“
“We assessed the effect of total large-joint arthroplasty combined with anti-tumor necrosis factor (TNF) therapy for rheumatoid arthritis (RA). We studied 45 RA patients (age 57.91 +/- A 12.74 years, RA duration 13.43 +/- A 8.28 years) who underwent total arthroplasty (35 knees, 19 hips, 3 elbows, and 1 ankle) between August 2002 and November 2009. All

patients received anti-TNF agents (infliximab, 22; etanercept, 33; adalimumab, 3) during the period of the study (that is, they were being treated with the agents when operated on and postoperatively). The disease activity score 28 (DAS28)-erythrocyte sedimentation rate (mean +/- A standard deviation) in all patients improved significantly from baseline (just before the operation; 4.32 +/- A 0.99) to 1 year after the operation (3.35 +/- A 0.93) in contrast with the HIF activation finding that the mean DAS28-ESR values had remained unchanged from 1 year before the operation TPX-0005 in vivo to the baseline. Changes in clinical variables in the 58 cases were investigated at baseline, and at 4, 12, and 52 weeks after the operation. The patients were divided by a median split of baseline demographics into 2 groups for further evaluation. Compared with the high-value groups,

those with low C-reactive protein and matrix metalloproteinase-3 values showed better results and had lower disease activity. Overall, the DAS28-ESR in both groups had improved 1 year after the operation. In RA patients who are being treated with anti-TNF agents, large-joint arthroplasty may be beneficial, not only for the relief of pain arising from joint destruction, but also for the systemic reduction of RA activity.”
“Pro-inflammatory

cytokines, such as IL-1 beta and TNF alpha, play a major role in activating leukocytes and endothelial cells during the systemic inflammatory response to endotoxin in the horse. beta(2) agonist drugs, such as clenbuterol, inhibit leukocyte activation. This study aimed to determine the effects of oral clenbuterol on clinical and leukocyte responses, including production of TNF alpha, in an in vivo endotoxin challenge model. In a randomised crossover design, horses received either clenbuterol or a placebo product prior to the administration CA4P inhibitor of low dose endotoxin (30 ng/kg over 30 min). Clinical signs were measured and leukocyte counts and serial blood samples were obtained over 6 h. Pre-treatment with oral clenbuterol (0.8 mu g/kg) significantly reduced (P = 0.046) the peak rectal temperature and the peak plasma TNF alpha concentration (P = 0.026) following endotoxin challenge. These data suggest that oral clenbuterol at the therapeutic dose has anti-inflammatory effects in horses challenged with a low dose of endotoxin. (C) 2013 Published by Elsevier Ltd.”
“Purpose: To investigate the factors that predict recovery of continence within 3 months after robot-assisted radical prostatectomy (RARP).

aestivum CBF genes (TaCBF15.2, TaCBFA19, TaCBFA2 and TaCBFD21) in crown tissue of two Bulgarian hexaploid winter wheat cultivars (Milena and Russalka) with distinct levels of low-temperature (LT) tolerance but same vernalization requirement, and the spring cultivar Chinese Spring. The transcription profiles of the selected TaCBF genes showed that they are induced by cold treatment at 2 degrees C. Analysis of transcript abundance revealed that the four TaCBF genes were expressed at higher levels in the frost tolerant Milena than in the susceptible Russalka. Largest differences (fivefold and

fourfold) in expression levels between both winter cultivars were observed Autophagy inhibitor in two of the analysed genes, TaCBF15.2 and TaCBFA19, respectively. The higher steady-state expression levels of TaCBF genes before the onset of the LT treatment in Milena, combined with stronger induction by cold treatment, suggest that

these molecular responses to LT are associated with superior FT development capacity. The results expand our understanding of the molecular mechanisms underlying LT acclimation in Bulgarian wheat and can be used for development of functional markers for improvement of FT wheat-breeding programmes.”
“PURPOSE: To evaluate the influence of posterior corneal astigmatism on total corneal astigmatism in patients with 1.00 diopter (D) or more of corneal astigmatism. SETTING: Private practice, Bologna, Italy. DESIGN: Prospective case series. METHODS: Corneal astigmatism was measured check details using a Scheimpflug camera combined with a corneal topographer (Sirius). Keratometric astigmatism, anterior corneal astigmatism, posterior corneal astigmatism, and total corneal astigmatism were evaluated. Vector analysis was performed according to the N ae ser method. RESULTS: One hundred fifty-seven eyes were enrolled.

