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Amputation as a life-saving measure for earthquake-trapped patients is supported by WHO and INSARAG guidelines. However, implementing these guidelines in highly stressful contexts can complicate decision-making. This report presents a case of life-saving amputation during the 2023 Turkey earthquake, adhering to recommended guidelines. The 16-year-old patient was trapped for 55 hours in a narrow corridor. Extensive interdisciplinary discussions led to the decision for a field amputation after alternative rescue attempts failed. Consent was obtained from the family, given the patient's delirium. Meticulous planning and anesthesia using midazolam and ketamine ensured successful amputation with minimal blood loss. Challenges encountered during the disaster response were discussed. Delays in administering antibiotics, a lack of cervical protection, ethical dilemmas, psychological concerns, and legal implications were highlighted. Continued improvement and addressing ethical, legal, and psychological aspects are essential for optimal disaster response outcomes.

Background: Emergency triage, which involves complex decision-making under stress and time constraints, may suffer from inaccuracies due to workplace distractions. A serious game was developed to simulate the triage process and environment. A pilot study was undertaken to collect preliminary data on the effects of distractors on emergency nurse triage accuracy., Method: A 2 × 2 factorial randomized controlled trial (RCT) was designed for the study. A sample of 70 emergency room nurses was randomly assigned to three experimental groups exposed to different distractors (noise, task interruptions, and both) and one control group. Nurses had two hours to complete a series of 20 clinical vignettes, in which they had to establish a chief complaint and assign an emergency level., Results: Fifty-five nurses completed approximately 15 vignettes each during the allotted time. No intergroup differences emerged in terms of triage performance. Nurses had a very favorable appreciation of the serious game focusing on triage., Conclusion: The results show that both the structure of our study and the serious game can be used to carry out a future RCT on a larger scale. The lack of a distractor effect raises questions about the frequency and intensity required to find a significant impact on triage performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Metastasis-directed therapy (MDT) significantly delays the initiation of palliative androgen deprivation therapy (pADT) in patients with oligorecurrent prostate cancer (PCa) with a positive impact on patient's quality of life. However, it remains unclear whether the addition of ADT improves polymetastatic free survival (PMFS) and metastatic castration refractory PCa-free survival (mCRPC-FS) and how long concomitant hormone therapy should be given. A significant overall survival (OS) benefit was shown when an androgen receptor targeted agent (ARTA) was added to pADT in patients with metastatic hormone sensitive PCa (HSPC). However, whether the addition of and ARTA to MDT in the treatment of oligorecurrent PCa results in better PMFS and mCRPC-FS has not been proven yet., Methods & Design: Patients diagnosed with oligorecurrent HSPC (defined as a maximum of 5 extracranial metastases on PSMA PET-CT) will be randomized in a 1:1:1 allocation ratio between arm A: MDT alone, arm B: MDT with 1 month ADT, or arm C: MDT with 6 months ADT together with ARTA (enzalutamide 4 × 40 mg daily) for 6 months. Patients will be stratified by PSA doubling time (≤ 3 vs. > 3 months), number of metastases (1 vs. > 1) and initial localization of metastases (M1a vs. M1b and/or M1c). The primary endpoint is PMFS, and the secondary endpoints include mCRPC-FS, biochemical relapse-free survival (bRFS), clinical progression free survival (cPFS), cancer specific survival (CSS), overall survival (OS), quality of life (QOL) and toxicity., Discussion: This is the first prospective multicentre randomized phase III trial that investigates whether the addition of short-term ADT during 1 month or short-term ADT during 6 months together with an ARTA to MDT significantly prolongs PMFS and/or mCRPC-FS., Trial Registration: ClinicalTrials.gov Identifier: NCT05352178, registered April 28, 2022., (© 2022. The Author(s).)

