We developed and validated a 30-item short adaptation of the MASQ: the MASQ-D30, which is more suitable for large-scale psychopathology research and has a clearer factor structure. The MASQ-D30 was developed through a process of item reduction and grouping of the appropriate subscales in a sample of 489 psychiatric outpatients,

using a validated Dutch translation, based on the original English MASQ as a starting point. Validation was done in two other large samples of 1461 and 2471 subjects, respectively, with an anxiety, somatoform and/or depression diagnosis or no psychiatric diagnosis. Psychometric properties were investigated and compared between the MASQ-D30 and the full (adapted) MASQ. A three-dimensional model (negative affect, positive affect and somatic arousal) was found to represent the data well, indicating good construct validity. The scales of the MASQ-D30 showed good internal consistency (all selleck alphas >0.87) in patient samples. Correlations of the subscales with other instruments indicated acceptable convergent validity. Psychometric

properties were similar for the MASQ-D30 and the full questionnaire. In conclusion, the MASQ-D30 is a valid instrument to assess dimensional aspects of depression and anxiety and can easily be implemented in psychopathology studies. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Introduction: Released sympathetic neurotransmitter norepinephrine (NE) in the heart is cleared by neuronal uptake-1 and extraneuronal uptake-2 transporters. Cardiac uptake-1 and -2 expression varies among species, but the uptake-1

is the primary transporter in humans. LMI1195 is an JPH203 research buy NE analog labeled with F-18 for PET evaluation of cardiac neuronal function. This study investigated the impact of cardiac neuronal uptake-1 associated with different species on LMI1195 heart uptake.

Methods: Cardiac Silmitasertib concentration uptake-1 was blocked by desipramine, a selective uptake-1 inhibitor, and sympathetic neuronal denervation was induced by 6-hydroxydopamine, a neurotoxin, in rats, rabbits and nonhuman primates (NHP). Tissue biodistribution and cardiac imaging of LMI1195 and I-123-metaiodobenzylguanidine (MIBG) were performed.

Results: In rats, uptake-1 blockade did not alter LMI1195 heart uptake compared to the control at 60-min post injection [1.41 +/- 0.07 vs. 1.47 +/- 0.23 % injected dose per gram tissue (%ID/g)]. In contrast, LMI1195 heart uptake was reduced by 80% in uptake-1 blocked rabbits. In sympathetically denervated rats, LMI1195 heart uptake was similar to the control (2.18 +/- 0.40 vs. 2.58 +/- 0.76 %ID/g). However, the uptake decreased by 79% in denervated rabbits. Similar results were found in MIBG heart uptake in rats and rabbits with uptake-1 blockade. Consistently, LMI1195 cardiac imaging showed comparable myocardial activity in uptake-1 blocked or sympathetically denervated rats to the control, but marked activity reduction in uptake-1 blocked or denervated rabbits and NHPs.

Single-minded 2 (Sim2), a basic helix-loop-helix (bHLH)-PAS transcriptional repressor, is thought to be involved in some symptoms of Down syndrome. We hypothesized that Sim2 mediated hyperglycaemia-induced neuronal injury and impairment of learning and memory. It was found that expression of Sim2 protein in cortical neurons was increased in streptozotocin-induced diabetes mellitus rat model. Drebrin, down-regulated by

Sim2, was subsequently decreased as detected by confocal laser scanning microscopy and Western blot analysis. The expression pattern of Sim2 and Drebrin correspond to 50 mmol/L glucose (hyperglycaemia) was also PD173074 supplier found in primary cultured neurons. Curcumin, one neuroprotective agent, inhibited hyperglycaemia-induced neurotoxicity. Moreover, curcumin alleviated Sim2 expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia. Finally, we found that silencing Sim2 expression this website decreased hyperglycaemia-induced neuronal

injury. In conclusion, Sim2 may mediate neurotoxicity during hyperglycaemia and thereby play a critical role in the development of hyperglycaemia-induced cognitive deficits. (C) 2013 Elsevier Inc. All rights reserved.”
“Genome-wide, absolute quantification of expressed proteins is not yet within reach for most eukaryotes. However, large numbers of MS-based protein identifications have been deposited in databases, together with information on the observation frequencies of each peptide spectrum (“”spectral counts”"). We have conducted a meta-analysis using several million peptide observations from five model eukaryotes, establishing a consistent, semi-quantitative analysis pipeline. By inferring and comparing protein abundances across orthologs, we observe: (i) the accuracy of spectral counting predictions increases with sampling depth and can rival that of direct biochemical measurements, (ii) the quantitative makeup of the consistently observed core proteome in eukaryotes is remarkably stable, with abundance correlations exceeding Bcl-w Rs = 0.7 at an evolutionary distance greater than 1000 million years, and (iii) some groups

