Disclosures: The following people have nothing to disclose: Joseph Roberts, William LeBlanc, Kiran Bambha Introduction: Nonalcoholic Fatty Liver Disease (NAFLD) is known to be related to risk factors of cardiovascular BYL719 molecular weight disease such as dyslipidemia, diabetes, and metabolic syndrome. Arterial stiffness is a strong predictor of future cardiovascular events and all-cause mortality, and it is one of the earliest detectable manifestations of adverse structural and functional change of vessel walls. Cardio-ankle vascular index (CAVI), a new index of arterial stiffness, is recently developed and is independent of blood pressure. In

recent studies, CAVI was the best reliable index of arterial stiffness in many cardiovascular diseases. We investigated whether NAFLD is associated with arterial stiffness

as measured CAVI in the apparently healthy general population. Methods: A total of 2,954 subjects (mean age 55.8 ± 9.8, male 64.7%) who visited health screening center were enrolled without known liver disease Selleckchem beta-catenin inhibitor (Hepatitis B, Hepatitis C, alcoholic, other hepatitis history) from 2010 to 2013. NAFLD was diagnosed by typical ultrasonographic findings. Clinical characteristics included sex, age, body mass index (BMI), waist circumference (WC), aspartate aminotrans-ferase (AST), alanine aminotransferase (ALT), total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), and glucose. Arterial stiffness was defined as age, sex-specific cutoff of upper quartile of CAVI. Results: CAVI was statistically significantly associated with age, BMI, WC, ALT, TG, HDL cholesterol, and with increased odds of diabetes, hypertension, dyslipidemia, and severity of NAFLD. Arterial stiffness (Increased CAVI) showed positive relationship with NAFLD (age, sex, BMI- adjusted odds ratio [OR] 1.41, 95% confidence interval [CI] 1.16-1.70, p<0.001) and dose-dependent association with moderate-severe NAFLD (OR 1.78, 95% CI 1.37-2.31, p<0.001). Multivariate regression analysis adjusted for age, sex, BMI, WC, diabetes, hypertension, smoking, total cholesterol, TG and HDL cholesterol MCE showed that arterial stiffness was significantly associated

with presence of NAFLD (OR 1.26, 95% CI 1.02-1.56) and moderate-severe NAFLD (OR 1.48, 95% CI 1.11-1.98). Conclusions: Patients with NAFLD are at high risk of arterial stiffness regardless of classical risk factors. Detection of NAFLD should alert to the existence of an increased cardiovascular risk. NAFLD per se might be the independent risk factor for arterial stiffness. Disclosures: The following people have nothing to disclose: Donghee Kim, Goh Eun Chung, Su-Yeon Choi, Min-Sun Kwak, Won Kim, Yoon Jun Kim, Jung-Hwan Yoon Background: NAFLD is the most common chronic liver disease in the United States affecting 30% of the adult population and 70% of individuals with the metabolic syndrome, who are at highest risk of developing severe disease. Yet, little is known about NAFLD awareness in individuals with fatty liver.

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“Molecular assays were used to determine the sex of 1,294 biopsied common dolphins (658 long-beaked common dolphins, Delphinus capensis, and 636 short-beaked common dolphins, D. delphis) in the Southern California Bight. Sex ratio differed substantially between the two species;

females comprised 241 (36.6%) of D. capensis samples and 410 (64.5%) of D. delphis samples. All biopsies were taken either from a large research ship or from a small, rigid-hull inflatable PLX4032 supplier boat (RHIB) launched from the larger ship. When conducting replicate biopsy effort on the same schools from each vessel/platform (“Tandem Biopsy Sampling”), we found evidence that disproportionately more female D. capensis were biopsied from the RHIB than from the ship but the same was not true for

