12–0.23) compared to female-female and mixed sex CoA (0.08–0.10). Female associations were strongly influenced by reproductive status, calf care, and social familiarity, but not by age class. Male associations were strongly influenced by age, access to females, and alliance formation.

[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 find more for victims’ health problems and did not specifically focus AZD6738 mw 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 ifoxetine 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.