of proteins are more constrained than others. We argue that our observations reveal stabilizing selection: central parts of the eukaryotic proteome appear to be expressed at well-balanced, near-optimal abundance levels. This is consistent with our further observations that essential proteins show lower abundance variations than non-essential proteins, and that gene families that tend to undergo gene duplications are less well constrained than families that keep a single-copy status.”
“Prevalent use of bisphenol-A (BPA) in the manufacture of resins, plastics and paper products has led to frequent exposure of most people to this endocrine disruptor. Some rodent studies have suggested that BPA can exert detrimental effects on brain development.

(c) 2008 Published by selleck Elsevier Ltd.”
“Antibodies that neutralize rotavirus infection target outer coat proteins VP4 and VP7 and inhibit viral entry. The structure of a VP7-Fab complex (S. T. Aoki, et al., Science 324: 1444-1447, 2009) led us to reclassify epitopes into two binding regions at inter-and intrasubunit boundaries of the calcium-dependent trimer. It further led us to show that antibodies binding at the intersubunit boundary inhibit uncoating

of the virion outer layer. We have now tested representative antibodies for each of the defined structural epitope regions and find that antibodies recognizing epitopes in either binding region neutralize by cross-linking VP7 trimers. Antibodies that bind at the intersubunit junction neutralize as monovalent Fabs, Temsirolimus mouse while those that bind at the intrasubunit region require divalency. The VP7 structure has also allowed us to design a disulfide cross-linked VP7 mutant which recoats double-layered particles (DLPs) as efficiently as does wild-type VP7 but which yields particles

defective in cell entry as determined both by lack of infectivity and by loss of alpha-sarcin toxicity in the presence of recoated particles. We conclude that dissociation of the VP7 trimer is an essential step in viral penetration into cells.”
“The nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma is a crucial cellular and metabolic switch that regulates many physiologic and disease processes. Emerging evidence reveals that PPAR gamma is also a key modulator of skeletal remodeling. Long-term use of rosiglitazone, a synthetic PPAR gamma agonist and a drug to treat insulin resistance, increases fracture rates BMS-777607 research buy among patients with diabetes. Recent studies have revealed that PPAR gamma activation not

only suppresses osteoblastogenesis, but also activates osteoclastogenesis, thereby decreasing bone formation while sustaining or increasing bone resorption. The pro-osteoclastogenic effect of rosiglitazone is mediated by a transcriptional network comprised of PPAR gamma, PPAR-gamma coactivator 113 and estrogen-related receptor a, which promotes both osteoclast differentiation and mitochondria! activation. Therefore, PPAR gamma plays dual roles in bone homeostasis by regulating both mesenchymal and hematopoietic lineages.”
“Opiate withdrawal syndrome may motivate opiate seeking and taking. Thus, development of an effective medical treatment for these symptoms is a primary research goal and strongly relies on improved experimental models. Opiate withdrawal syndrome is characterized by several behavioral signs such as wet dog shake, teeth chattering, sniffing, scratching, chewing, diarrhea, rearing, ptosis and jumping. The goal of present study was to evaluate the impact of the cylindrical chamber height on the expression of jumping behavior in morphine dependent rats. Adult male Wistar rats were rendered dependent on morphine by subcutaneous (s.c.

