122 Other approaches have looked at transdifferentiation of hepatocytes from other progenitor cell sources. Mesenchymal stem cells,

whether from bone marrow, cord blood, cord lining cells, cord matrix cells, amniotic cells, adipose progenitor and muscle progenitors have been demonstrated to be capable of differentiation into hepatocytes in vitro.110,118 While it would be exhaustive to describe all human transplantation studies to date, a review on liver regeneration would be incomplete if studies relating to the original aims of understanding regeneration are not covered. To date, some 20 human studies have been undertaken, in which attempts were made to enhance liver regeneration. These can be grouped into Ferroptosis activation adult hepatocyte transplantation, fetal hepatocyte transplantation and bone marrow stem cell transplantation. As mature hepatocytes are the main cells that

regenerate the injured liver, roughly 25 patients with acute liver failure Torin 1 clinical trial have been transplanted with 107–9 hepatocytes in an attempt to salvage the failing liver.123 Instead of adult hepatocytes, Habibullah et al.124 transplanted 6 patients with acute liver failure with 107 fetal hepatocytes. In these studies, there were transient clinical improvements in encephalopathy and ammonia levels, but there was no overall transplant-free survival benefit. It is likely that the quantity of cells (up to 5% of liver mass) transplanted for each patient may have been too low to register a clinical benefit, and that the window period was too narrow for these cells to regenerate. Although the use

of bone marrow stem cells as candidates for liver regeneration is controversial, the availability of these cells and ease by which they can be harvested has lead to the transplantation of bone marrow stem cells or peripheral blood stem cells in more than 100 MCE公司 patients with cirrhosis. Of note, one small study employed the infusion of AC133+ cells mobilized from the bone marrow after one lobe of the liver has been deliberately embolised, and showed that regeneration in the remaining lobe was augmented.125 Most of these studies are uncontrolled, but clinical improvement in measurable parameters has been claimed.126 The mechanisms by which improvement has occurred are still not known, but studies have shown that remodeling in cirrhotic liver can occur by paracrine signals (metalloproteinases) from bone marrow mesenchymal cells, without actual transdifferentiation into hepatocytes. Whether this work represents true progenitor cell regeneration or the modulation of local environment for native hepatocytes to regenerate, this strategy may yet be promising as long as liver regeneration occurs and clinical outcome is improved.

However, it has been thought too difficult to distinguish them pathologically or genetically so far. On the other hand, molecular biological research has been going on to explore new candidate genes which are related to characteristics of GIST. The aim of study

is to explore novel candidate markers to predict high-risk GIST. Methods: 293T cell line which expresses mutated c-kit (Mut-kit 293T) constitutively was established and maintained. Mut-kit 293T contained codon 557 and 558 of exon 11 deletion, which is reported association with a poor prognosis. Comparison of gene expression between 293T and Mut-kit 293T were Palbociclib nmr performed by microarray analysis and high variation gene was selected. By using 12 resected samples (4 non-GIST, 4 low-risk GIST, 4 high-risk GIST), mRNA expression of these target genes were evaluated by real time PCR and were compared them with clinical risk classification. Results: Exogenous Mutated c-kit varied eleven genes expression dramatically. 10 out of 11 target

genes were confirmed their expression in clinical samples. However, there were no genes which expressed exclusively in GIST like c-kit www.selleckchem.com/products/Cilomilast(SB-207499).html or Ano1. One gene expression (ANKRD36BP2) of high-risk GIST was completely different from low-risk GIST. Four genes (CD86, HES5, HMBOX1 and SMCR7L) showed comparatively different expression between low-risk and high-risk GIST. Conclusion: Our study suggests 5 genes as new candidate biomarkers to predict high-risk GIST. This study is preliminary, so it is necessary to analyze more additional clinical medchemexpress samples in order to confirm clinical application. Key Word(s): 1. gist Presenting Author: MI AH HAN Additional Authors: MYUENG GUEN OH, NA RA YUN, DONG MIN KIM, JONG PARK, SO YEON RYU, SEONG WOO CHOI Corresponding Author: MI AH HAN Affiliations: Chosun University Hospital, Chosun University Hospital, Chosun University Hospital, College of Medicine, Chosun University,

College of Medicine, Chosun University, College of Medicine, Chosun University Objective: Cancer survivors are at an increased risk of developing influenza-related complications. The purpose of this study was to investigate the vaccination rate and related factors among cancer survivors in Korea using the Korea National Health and Nutrition Examination Survey (KNHANES). Methods: Adult cancer survivors were selected from the third (2005), fourth (2007–2009) and fifth (2010–2012) KNHANES (n = 1,294). General characteristics, cancer-related data, and influenza vaccination status were collected using self-report questionnaire. Chi-square tests and multiple logistic regression analyses were performed to investigate the association between influenza vaccination rate and associated factors. Results: Overall, 53.