Purpose: To evaluate the technical efficacy, safety, and reproducibility of automated percutaneous lumbar discectomy (APLD) under CT and fluoroscopic guidance, for treating radiculopathy caused by lumbar disc herniation in patients impervious to conservative treatment., Methods: A total of 77 patients with symptomatic lumbar disc herniation were treated with APLD in a prospective multicentric study performed in four centers across three countries. Magnetic resonance imaging and/or computed tomography was used to evaluate the disc herniation before and after the procedure. Only local anesthesia was used during these procedures. Clinical outcomes were measured with the visual analog scale (VAS) for pain at one and 6 months after the procedure., Results: Technical success rate was 100% with a mean intervention duration of 30 min (15-45 min). No complications occurred during the procedure. Post-lumbar puncture syndrome occurred in three patients who were successfully treated with blood patches. VAS decreased from a mean of 8 before the intervention to 3 1 month after (p value = 0.001). The requirement for analgesia decreased from 100 to 27%. No statistically significant differences in outcomes were found between the centers., Conclusion: APLD with dual imaging guidance under local anesthesia is a safe, feasible, and reproducible technique to treat symptomatic lumbar disc herniation.

We evaluated the long-term serological follow-up of patients with vascular risk factors for chronic Q fever that were previously Coxiella burnetii seropositive. C. burnetii phase I IgG titers were reevaluated in patients that gave informed consent or retrospectively collected in patients already deceased or lost to follow-up. Of 107 patients, 25 (23.4%) became seronegative, 77 (72.0%) retained a profile of past resolved Q fever infection, and five (4.7%) developed chronic Q fever. We urge clinicians to stay vigilant for chronic Q fever beyond two years after primary infection and perform serological testing based on clinical presentation.

Introduction: Peripheral arterial disease (PAD) is an occlusive vascular disease of the lower extremities with increasing incidence and prevalence numbers and therefore rising health care costs. Mobile applications have great potential to improve health system efficiency and can assist in overcoming the increasing health care costs. In this review all available mobile applications developed for PAD are summarized and a new innovative application is introduced. Areas covered: Available applications for PAD are scarce and currently aim at prevention, teleconsultation and telemonitoring via questionnaires and activity tracking. Integration in the daily workflow of the physician is an overlooked aspect of these applications. JBZetje is an innovative mobile application that provides remote care, information services and self-service tools, and enables connection with the electronic health record (EHR). Expert opinion: Connection of the application with the EHR generates a complete overview of a patient's current health status. This will reinforce the tendency toward personalized medicine and will probably lead to reduced health care costs and increase the quality of care. Future feasibility studies should answer the question whether the use of mobile applications is feasible in the PAD population.

A long-term partnership among the Butaro Cancer Center of Excellence (BCCOE) in Rwanda, Partners in Health (PIH)/Inshuti Mu Buzima, and Dana-Farber Cancer Institute (DFCI) supports the development of oncology nurses through a clinical nurse educator role. Two senior Rwandan oncology nurses at BCCOE were hired as nurse educators and were mentored by a PIH/DFCI oncology nurse educator using the accompaniment approach. The formalized mentorship process included long-term accompaniment for all educator projects spanning staff training, quality improvement, research, and clinical practice, as well as development of nurse educator competencies and creation of a repository of resources.

