The data support a view in which the microenvironment can play an active role in the evolution of myelodysplasia and myeloproliferative disorders, thus providing further rationale to explore therapeutic

targeting of mesenchymal-hematopoietic interactions in these diseases.”
“Incidences of esophageal cancer and obesity are both rising in the United States. The aim of this study was to determine the influence of elevated body mass index on outcomes after esophagectomy for cancer.\n\nOverall and disease-free survivals in obese (BMI a parts per thousand yen 30), overweight (BMI 25-29), and normal-weight (BMI 20-24) patients undergoing esophagectomy constituted the study end points. Survivals were calculated by Ferrostatin-1 datasheet the Kaplan-Meier method,

and differences were analyzed by log rank method.\n\nThe study included 166 obese, 176 overweight, and 148 normal-weight patients. These three groups were similar in terms of demographics and comorbidities, with the exception of younger age (62.5 vs. 66.2 vs. 65.3 years, P = 0.002), and higher incidence of diabetes (23.5 vs. 11.4 vs. 10.1%, P = 0.001) and hiatal hernia (28.3 vs. 14.8 vs. 20.3%, P = 0.01) in obese patients. Rates of adenocarcinoma histology were higher in obese patients (90.8 vs. 90.9 vs. 82.5%, P = 0.03). Despite similar preoperative stage, obese patients were less likely to receive neoadjuvant treatment (47.6 vs. 54.5 vs. 66.2%, P = 0.004). Response to neoadjuvant treatment, selleck kinase inhibitor type of surgery performed, extent Adavosertib of lymphadenectomy, rate of R0 resections, perioperative complications, and administration of adjuvant chemotherapy were not influenced by BMI. At a median follow-up of 25 months, 5-year overall and disease-free survivals were longer in obese patients (respectively, 48, 41, 34%, P = 0.01 and 48, 44, 34%, P = 0.01).\n\nIn our experience, an elevated BMI did not reduce overall and disease-free survivals after esophagectomy for cancer.”
“The potential for human exposure to engineered nanoparticles due to the use of nanotechnology-based consumer sprays (categorized as such by the Nanotechnology Consumer Products Inventory) is examined along with analogous products, which are not specified

as nanotechnology-based (regular products). Photon correlation spectroscopy was used to obtain particle size distributions in the initial liquid products. Transmission electron microscopy was used to determine particle size, shape, and agglomeration of the particles. Realistic application of the spray products near the human breathing zone characterized airborne particles that are released during use of the sprays. Aerosolization of sprays with standard nebulizers was used to determine their potential for inhalation exposure. Electron microscopy detected the presence of nanoparticles in some nanotechnology-based sprays as well as in several regular products, whereas the photon correlation spectroscopy indicated the presence of particles <100nm in all investigated products.

[Conclusion] The reason why acute maximal load did not have a significant effect on the MDA activation which is an indicator of lipid peroxidation is that acute maximal load raised the free radical level and the lipid peroxide level; and had a defense mechanism against the generation of free radicals; thus restrained lipid peroxides from

being generated by free radicals; consequently they could not have any effect on antioxidation capability.”
“Parathyroid hormone (PTH) inhibits Na+-K+-ATPase activity by serine phosphorylation of the alpha(1)-subunit through ERK-dependent phosphorylation and translocation of protein kinase C alpha (PKC alpha ). On the basis of previous studies, we postulated that PTH regulates sodium pump activity through Src GW4869 kinase, PLC, and calcium-dependent ERK phosphorylation. Combretastatin A4 supplier In the present work utilizing opossum kidney cells, a model of renal proximal tubule, PTH-stimulated ERK phosphorylation and membrane translocation of PKC alpha were prevented by inhibition of Src kinase, PLC, and calcium entry. Pharmacological inhibition of PLA(2) did not prevent PTH-stimulated ERK phosphorylation but completely prevented PKC alpha translocation. Silencing the expression of cytosolic or calcium-independent PLA(2) also prevented

