Farnesoid X receptor knockout mice (with a hydrophilic

BA pool) were completely protected from CBDL-induced renal fibrosis. Prefeeding of hydrophilic norursodeoxycholic acid inhibited renal tubular epithelial injury in CBDL mice. In addition, we provide evidence for renal tubular injury in cholestatic patients selleck compound with cholemic nephropathy. Conclusion: We characterized a novel in vivo model for cholemic nephropathy, which offers new perspectives to study the complex pathophysiology of this condition. Our findings suggest that urinary-excreted toxic BAs represent a pivotal trigger for renal tubular epithelial injury leading to cholemic nephropathy in CBDL mice. (Hepatology 2013; 58:2056–2069) Acute kidney injury (AKI) is a common complication in patients with end-stage liver disease and represents a high-risk situation.[1] Because of the fact that hepatorenal syndrome (HRS), an important and principally reversible

Gefitinib cell line cause of renal failure in patients with liver cirrhosis, may be difficult to differentiate from other causes of AKI in clinical practice, a revised clinical classification has been proposed.[2] Interestingly, recent studies revealed a high proportion of structural abnormalities, including vascular and tubular epithelial injuries, on renal biopsies in patients with cirrhosis with impaired renal function without proteinuria and hematuria.[3, 4] In addition, chronic cholestatic liver diseases are frequently associated with tubulointerstitial nephropathies.[5, 6] Likewise, patients with obstructive jaundice have an increased incidence of AKI and renal failure in the perioperative phase[7, 8] and frequently

show acute tubular epithelial injury on renal biopsy, despite careful volume replacement therapy.[4] Such renal alterations in cholestasis were previously also referred to as cholemic nephropathy.[9] Cholestasis, Protein tyrosine phosphatase characterized by increased hepatic and serum bile acid (BA) levels,[10] has also been linked to organ dysfunction in cirrhosis.[11] Cholestatic hepatocytes attempt to limit intracellular accumulation of BAs by induced basolateral hepatocellular export and adaptive changes in the proximal renal tubule collectively facilitating their renal elimination at the expense of increasing the BA burden for the renal tubular system.[12, 13] This could cause kidney injury by BA-induced oxidative stress, endotoxemia caused by increased translocation from the intestine resulting from the enteral lack of BAs, increased production, or expression of vasoactive mediators and their receptors as well as volume depletion.[14-18] However, little is known whether and how increased urinary excreted BAs may be causally linked to AKI in cholestatic patients. Long-term common bile duct ligation (CBDL) in mice was shown to be associated with chronic cholestasis, ascites formation, and hyperaldosteronemia,[19] but it remains undefined whether this is associated with renal pathology.

1A). Then we checked its expression in 52 pairs of matched liver tissue samples and found that the expression level of EphrinA2 was significantly

higher in HCC tissues compared with their normal counterparts in Gamma-secretase inhibitor most cases (Fig. 1B). The expression pattern of EphrinA2 in both cell lines and clinical samples suggested its involvement in the pathogenesis of HCC. The expressions of receptors for EphrinA2 were also tested in both cell lines and clinic samples. However, no significant change has been observed (Supporting Fig. 1). HCC carries a high risk of invasion of the portal vein. Portal vein tumor thrombus markedly deteriorates hepatic function and serves as a poor prognostic factor, associated with frequent recurrences and intrahepatic metastasis.21 Thus, we assumed that the expression level of EphrinA2 may be further elevated in this

context. As expected, we found that the protein level of EphrinA2 was lowest in normal liver tissues, relatively higher in the primary HCCs, and further increased in portal vein tumor thrombus, indicating its role not only at the onset but also in the progression of HCC (Fig. 1C, D). To further investigate the function of EphrinA2 in HCC, we developed stable clones overexpressing EphrinA2 from 7404 cells, which exhibited relatively low expression level of EphrinA2 among HCC cell lines, and three 7404/EphrinA2