These “”elite”" controllers are of high interest as they may provide novel insights regarding host mechanisms of virus control. The degree to which these individuals have residual plasma viremia has not been well defined. We performed a longitudinal study of 46 elite controllers, defined as HIV-seropositive, antiretroviral-untreated individuals with plasma HIV RNA levels of <50 to 75 copies/ml. The median duration of HIV diagnosis was 13 years, the median baseline CD4(+) T-cell count was 753 cells/mm(3), and the median duration of follow-up was 16 months. Plasma and cellular

HIV RNA levels were measured using the transcription-mediated amplification (TMA) assay (estimated limit of detection of <3.5 copies RNA/ml). A total of 1,117 TMA assays were performed (median of five time points/subject and four replicates/time point). LY3009104 mouse All but one subject had detectable plasma HIV RNA on at least one time point, and 15 (33%) subjects had detectable RNA at all time points. The majority of controllers also had detectable cell-associated RNA and proviral DNA. A mixed-effect linear model showed no strong evidence of change

in plasma RNA levels over time. In conclusion, the vast majority (98%) of elite controllers had measurable plasma HIV RNA, often at levels higher than that observed in antiretroviral-treated patients. This I-BET-762 confirms the failure to eradicate the virus, even in these unique individuals who are able to reduce plasma viremia to very low levels without antiretroviral therapy.”
“Acute organophosphate (OP) poisoning causes respiratory failure through two mechanisms: central apnea and pulmonary dysfunction. The vagus nerve is involved in both the central control of respiratory rhythm

as well as the control of pulmonary vasculature, airways and secretions. We used a rat model of acute OP poisoning with and without a surgical vagotomy to explore the role of the vagus in OP-induced Y 27632 respiratory failure. Dichlorvos (2,2-dichlorovinyl dimethyl phosphate) injection (100 mg/kg subcutaneously, 3 x LD50) resulted in progressive hypoventilation and apnea in all animals, irrespective of whether or not the vagi were intact. However, vagotomized animals exhibited a more rapidly progressive decline in ventilation and oxygenation. Artificial mechanical ventilation initiated at onset of apnea resulted in improvement in oxygenation and arterial pressure in poisoned animals with no difference between vagus intact or vagotomized animals. Our observations suggest that vagal mechanisms have a beneficial effect during the poisoning process.

Control participants made more accurate estimates of the mean identity and emotion when faces were upright than inverted. In all conditions. DPs performed equivalently to controls. This finding

demonstrates that integration across different faces in a crowd Alisertib chemical structure is possible in the prosopagnosic population and appears to be intact despite their face recognition deficits. Results also demonstrate that ensemble representations are derived differently for upright and inverted faces, and the effects are not due to low-level visual information. (C) 2012 Elsevier Ltd. All rights reserved.”
“Objective: Sublobar resection (SR) is commonly used for patients considered high risk for lobectomy. Nonoperative therapies are increasingly being reported for patients with

similar risk because of perceived lower morbidity. We report 30- and 90-day adverse events (AEs) from American College of Surgeons Oncology Group Z4032, a multicenter phase III study for high-risk patients with stage I non-small cell lung cancer.

Methods: Data from 222 evaluable patients randomized to SR (n = 114) or SR with brachytherapy (n = 108) are reported. AEs were recorded Mocetinostat supplier using the Common Terminology Criteria for Adverse Events, Version 3.0, at 30 and 90 days after surgery. Risk factors (age, percent baseline carbon monoxide diffusion in the lung [DLCO%], percent forced expiratory volume in 1 second [FEV1%], upper lobe vs lower lobe resections, performance status, surgery approach, video-assisted thoracic surgery vs open and extent, and wedge vs segmentectomy) were analyzed using a multivariable logistic model for their impact on the incidence of grade 3 or higher (G3+) AEs. Respiratory AEs were also specifically analyzed.

Results:

Median age, FEV1%, and DLCO% were similar in the 2 treatment groups. There was no difference in the location of resection (upper vs lower lobe) or the use of segmental or wedge resections. There were no differences between the groups with respect IWP-2 mw to “”respiratory” G3+AEs (30 days: 14.9% vs 19.4%, P = .35; 0-90 days: 19.3% vs 25%, P = .31) and “”any” G3+ AEs (30 days: 25.4% vs 30.6%, P = .37; 0-90 days: 29.8% vs 37%, P = .25). Further analysis combined the 2 groups. Mortality occurred in 3 patients (1.4%) by 30 days and in 6 patients (2.7%) by 90 days. Four of the 6 deaths were thought to be due to surgery. When considered as continuous variables, FEV1% was associated with “”any” G3+ AE at days 0 to 30 (P = .03; odds ratio [OR] = 0.98) and days 0 to 90 (P = .05; OR = 0.98), and DLCO% was associated with “”respiratory” G3+ AE at days 0 to 30 (P = .03; OR = 0.97) and days 0 to 90 (P = .05; OR = 0.98). Segmental resection was associated with a higher incidence of any G3+ AE compared with wedge resection at days 0 to 30 (40.3% vs 22.7%; OR = 2.56; P < .01) and days 0 to 90 (41.5% vs 29.7%; OR = 1.96; P = .04).