The objective is to evaluate our center's experience with the safety and efficacy of the percutaneous approach to endovascular abdominal aortic aneurysm repair (PEVAR) with use of the Perclose Proglide device, in the first period after introduction in our center in 2014. We retrospectively identified all patients that underwent PEVAR or endograft extension with percutaneous approach in our center in the urgent and elective setting. Included were all procedures performed between the introduction of the technique in January 2014 and February 2016 when PEVAR had become the predominant technique in our center. Exclusion progressed from expected difficulty of the procedure as estimated by the operator to total calcification of the ventral wall of the CFA towards the end of the study period. Surgical and clinical reports were used to analyze patient characteristics, procedural success, and short-term outcome after 30 days. Follow-up imaging was used to assess mid-term access site complications at 1 and 2 years postoperatively. A univariate regression analysis was conducted to determine significant predictors of access-related complications with the Perlcose Proglide system. Of all 78 patients (mean age 74, SD: 7 years, 70 men), 68 (87.2%) underwent PEVAR and 10 (12.8%) underwent endograft extension procedures with percutaneous approach. Sixty-seven (85.9%) patients underwent an elective procedure and 11 (14.1%) patients underwent urgent PEVAR. The total number of vessels that was percutaneously accessed was 142. Direct technical success of the procedure as analyzed per vessel was 98.6% (140/142), with two cases of conversion to the femoral cut-down approach. A total of 274 Perclose Proglide devices were placed. Device failure of the Perclose device occurred in 5.8% (16/274) and was reason for conversion to cut-down procedure in one case. Mean duration of the procedure and median time of hospitalization were 100 (SD: 34) min and 2 (IQR 1, 3) days, respectively. Event-free survival per vessel after 30 days was 91.0%, with two minor access-related complication. Fifty-five individual patients (105 vessels) were eligible for inclusion in the 1-year follow-up analysis. Of these patients, 19 (34 vessels) could be included in the 2-year follow-up analysis. No additional access site complications occurred at mid-term follow-up. No significant predictors of device failure were found. The percutaneous approach to EVAR appears to be a safe and effective option with high success rate and low complication rate in a real-world setting. Based on our findings, we conclude that the technique can safely be introduced in a vascular center.