clones were selected for further studies (Fig. 2A). No significant difference was observed in in vitro proliferation between the control cells and ABT-888 in vivo Carnitine dehydrogenase 7404/EphrinA2 cells (Supporting Fig. 2A, 2B). However, 7404/EphrinA2 cells generated larger xenografts in nude mice than control cells (Fig. 2B, left panel), indicating that EphrinA2 stimulated in vivo tumor growth. To verify the specificity of this tumor-promoting effect, we knocked down the EphrinA2 level in 7404 transfectants by small interfering RNA (siRNA). Once the expression of EphrinA2 was blocked, the in vivo tumor growth of 7404 transfectants was retarded accordingly (Fig. 2B, right panel). More importantly, the EphrinA2 targeting siRNA can also knockdown the endogenous EphrinA2 in both 7402 and HepG2 cells, which expressed a relative high level of EphrinA2 (Fig. 2C), and the down-regulation of EphrinA2 strongly inhibited the tumor growth of 7402 cells in nude mice (Fig. 2D). Furthermore, we found that EphrinA2 dramatically enhanced the capability of 7404 cells to develop tumors in distant organs (Fig. 2E). Taken together, these results suggested that EphrinA2 could promote initiation or progression of HCC. To disclose the underlying mechanism responsible for the tumorigenetic promotion in nude mice, we examined the influence of EphrinA2 on cell proliferation and apoptosis in vivo, respectively.

1A). Then we checked its expression in 52 pairs of matched liver tissue samples and found that the expression level of EphrinA2 was significantly

higher in HCC tissues compared with their normal counterparts in BMS-777607 in vivo most cases (Fig. 1B). The expression pattern of EphrinA2 in both cell lines and clinical samples suggested its involvement in the pathogenesis of HCC. The expressions of receptors for EphrinA2 were also tested in both cell lines and clinic samples. However, no significant change has been observed (Supporting Fig. 1). HCC carries a high risk of invasion of the portal vein. Portal vein tumor thrombus markedly deteriorates hepatic function and serves as a poor prognostic factor, associated with frequent recurrences and intrahepatic metastasis.21 Thus, we assumed that the expression level of EphrinA2 may be further elevated in this

context. As expected, we found that the protein level of EphrinA2 was lowest in normal liver tissues, relatively higher in the primary HCCs, and further increased in portal vein tumor thrombus, indicating its role not only at the onset but also in the progression of HCC (Fig. 1C, D). To further investigate the function of EphrinA2 in HCC, we developed stable clones overexpressing EphrinA2 from 7404 cells, which exhibited relatively low expression level of EphrinA2 among HCC cell lines, and three 7404/EphrinA2

clones were selected for further studies (Fig. 2A). No significant difference was observed in in vitro proliferation between the control cells and SAR245409 in vitro GNAT2 7404/EphrinA2 cells (Supporting Fig. 2A, 2B). However, 7404/EphrinA2 cells generated larger xenografts in nude mice than control cells (Fig. 2B, left panel), indicating that EphrinA2 stimulated in vivo tumor growth. To verify the specificity of this tumor-promoting effect, we knocked down the EphrinA2 level in 7404 transfectants by small interfering RNA (siRNA). Once the expression of EphrinA2 was blocked, the in vivo tumor growth of 7404 transfectants was retarded accordingly (Fig. 2B, right panel). More importantly, the EphrinA2 targeting siRNA can also knockdown the endogenous EphrinA2 in both 7402 and HepG2 cells, which expressed a relative high level of EphrinA2 (Fig. 2C), and the down-regulation of EphrinA2 strongly inhibited the tumor growth of 7402 cells in nude mice (Fig. 2D). Furthermore, we found that EphrinA2 dramatically enhanced the capability of 7404 cells to develop tumors in distant organs (Fig. 2E). Taken together, these results suggested that EphrinA2 could promote initiation or progression of HCC. To disclose the underlying mechanism responsible for the tumorigenetic promotion in nude mice, we examined the influence of EphrinA2 on cell proliferation and apoptosis in vivo, respectively.