81, 95% CI 0.69-0-94; p=0.006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0.84, 95% CI 0.71-0.99; p=0.04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5.0-29.5) and the NNT to achieve viral load suppression was 11 (5.8-227.3).

Interpretation Patients who received SMS support had significantly improved ART adherence and rates of viral suppression

compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings.”
“The mechanisms underlying sound-evoked Danusertib concentration suppression of neuronal firing in the auditory system are poorly understood. To explore these mechanisms in the inferior colliculus (IC), agonists and antagonists targeting different groups of metabotropic glutamate receptors (mGluRs) were applied iontophoretically to IC neurons in awake mice. We found that a group l-specific mGluR agonist predominantly increased neuronal firing in 52% of neurons, whereas group I antagonist had CBL0137 datasheet the opposite effect in 51% of neurons. A group II specific agonist showed no effect on neuronal firing but an antagonist increased firing rate in 48% of neurons. Neither a group Ill-specific mGluR agonist nor an antagonist

had an effect on neuronal firing in the IC. We also found that sound stimuli triggered suppression of spontaneous firing in 70% of IC neurons. This suppression was reversibly blocked by group I mGluR antagonists. There is a possible link between this suppression and two perceptual phenomena: forward masking and “”residual inhibition,”" the brief reduction/elimination of tinnitus ZD1839 order following an appropriate masking sound. Published by Elsevier Ireland Ltd.”
“Background Young people (aged 0-18 years) have been disproportionately affected by pandemic influenza A H1N1 infection. We aimed to analyse paediatric mortality to inform clinical and

public health policies for future influenza seasons and pandemics.

Methods All paediatric deaths related to pandemic influenza A H1N1 infection from June 26,2009, to March 22,2010 in England were identified through daily reporting systems and cross-checking of records and were validated by confirmation of influenza infection by laboratory results or death certificates. Clinicians responsible for each individual child provided detailed information about past medical history, presentation, and clinical course of the acute illness. Case estimates of influenza A H1N1 were obtained from the Health Protection Agency. The primary outcome measures were population mortality rates and case-fatality rates.

Findings 70 paediatric deaths related to pandemic influenza A H1N1 were reported. Childhood mortality rate was 6 per million population. The rate was highest for children aged less than 1 year.

The MR:GR balance is altered by gene variants of these receptor complexes and experience-related factors, which can induce lasting epigenetic changes in the expression of these receptors. A particular potent epigenetic stimulus is the maternal environment which is fundamental for the Maternal Mediation Hypothesis. The outcome of perinatal gene x environ-environment interaction, and thus of MR:GR-mediated functions depends however, on the degree

of ‘matching’ with Belnacasan environmental demands in later life. The Predictive Adaptation Hypothesis therefore presents a conceptual framework to examine the role of glucocorticoids in understanding individual phenotypic differences in stress-related behaviours over the selleckchem lifespan. (C) 2009 Elsevier Ltd. All rights reserved.”
“The lipid peroxidation product 4-hydroxynonenal (4-HNE) forms as a consequence of oxidative stress. By electrophilic attack on biological macromolecules, 4-HNE mediates signaling or may cause toxicity. A major route of 4-HNE disposal is via glutathione conjugation, in the mouse catalyzed primarily by glutathione transferase mGSTA4-4. Unexpectedly, mGsta4-null mice, in which 4-HNE detoxification is impaired, have an extended life span. This finding could be explained by the observed activation of the transcription factor Nrf2 in the knockout mice, which in turn leads to an induction

of antioxidant and antielectrophilic defenses. Especially, the latter could provide a detoxification mechanism that contributes to enhanced longevity. We propose that disruption of 4-HNE conjugation elicits a hormetic response in which an initially increased supply of 4-HNE is translated into activation of Nrf2, leading to a new steady state in which the rise of 4-HNE concentrations is dampened, but life-extending detoxification mechanisms are concomitantly induced.”
“Children who spend early portions of their lives in institutions