Objective: After primary infection with Coxiella burnetii, patients may develop acute Q fever, which is a relatively mild disease. A small proportion of patients (1%-5%) develop chronic Q fever, which is accompanied by high mortality and can be manifested as infected arterial or aortic aneurysms or infected vascular prostheses. The disease can be complicated by arterial fistulas, which are often fatal if they are left untreated. We aimed to assess the cumulative incidence of arterial fistulas and mortality in patients with proven chronic Q fever., Methods: In a retrospective, observational study, the cumulative incidence of arterial fistulas (aortoenteric, aortobronchial, aortovenous, or arteriocutaneous) in patients with proven chronic Q fever (according to the Dutch Chronic Q Fever Consensus Group criteria) was assessed. Proven chronic Q fever with a vascular focus of infection was defined as a confirmed mycotic aneurysm or infected prosthesis on imaging studies or positive result of serum polymerase chain reaction for C. burnetii in the presence of an arterial aneurysm or vascular prosthesis., Results: Of 253 patients with proven chronic Q fever, 169 patients (67%) were diagnosed with a vascular focus of infection (42 of whom had a combined vascular focus and endocarditis). In total, 26 arterial fistulas were diagnosed in 25 patients (15% of patients with a vascular focus): aortoenteric (15), aortobronchial (2), aortocaval (4), and arteriocutaneous (5) fistulas (1 patient presented with both an aortocaval and an arteriocutaneous fistula). Chronic Q fever-related mortality was 60% for patients with and 21% for patients without arterial fistula (P < .0001). Primary fistulas accounted for 42% and secondary fistulas for 58%. Of patients who underwent surgical intervention for chronic Q fever-related fistula (n = 17), nine died of chronic Q fever-related causes (53%). Of patients who did not undergo any surgical intervention (n = 8), six died of chronic Q fever-related causes (75%)., Conclusions: The proportion of patients with proven chronic Q fever developing primary or secondary arterial fistulas is high; 15% of patients with a vascular focus of infection develop an arterial fistula. This observation suggests that C. burnetii, the causative agent of Q fever, plays a role in the development of fistulas in these patients. Chronic Q fever-related mortality in patients with arterial fistula is very high, in both patients who undergo surgical intervention and patients who do not., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The aim was to identify the prevalence of inadequate health literacy in patients with arterial vascular disease. This was a cross sectional study., Methods: Patients with arterial vascular disease visiting the outpatient clinic between January 5, 2015 and December 28, 2016, were randomly included and screened for inadequate health literacy with the Newest Vital Sign-Dutch (NVS-D), a validated health literacy assessment measure. A score of <4 out of six identified individuals with inadequate health literacy. Age, gender, highest education level, and reason for consultation were also registered. Data analysis was performed using Student's t-test or the Mann-Whitney U test and chi-square test. Logistic regression with backward elimination was applied to identify independent predictors., Results: A total of 202 patients were included. The mean NVS-D score was 1.91 (SD ± 1.948, median 1). The prevalence of inadequate health literacy was 76.7%. A significantly higher prevalence of inadequate health literacy was found in patients ≥65 years (p < .001) and patients with a lower education level (p < .001). No significant difference was found between female/male patients (p = .056), nor between participants with peripheral arterial occlusive disease and abdominal aortic aneurysm (p = .116). Age (OR 1.060; 95% CI 1.017-1.104; p = .005) and education level (OR 0.164; 95% CI 0.078-0.346; p < .001) were identified as independent predictors of inadequate health literacy., Conclusion: This study shows a prevalence of inadequate health literacy of 76.7% in patients with arterial vascular disease, with a significantly higher prevalence in patients ≥ 65 years and patients with a lower education level. The high prevalence of inadequate health literacy should be considered when information is provided, and suggests the need to further investigate the best methods to convey medical information to this group of vulnerable patients., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Here, we describe the production of stable isotope-labeled human immunoglobulin G1 ([ 13 C]-hIgG1) using [ 13 C]-L-lysine/arginine-labeled hIgG1. The fermentation process was run in shake flasks containing labeled arginine and lysinethat were incorporated into the produced recombinant hIgG1. The [ 13 C]-hIgG1 was purified, and label incorporation was determined to be >99% at all lysine and arginine moieties. Sequence coverage was confirmed by peptide mapping. [ 13 C]-hIgG1 was then used as an internal standard (IS) for the development of a liquid chromatography-tandem mass spectrometry method applicable to the quantitative analysis of all human types of hIgG1 in rat serum. Four conserved peptides, namely, GPSVFPLAPSSK, TTPPVLDSDGSFFLYSK, VVSVLTVLHQDWLNGK, and FNWYVDGVEVHNAK, originating from different parts of the fraction crystallizable region of hIgG1, were used for quantitation of hIgG1 in rat serum. The calibration curves with a coefficient of determination (r 2 ) between 0.9950 and 0.9962 resulting from the peak area ratio of each peptide to its respective labeled IS were reproducible. A mean bias within ±20.0% of the nominal values and a precision of ≤20.0 % were obtained for the calibration standards and quality control samples for each peptide. [ 13 C]-hIgG1 was shown as a suitable IS for quantitative hIgG1 analysis in preclinical species by LC-MS/MS., (Copyright © 2016 John Wiley & Sons, Ltd.)

In vitro and in vivo studies attribute potent immune regulatory properties to the vitamin D receptor (VDR). Yet, it is unclear to what extend these observations translate to the clinical context of (vascular) inflammation. This clinical study evaluates the potential of a VDR agonist to quench vascular inflammation. Patients scheduled for open abdominal aneurysm repair received paricalcitol 1 μg daily during 2-4 weeks before repair. Results were compared with matched controls. Evaluation in a parallel group showed that AAA patients are vitamin D insufficient (median plasma vitamin D: 43 (30-62 (IQR)) nmol/l). Aneurysm wall samples were collected during surgery, and the inflammatory footprint was studied. The brief paricalcitol intervention resulted in a selective 73% reduction in CD4+ T-helper cell content (P<0.024) and a parallel 35% reduction in T-cell (CD3+) content (P<0.032). On the mRNA level, paricalcitol reduced expression of T-cell-associated cytokines IL-2, 4, and 10 (P<0.019). No effect was found on other inflammatory mediators. On the protease level, selective effects were found for cathepsin K (P<0.036) and L (P<0.005). Collectively, these effects converge at the level of calcineurin activity. An effect of the VDR agonist on calcineurin activity was confirmed in a mixed lymphocyte reaction. In conclusion, brief course of the VDR agonist paricalcitol has profound effects on local inflammation via reduced T-cell activation. The anti-inflammatory potential of VDR activation in vitamin D insufficient patients is highly selective and appears to be mediated by an effect on calcineurin-mediated responses.