3, 95% confidence interval 1.5-12.6, P= .0063) after adjusting for potential confounders. We observed that approximately one-fourth of patients with severe neurological

deficits have clinical–radiological severity mismatch. Such patients appear to have a high rate of favorable outcomes at 1 year. “
“To review [123I]FP-CIT (Ioflupane I 123, selleck compound DaTscan) SPECT imaging and its role in clinical practice. [123I]FP-CIT is a radiopharmaceutical that binds reversibly to striatal presynaptic dopamine transporters. We review the two principal multicenter clinical trials of [123I]FP-CIT SPECT imaging and provide additional, previously unreported information. Study 1 was a trial of [123I]FP-CIT SPECT in patients with early suspected parkinsonism that compared baseline scans to the consensus clinical diagnosis established 3 years later. Study 2 was a trial of [123I]FP-CIT SPECT in patients

with established diagnoses of parkinsonian syndrome (PS) or essential tremor (ET). In Study 1, positive percent agreement (abnormal baseline scan and clinical diagnosis of PS at 36 months [n= 71]) was 78-79%. Negative percent agreement (normal baseline scan and a clinical diagnosis of non-PS at 36 months [n= 28]) was 97%. In study 2, positive percent agreement (abnormal scan and a clinical diagnosis of PS [n= 158]) was 92-97%. Negative percent agreement (normal scan and a clinical diagnosis of ET [n= 27]) was 74-96%. [123I]FP-CIT SPECT brain imaging is used to assist in the evaluation of adult patients with suspected PS and may help differentiate MAPK Inhibitor Library mouse ET from PS as an adjunct to other diagnostic evaluations. “
“The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied CHIR-99021 cell line to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic

and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps.

3, 95% confidence interval 1.5-12.6, P= .0063) after adjusting for potential confounders. We observed that approximately one-fourth of patients with severe neurological

deficits have clinical–radiological severity mismatch. Such patients appear to have a high rate of favorable outcomes at 1 year. “
“To review [123I]FP-CIT (Ioflupane I 123, buy SB203580 DaTscan) SPECT imaging and its role in clinical practice. [123I]FP-CIT is a radiopharmaceutical that binds reversibly to striatal presynaptic dopamine transporters. We review the two principal multicenter clinical trials of [123I]FP-CIT SPECT imaging and provide additional, previously unreported information. Study 1 was a trial of [123I]FP-CIT SPECT in patients with early suspected parkinsonism that compared baseline scans to the consensus clinical diagnosis established 3 years later. Study 2 was a trial of [123I]FP-CIT SPECT in patients

with established diagnoses of parkinsonian syndrome (PS) or essential tremor (ET). In Study 1, positive percent agreement (abnormal baseline scan and clinical diagnosis of PS at 36 months [n= 71]) was 78-79%. Negative percent agreement (normal baseline scan and a clinical diagnosis of non-PS at 36 months [n= 28]) was 97%. In study 2, positive percent agreement (abnormal scan and a clinical diagnosis of PS [n= 158]) was 92-97%. Negative percent agreement (normal scan and a clinical diagnosis of ET [n= 27]) was 74-96%. [123I]FP-CIT SPECT brain imaging is used to assist in the evaluation of adult patients with suspected PS and may help differentiate http://www.selleckchem.com/products/epacadostat-incb024360.html ET from PS as an adjunct to other diagnostic evaluations. “
“The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied PTK6 to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic

and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps.