or those maltreated in their families of origin are at risk for developing emotional and behavioral problems reflecting disorders of emotion and attention regulation. Animal models may help explicate the mechanisms producing these effects. Despite the value of the animal models, many questions remain in using Buparlisib the animal data to guide studies of human development. In 1999, the National Institute of Mental Health in the United States funded a research network to address unresolved issues and enhance translation of basic animal early experience research to application in child research. Professor Seymour Levine was both the inspiration for and an active member of this research network until his death in October of 2007. This review pays tribute to his legacy by outlining the conceptual model which is now guiding our research studies. (C) 2009 Elsevier Ltd. All rights reserved.

14 mg/day) or vehicle (0.1M NaOH) daily gavage for 5 weeks. Laser-capture microdissection (LCM) was used to isolate renal proximal tubules for molecular analyses. mtDNA abundance and ultrastructural SBI-0206965 pathology were analyzed. mtDNA abundance in whole kidneys from both KO and WT was unchanged regardless of treatment. Renal proximal tubular mtDNA abundance from OAT1 KO also

remained unchanged, suggesting prevention of TDF toxicity due to loss of tenofovir transport into proximal tubules. In contrast, renal proximal tubules from MRP4 KO exhibited increased mtDNA abundance following TDF treatment compared with WT littermates, suggesting compensation. Renal proximal tubules from TDF-treated WT and MRP4 KO exhibited increased numbers of irregular mitochondria with sparse, fragmented PSI-7977 in vivo cristae compared with OAT1 KO. Treatment with ddI had a compensatory effect on mtDNA abundance in OAT1 KO but not in MRP4 KO. Both OAT1 and MRP4 have a direct role in transport

and efflux of tenofovir, regulating levels of tenofovir in proximal tubules. Disruption of OAT1 activity prevents tenofovir toxicity but loss of MRP4 can lead to increased renal proximal tubular toxicity. These data help to explain mechanisms of human TDF renal toxicity. Laboratory Investigation (2011) 91, 852-858; doi:10.1038/labinvest.2011.48; published online 14 March 2011″
“The p75 neurotrophin receptor (p75(NTR)) is expressed on many cell types and can influence a variety of cellular functions. This receptor can mediate cell survival or cell death, can promote or inhibit axonal growth and can facilitate or attenuate proliferation, depending on the cell context. The emerging picture regarding

p75(NTR) indicates that it can partner with different Roscovitine coreceptors to dictate specific responses. It then signals by recruiting intracellular binding proteins to activate different signaling pathways. The function of p75(NTR) has mainly been studied in neurons; however, it is also expressed in a variety of glial populations, especially during development and after injury, where its roles have been poorly defined. In this review, we will examine the potential roles for p75(NTR) in glial function.”
“Many studies have shown widespread but subtle pathological changes in gray matter in patients with schizophrenia. Some of these studies have related specific alterations to the genesis of auditory hallucinations, particularly in the left superior temporal gyrus, but none has analysed the relationship between morphometric data and a specific scale for auditory hallucinations. The present study aims to define the presence and characteristics of structural abnormalities in relation with the intensity and phenomenology of auditory hallucinations by means of magnetic resonance voxel-based morphometry (MR-VBM) method applied on a highly homogeneous group of 18 persistent hallucinatory patients meeting DSM-IV criteria for schizophrenia compared to 19 healthy matched controls.

The level of caffeine was high in brain and liver, and the SSAO activity in all tissues was found to be inhibited

by caffeine. As the concentration of caffeine increased, the https://www.selleckchem.com/products/shp099-dihydrochloride.html SSAO activity decreased. The inhibition ratio was correlated to the levels of caffeine present. We presume that caffeine may treat with SSAO activity associated diseases. (C) 2012 Elsevier Inc. All rights reserved.”
“In probing the mechanism of inhibition of hypoxia inducible factor (HIF-1) by campothecins, we investigated the ability of human topoisomerase I to bind and cleave HIF-1 response element (HRE), which contains the known camptothecin-mediated topoisomerase I cleavage site 5′-TG. We observed that the selection of 5′-TG by human topoisomerase I and topotecan depends to a large extent on the specific flanking sequences,