Keratometric astigmatism was with the rule (WTR), against the rule (ATR), and oblique in 84.0%, 11.5%, and 4.5% of eyes, respectively. Posterior corneal astigmatism exceeded Citarinostat datasheet 0.50 D and 1.00 D in 55.4% of eyes and 5.7% of eyes, respectively. The mean posterior corneal astigmatism was 0.54 D, inclined 91 degrees in relation to the steeper anterior corneal meridian. The steepest meridian was vertically aligned in 93.0% of cases. Compared with total corneal astigmatism, keratometric astigmatism overestimated WTR astigmatism by a mean of 0.22 D +/- 0.32 (SD), underestimated ATR astigmatism by 0.21 +/- 0.26 D, and overestimated oblique astigmatism by 0.13 +/- 0.37 D. In the whole sample, a difference in astigmatism magnitude of 0.50 D or more was detected between keratometric astigmatism and total corneal astigmatism in 16.6% of cases and the difference in the location of the steep meridian was greater than 10 degrees in 3.8% of cases. CONCLUSION: In patients who are candidates for surgical correction of astigmatism, measuring only the anterior corneal curvature can lead to inaccurate evaluation of the total corneal astigmatism.

Perinatal copper deficiency was produced in Holtzman rat dams by restricting dietary copper during the learn more last two thirds of gestation and lactation. Male offspring were evaluated at postnatal day 25. Compared to cerebella from copper-adequate pups, the CuD pups had larger Purkinje cell (PC) size and irregularities in the Purkinje cell monolayer. These results suggest that the ataxic behavioral phenotype of CuD rats may result from disrupted inhibitory pathways in the cerebellum. A similar

PC phenotype is seen in Menkes disease and in mottled mouse mutants with genetic copper deficiency, suggesting that copper deficiency and not just specific loss of ATP7A function is responsible.”
“In Wnt signaling this paper, we consider a Rayleigh fading half-duplex system where multiple source-destination pairs communicate with the help of a single relay. The relay performs the analog network coding (ANC) to assist the transmissions from the sources to the destinations, which is a well-known amplify-and-forward-based protocol. We derive the closed-form expressions for outage probabilities in the high-SNR regime for the system with an arbitrary number of the source-destination pairs. The diversity-multiplexing tradeoff (DMT) of the ANC is also derived, which is based on the outage probabilities.

It is shown that the derived outage probabilities match the results of Monte Carlo simulations in the high-SNR regime. The ANC is shown to achieve the same DMT as the XOR network coding strategy that assumes an ideal condition that each destination node perfectly overhears the data from other sources.”
“Background: The Human

papillomavirus (HPV) vaccine has been available for protection against HPV-associated cervical cancer and genital warts since 2006. Nonetheless, uptake has varied among countries and populations within countries. Studies have found that individuals’ knowledge and attitudes toward the vaccine are associated with immunization uptake. The purpose of the current review is to summarize and evaluate the evidence for educational interventions to increase HPV vaccination acceptance. Methods: We searched the databases of PubMed and Web of Science for English-language articles describing educational interventions designed to improve ML323 HPV vaccination uptake, intention or attitude. Results: We identified 33 studies of HPV vaccination educational interventions: 7 tested the effectiveness of interventions with parents, 8 with adolescents or young adults, and 18 compared the effectiveness of different message frames in an educational intervention among adolescents, young adults or their parents. Most studies involved populations with higher educational attainment and most interventions required participants to be literate. The minority of studies used the outcome of HPV vaccine uptake.