Previous investigations by Natarajan and colleagues have provided evidence that angiotensin II can up-regulate 12-LO mRNA and protein in human mononuclear cells

and in human and porcine aortic smooth muscle cells.25, 26 These authors have also demonstrated the up-regulation of 12-LO in response to high-glucose concentrations and have suggested that both angiotensin II and glucose may induce 12-LO expression by activation of protein kinase C.25, 26 Moreover, these authors have demonstrated the ability of selected cytokines (IL-1 and IL-8) and growth factors (platelet-derived growth factor) Trichostatin A ic50 to act as potent inducers of 12-LO expression in porcine vascular smooth muscle cells.39, 40 Importantly, angiotensin II, IL-1, IL-8, and platelet-derived growth factor are invariably found to be increased in the liver in human and experimental NAFLD.41-43 In this study, we were able to define the identity of the 12/15-LO-derived product potentially implicated in liver damage in ApoE−/− mice. In this regard, using RP-HPLC analysis, we detected a peak coeluting with synthetic 12-HETE, which, compared with controls, was increased in livers from ApoE−/− mice. In contrast, 15-HETE was undetectable by check details RP-HPLC in these samples. This finding is consistent with the observation that 12/15-LO produces

12-HETE and minor amounts of 15-HETE from arachidonic acid.44 It is clear Rucaparib datasheet that among the 12/15-LO–derived products, 12-HETE exerts profound detrimental effects on cell metabolism and survival. For instance, 12-HETE is a recognized

inflammatory mediator that induces the expression of MCP-1, TNFα, and IL-6 in macrophages.33, 45 In addition, 12-HETE has been shown to activate protein kinase C, p38 mitogen-activated protein kinase, and JNK in adrenal cells and cardiac fibroblasts and to promote cell death in pancreatic β cells.9, 46-48 In adipocytes, 12-HETE up-regulates inflammatory adipokines such as MCP-1, TNFα, and IL-6 and impairs insulin sensitivity through augmented JNK phosphorylation and impaired IRS-1 and Akt signaling.10 Interestingly, in our study, Alox15 disruption did not completely abrogate hepatic 12-HETE formation, suggesting the presence of alternative biosynthetic pathways, possibly cytochrome P450 (highly present in hepatocytes) or other 12-LO isoforms in this tissue. Also, a peak coeluting with 5-HETE was detected in liver samples, although it remained unaltered in ApoE−/− and ApoE−/−/12/15-LO−/− mice, suggesting that hepatic arachidonic acid metabolism was not redirected from the 12/15-LO to the 5-LO pathway as described.19 This finding also suggests that other products of the 5-LO pathway such as leukotriene B4 and cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are responsible for the observed pathological role of 5-LO in experimental liver disease.

It can serve as an important instrument in national public health

planning and evaluation initiatives to improve health outcomes and health care delivery for individuals who have rare and under-recognized genetic bleeding disorders. The authors are grateful for the dedication of the US Hemophilia Treatment Center network staff that collected these data, the Regional Coordinators for data management and CDC staff who collated the HDS in the earlier years. Preliminary versions of these data were presented at the 1st and 2nd National Conferences BTK inhibitor purchase on Blood Disorders and Public Health in 2010 and 2012, Atlanta, GA; at the 2011 American Thrombosis and Hemostasis Network Summit, Chicago IL; and at the HRSA 2011 Hemophilia Data Summit, Alexandria, VA. Ms. Baker, Riske, Forsberg and Mr. Drake designed the study. Ms. Baker and Mr. Drake acquired the data. Mr. Drake and Mr. Shearer analysed the data. Ms. Baker, Riske, Forsberg, Voutisis, Mr. Drake and Atwood interpreted the data and wrote the manuscript. Ms. Baker provided

overall direction. The authors stated that they had no interests which might be perceived as posing a conflict or bias. “
“Summary.  Accuracy and reproducibility of laboratory measurements are important in the diagnosis and treatment of bleeding disorders. This article describes the process of establishment selleck screening library of international standards and some of the problems that have arisen in standardization of these measurements. During the last 50 years a worldwide system of standardization has been developed to ensure reproducibility of measurements in haemostasis, both in patients’ plasma and in therapeutic materials. Assays of most components of the haemostatic system, and of many therapeutic materials used to treat disorders of haemostasis, are carried out on a comparative basis, relative to a standard of known potency. To relate results in one laboratory to those in other laboratories there must be some means of linking the standards used