PTH-mediated phosphorylation of Na+-K+-ATPase alpha(1)-subunit and PKC alpha without blocking ERK phosphorylation. Inhibition of Na+-K+-ATPase activity by the PLA(2) metabolites arachidonic acid and 20-hydroxyeicosatetraenoic acid was prevented by specific inhibition of PKC alpha but not by U0126, a MEK-1 inhibitor. Transient transfection of constitutively active MEK-1 cDNA induced phosphorylation

of Na+-K+-ATPase alpha(1)-subunit and PKC alpha , which was prevented by PLA(2) inhibition. We conclude that PTH stimulates Na+-K+-ATPase phosphorylation and decreases the activity of Na+-K+-ATPase by a sequential activation of a signaling pathway involving Src kinase, PLC, ERK, PLA(2), and PKC alpha .”
“Bacteria of the genus Bartonella are emerging zoonotic bacteria recognized in a variety of human diseases. Due to their poor chemical reactivity, these fastidious bacteria are poorly characterized using routine phenotypic laboratory FDA approved Drug Library chemical structure tests. Identification is usually achieved using molecular techniques that are time-consuming, expensive and technically demanding. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has emerged as a new technique for bacterial species identification. This study evaluated the use of MALDI-TOF MS for rapid genus and species identification of Bartonella species. Reference strains representing 17 recognized Bartonella species were studied. For each species, MS spectra for four colonies were analysed.

Our data support the concept of targeting systemic inflammation and BBB for the prevention of status epilepticus. (C) 2008 Published by Elsevier Inc.”
“The field of oxidative stress, free radicals, cellular defense and antioxidants is a burgeoning field of research. An important biomarker of oxidative stress is ascorbate and alterations in ascorbate have been shown to be a reliable measure of oxidative stress mechanisms. The purpose of this pharmacological study was to assess changes in ascorbate in a morphine/ascorbate animal model using novel sensors which selectively detect electrochemical signals for ascorbate, dopamine (DA) and serotonin (5-HT). Studies were also performed to

show reversal of morphine-induced effects by the opioid antagonist, naloxone. In vivo studies were modeled after (Enrico et al. 1997, 1998) in which the oxidative biomarker, ascorbate, was reported to compensate for free radicals produced by morphine-induced buy AZD6244 increases in DA and 5-HT. In vivo studies consisted of inserting the Laurate sensor in ventrolateral nucleus

accumbens (v1NAcc), in anesthetized male, Sprague-Dawley rats. In separate studies, laboratory rats were injected with (1) ascorbate, (5-35mg/kg, ip) or (2) dehydroascorbate (DHA) (20-100mg/kg, ip). In another study, (3) morphine sulfate (10-20mg/kg, sc) was injected followed by a single injection of naloxone (5mg/kg, ip) in the same animal. Results showed that in vlNAcc, (1) neither ascorbate nor DHA injections produced ascorbate release, (2) morphine significantly increased DA and 5-HT release, but did not alter ascorbate release, and (3) naloxone significantly LDN-193189 reversed the increased DA and 5-HT release produced by morphine. Moreover, the sensors, N-stearoyl cerebroside and laurate were studied in vitro, in separate studies, in order to assess Nutlin-3a manufacturer selective and separate electrochemical detection of ascorbate, DA and 5-HT, neuromolecules

involved in oxidative stress mechanisms. In vitro studies consisted of pretreatment of each sensor with a solution of phosphotidylethanolamine (PEA) and bovine serum albumin (BSA) which simulates the lipid/protein composition of brain. Each new sensor was tested for stability, sensitivity and selectivity by pipetting graduated increases in concentration of ascorbate, DA and 5-HT into an electrochemical cell containing saline/phosphate buffer. Multiple and repetitive images of electrochemical signals from ascorbate, DA and 5-HT were recorded. Results showed that both sensors produced three well-defined cathodic, selective and separate electrochemical signals for ascorbate, DA and 5-HT at characteristic oxidation potentials. Dopamine and 5-HT were detected at nM concentrations while ascorbate was detected at mu M concentrations. In summary, the data show that very low concentrations of ascorbate occurred in vlAcc since novel sensors detected ascorbate at high concentrations in vitro.

formula only (n = 437) and cesarean section v. vaginal delivery (n = 1236). Data were drawn from a prospective pre-birth PD173074 research buy cohort study, Project Viva. The goal is to demonstrate the necessity and usefulness, and approaches for multiple confounding adjustment methods to analyze observational data. Unadjusted (univariate) and covariate-adjusted linear regression associations of breastfeeding with BMI z-score were -0.33 (95% CI -0.53, -0.13) and -0.24 (-0.46, -0.02), respectively.