www.selleckchem.com/products/rxdx-106-cep-40783.html D. delphis. We suspect that these results are driven by bowriding-behavior differences between the two species. Biopsy duration, geographic location, school size, and Julian date were considered as potential covariates with sex ratio; geographic location was the only one to show strong evidence of correlation. This study also presents an alternative to the erroneous practice of comparing sex ratios to a theoretical assumption of parity (i.e., 50:50 sex ratio) when researchers avoid sampling animals paired with calves. “
“Development implies a change in allocation of resources from somatic growth to reproduction. In a highly variable environment, growth can vary from year to year thereby influencing the long-term life history perspective. The Galapagos sea lion (Zalophus wollebaeki) lives in a highly unpredictable marine environment in which food abundance varies not only seasonally, but also annually due to El Niño. Galapagos sea lions are restricted to a patch of cold upwelling waters surrounding the archipelago and are closely tied to land as nursing females alternate between foraging at sea and nursing ashore. Therefore, their offspring are especially vulnerable to ocean warming causing reduced food abundance. We found

a significant correlation between sea surface temperature (SST) and early growth: Both mass 上海皓元 at birth and linear growth within the first 2 mo of life correlated negatively with SST. Absolute mass gain was higher for males, but both sexes gained equally 1.9% of birth mass per day. Until the age of 3 yr male and female juveniles showed similar growth to an asymptotic mass of 40 and 35 kg, respectively. As a consequence of the highly variable environment, the plasticity in growth strategy of Galapagos sea lion juveniles appears wider than that of all other sea lions allowing them to cope with poor conditions. “
“Historically, the range of the southern right whale (SRW) included winter calving grounds around the North and South Islands (mainland) of New Zealand (NZ) and in the NZ subantarctic Auckland and Campbell Islands.

1). The characteristics of the HCV-RNA+ve infants and their parents are described in Table 1. The rate of HCV-VT was higher for infants born to mothers with high HCV viremia (>600,000 IU/mL) than for infants born to mothers with low HCV viremia (<600,000; Table 2; P = 0.02). Neither gender, nor weight, nor viral genotype (genotype 1 versus genotype non-1), nor type of birth (cesarean versus noncesarean), nor breast-feeding were associated with increased risk of HCV-VT. None of the

infected infants were HCV-RNA-positive at birth and the mean age at the first HCV-RNA-positive result was 3.81 ± 0.91 months. The infected children presented a lower birth weight (nonsignificant) than that of the noninfected children. 37% of the noninfected children BAY 73-4506 presented ALT levels > 40 U/L whereas 68% of the infected infants had high levels of ALT (>40 U/L, P = 0.016). The study of risk factors for chronic infection was performed in HIV-negative mothers using a stored blood sample (Study Cohort, Fig. 1). Fourteen of the 22 HCV-VT-infected infants (64%) cleared the HCV virus spontaneously (transient viremia group) and eight infants (36%) had persistent infection (chronic group). The rate

of HCV chronic infection was higher among the infants with viral genotype 1 than among those with genotype non-1 (Table 3; P = 0.02). In fact, no chronic infection BGJ398 was noted in the infants with genotype non-1 (n = 7, of whom six had genotype 3 and one had genotype 4), whereas only 1/9 infants with genotype non-1 in the general cohort had persistent infection at the end of the study (this infant was a boy whose mother was genotype 3 but HIV-positive). Neither gender, nor weight, nor the mother’s HCV viral load, nor the type of birth (cesarean versus noncesarean), nor breast-feeding were associated with increased MCE risk of HCV chronic infection among these infants.