Objective: To evaluate the feasibility and anatomical success of endovenous laser ablation (EVLA) of incompetent perforating veins (IPV)., Methods: All 135 consecutive patients with IPV treated with ELVA (intention-to-treat) from January 2008 to December 2013 were included. Up to the end of 2011, an 810-nm laserset (14 W) was used, and afterwards, a 1470-nm laserset (6 W) was introduced. Duplex ultrasound was performed at 6 weeks' follow-up to assess anatomical success., Results: Overall anatomical success at 6 weeks' follow-up was 56%. Anatomical success was 63% after treatment with 810 nm and 45% with 1470 nm (p = 0.035). This difference in the success rate seems associated with the significantly higher amount of energy delivered in the 810 nm cohort (560 J) versus 1470 nm (186 J). Regardless of the type of laser, anatomical success was significantly higher after treatment with more than 400 J (66%) compared with 0-200 J (40%, p = 0.009) and 200-400 J (43%, p = 0.029). Complications were limited to two cases of transient paresthesia., Conclusions: EVLA of IPVs is safe and feasible. The amount of energy is highly important in achieving anatomical success., (© The Author(s) 2015.)

Objective: Since chronic Q fever often develops insidiously, and symptoms are not always recognized at an early stage, complications are often present at the time of diagnosis. We describe complications associated with vascular chronic Q fever as found in the largest cohort of chronic Q fever patients so far., Methods: Patients with proven or probable chronic Q fever with a focus of infection in an aortic aneurysm or vascular graft were included in this study, using the Dutch national chronic Q fever database., Results: A total of 122 patients were diagnosed with vascular chronic Q fever between April 2008 and June 2012. The infection affected a vascular graft in 62 patients (50.8%) and an aneurysm in 53 patients (43.7%). Seven patients (5.7%) had a different vascular focus. Thirty-six patients (29.5%) presented with acute complications, and 35 of these patients (97.2%) underwent surgery. Following diagnosis and start of antibiotic treatment, 26 patients (21.3%) presented with a variety of complications requiring surgical treatment during a mean follow-up of 14.1 ± 9.1 months. The overall mortality rate was 23.7%. Among these patients, mortality was associated with chronic Q fever in 18 patients (62.1%)., Conclusions: The management of vascular infections with C. burnetii tends to be complicated. Diagnosis is often difficult due to asymptomatic presentation. Patients undergo challenging surgical corrections and long-term antibiotic treatment. Complication rates and mortality are high in this patient cohort., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