and that the presence of a G at the 22 position (where cleavage occurs between 21 and 11) prevents the HRE site from being a preferred site for such cleavage. Furthermore, the presence of 22 T/A can induce the cleavage at a less preferred TC or TA site. However, in the absence of a more preferred site, the HRE site is shown to be cleaved by human topoisomerase I in the presence of topotecan. Thus, it is implied that the 22 base has a significant influence on the selection of the camptothecin-mediated Topo I cleavage site, which can overcome the preference for +1G. While the cleavage site recognition has been known to be based on the concerted effect of several bases spanning the cleavage site,

such a determining effect of an individual Verubecestat ic50 base has not been previously recognized. A possible base-specific interaction between DNA and topoisomerase I may be responsible for this sequence selectivity.”
“We report the case of a 32-year-old man with severe polytrauma, submitted to urgent endovascular exclusion of a posttraumatic thoracic aortic pseudoaneurysm. Two years later, computed tomography scan showed asymptomatic mural atherothrombosis Low-density-lipoprotein receptor kinase of the aortic stent graft in its middle-distal portion, and the patient was placed on oral anticoagulants. As subsequent computed tomography scan showed progression of the thrombosis, the patient underwent surgical conversion, with stent graft explantation and in situ aortic replacement. Gross examination revealed mural organized thrombosis and a significant infolding of the distal end of the stent graft. (J Vase Surg 2012;55:538-41.)”
“Acrylamide (ACR) intoxication in its monomeric form leads to neuronal damage in both experimental animals and humans. Oxidative stress is one of the principle mechanisms related to the neurotoxicity of ACR exposure. Hence, the present study aimed to recapitulate the potential of ACR to cause oxidative stress and neurotoxic effects in Drosophila melanogaster. Exposure of adult male flies (Oregon K strain) to ACR (1-10 mM, 7 d) in the diet resulted in a concentration and time dependent mortality, while the survivors exhibited significant locomotor deficits.

In the myxomatous group, freedom from reoperation was lower in patients with anterior leaflet pathology (P = .0008).

Conclusion: Follow-up data to 36 years demonstrate that cause strongly determines survival and durability of mitral valvuloplasty; patients with rheumatic valve disease who survive more than 20 years require reoperation, whereas functional mitral regurgitation carries the highest short- and long-term mortality rates and lowest freedom from reoperation. Mitral valvuloplasty for myxomatous

valves https://www.selleckchem.com/products/cx-4945-silmitasertib.html demonstrates the longest durability, with many patients free from reoperation at 30 years. (J Thorac Cardiovasc Surg 2010; 139: 76-84)”
“Neural correlates of control mechanisms in human working memory are discussed at two levels in this review: (i) at ‘item level’, where in multi-item working memory information needs to be organized into sequential memory representations, and (ii) at a ‘process level’, indicating the integration and control of a variety of

cognitive functions involved in working memory, independent of item representations per se. It will be discussed that at both levels electroencephalographic theta activity is responsible Rabusertib molecular weight for control of working memory functions. On item level, exact phase coding, e.g., approached by coupling between theta and gamma oscillations or phase resetting of theta frequency, is suggested to integrate information into working memory representations. At process level until interregional theta synchronization is discussed to integrate brain structures necessary for working memory. When discussing the specificity of theta activity for control of working memory processes it will be suggested that theta oscillations might play an important general integrative role in organization of brain activity. And as working memory often involves a variety of cognitive processes which need to be coordinated there is

particular need for an integrative brain mechanism like theta activity as suggested in this review. (C) 2009 Elsevier Ltd. All rights reserved.”
“Objectives: In proximal chronic thromboembolic pulmonary hypertension, pulmonary endarterectomy is the treatment of first choice. In general, medical treatment before pulmonary endarterectomy is not indicated. However, selected “”high-risk”" patients might benefit by optimization of pulmonary hemodynamics. Moreover, in patients whose surgery is delayed owing to limited medical resources, pretreatment may prevent clinical deterioration. The primary objective of this study was to determine whether the dual endothelin-1 antagonist bosentan improves pulmonary hemodynamics and functional capacity in patients with proximal chronic thromboembolic pulmonary hypertension waiting for pulmonary endarterectomy.

Methods: We used an investigator-initiated, randomized, controlled single-blind study. Patients were randomized to receive bosentan (n = 13) or no bosentan (n = 12) for 16 weeks, next to “”best standard of care.