Among the HCV chronic group of infants, the first HCV-RNA-positive result was recorded at a mean age of 2.33 ± 0.3 months, whereas the corresponding value for the transient viremia group was 4.15 ± 1.1 months (nonsignificant). Furthermore, the chronic HCV infants had a lower birth weight than did the transient viremia children (nonsignificant). In all, 50% of the infants with transient viremia presented ALT levels >40 U/L, whereas all the chronic infants presented ALT levels above 40 U/L (P = 0.02). This study was performed among the HIV-negative mothers using a stored blood sample (n = 105, Study Cohort; Fig. 1. In six mothers it was not possible to determine the IL28B polymorphism). Of the 31 mothers with IL28B CC polymorphism, 19 were HCV-RNA-positive (61%), whereas among the 68 mothers with non-CC polymorphism (CT or TT polymorphism), 56 were HCV-RNA-positive (82%). Accordingly, the mothers with non-CC IL28B polymorphism had a greater probability of being HCV-RNA-positive than did those with CC polymorphism (OR = 2.95; 95% CI: 1.1-7.7; P = 0.026).

These results demonstrate activity of SB 9200 against a diverse range of HCV genotypes in vitro. Of note, this compound shows potent activity against patient-derived G3 isolates. These results support the potential role of SB 9200 as a pan-genotypic host-targeting anti-HCV agent. Figure 1. Sensitivity of patient-derived G1 DMXAA solubility dmso or G3 HCV to SB 9200, alisporivir or telaprevir in the capture-fusion assay. X axes show concentration of each drug, y axes

show degree of inhibition of replication. Values are mean ± s.e.m. Disclosures: Radhakrishnan P. Iyer – Employment: Spring Bank Pharmaceuticals, Inc Graham R. Foster – Advisory Committees or Review Panels: GlaxoSmithKline, Novartis, Boehringer Ingelheim, Tibotec, Chughai, Gilead, Janssen, Idenix, GlaxoSmithKline, Novartis, Selleck Ibrutinib Roche, Tibotec, Chughai, Gilead, Merck, Janssen, Idenix, BMS; Board Membership: Boehringer Ingelheim; Grant/Research Support: Chughai, Roche, Chughai; Speaking and Teaching: Roche, Gilead, Tibotec, Merck, BMS, Boehringer Ingelheim, Gilead, Janssen The following people have nothing to disclose: Morven E. Cunningham, Joseph D. Wright, Rajendra K. Pandey, Anjaneyulu Sheri, Seetharamaiyer Padmanabhan Alisporivir (ALV) is a cyclophilin

inhibitor, in development for treatment of hepatitis C. Acute pancreatitis cases were reported in the clinical program – 6/1728 (0.35%) patients treated with ALV plus PegIFN/ribavirin; 2/489 (0.41%) patients treated with PegIFN/ribavirin only, and none with ALV IFN-free regimens. Previous studies with mouse models showed that genetic or pharmacological (ALV) inhibition of cyclophilin D reduces pancreas damage both in bile acid and in cerulein-induced models of pancreatitis. The purpose of this study was to determine the effects of ALV, interferon-alpha, and ribavirin on pancreatitis; we tested the outcome with these compounds, alone and in combinations, in a rat model of cerulein-induced pancreatitis. ALV (30 mg/kg/day) and ribavirin (100 mg/kg/day) were administered

either alone or in combination orally to Sprague Dawley rats for 7 consecutive days prior to receiving rodent interferon alpha (500,000 IU/kg sub-cutaneous once per hour for 5x) and cerulein (50 ug/kg intra peritonea 上海皓元 l 2× per hour). Cyclosporine A was included as a control. Pancreas was examined microscopically, a panel of biomarkers measured 3 and 24 hour after the last injection of cerulein, and the hepatic gene expression profile was determined at 24 hours. Administration of cerulein caused acinar degeneration, and in some animals ductular degeneration/necrosis in the pancreas. Cyclosporine A at ≥10 mg/kg caused a dose-related increase in severity of cerulein-induced acinar degeneration. Neither ALV nor ribavirin nor IFNα alone or in combination exacerbated the pancreas damage. However, co-administration of IFNα/ribavirin/ caused an increased incidence and severity of cerulein-induced pancreatic duct degeneration/necrosis.