in local laboratory assays. The concept of a single biological standard that could provide such a link was first established for insulin in the early twentieth century by Sir Henry Dale [1]. This has been developed into a well-established international system for many biological components under the auspices of the World Health Organisation (WHO). The first International Standard (IS) in the area of haemostasis was for heparin, established Unoprostone in 1942 by the League of Nations, which subsequently became the WHO [2]. In the 1960s, work commenced on establishing WHO Reference Preparations for thromboplastin reagents, because of their widespread use in control of oral anticoagulation [3]. This was soon followed by the establishment of the first IS for one of the clotting factors, factor VIII (FVIII) [4]. Since then, IS have been established for most of the components of the haemostatic system. Further information about these and other standards can be found on the WHO website (www.who.int/biologicals).

A weaker association was observed for FV and FVII deficiencies [10, 11]. No association between coagulation factor activity level and clinical bleeding severity was observed for FXI selleck chemical deficiency, thus FXI coagulation factor activity does not predict clinical bleeding severity [10, 11]. For FII deficiency, the sample size was too small to report on correlation [11]. The lack of association between coagulation factor activity level and bleeding severity in patients with RBDs may be attributed to the potential role of

other factors in determining bleeding severity, such as platelets and fibrinolytic potential. There is a high degree of variability in the coagulation factor activity levels observed to be necessary to ensure complete absence of bleeding episodes and the levels that correspond with a probability of major spontaneous bleeding in the different rare coagulation deficiencies. The EN-RBD database has proven to be a valuable tool for the extrapolation

selleck compound of information relevant to clinical practice and further validation of bleeding risk assessments. A more detailed evaluation of each single factor deficiency is necessary. A project collecting prospective data from patients with RBDs (PRO-RBDD) has been established with the aim of increasing the knowledge of clinical and therapeutic aspects of these disorders. Establishing a consensus on factor assay methodology is important to ensure that values from different laboratories/centres can be compared and to inform further research into the potential role of global coagulation assays in the accurate prediction of haemorrhagic risk. FP received

speaker fees Etomidate from Novo Nordisk and CSL Behring and an unrestricted grant from Novo Nordisk. PJ has received research funding and honoraria from CSL Behring and Octapharma for educational presentations. OS and DM have nothing to disclose. “
“Summary.  Acquired haemophilia (AH) is a rare autoimmune bleeding disorder, which arises as a result of the spontaneous production of autoantibodies against endogenous factor VIII. The breakdown in immune tolerance is thought to be a result of a combination of genetic and environmental factors. Both human leucocyte antigen (HLA) and cytotoxic T lymphocyte antigen 4 (CTLA-4) play an important role in the maintenance of peripheral T-cell tolerance. A higher frequency of HLA class II alleles and single nucleotide polymorphisms of the CTLA-4 gene have been observed in some autoimmune diseases and severe haemophilia A. In 57 patients with AH, significantly higher frequencies of the HLA class II alleles DRB*16 [odds ratio (OR) 10.2] and DQB1*0502 (OR 2.5) have been detected when compared with controls. The CTLA-4 + 49 G allele has also presented with a significantly higher frequency in the same cohort of patients with AH (OR 2.17).

muticum increased the rates of respiration and light-use efficiency of macroalgal assemblages. However, this effect was only a consequence of additional biomass and thus it disappeared when S. muticum lost most of its biomass after senescence. In addition, the increased predictability

between species richness and ecosystem function found in native macroalgal assemblages disappeared in invaded assemblages. The introduction of species with traits not found in the recipient ABT-263 price assemblage can produce large-scale alterations of ecosystem processes and structure (Ruesink et al. 2006). In this study, S. muticum when present at elevated biomass modified respiration and light-use efficiency of assemblages. However, as a habitat modifier, S. muticum individuals may also modify a variety of other ecosystem processes (Wallentinus