The other approaches resulted in smaller n (204-276) because of poor overlap of covariates, but CIs were of similar width except for inverse probability weighting (75% wider) and PS matching with a wider caliper (76% wider). Point estimates ranged

widely, however, from -0.01 to -0.38. For cesarean section, because of better covariate overlap, the covariate-adjusted regression estimate (0.20) was remarkably robust to all adjustment methods, and the widths of the 95% CIs differed less than in the breastfeeding example. Choice of covariate adjustment method can matter. Lack of overlap in covariate structure between exposed and unexposed participants in observational studies can lead to erroneous covariate-adjusted estimates and confidence intervals. We recommend inspecting covariate overlap and using multiple confounding adjustment methods. Similar results bring reassurance. Contradictory results suggest issues with either the data Selleckchem ARN-509 or the analytic method.”
“Background/Aims: Alcohol-related

click here problems are relevant in the elderly, particularly in developed countries, but there is a lack of cross-country comparisons. The present work aims to examine the frequency and patterns of alcohol consumption in older adults across different European countries, and to analyze the relationship between socioeconomic status and gender with alcohol consumption. Methods: General population-based household surveys of randomly selected adults over 60 years of age in 14 European countries. Participants: 10,119 subjects [mean age: 70.4 (SD = 7.1)], 61.9% women. Results: There are marked differences in alcohol consumption across countries. Except for three countries from eastern regions, most people in all countries present moderate consumption regarding the amount of alcohol and pattern of use. However, there are marked gender differences, with a higher intake in men (effect sizes ranging from 0.57 to 1.27), although these differences are relatively proportional across countries. Finally, a higher socioeconomic status is positively related (B = 0.845, 95% CI: 0.30/1.40) with alcohol consumption after controlling for gender, age, health-functioning status and the country’s development level. Conclusions: There are marked differences in consumption of alcohol in the elderly between the different countries, and male gender, as well as a higher SES, were associated with higher alcohol consumption. (C) 2014 S.

3) patients showed 1 transmitted RAM affecting the NRTIs (10/193, 5.2), non-nucleoside reverse transcriptase inhibitors (4/193, 2.1) or protease inhibitors (2/193, 1.0). No additional RAMs were detected by AS-PCR (n152) and UDS (n24); PBMCSS (n91) yielded two additional samples with one RAM each. Over 48 weeks, 4/79 (5.1) patients on etravirine and 7/78 (9.0) on efavirenz

experienced virological failure; none had baseline RAMs. Conversely, 11/79 (13.9) patients randomized to etravirine had one polymorphic RAM from the etravirine score in baseline plasma (V90I, V106I or E138A), without any impact on virological outcomes. The detection of resistance increased marginally with PBMC testing but did not increase with sensitive plasma testing. A careful consideration is required Ruboxistaurin datasheet of the cost-effectiveness of different strategies for baseline HIV drug resistance testing.”
“Poly(ADP-ribose) learn more polymerase (PARP) inhibitors are strikingly toxic to cells with defects in homologous recombination (HR). The mechanistic basis for these findings is incompletely understood. Here, we show that PARP inhibitor treatment induces phosphorylation