22 The more likely explanation is that these individuals had abnormal levels of reflux, but that this defect caused such low levels of reflux-induced symptoms that their reflux disease never came to medical attention. The fact that reflux disease is asymptomatic in a significant Roscovitine minority, whether BE is present or not, is now well established. It is relatively unusual for the observed extent of the metaplastic segment to increase over years, or for BE to appear de novo during clinical observation of reflux disease,2–4 even if this is not treated adequately. This suggests that, in most

cases, columnar metaplasia develops abruptly. Since only a minority (around 10–15%) of patients with reflux esophagitis has BE,2–4 there must be additional factors that play important roles in determining the apparently sudden development of BE. One plausible trigger factor is major acute esophageal mucosal injury, superimposed on continuing reflux-induced esophageal mucosal damage. This “double trouble” might prevent normal esophageal mucosal healing with squamous mucosa. Though this is an uninvestigated hypothesis, it has strong indirect support from

both observations of esophageal mucosal healing after endoscopic mucosal ablation or resection of areas of esophageal metaplasia and animal models; much data from these scenarios show consistently that the presence or absence of damaging reflux determines whether esophageal mucosa 上海皓元医药股份有限公司 that is severely and acutely injured heals with squamous or metaplastic columnar epithelium.2–4 Several categories of transient, but sometimes very severe esophageal mucosal damage EPZ6438 could cause “double trouble”, including, for example, acute infective esophagitis, “pill-induced” esophagitis

and the severe stasis “drunkard’s esophagitis”. These are speculative causes, but development of esophageal columnar metaplasia has been documented in a patient after severe mucositis caused by cancer chemotherapeutic agents23 and in another with caustic esophageal mucosal injury.24 Unfortunately, neither of these patients was adequately investigated for reflux disease.23,24 Interestingly, in the case of lye-induced injury, BE was confined to the mid-esophagus, presumably the area of most severe acute mucosal lye-induced damage.24 In a long-term follow-up study of achalasia patients treated by a relatively aggressive open esophageal/gastric myotomy, coupled with a Dor patch antireflux procedure, BE was found to develop in 12/67 (18%) of patients.25 This could represent “double trouble” of a different type—chronic esophageal stasis with a superimposed therapy-induced defect of gastroesophageal competence, since all but one of the BE patients had abnormal esophageal acid exposure. Several systemic factors have been identified which may predispose to columnar metaplastic healing of the previously squamous esophageal mucosa.

3A,B). In order to determine whether MitoQ had an effect on the ethanol metabolizing enzymes, we measured protein expression levels of CYP2E1 and ALDH2 in liver homogenates (Supporting Fig. 2A,B). Consistent with previous reports, CYP2E1 protein expression was increased in all ethanol-fed animals.12 Importantly, CYP2E1 protein expression was similar in ethanol-fed control animals, indicating similar exposure to ethanol in all treatment groups when compared to treatment with MitoQ. Similarly, ALDH2 protein levels were not affected by ethanol consumption or modified by MitoQ. These data suggest that MitoQ treatment does not affect the key enzymes that are responsible for ethanol metabolism. We next investigated

Selleckchem AZD1152 HQPA whether MitoQ would alter levels of protein kinase (AMPK) and the level of phosphorylation of its downstream target acetyl CoA carboxylase (ACC) because it has been reported that total AMPK levels are decreased upon chronic ethanol consumption when compared

to controls.49 In the current study we observed only modest effects on the AMPK system which only showed significance by MitoQ at 25 mg/kg/day (Supporting Fig. 2C). Furthermore, levels of p-ACC were not different between ethanol-fed animals and their pair-matched controls. MitoQ at 5 mg/kg/day had no effect; however, MitoQ at 25 mg/kg/day had a modest, but significant effect on the p-ACC/total protein ratio in both the control and ethanol-fed animals (Supporting Fig. 2D). Chronic ethanol consumption results in find protocol decreased activity of mitochondrial respiratory chain proteins coded for by mitochondrial DNA.15 Consistent with previous studies, chronic ethanol consumption resulted in decreases in the activities of complex I, III, IV, and V and a small increase in citrate synthase activity in isolated mitochondria but was not changed by MitoQ (Table 2).