Clearly, HSCs were again inferior to LSECs in cross-presentation of circulating antigen ingested in vivo (Fig. 1B). These results demonstrate that HSCs do not possess antigen-processing capability similar to DCs, suggesting that if already antigen uptake is inefficient, downstream mechanisms, such as peptide trimming in the endoplasmic reticulum (ER), are unlikely to improve APC function. A recent report also showed that primary HSCs have little, if any, APC function for CD4 T cells, even after stimulation with exogenous interferon gamma.8 Taken together, these results demonstrate a hierarchy in the performance

of APC function for DCs being learn more most efficient in antigen processing, macrophages and LSECs compensating for inefficient antigen processing by high antigen uptake, and HSCs showing low antigen uptake and inefficient antigen processing. These data call into question a prominent role for HSCs as liver-resident APCs. Frank

A. Schildberg*, Christian Kurts*, Percy A. Knolle MD*, * Institutes of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-Universität Bonn, Bonn, Germany. “
“Several studies have indicated that primary biliary cirrhosis (PBC) may be associated with increased risk of some cancers, but PD-0332991 ic50 the results are controversial. We conducted a systematic review of studies to examine the association of PBC with cancer risk by meta-analysis. We searched the PubMed and EMBASE databases for English-language studies published before November 2011.

Studies were included if they reported relative risk estimates with 95% confidence intervals (CIs) or related data for the association between PBC and cancer risk. Approximately 16,300 PBC patients from several countries were included in this analysis. Of the 3510 titles identified, 16 publications involving 17 studies meeting the inclusion criteria were included in the meta-analysis. Compared with the general population, PBC patients had a significantly higher risk of overall cancer (pooled rate ratio [RR], 1.55; 95% CI, 1.28-1.83) and hepatocellular carcinoma (HCC) (pooled RR, 18.80; 95% CI, 10.81-26.79). For stomach and pancreas cancers, the results of one study 上海皓元医药股份有限公司 that only examined male patients with PBC indicated that PBC patients had increased risk of stomach cancer and pancreatic cancer, whereas the results of other studies of mixed-sex patients showed no significant association. Therefore, despite inconsistent results, the meta-analysis could not be conducted for assessing the association. PBC was not significantly associated with increased risk of other cancers. Conclusion: The present systematic review and meta-analysis demonstrate that PBC is closely associated with a greater risk of overall cancer and HCC, but not with other cancers. The data regarding the association between PBC and risks of several cancers need to be further confirmed in future studies.

001), platelets (P < 0.001) and stiffness (P < 0.001) were independently associated with CSPH. R428 solubility dmso When categorizing patients according to vWF-Ag levels below or above 241%, OR for the presence of CSPH was 4.17 (P = 0.017; corrected for liver stiffness and platelet count). Using Liver stiffness measured by TE for the diagnosis of CSPH resulted in an AUC of 0.907 (CI: 0.855-0.960) and in an AUC

of 0.886 (CI: 0.829-0.943) for the diagnosis of severe PH in compensated cirrhosis (Table 2). Comparing the AUC in patients with valid TE measurement and vWF-Ag, there was no significant difference in the AUCs (P = 0.08). Because TE was unsuccessful in 41 of 128 of compensated patients (mainly because of obesity), we calculated ROC curves with the ITD approach. AUC-ITD for TE—including all patients regardless of success of TE—was 0.79 (CI: 0.71-0.86). Ibrutinib mw To compare the predictive power of TE and vWF-Ag for noninvasive diagnosis of CSPH and severe PH, a comparison of AUCs (AUC-ITD for TE and AUC for vWF-Ag) was computed, resulting in a similar performance of vWF-Ag if the unsuccessful cases of TE were included (P = 0.135). The median follow-up

time was 33 months (95% CI: 30-36 months). Overall, 91 patients died during follow-up. Overall median transplant-free survival time was 59 months. Median vWF-Ag was significantly higher in patients who died during follow-up period, compared to patients who were still alive at the end of follow-up (387% [IQR 288%-457%] versus 271% [IQR 200%-358%]; P < 0.0001). The adjusted HR for mortality was 4.1% per increase of vWF-Ag 上海皓元医药股份有限公司 of 10% points. At a cutoff of vWF-Ag of 315% for mortality, the HR was