of DNA-dependent protein kinase substrates and stimulates error-prone nonhomologous end joining (NHEJ) selectively in HR-deficient cells. Notably, inhibiting DNA-dependent protein kinase activity reverses the genomic instability previously reported in these cells after PARP inhibition. Moreover, disabling NHEJ by using genetic or pharmacologic approaches rescues the lethality of PARP inhibition or down-regulation in cell lines lacking BRCA2, BRCA1, or ATM. Collectively, our results not only implicate PARP1 catalytic activity in the regulation of NHEJ in HR-deficient cells, but also indicate that deregulated NHEJ plays a major role in generating the genomic instability and cytotoxicity in HR-deficient cells treated with PARP inhibitors.”
“Introduction: The GOLD guidelines advocate not to institute inhaled corticosteroids (ICS) in patients with mild-to-moderate COPD. However, many patients do use ICS and in some patients,

withdrawal is associated with deteriorating lung function and increased exacerbation rates. Unfortunately, LY294002 physicians do not know in which patients they can stop ICS treatment safely.\n\nAim: To identify predictors of COPD exacerbations after ICS withdrawal.\n\nMethods: During ICS treatment, post-bronchodilator spirometry, body plethysmography, and health status assessment were performed in 68 COPD patients using ICS. Additionally, sputum cell differentials, supernatant leukotriene B(4), eosinophilic cationic protein, and myeloperoxidase, serum C-reactive protein and soluble intracellular adhesion molecule, and urinary desmosine were assessed. Sputum was also analysed for mRNA levels of haemoxygenase-1, tumour necrosis factor-alpha, RANTES, interleukin 5(IL-5), IL-10, IL-12, IL-13, transforming growth factor-beta, and interferon-gamma.

We test the method using simulations. If data meet the assumptions of the analysis model, estimates of alpha show little bias, even when

there is little or no recombination. However, population size differences between the divergence and polymorphism phases may cause alpha to be over or underestimated by a predictable factor www.selleckchem.com/products/U0126.html that depends on the magnitude of the population size change and the shape of the distribution of effects of deleterious mutations. We analyze several data sets of protein-coding genes and noncoding regions from hominids and Drosophila. In Drosophila genes, we estimate that approximately 50% of amino acid substitutions and approximately 20% of substitutions in introns are adaptive. In protein-coding and noncoding data sets of humans, comparison to macaque sequences reveals

little evidence for adaptive substitutions. However, the true frequency of adaptive substitutions in human-coding DNA could be as high as 40%, because estimates based on current polymorphism may be strongly downwardly biased by a decrease in the effective population MK-8776 mouse size along the human lineage.”
“Background: Stress of the endoplasmic reticulum (ER) leading to activation of the unfolded protein response (UPR) and alveolar epithelial cell (AEC) apoptosis may play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our objectives were to determine whether circulating caspase-cleaved cytokeratin-18 (cCK-18) is a marker of AEC apoptosis in IPF, define

the relationship of cCK-18 with activation of the UPR, and assess its utility as a diagnostic biomarker.\n\nMethods: IPF and normal lung tissues were stained with the antibody (M30) AS1842856 nmr that specifically binds cCK-18. The relationship between markers of the UPR and cCK-18 was determined in AECs exposed in vitro to thapsigargin to induce ER stress. cCK-18 was measured in serum from subjects with IPF, hypersensitivity pneumonitis (HP), nonspecific interstitial pneumonia (NSIP), and control subjects.\n\nResults: cCK-18 immunoreactivity was present in AECs of IPF lung, but not in control subjects. Markers of the UPR (phosphorylated IRE-1 alpha and spliced XBP-1) were more highly expressed in IPF type II AECs than in normal type II AECs. Phosphorylated IRE-1 alpha and cCK-18 increased following thapsigargin-induced ER stress. Serum cCK-18 level distinguished IPF from diseased and control subjects. Serum cCK-18 was not associated with disease severity or outcome.\n\nConclusions: cCK-18 may be a marker of AEC apoptosis and UPR activation in patients with IPF. Circulating levels of cCK-18 are increased in patients with IPF and cCK-18 may be a useful diagnostic biomarker.”
“Background.