As previously shown, chronic ethanol consumption decreased complex I (30 kDa subunit), complex IV (subunits I and IV), and complex III (Rieske FeS) proteins levels, although no effects on complex II or complex III core protein 2 were observed (Supporting 上海皓元医药股份有限公司 Fig. 3).15 Overall, treatment with MitoQ had only a modest effect on complex I, 30 kD subunit and complex IV subunit IV and was only evident at the dose of 5 mg/kg/day MitoQ. Chronic ethanol consumption increased hepatic macro- and microvesicular steatosis compared to the pair-fed controls (Fig. 4). Macrosteatototic vesicles distributed around the pericentral region, in contrast, microvesicular steatosis is predominantly present around the portal tract (zone 1) and to a lesser extent in the pericentral region (Fig. 4A). MitoQ (5 and 25 mg/kg/day) significantly decreased macro- and microsteatosis in ethanol-fed rats. In contrast to macrosteatosis, MitoQ did not demonstrate complete protection of microsteatosis at 25 mg/kg/day (Fig. 4B). MitoQ alone at either dose had no effect on steatosis in the control animals.

No patients in placebo group presented a clinically relevant decrease in HVPG, while 4 patients (36%) in the simvastatin group reached this endpoint (p=0.045). Considering only patients with severe portal hypertension at baseline (HVPG ≥ 12mmHg, n=13), the decrease was achieved by 50% of them, all patients in simvas-tatin group. The baseline mean AzBF were 501.2 ± 385 mL/ min in placebo group and 532.7 ± 365 mL/min in simvastatin group, and present a decrease of 19% and 38%, respectively, at the end of the protocol (p=0.02). Although both HVPG and AzBF reduced after simvastatin use, the correlation between the methods was weak (r=0,39). Two thirds of the patients were taking nonselective

beta adrenergic blockers and these drugs did not interfere with simvastatin hemodynamic effect. Moderate and severe adverse events did not occur in

simvastatin group. CONCLUSION: Dabrafenib in vivo Simvastatin seems to be safe in liver cirrhosis and can significantly lower portal pressure. This effect is more evident in patients with severe portal hypertension, precisely the group most in need of prevention of its complications. The correlations between the HVPG and the AzBF is weak probably because the azygos system is only one of several drainage pathways in portal hypertension. These results reinforce the trend of incorporating statins in the therapeutic arsenal of cirrhotic portal hypertension. Disclosures: The following people have nothing to disclose: click here Priscila P. Flores, Guilherme F. Rezende, Ubiratan Cassano, Monica Soldan BACKGROUND AND AIMS: The increase of intrahepatic availability of nitric oxide induced by statins 上海皓元医药股份有限公司 makes this drugs a potential option for the treatment of portal hypertension. This clinical trial was designed to evaluate the effects of simvastatin on the hepatic venous pressure gradient (HVPG) and on the azygos vein blood flow (AzBF) in cirrhotic patients. METHODS: A prospective, randomized, controlled, triple-blind trial with simvastatin and placebo was conducted, including patients with

cirrhosis and portal hypertension detected by abdominal ultrasound with color Doppler flowmetry or upper digestive endoscopy. Placebo or simvastatin (40 mg) was given daily; HVPG was determined by hepatic vein catheterization and AzBF was measured by color Doppler echoendoscopy (EUS-Cd), both procedures performed at the beginning and after three months of treatment. The main endpoint was a decrease in HVPG of at least 20% from baseline or to ≤ 12 mm Hg after treatment, considered clinically relevant. The correlation between HVPG and AzBF was also tested. RESULTS: Thirty four patients were prospectively enrolled in the study and 22 of them completed the 3 month-protocol. The two groups of treatment were similar at baseline in terms of clinical aspects, liver disease and portal hypertension severity.