3.37 (95% CI: 2.21-5.15). This cutoff also predicted mortality (HR: 2.92; 95% CI: 1.72-4.97) (P < 0.001) independently of CPS, MELD, HCC, and HVPG in multivariate analysis. In patients without HCC (n = 235), the HR ratio (univariate) for mortality in case of vWF-Ag >315% was 4.42 (95% CI: 2.5-7.7; P < 0.001), whereas in multivariate analysis, considering CPS, MELD, HVPG, and vWF-Ag >315% as a categorical variable, the HR was 3.49 (95% CI: 1.8-6.6; P < 0.001). vWF-Ag equals MELD in mortality prediction (AUC = 0.71 [95% CI: 0.65-0.77] versus AUC = 0.65 [95% CI: 0.58-0.72]; P = 0.197) (Fig. 4). Considering only patients with CSPH, AUC of vWF-Ag was not significantly different, compared to MELD (0.690 [95% CI: 0.618-0.763] versus 0.620 [95% CI: 0.540-0.699]; P = 0.222). Twenty-five percent mortality level was reached after 53 months if the baseline vWF-Ag was <315%, compared to 9 months in patients with vWF-Ag >315% (P < 0.001) (Fig. 5A–C). Compensated patients had 25% mortality after 53 months if the baseline vWF-Ag was <315%, compared to 15 months in patients with vWF-Ag >315% (P < 0.001). Decompensated patients had a mortality of 25% after 37 and 7 months if their vWF Ag was <315% and if vWF-Ag was >315%, respectively (P = 0.002).

001), platelets (P < 0.001) and stiffness (P < 0.001) were independently associated with CSPH. CP868596 When categorizing patients according to vWF-Ag levels below or above 241%, OR for the presence of CSPH was 4.17 (P = 0.017; corrected for liver stiffness and platelet count). Using Liver stiffness measured by TE for the diagnosis of CSPH resulted in an AUC of 0.907 (CI: 0.855-0.960) and in an AUC

of 0.886 (CI: 0.829-0.943) for the diagnosis of severe PH in compensated cirrhosis (Table 2). Comparing the AUC in patients with valid TE measurement and vWF-Ag, there was no significant difference in the AUCs (P = 0.08). Because TE was unsuccessful in 41 of 128 of compensated patients (mainly because of obesity), we calculated ROC curves with the ITD approach. AUC-ITD for TE—including all patients regardless of success of TE—was 0.79 (CI: 0.71-0.86). Erlotinib datasheet To compare the predictive power of TE and vWF-Ag for noninvasive diagnosis of CSPH and severe PH, a comparison of AUCs (AUC-ITD for TE and AUC for vWF-Ag) was computed, resulting in a similar performance of vWF-Ag if the unsuccessful cases of TE were included (P = 0.135). The median follow-up

time was 33 months (95% CI: 30-36 months). Overall, 91 patients died during follow-up. Overall median transplant-free survival time was 59 months. Median vWF-Ag was significantly higher in patients who died during follow-up period, compared to patients who were still alive at the end of follow-up (387% [IQR 288%-457%] versus 271% [IQR 200%-358%]; P < 0.0001). The adjusted HR for mortality was 4.1% per increase of vWF-Ag MCE公司 of 10% points. At a cutoff of vWF-Ag of 315% for mortality, the HR was

3.37 (95% CI: 2.21-5.15). This cutoff also predicted mortality (HR: 2.92; 95% CI: 1.72-4.97) (P < 0.001) independently of CPS, MELD, HCC, and HVPG in multivariate analysis. In patients without HCC (n = 235), the HR ratio (univariate) for mortality in case of vWF-Ag >315% was 4.42 (95% CI: 2.5-7.7; P < 0.001), whereas in multivariate analysis, considering CPS, MELD, HVPG, and vWF-Ag >315% as a categorical variable, the HR was 3.49 (95% CI: 1.8-6.6; P < 0.001). vWF-Ag equals MELD in mortality prediction (AUC = 0.71 [95% CI: 0.65-0.77] versus AUC = 0.65 [95% CI: 0.58-0.72]; P = 0.197) (Fig. 4). Considering only patients with CSPH, AUC of vWF-Ag was not significantly different, compared to MELD (0.690 [95% CI: 0.618-0.763] versus 0.620 [95% CI: 0.540-0.699]; P = 0.222). Twenty-five percent mortality level was reached after 53 months if the baseline vWF-Ag was <315%, compared to 9 months in patients with vWF-Ag >315% (P < 0.001) (Fig. 5A–C). Compensated patients had 25% mortality after 53 months if the baseline vWF-Ag was <315%, compared to 15 months in patients with vWF-Ag >315% (P < 0.001). Decompensated patients had a mortality of 25% after 37 and 7 months if their vWF Ag was <315% and if vWF-Ag was >315%, respectively (P = 0.002).