Furthermore, the calculations suggest that the differences in the experimental NMR find more data and electronic absorption spectra for pKSI and tKSI two homologous bacterial forms of the enzyme, are due predominantly to the third tyrosine that is present in the hydrogen bonding network of pKSI but not tKSI. These

studies also provide experimentally testable predictions about the impact of mutating the distal tyrosine residues in this hydrogen bonding network on the NMR chemical shifts and electronic absorption spectra.”
“Background and purpose: The adenosine 2B (A(2B)) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A(2B) receptor, adenosine mediates chloride secretion, as well as fibronectin

and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A(2B) receptor mRNA and protein expression are increased AICAR nmr during human and murine colitis. However, the effect of the A(2B) receptor in the activation of the intestinal inflammatory response is not known. In this study, we examined the effect of A(2B) receptor antagonism on murine colitis.\n\nExperimental approach: Dextran sodium sulphate (DSS)-treated mice and piroxicam-treated IL-10(-/-) mice were used as animal models of colitis. The A(2B) receptor-selective antagonist, ATL-801, was given in the diet.\n\nKey results: Mice fed ATL-801 along with DSS showed a significantly lower extent and severity of colitis

than mice treated with DSS alone, as shown by reduced clinical symptoms, histological scores, IL-6 levels and proliferation indices. The administration of ATL-801 prevented weight loss, suppressed the inflammatory infiltrate into colonic mucosa and decreased Duvelisib clinical trial epithelial hyperplasia in piroxicam-treated IL-10(-/-) mice. IL-6 and keratinocyte-derived chemokine (KC) concentrations in the supernatants of colonic organ cultures from colitic mice were significantly reduced by ATL-801 administration.\n\nConclusions and implications: Taken together, these data demonstrate that the intestinal epithelial A(2B) receptor is an important mediator of pro-inflammatory responses in the intestine and that A(2B) receptor blockade may be an effective therapeutic strategy to treat inflammatory bowel disease.”
“One of the effects of climate change can be the change in geographic distribution and intensity of the transmission of vector-borne diseases such as malaria. Given the most conservative estimate of change, these diseases are expected to occur, compared with the past and presence, at higher latitudes and altitudes. A slight rise in ambient temperature and rainfall can extend the duration of the season in which mosquito vectors are transmitting the causative agents of malaria. The parasites that they transmit usually benefit from increased temperatures, as both their reproduction and development are then accelerated, too.

In the final step, alpha-ketoglutarate semialdehyde is oxidized by a dehydrogenase to alpha-ketoglutarate, an intermediate in the citric acid cycle. An X-ray structure for the LyxD from Labrenzia aggregata IAM 12614 with Mg2+ in the active site was determined that confirmed the expectation based on sequence alignments that LyxDs possess a conserved catalytic His-Asp dyad at the end of seventh and sixth beta-strands of the (beta/alpha)(7)beta-barrel domain as well as a conserved KxR motif at the end of second beta-strand;

substitutions for His 316 or Arg 179 inactivated the enzyme. This is the first example of both the LyxD function in the enolase superfamily and a pathway for the catabolism of L-lyxonate.”
“Background: Pelvic lymph node dissection in find more patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop MAPK Inhibitor Library order a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. Methods: We analysed data from 4770 patients treated with radical prostatectomy and

pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from Autophagy inhibitor solubility dmso a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed

a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. Results: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. Conclusions: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.”
“Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG).

“
“Objective-Transgenic mice overexpressing angiopoietin-related growth factor (AGF) exhibit enhanced angiogenesis, suggesting that AGF may be a useful drug target in ischemic disease. Our goal was to determine whether AGF enhances blood flow in a mouse hind-limb

ischemia model and to define molecular mechanisms AZD9291 cell line underlying AGF signaling in endothelial cells.\n\nMethods and Results-Intramuscular injection of adenovirus harboring AGF into the ischemic limb increased AGF production, which increased blood flow through induction of angiogenesis and arteriogenesis, thereby reducing the necessity for limb amputation. In vitro analysis showed that exposing human umbilical venous