A large community outbreak of Q fever occurred in the Netherlands in the period 2007 to 2010. Some of the infected patients developed chronic Q fever, which typically includes pathogen dissemination to predisposed cardiovascular sites, with potentially fatal consequences. To identify the immune mechanisms responsible for ineffective clearance of Coxiella burnetii in patients who developed chronic Q fever, we compared serum concentrations of 47 inflammation-associated markers among patients with acute Q fever, vascular chronic Q fever, and past resolved Q fever. Serum levels of gamma interferon were strongly increased in acute but not in vascular chronic Q fever patients, compared to past resolved Q fever patients. Interleukin-18 levels showed a comparable increase in acute as well as vascular chronic Q fever patients. Additionally, vascular chronic Q fever patients had lower serum levels of gamma interferon-inducible protein 10 (IP-10) and transforming growth factor β (TGF-β) than did acute Q fever patients. Serum responses for these and other markers indicate that type I immune responses to C. burnetii are affected in chronic Q fever patients. This may be attributed to an affected immune system in cardiovascular patients, which enables local C. burnetii replication at affected cardiovascular sites., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The aim of this study was to describe specific histological findings of the Coxiella burnetii-infected aneurysmal abdominal aortic wall. Tissue samples of the aneurysmal abdominal aortic wall from seven patients with chronic Q fever and 15 patients without evidence of Q fever infection were analysed and compared. Chronic Q fever was diagnosed using serology and tissue PCR analysis. Histological sections were stained using haematoxylin and eosin staining, Elastica van Gieson staining and immunohistochemical staining for macrophages (CD68), T lymphocytes (CD3), T lymphocyte subsets (CD4 and CD8) and B lymphocytes (CD20). Samples were scored by one pathologist, blinded for Q fever status, using a standard score form. Seven tissue samples from patients with chronic Q fever and 15 tissue samples from patients without Q fever were collected. Four of seven chronic Q fever samples showed a necrotizing granulomatous response of the vascular wall, which was characterized by necrotic core of the arteriosclerotic plaque (P = 0.005) and a presence of high numbers of macrophages in the adventitia (P = 0.007) distributed in typical palisading formation (P = 0.005) and surrounded by the presence of high numbers of T lymphocytes located diffusely in media and adventitia. Necrotizing granulomas are a histological finding in the C. burnetii-infected aneurysmal abdominal aortic wall. Chronic Q fever should be included in the list of infectious diseases with necrotizing granulomatous response, such as tuberculosis, cat scratch disease and syphilis., (© 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.)

Objectives: The aim of this study was to estimate the seroprevalence of Q fever and prevalence of chronic Q fever in patients with abdominal aortic and/or iliac disease after the Q fever outbreak of 2007-2010 in the Netherlands., Methods: In November 2009, an ongoing screening program for Q fever was initiated. Patients with abdominal aortic and/or iliac disease were screened for presence of IgM and IgG antibodies to phase I and II antigens of Coxiella burnetii using immunofluorescence assay and presence of C. burnetii DNA in sera and/or vascular wall tissue using polymerase chain reaction (PCR)., Results: A total of 770 patients with abdominal aortic and/or iliac disease were screened. Antibodies against C. burnetii were detected in 130 patients (16.9%), of which 40 (30.8%) patients showed a serological profile of chronic Q fever. Three patients presented with acute Q fever, one of which developed to chronic Q fever over time. The number of aneurysm-related acute complications in patients with chronic Q fever was significantly higher compared to patients negative for Q fever (p = 0.013); 9.0% (30/333) vs. 30.0% (6/20). Eight out of 46 patients with past resolved Q fever (8/46, 17.4%) presented with aneurysm-related acute complications (no significant difference)., Conclusion: The prevalence of chronic Q fever in C. burnetii seropositive patients with abdominal aortic and/or iliac disease living in an epidemic area in the Netherlands is remarkably high (30.8%). Patients with an aneurysm and chronic Q fever present more often with an aneurysm-related acute complication compared to patients without evidence of Q fever infection., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Persistent organochlorine pollutants such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p'-DDE), and polybrominated diphenyl ethers (PBDEs) are stable, bioaccumulative, and widely found in the environment, wildlife, and the human population. To explore the hypothesis that reproduction in male fish is associated with environmental exposures in the lower Columbia River (LCR), reproductive and endocrine parameters were studied in male resident, non-anadromous largescale sucker (Catostomus macrocheilus) (LSS) in the same habitats as anadromous salmonids having conservation status. Testes, thyroid tissue and plasma collected in 2010 from Longview (LV), Columbia City (CC), and Skamania (SK; reference) were studied. Sperm morphologies and thyrocyte heights were measured by light microscopy, sperm motilities by computer-assisted sperm motion analysis, sperm adenosine triphosphate (ATP) with luciferase, and plasma vitellogenin (VTG), thyroxine (T4), and triiodothyronine (T3) by immunoassay. Sperm apoptosis, viability, mitochondrial membrane potential, nuclear DNA fragmentation, and reproductive stage were measured by flow cytometry. Sperm quality parameters (except counts) and VTG were significantly different among sites, with correlations between VTG and 7 sperm parameters. Thyrocyte heights, T4, T3, gonadosomatic index and Fulton's condition factor differed among sites, but not significantly. Sperm quality was significantly lower and VTG higher where liver contaminants and water estrogen equivalents were highest (LV site). Total PCBs (specifically PCB-138, -146, -151, -170, -174, -177, -180, -183, -187, -194, and -206) and total PBDEs (specifically BDE-47, -100, -153, and -154) were negatively correlated with sperm motility. PCB-206 and BDE-154 were positively correlated with DNA fragmentation, and pentachloroanisole and VTG were positively correlated with sperm apoptosis and negatively correlated with ATP. BDE-99 was positively correlated with sperm counts and motility; T4 was negatively correlated with counts and positively correlated with motility, thus indicating possible androgenic mechanisms and thyroid endocrine disruption. Male LSS proved to be an informative model for studying reproductive and endocrine biomarkers in the LCR., (© 2013.)