Improvements in identification and metabolic characterization of this Cobimetinib NAFLD at-risk population, combined with targeted therapeutics, can then result in the greatest impact on overall and cardiovascular mortality. Dr. Chalasani serves as a paid consultant for many pharmaceutical companies but none represent a potential conflict for

this article. “
“Nonalcoholic steatosis is a liver pathology characterized by fat accumulation and severe metabolic alterations involving early mitochondrial impairment and late hepatocyte cell death. However, mitochondrial dysfunction mechanisms remain elusive. Using four models of nonalcoholic steatosis, i.e., livers from patients with fatty liver disease, ob/ob mice, mice fed a high-fat diet, and in vitro models of lipotoxicity, we show that outer mitochondrial membrane permeability is altered and

identified a posttranslational modification of voltage-dependent anion channel (VDAC), a membrane channel and NADH oxidase, as a cause of early mitochondrial dysfunction. Thus, in nonalcoholic steatosis VDAC exhibits reduced threonine phosphorylation, which increases the influx of water and calcium into mitochondria, sensitizes the organelle to matrix swelling, depolarization, and cytochrome c release without inducing cell death. This also amplifies VDAC enzymatic and channel activities regulation by calcium and modifies its interaction with proteic partners. Moreover,

lipid accumulation triggers a rapid lack of VDAC phosphorylation by glycogen synthase kinase 3 (GSK3). Pharmacological and mTOR inhibitor genetic manipulations proved GSK3 to be responsible for VDAC phosphorylation in normal cells. Notably, VDAC phosphorylation level correlated with steatosis severity in patients. Conclusion: VDAC acts as an early sensor of lipid toxicity and its GSK3-mediated phosphorylation status controls outer mitochondrial membrane permeabilization in MCE hepatosteatosis. (HEPATOLOGY 2013) Nonalcoholic fatty liver disease (NAFLD) is accompanied by hepatosteatosis, a clinical condition characterized by excessive accumulation of lipids within hepatocytes and complex metabolic alterations.1, 2 Although reversible in early stages, steatosis can lead to more aggressive forms of liver injury such as hepatitis, cirrhosis, and hepatocarcinoma.3 Investigation of patients with hepatosteatosis showed that mitochondria harbor prominent morphologic and functional abnormalities, suggesting a central role of these organelles in the pathogenesis.4 Mitochondria can influence cell fate at the levels of energy production, lipid metabolism, production, and detoxification of reactive oxygen species (ROS) and release of proapoptotic proteins.5 All these alterations favor an increase in apoptotic and necrotic hepatocyte cell death.

Improvements in identification and metabolic characterization of this selleck screening library NAFLD at-risk population, combined with targeted therapeutics, can then result in the greatest impact on overall and cardiovascular mortality. Dr. Chalasani serves as a paid consultant for many pharmaceutical companies but none represent a potential conflict for

this article. “
“Nonalcoholic steatosis is a liver pathology characterized by fat accumulation and severe metabolic alterations involving early mitochondrial impairment and late hepatocyte cell death. However, mitochondrial dysfunction mechanisms remain elusive. Using four models of nonalcoholic steatosis, i.e., livers from patients with fatty liver disease, ob/ob mice, mice fed a high-fat diet, and in vitro models of lipotoxicity, we show that outer mitochondrial membrane permeability is altered and

identified a posttranslational modification of voltage-dependent anion channel (VDAC), a membrane channel and NADH oxidase, as a cause of early mitochondrial dysfunction. Thus, in nonalcoholic steatosis VDAC exhibits reduced threonine phosphorylation, which increases the influx of water and calcium into mitochondria, sensitizes the organelle to matrix swelling, depolarization, and cytochrome c release without inducing cell death. This also amplifies VDAC enzymatic and channel activities regulation by calcium and modifies its interaction with proteic partners. Moreover,