endothelial cells to AGF increased nitric oxide (NO) production through activation of an ERK1/2-endothelial NO synthetase (eNOS) signaling pathway. AGF-stimulated eNOS phosphorylation, NO production, and endothelial cell migration were all abolished by specific MEK1/2 inhibitors. Moreover, AGF did not restore blood flow to ischemic hind-limbs of either mice receiving NOS inhibitor L-NAME or eNOS knockout mice.\n\nConclusion-Activation of an ERK1/2-eNOS-NO pathway is a crucial signaling mechanism by which AGF increases blood flow through induction of angiogenesis and arteriogenesis. Further investigation of the regulation underlying AGF signaling pathway may contribute to develop a new clinical strategy for ischemic vascular diseases.”
“Juvenile idiopathic Taselisib nmr arthritis (JIA) is not a disease but an exclusion diagnosis that includes

all forms of chronic arthritis of unknown origin with onset before 16 years of age. The current classification identifies several different categories. While some of them appear to represent rather IPI 145 homogeneous entities others seem still to include heterogeneous conditions. The advent of the new biological treatments has dramatically changed both the observed responses to treatment and the expectations of treatments. International research networks of paediatric rheumatology have contributed to fostering the conduct of controlled clinical trials and also the development of validated outcome measures. However, despite a dramatic advance in the understanding of JIA categories, pathobiology and treatments, much remains to be done.”
“Background: Mitochondria play a vital role in the energy production and apoptotic process of eukaryotic cells. Proteins in the mitochondria are encoded by nuclear and mitochondrial genes. Owing to a large increase in the number of identified mitochondrial protein sequences and completed mitochondrial genomes, it has become necessary to provide a web-based database of mitochondrial protein information.

Materials and methods: Forty-eight acromegalic patients and 41 age-and gender-matched controls were enrolled in the study. The median ages of the patients and controls were 48 (25-75) and 50 (25-67) yr, respectively. Berg Balance Scale (BBS) and one-leg stance test (OLST) were used to compare dynamic and static balance respectively, 50 meters walking test was used to compare functional capacity and falls efficacy scale-international (FES-I) was used to compare fear of falling between Selleck 4-Hydroxytamoxifen the groups. Results: Balance tests (BBS and 50 meter walking test) and fear of falling (FES-I) were significantly disturbed in patients compared with controls. There was no significant difference

in OLST. BBS and OLST were negatively and FES-I was positively correlated with age. FES-I was negatively correlated with BBS and OLST was positively correlated with 50 meters walking test. Only OLST was negatively correlated with disease duration. Logistic regression analysis revealed that balance was not affected by

the presence of co-morbidities, postoperative vision loss and disease control. Conclusions: This is the first study showing that balance is disturbed in acromegalic patients. This disturbance is not related to disease control and co-morbidities but somewhat to disease duration. (J. Endocrinol. Invest. 36: 759-763, 2013) (C) 2013, Editrice Kurtis”
“This paper describes the results of an experimental programme to determine the fatigue behaviour of bamboo. Bamboo is subjected to cyclic loading, both in the plant itself and subsequently when the material is used in load-bearing applications in the construction industry. selleck screening library However, there is currently no data in the literature describing fatigue in this material. We found that sections of bamboo culm loaded parallel to the culm axis did not undergo fatigue failure: samples either failed on the first loading cycle, or not at all. By contrast, fatigue was readily

apparent in samples loaded in compression across the diameter of the culm. The number of cycles to failure increased as the cyclic load range decreased in a manner similar to that found in many engineering materials: Sapanisertib ic50 fatigue occurred at applied loads as small as 40% of the ultimate strength. Two different species of bamboo were tested and found to have different ultimate strengths but similar high-cycle fatigue strengths. Finite element analysis was used to help understand the progression of fatigue damage and the effect of stress concentration features. Some tentative design rules are proposed to define stress levels for the safe use of bamboo, taking fatigue into account. (C) 2015 Elsevier Ltd. All rights reserved.”
“Agonistic AT, receptor autoantibodies (AT(1)-AAs) have been described in the patients with malignant hypertension or preeclampia. Furthermore, AT(1)-AAs were highly associated with refractory hypertension.