Daily treatment with quercetin (2.5, 5 and 10 mg/kg, p.o.) starting from the first dose of STZ showed a dose-dependent restoration of CBF and ATP

content. Further, quercetin prevented PKA inhibitor STZ induced memory impairment as assessed by Morris water maze and passive avoidance tests. Biochemical analysis revealed that STZ significantly increased malondialdehyde (MDA), nitrite and depleted glutathione (GSH) levels in the mice brain. Quercetin decreased oxidative and nitrosative stress as evidenced by a significant decrease in MDA, nitrite and increase in GSH levels. Quercetin also attenuated elevated acetylcholinesterase activity in the STZ-treated mice. Neither STZ (i.c.) nor quercetin showed any change

in locomotor activity and blood glucose level. The present study demonstrates the beneficial effects of quercetin in improving CBF along with preventing memory impairment, oxidative stress, altered brain energy metabolism and cholinergic dysfunction caused by STZ in mice. Therefore, consumption of dietary stuff rich in quercetin should be encouraged to ward off dementia associated with vascular and neurodegenerative disorders. (C) 2010 Elsevier B.V. All rights reserved.”
“Procyanidin oligomers in Cinnamon are thought to be responsible for the biological activity in the treatment of diabetes mellitus (DM). To clarify types of procyanidin AC220 oligomers in different Cinnamon species and investigate their different effects, the present study investigated procyanidin oligomers in polyphenolic oligomer-rich extracts of three Cinnamon

samples by LC-MS methods, and their hypoglycemic activities were detected in vivo and in vitro. The results showed that two of the three samples from Cinnamomum cassia were rich in B-type procyanidin oligomers, and the other sample was rich in A-type procyanidin oligomers. The Cinnamon extracts were administered at doses of 200 and 300 mg/kg body wt. in high-fat diet-fed and low-dose streptozotocin (STZ)-induced diabetic mice for 14 days. The results showed that blood glucose concentrations were significantly this website decreased in all Cinnamon extract groups compared with the control group (p<0.05). Administration of the Cinnamon extracts significantly increased the consumption of extracellular glucose in insulin-resistant HepG2 cells and normal HepG2 cells compared with the control group. These results suggest that both A- and B-type procyanidin oligomers in different Cinnamon species have hypoglycemic activities and may improve insulin sensitivity in type 2 DM. (C) 2010 Elsevier GmbH. All rights reserved.”
“Aims\n\nThis study used Ecological Momentary Assessment (EMA) data from smokers trying to quit to assess relations among coping, positive affect, negative affect and smoking. The effects of stress coping on affect and smoking were examined.

Average autonomy quantifies the extent in which estimated genetic (co)variances constrain the rate of evolutionary www.selleckchem.com/products/MK-2206.html change of behavioral traits forming a syndrome when these traits are under selections in all possible directions of multivariate trait-space. However, it is not clear whether

a calculated average autonomy value of an observed syndrome constitutes a significant evolutionary constraint or not. I here outline an approach for testing evolutionary constraint in a syndrome, which is based on comparing the observed genetic (co)variance structure to the one where the genetic covariances are assumed to be zero and taking onboard the uncertainty in the (co)variances between behaviors into the calculations of average autonomy. The approach can be implemented in the context of parametric bootstrap or Bayesian

statistics, and I provide a worked example of the latter. I further highlight that when genetic (co)variances are unattainable, the between-individual (co)variances HER2 inhibitor act as an interesting proxy, which is within reach for many behavioral studies. I provide R code for all calculations.”
“Three new phenolic bisabolane sesquiterpenes, peniciaculins A (1) and B (2) and (7S)-(-)-10-hydroxysydonic acid (3), together with a new nor-bisabolane derivative, 1-hydroxyboivinianin A (4), as well as six known bisabolanes (5-10), were identified from the culture of Penicillium aculeatum SD-321, a fungus isolated from deep-sea sediments. The structures of these compounds were mainly determined by analysis of spectroscopic data, and the absolute configurations of compounds 1-4 were established by comparing their ECD spectra with those of known analogues or by TDDFT-ECD calculations. Compound 1 represents the first example of a bisabolane analogue linked to a diphenyl ether moiety via an ether bond, while compound 2 appears to be the first dimeric bisabolane analogue where the two monomers are coupled to each other via an ester bond. The isolated compounds were evaluated for antimicrobial