lipid accumulation triggers a rapid lack of VDAC phosphorylation by glycogen synthase kinase 3 (GSK3). Pharmacological and Dabrafenib in vivo genetic manipulations proved GSK3 to be responsible for VDAC phosphorylation in normal cells. Notably, VDAC phosphorylation level correlated with steatosis severity in patients. Conclusion: VDAC acts as an early sensor of lipid toxicity and its GSK3-mediated phosphorylation status controls outer mitochondrial membrane permeabilization in 上海皓元 hepatosteatosis. (HEPATOLOGY 2013) Nonalcoholic fatty liver disease (NAFLD) is accompanied by hepatosteatosis, a clinical condition characterized by excessive accumulation of lipids within hepatocytes and complex metabolic alterations.1, 2 Although reversible in early stages, steatosis can lead to more aggressive forms of liver injury such as hepatitis, cirrhosis, and hepatocarcinoma.3 Investigation of patients with hepatosteatosis showed that mitochondria harbor prominent morphologic and functional abnormalities, suggesting a central role of these organelles in the pathogenesis.4 Mitochondria can influence cell fate at the levels of energy production, lipid metabolism, production, and detoxification of reactive oxygen species (ROS) and release of proapoptotic proteins.5 All these alterations favor an increase in apoptotic and necrotic hepatocyte cell death.

Although the study was open-label, the sponsor was blinded to treatment allocation and viral load results until treatment week 12. Patients were enrolled at 51 centers in the United States. Patients were stratified by serum HCV RNA titers (≤780,000 IU/mL or >780,000 IU/mL) and baseline weight (≤75 or >75 kg). An interactive voice response system was used to randomize patients in a 1:1:1:1 ratio to receive weight-based TBV 20 mg/kg/day, 25 mg/kg/day, or 30 mg/kg/day (Valeant Pharmaceuticals North America, Aliso Viejo, CA) or weight-based RBV at 800, 1000, 1200, or 1400 mg/day (Copegus; Selleckchem Alectinib Hoffmann-La

Roche, Nutley, NJ) in combination with peg-IFN alfa 2b (PegIntron; Schering Corp., Kenilworth, NJ). All patients received doses twice

daily with their morning and evening meals. Patients were treated for 48 weeks, but treatment was discontinued for evidence of nonresponse defined as <2-log decline at week 12 or a positive viral load at week 24. Study treatment was initiated on day 1 and clinic visits occurred at treatment weeks (TWs) 1, 2, 3, 4, 8, 12, 18, 24, 30, 36, and 48, as well as posttreatment follow-up weeks (FWs) 4, 12, 20, and 24. All patients who completed treatment with study drug or discontinued treatment prematurely (except nonresponders) immediately entered a 24-week follow-up period. The study protocol was approved by the institutional review boards of participating institutions and was conducted in accordance with the Declaration of Helsinki and provisions of Good Clinical Practices. All patients provided written Rapamycin chemical structure informed consent. The objective of this study was to select an optimal dose of TBV by comparing the efficacy and safety of three TBV dose levels MCE versus RBV based on body weight, both administered

with peg-IFN alfa-2b to therapy-naive compensated patients with genotype 1 chronic hepatitis C. The primary efficacy endpoint was early virologic response (EVR) defined as the proportion of patients with at least a 2-log decrease from baseline in serum HCV RNA levels at TW12. Additional efficacy endpoints assessed in the trial included SVR; undetectable HCV RNA at TW4, TW24, and TW48; and viral relapse for those who were responders at the end of treatment. Subgroup analyses were carried out to determine the impact of various baseline demographic factors such as sex, age, race, weight, baseline HCV RNA, and fibrosis score on response. Lack of efficacy was defined as less than a 2-log decrease of HCV RNA (IU/mL) at TW12 or detectable HCV RNA at TW24. Relapse rates were calculated by measuring the proportion of responding patients whose plasma HCV levels changed from undetectable at end of treatment to detectable at FW24. The primary safety endpoint was the proportion of patients with Hb < 10 g/dL at any time during the treatment period.