and Nyberg 2007). S. muticum has a high growth capacity and is known to influence assemblages by modifying levels of light (Britton-Simmons 2004, Strong et al. 2006), water movement, and temperature (Strong et al. 2006) within canopy areas. Considered an invasive species in its introduced range all around the world (Critchley et al. 1983), S. muticum varies greatly in its ability to impact native systems due to its seasonal reproduction, followed by a rapid shedding of the reproductive tissues (Arenas and Fernández 1998). In the autumn, after a substantial loss of biomass, our results suggest that S. muticum acts as a weak invader and becomes a minor component of native assemblages. crotamiton In the spring, due to the elevated selleck chemicals biomass, this species becomes dominant at the expense of native species and processes and acts as a strong invader (sensu Ortega and Pearson 2005). The different morphological forms of S. muticum

individuals between seasons may have significant differences in the percentage of photosynthetic tissue, net photosynthesis, and specific growth rate, as previously demonstrated for the red alga Gracilaria tikvahiae McLachlan 1979 (Hanisak et al. 1988). Thus, these varying results between seasons are not totally unexpected, although the type of relationship may be. In a previous study using intertidal macroalgal assemblages, also in November/December, correlations with evenness were not significant for any functional variable addressed (Arenas et al. 2009), contrasting with the negative relationship found in this study. The impact of S. muticum can be related to its biomass dominance in the invaded assemblages, in agreement with the sampling effect hypothesis, i.e., the increasing probability of selecting a species with a specific property with increasing species richness (Huston 1997). It has been suggested that native species with a long history of co-evolution may influence ecosystem processes through resource use efficiency, whereas NIS effects on the recipient assemblage occurs through sampling effects (Ruesink et al. 2006).

The start date for analyses was the date of liver biopsy, with any events occurring in the first 6 months excluded. Patients were monitored every 3-6 months Everolimus order and followed up until death or liver transplantation, whichever occurred first, or until data analysis. For those lost to follow-up, up-to-date clinical information was sought by

the following: (1) contact with the primary care physician; (2) telephone interview; and (3) checking the respective death and transplant registries. Patients were censored at time of death or transplantation or last clinic visit, and those lost to follow-up were censored at the time last seen. All clinical outcomes were confirmed by a physician at each center, utilizing patient records and physician diagnoses. The following outcomes

were assessed: (1) liver complications, including liver failure, gastroesophageal varices (± hemorrhage), ascites, encephalopathy, hepatopulmonary syndrome, and HCC; (2) liver-related death or liver transplantation (for calculation of survival probability, transplantation was considered as an equivalent end-point); (3) all-cause mortality; and (4) total Akt inhibitor vascular events (including myocardial infarction, stroke, and vascular deaths).13 HCC was diagnosed if the following were present: (1) pathological changes consistent with HCC identified by histological examination of liver tissue obtained by fine-needle aspiration, liver biopsy, or liver explant at transplantation or autopsy or (2) one or more hepatic space-occupying lesions that had vascular patterns typical of HCC by angiography, Celecoxib triple-phase computed tomography, or magnetic resonance imaging. All patients were followed according to standards of care and guidelines without experimental or therapeutic interventions for NAFLD or HCV. Weight management was performed with lifestyle intervention, such as dietary modification, and exercise was recommended at outpatients in overweight/obese patients. Other treatments, such as oral hypoglycemics, cholesterol-lowering

medications, and antihypertensive medications, were only given in the context of management of concomitant diabetes mellitus, hypercholesterolemia, or hypertension, respectively. Neither pharmacological nor lifestyle interventions were recorded systematically after baseline. Statistical analyses were performed using SPSS version 13.0 (SPSS, Inc., Chicago IL). Results are reported as means ± standard deviation (SD) or frequency (i.e., percentage), as appropriate. Continuous variables were compared using the two-tailed Student’s t-test. Categorical data were compared using the chi-square test. Variables with a P value of ≤0.1 on univariate analysis were further analyzed by multiple logistic regression to determine the independent determinants of outcome variables.