activity against 10 human and aquatic pathogenic bacteria and three plant-pathogenic fungi.”
“In order to explore effects of prenatal alcohol exposure on functional lateralization, item tasks measuring preferences of hand, foot, eye, and ear SBE-β-CD were administered to a sample of 23 children diagnosed with fetal alcohol syndrome (FAS) compared with typically developing (TD) children. In addition, a dichotic listening task was administered to a subsample of 11 children with FAS and a TD group of comparable age, sex and handedness. The children with FAS were characterized by increased nonright-handedness compared with TD children. No differences were evident for preferential use of foot, eye, or ear Moreover children with FAS displayed more right ear extinctions during dichotic listening relative to TD children, indicating a lack of right ear advantage.

01). We conclude that treatment with early-passage MSCs improved survival in patients with therapy-resistant GVHD. Death from infection was common in MSC-treated patients, but there was no increase in leukemia relapse. Biol Blood Marrow Transplant 18: 557-564 (2012) (C) 2012 American Society for Blood and Marrow Transplantation”
“Background\n\nPerceived age is important to women and is a primary driver for topical product use

and facial cosmetic surgery. Changes in facial features and biophysical AZD8931 skin parameters with chronological age and their associations with perceived age have not been described in Asian populations.\n\nObjective\n\nTo investigate the relationship between Ricolinostat in vitro biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women.\n\nMethods\n\nFacial photographs were collected of 250 Chinese women, aged 25-70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments

of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age.\n\nResults\n\nLarge discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans-epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly

higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same Selleck HM781-36B average chronological age.\n\nConclusions\n\nWe have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.”
“The use of tissue microarrays (TMAs) in the preclinical and translational research settings has become ubiquitous as they allow for high-throughput in situ biomarker analysis of hundreds of patient samples, with time and cost efficiency. Coupled with advanced imaging and image-analysis technologies that allow for objective and standardized biomarker expression assessment, TMAs have become critical tools for the development and validation of clinically meaningful biomarker diagnostic assays.

meleagrimitis. Together these rDNA types formed a well-supported E. meleagrimitis clade. Types A and B 18S rDNA sequences from E. meleagrimitis had a mean sequence identity of only 97.4% whereas mean sequence identity within types was 99.1-99.3%. The observed intraspecific sequence divergence among E. meleagrimitis 18S rDNA sequence types was even higher (approximately 2.6%) than the interspecific

sequence divergence present between some well-recognized species such as Eimeria tenella and Eimeria necatrix (1.1%). Our observations suggest that, unlike COI sequences, 18S rDNA sequences are not reliable molecular markers to be used alone for species identification with coccidia, although 18S rDNA sequences have clear utility for phylogenetic reconstruction of apicomplexan parasites at the genus and higher taxonomic Proton Pump inhibitor ranks. (C) 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.”
“The consequences of chronic infection Rabusertib purchase with the HCV on immunity to distinct pathogens are not fully appreciated, despite the potent modulatory effects of HCV on the immune system.

We observed that upon TLR4 ligation, monocytes from chronic HCV patients demonstrated three to five times lower TNF and IL-12p40 production as compared with healthy individuals. However, augmented production of TNF, IL-12p40, and IL-12p70 by monocytes was observed upon stimulation with R848. Importantly, we observed that the levels of IL-10 in chronic HCV patients are higher in serum and that more IL-10 is produced by monocytes as compared with healthy individuals. The inhibitory effect of IL-10 on the production of proinflammatory cytokines by monocytes was only observed upon LPS stimulation but not upon R848 stimulation, showing that only the TLR4 pathway in monocytes is sensitive to the suppressive effects of IL-10. Interestingly,

monocytes stimulated with the TLR4 agonist, but not TLR8 agonist, produced higher levels of IL-10 when exposed to patient serum as compared with serum Y-27632 nmr from healthy individuals. Our results indicate that by differentially affecting TLR4 and TLR8 pathways, IL-10 may mediate highly selective modulation of the function of monocytes observed in chronic HCV patients. This suggests that there is no overall increased susceptibility to pathogens but a specific suppression of the functionality of TLR4 signaling pathway in monocytes, which is, at least partly, mediated via IL-10. J. Leukoc. Biol. 89: 981-988; 2011.”
“Background. Hemorrhage induces an imbalance in histone acetyl transferase/histone deacetylase (HAT/HDAC) ratio. Correction of this,imbalance with histone deacetylase inhibitors (HDACI) improves survival. We aimed to identify whether this was due to modulation of the post-shock immune response.\n\nMethods.

Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.”
“The goal of this study was to investigate the clinical utility of a new enzymatic assay for use on COBAS INTEGRA systems (Roche Total MPA assay). From 134 patients, plasma mycophenolic

acid GSK3326595 (MPA) concentrations were measured with both the enzymatic method and a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) procedure, to compare these assays. The test principle of the enzymatic assay is inhibition of inosine monophosphate dehydrogenase. Method comparison studies revealed good agreement of results (r > 0.99), overall and in patients with delayed graft function or hypoalbuminemia. MPA area under Crenigacestat cell line the concentration-time curve (AUCs) obtained with LC-MS/MS (x) and the enzymatic method (v) compared excellent in patients on cyclosporine (y = 1.04x – 1.05, r = 0.992) or tacrolimus (y = 1.02x – 0.63, r = 0.987). MPA exposure determined with either method at different time points after transplantation agreed well (eg, 25th/50th/75th percentile of day 10 AUCs-LC-MS/MS: 25.8/33.8/45.2 versus enzymatic

assay: 26.2/34.4/45.3 mg.h/L). AUCs calculated for both methods were lower at the first 3 time points in patients on cyclosporine compared with tacrolimus (week 4 median cyclosporine/tacrolimus: LC-MS/MS 39.6/56.4 versus enzymatic assay 40.5/56.0

mg.h/L). Both LC-MS/MS and the enzymatic methods revealed a tendency toward lower AUCs and predose levels in patients with biopsy-proven acute rejection (BPAR) (day 10 median: 0.9 mg/L with BPAR and 1.7 mg/L without BPAR). The Roche Total MPA assay is a reliable alternative to LC-MS/MS. It can be applied see more in the clinical setting allowing for easy, fast, and optimized patient management.”
“Disorders of sex development (DSD) are defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical. DSD patients with gonadal dysgenesis or hypovirilization, containing part of the Y chromosome (GBY), have an increased risk for malignant type II germ cell tumors (GCTs: seminomas and nonseminomas). DSD may be diagnosed in newborns (e.g., ambiguous genitalia), or later in life, even at or after puberty. Here we describe three independent male patients with a GCT; two were retrospectively recognized as DSD, based on the histological identification of both carcinoma in situ and gonadoblastoma in a single gonad as the cancer precursor. Hypospadias and cryptorchidism in their history are consistent with this conclusion. The power of recognition of these parameters is demonstrated by the third patient, in which the precursor lesion was diagnosed before progression to invasiveness.

Survivors are encouraged to consider additional interventions, including psychosocial support and physical exercise.”
“Background: Staphylococcus aureus has been recognized as a major human pathogen and is the major cause of nosocomial infections. Gamma-toxin, leukocidin and other bi-component toxins are a family of proteins encoded by the hlg and luk-PV, respectively. Panton-Valentine leukocidin (PVL) is an example of these toxins

and causes leukocyte destruction and tissue DNA Damage inhibitor necrosis. The aim of this study was to determine the prevalence of bi-component leukocidin in Methicillin – Resistant Staphylococcus aureus (MRSA) isolates in staphylococcal infections.\n\nMethods: Collectively, 143 isolates of S. aureus were obtained from Tehran University of Medical Sciences hospitals and confirmed with biochemical tests. Then polymerase chain reaction was used to detect DZNeP luk-PV loci and luk-E/D. Coagulase gene was used as internal control. The antibiotic susceptibility patterns of isolates were determined using disk diffusion method.\n\nResults: Out of 149 S. aureus isolates 24.2% were luk-PV positive and 73.8% were luk-E/D positive.\n\nConclusion: There was PVL-positive MRSA isolates with high prevalence