No patients in placebo group presented a clinically relevant decrease in HVPG, while 4 patients (36%) in the simvastatin group reached this endpoint (p=0.045). Considering only patients with severe portal hypertension at baseline (HVPG ≥ 12mmHg, n=13), the decrease was achieved by 50% of them, all patients in simvas-tatin group. The baseline mean AzBF were 501.2 ± 385 mL/ min in placebo group and 532.7 ± 365 mL/min in simvastatin group, and present a decrease of 19% and 38%, respectively, at the end of the protocol (p=0.02). Although both HVPG and AzBF reduced after simvastatin use, the correlation between the methods was weak (r=0,39). Two thirds of the patients were taking nonselective

beta adrenergic blockers and these drugs did not interfere with simvastatin hemodynamic effect. Moderate and severe adverse events did not occur in

simvastatin group. CONCLUSION: selleck chemicals llc Simvastatin seems to be safe in liver cirrhosis and can significantly lower portal pressure. This effect is more evident in patients with severe portal hypertension, precisely the group most in need of prevention of its complications. The correlations between the HVPG and the AzBF is weak probably because the azygos system is only one of several drainage pathways in portal hypertension. These results reinforce the trend of incorporating statins in the therapeutic arsenal of cirrhotic portal hypertension. Disclosures: The following people have nothing to disclose: www.selleckchem.com/products/gsk126.html Priscila P. Flores, Guilherme F. Rezende, Ubiratan Cassano, Monica Soldan BACKGROUND AND AIMS: The increase of intrahepatic availability of nitric oxide induced by statins medchemexpress makes this drugs a potential option for the treatment of portal hypertension. This clinical trial was designed to evaluate the effects of simvastatin on the hepatic venous pressure gradient (HVPG) and on the azygos vein blood flow (AzBF) in cirrhotic patients. METHODS: A prospective, randomized, controlled, triple-blind trial with simvastatin and placebo was conducted, including patients with

cirrhosis and portal hypertension detected by abdominal ultrasound with color Doppler flowmetry or upper digestive endoscopy. Placebo or simvastatin (40 mg) was given daily; HVPG was determined by hepatic vein catheterization and AzBF was measured by color Doppler echoendoscopy (EUS-Cd), both procedures performed at the beginning and after three months of treatment. The main endpoint was a decrease in HVPG of at least 20% from baseline or to ≤ 12 mm Hg after treatment, considered clinically relevant. The correlation between HVPG and AzBF was also tested. RESULTS: Thirty four patients were prospectively enrolled in the study and 22 of them completed the 3 month-protocol. The two groups of treatment were similar at baseline in terms of clinical aspects, liver disease and portal hypertension severity.

As shown Fig. 4C, two out of three woodchucks treated with CTX responded with wIFN-γ production after IL-12 in vitro stimulation. Viral load was analyzed 30 and 10 days before and then again at 1, 4, 10, 30, 50, 70, and 90 days after CTX treatment and no antiviral effect was observed (Fig. 4D). After demonstrating that TGF-β1 inhibition and Treg depletion are able to restore the responsiveness to IL-12 in chronic WHV carriers with high viral load, we proceeded to treat these animals with a gene therapy vector encoding IL-12, alone or in combination with P17 or CTX administration. http://www.selleckchem.com/products/PD-0325901.html A single dose of 1 × 1011 infectious units of HC-Ad/RUmIL-1218, 19 (a high-capacity adenoviral vector that express IL-12

under the control of a liver-specific, mifepristone-inducible promoter) was administered during laparotomy by intrahepatic injection into three different liver areas. Three woodchucks received the vector alone, three other animals received the vector in combination with P17 peptide, three other animals received the vector in combination with a low dose of CTX, and four other animals were left untreated and served as controls. A schematic representation of the experimental design is provided in Fig. 5A. IL-12 expression was induced daily for 40 days by intraperitoneal administration of 500 μg/kg mifepristone, starting 40 days after vector administration. The P17 peptide was administered