Although the study was open-label, the sponsor was blinded to treatment allocation and viral load results until treatment week 12. Patients were enrolled at 51 centers in the United States. Patients were stratified by serum HCV RNA titers (≤780,000 IU/mL or >780,000 IU/mL) and baseline weight (≤75 or >75 kg). An interactive voice response system was used to randomize patients in a 1:1:1:1 ratio to receive weight-based TBV 20 mg/kg/day, 25 mg/kg/day, or 30 mg/kg/day (Valeant Pharmaceuticals North America, Aliso Viejo, CA) or weight-based RBV at 800, 1000, 1200, or 1400 mg/day (Copegus; Lorlatinib Hoffmann-La

Roche, Nutley, NJ) in combination with peg-IFN alfa 2b (PegIntron; Schering Corp., Kenilworth, NJ). All patients received doses twice

daily with their morning and evening meals. Patients were treated for 48 weeks, but treatment was discontinued for evidence of nonresponse defined as <2-log decline at week 12 or a positive viral load at week 24. Study treatment was initiated on day 1 and clinic visits occurred at treatment weeks (TWs) 1, 2, 3, 4, 8, 12, 18, 24, 30, 36, and 48, as well as posttreatment follow-up weeks (FWs) 4, 12, 20, and 24. All patients who completed treatment with study drug or discontinued treatment prematurely (except nonresponders) immediately entered a 24-week follow-up period. The study protocol was approved by the institutional review boards of participating institutions and was conducted in accordance with the Declaration of Helsinki and provisions of Good Clinical Practices. All patients provided written LY2606368 purchase informed consent. The objective of this study was to select an optimal dose of TBV by comparing the efficacy and safety of three TBV dose levels MCE公司 versus RBV based on body weight, both administered

with peg-IFN alfa-2b to therapy-naive compensated patients with genotype 1 chronic hepatitis C. The primary efficacy endpoint was early virologic response (EVR) defined as the proportion of patients with at least a 2-log decrease from baseline in serum HCV RNA levels at TW12. Additional efficacy endpoints assessed in the trial included SVR; undetectable HCV RNA at TW4, TW24, and TW48; and viral relapse for those who were responders at the end of treatment. Subgroup analyses were carried out to determine the impact of various baseline demographic factors such as sex, age, race, weight, baseline HCV RNA, and fibrosis score on response. Lack of efficacy was defined as less than a 2-log decrease of HCV RNA (IU/mL) at TW12 or detectable HCV RNA at TW24. Relapse rates were calculated by measuring the proportion of responding patients whose plasma HCV levels changed from undetectable at end of treatment to detectable at FW24. The primary safety endpoint was the proportion of patients with Hb < 10 g/dL at any time during the treatment period.

[19] Notwithstanding the effectiveness of GON blockades

for migrainuers,20-22 the mechanism(s) for the successful outcome remain uncertain.[23] It has been postulated that GON blockade influences central pain processing mechanisms by modulating responses to convergent synaptic input from cervical and trigeminal nociceptive afferents.[23] In our clinical experience, patients often report lessening of their referred, usual pain as the examination of the cervicospinal segment is sustained. The pain usually lessens (to a variable degree, but often with complete resolution) within 90 seconds. Moreover, sustaining the examination repeatedly results not only in decreasing intensity of head Selumetinib in vivo pain referral but also in more expeditious resolution. Furthermore, patients presenting with allodynia frequently report that after lessening of their referred pain, the allodynia has decreased

or resolved,24-26 perhaps indicating that a pre-existing central sensitization state had diminished. The purpose of the present study was to investigate cervical, interictal referral of usual head pain and its effect on the nBR in migraineurs. In particular, effects of PAIVMs of the AO and C2-3 spinal segments on referred head pain and trigeminal nociceptive activity were examined interictally. It was hypothesized that as referred check details head pain decreased, there would be a corresponding increase in latency and decrease in the AUC of R2, reflecting a decrease in excitability of the TCN. Fifteen volunteers participated

in the study (14 females, 1 male; age 24-44 years, mean age 33.3 years). All participants met the International Headache Society’s diagnostic classification criteria for migraine with or without aura, experiencing 2-8 attacks of migraine within the previous 3 months.[2] Each participant had been free from migraine for at least 24 hours. Informed consent was obtained from all participants, and the study was approved by the Ethics Committee of Murdoch University. The PAIVM examination was performed by a single clinician (D.H.W. – Musculoskeletal Physiotherapist) with 22 years of experience, whose medchemexpress practice is limited to examination and treatment of the upper cervical spine in primary headache conditions. Intra-examiner reliability was analyzed using Cohen’s Kappa in a previous study[27] that demonstrated perfect agreement in 17 of 22 PAIVM techniques. Of the 5 remaining tests, the lowest Kappa score was k = 0.667, P = .01, which indicated good agreement. Critical to our study was that usual head pain could be reproduced during the cervical examination. Therefore, to exclude participants who did not develop head pain during this procedure, an “inclusion/exclusion” examination was performed prior to commencing the study.