in evaluated hospitals. The diseases from these bacteria are with extensive necrosis, leucopenia and even death. We desire that, prevent from progress and death by diagnosis and right treatment.”
“Biophysical models that describe the outcome of white CT99021 matter diffusion MRI experiments have various degrees of complexity. While the simplest models assume equal-sized and parallel axons, more elaborate ones may include distributions of axon diameters and

axonal orientation dispersions. These microstructural features can be inferred from diffusion-weighted signal attenuation curves by solving an inverse problem, validated in several Monte Carlo simulation studies. Model development has been paralleled by microscopy studies of the microstructure of excised and fixed nerves, confirming that axon diameter estimates from diffusion measurements agree with those from microscopy. However, results obtained in vivo are less conclusive. For example, the amount of slowly diffusing water is lower than expected, and the diffusion-encoded signal is apparently insensitive to diffusion time variations, contrary to what may be expected. Recent understandings of the resolution limit in diffusion MRI, the rate of water exchange, and the presence of microscopic axonal undulation and axonal orientation dispersions may, however, explain such apparent contradictions. Knowledge of the effects of biophysical mechanisms on water diffusion in tissue can be used to predict the outcome of diffusion tensor imaging (DTI) and of diffusion kurtosis imaging (DKI) studies. Alterations of DTI or DKI parameters found in studies of pathologies such as ischemic stroke can thus be compared with those predicted by modelling.

The lowest mean CIMT was observed in Group 3, and the highest fasting glucose levels were in Group 4, while the lowest mean free testesterone was measured in Group 1. BMI, LDL-C, and total cholesterol showed significant positive correlations with CIMT (r = 0.411, P = 0.001; r = 0.258, P = 0.006; r = 0.199,

P = 0.033). The lowest LDL-C, total cholesterol, and BMI were found in Group 3, but differences were not statistically significant. High-sensitive CRP levels were similar among the groups (P = 0.103). Group 3 PCOS with PCO and hyperandrogenemia phenotype has lower cardiovascular disease risk compared to other phenotypes.”
“Conformationally constrained mimetics of the laminin cell-adhesion site, YIGSR, are

described. The site is the natural antagonist of the integrin-associated laminin receptor 1 (LAMR1) Z-DEVD-FMK known to mediate metastatic AZD6738 PI3K/Akt/mTOR inhibitor tumor adhesion. The attachment of selected metastatic cell lines toward the constrained antagonists has been assessed. Observed differential responses prompted by folding preferences of the mimetics revealed stronger attachment activities for turnlike structures. The results permit the conformational design of antimetastatic disintegrins.”
“As a unique member of the voltage-gated potassium channel family, a large conductance, voltage-and Ca2+-activated K+ (BK) channel has a large cytosolic domain that serves as the Ca2+ sensor, in addition to a membrane-spanning domain that contains the voltage-sensing (VSD) HDAC inhibitor and pore-gate domains. The conformational changes of the

cytosolic domain induced by Ca2+ binding and the conformational changes of the VSD induced by membrane voltage changes trigger the opening of the pore-gate domain. Although some structural information of these individual functional domains is available, how the interactions among these domains, especially the noncovalent interactions, control the dynamic gating process of BK channels is still not clear. Previous studies discovered that intracellular Mg2+ binds to an interdomain binding site consisting of D99 and N172 from the membrane-spanning domain and E374 and E399 from the cytosolic domain. The bound Mg2+ at this narrow interdomain interface activates the BK channel through an electrostatic interaction with a positively charged residue in the VSD. In this study, we investigated the potential interdomain interactions between the Mg2+-coordination residues and their effects on channel gating. By introducing different charges to these residues, we discovered a native interdomain interaction between D99 and E374 that can affect BK channel activation. To understand the underlying mechanism of the interdomain interactions between the Mg2+-coordination residues, we introduced artificial electrostatic interactions between residues 172 and 399 from two different domains.