in 10 doses of 5 mg/kg given every other day and starting 30 days Selleckchem Roxadustat prior to IL-12 induction, P17 treatment and IL-12 induction was separated because the recovery of lymphocyte response to IL-12 stimulation only occurs after a considerable

time lag following P17 administration, as demonstrated for the majority of woodchucks that showed maximum IFN-γ production at day 52 following the initial dose of P17 peptide (Fig. 3C). CTX was administered at a single low dose of 20 mg/kg and IL-12 induction 上海皓元 was initiated 10 days later, when FoxP3 expression was undetectable in the liver of CTX-treated animals, as shown in Fig. 4B. Liver biopsies were obtained prior to vector injection during laparotomy, and then again 20 days after the completion of the induction cycle. Following mifepristone administration, IL-12 expression was highly variable in individual woodchucks but was comparable between the three experimental groups (Fig. 5B). Viremia in serum was analyzed weekly but no changes in viral load were detected (Fig. 5C). Notably, the analysis of hepatic expression of immunosuppressive molecules revealed an increased tolerogenic environment of the liver. Specifically, an increase in FoxP3 expression was observed in all animals treated with IL-12 (Fig. 6A). This finding was confirmed by immunohistochemical staining with an anti-FoxP3 antibody (Fig. 6B). A significant increase in PD-1 mRNA expression was also observed in the majority of animals (Fig. 6A).

5 mg/mL, irregular heart rate or heart rate > 100 beats per minute). Also, hyperacute stroke patients eligible for reperfusion therapy were not considered for this study until their neurologists confirmed that they could be approached for consent without delaying treatment. Erismodegib clinical trial Our institutional review board approved this study and informed consent was obtained for each patient. CT studies were performed on a 64-slice multidetector CT scanner (“Lightspeed VCT,” General Electric)

without prior administration of beta-blockers or nitroglycerin. A combined carotid-coronary CT angiography (CTA) series was obtained and consisted of two helical acquisitions and a dual phase contrast injection (Supp Fig 1). The first acquisition was non-ECG-gated,

ascending from http://www.selleckchem.com/products/Gefitinib.html the aortic arch to the vertex of the head. The second acquisition was performed during a breath-hold and was retrospectively ECG-gated, descending from the aortic arch to the diaphragm. The acquisition parameters were as follows: 64 mm × .625 mm collimation, 0.33-second gantry rotation-time, 120 kV tube voltage, and 850 mA tube current. A slice-thickness of 1.25 mm and a pitch of .92 were used for the aortic arch, carotid, and intracranial arteries, whereas a slice-thickness of .625 mm and a pitch of .2 were used for the coronary arteries. The time to maximal enhancement on bolus testing was used to calculate the contrast transit time. This transit time determined the delay between the initial contrast injection and the first acquisition. The dual phase contrast injection consisted

of two boluses of 30 cc and 60 cc iodinated contrast material (iohexol, Omnipaque, Amersham Health, Princeton, NJ, USA; 350 mg/mL of iodine) injected into the right or left (preferably the right) cubital vein, followed by saline injection phases of 15 cc and 60 cc, respectively. The injection rate was 5 cc/second for both the contrast and the saline. Radiation dose associated with our CTA protocol was exactly 上海皓元 the same as for a regular neck CTA protocol, with an effective dose in the order of 3–4 mSv. The CTA studies were exported to an off-line PC computer and were processed automatically using a custom, automated classifier computer algorithm. This computer algorithm was developed using Matlab-based software (The MathWorks, Inc., Novi, MI, USA) and was validated using histology derived from carotid endarterectomy specimens as gold standard.[20] The algorithm automatically segments the inner and outer contours of the carotid artery wall and distinguishes among its histological components (lipid, calcium, fibrous tissue) using appropriate thresholds of CT density.[20] It then creates a color overlay that visually displays the composition of the carotid artery wall for each CTA image slice (Supp Fig 2).