We report 2 patients with symptomatic aortic aneurysm and serologic evidence of acute Q fever with positive Coxiella burnetii PCR in blood/tissue. This suggests a role for acute Q fever in aneurysm progression. Diagnostic testing for Q fever infection in patients with symptomatic aneurysms in Q fever areas is recommended., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Community detection helps us simplify the complex configuration of networks, but communities are reliable only if they are statistically significant. To detect statistically significant communities, a common approach is to resample the original network and analyze the communities. But resampling assumes independence between samples, while the components of a network are inherently dependent. Therefore, we must understand how breaking dependencies between resampled components affects the results of the significance analysis. Here we use scientific communication as a model system to analyze this effect. Our dataset includes citations among articles published in journals in the years 1984-2010. We compare parametric resampling of citations with non-parametric article resampling. While citation resampling breaks link dependencies, article resampling maintains such dependencies. We find that citation resampling underestimates the variance of link weights. Moreover, this underestimation explains most of the differences in the significance analysis of ranking and clustering. Therefore, when only link weights are available and article resampling is not an option, we suggest a simple parametric resampling scheme that generates link-weight variances close to the link-weight variances of article resampling. Nevertheless, when we highlight and summarize important structural changes in science, the more dependencies we can maintain in the resampling scheme, the earlier we can predict structural change.

7β-Hydroxy-epiandrosterone (7β-OH-EpiA), an endogenous androgenic derivative of dehydroepiandrosterone, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-Δ(12,14)-PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-OH-EpiA (1-100nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogen-dependent mammary cancers. Estrogen induced PGE2 production and cell proliferation via its binding to estrogen receptors (ERs) in these tumors. Our objective was to test the effects of 7β-OH-EpiA on the proliferation (by counting with trypan blue exclusion), cell cycle and cell apoptosis (by flow cytometry) of breast cancer cell lines MCF-7 (ERα+, ERβ+, G-protein coupled receptor 30: GPR30+) and MDA-MB-231 (ERα-, ERβ+, GPR30+) and to identify a potential target of this steroid in these cell lineages (by transactivations) and in the nuclear ER-negative SKBr3 cells (GPR30+) (by proliferation assays). 7β-OH-EpiA exerted anti-estrogenic effects in MCF-7 and MDA-MB-231 cells associated with cell proliferation inhibition and cell cycle arrest. Moreover, transactivation and proliferation with ER agonists assays indicated that 7β-OH-EpiA interacted with ERβ. Data from proliferation assays on the MCF-7, MDA-MB-231 and SKBr3 cell lines suggested that 7β-OH-EpiA may also act through the membrane GPR30 receptor. These results support that this androgenic steroid acts as an anti-estrogenic compound. Moreover, this is the first evidence that low doses of androgenic steroid exert antiproliferative effects in these mammary cancer cells. Further investigations are needed to improve understanding of the observed actions of endogenous 7β-OH-EpiA., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Delirium is a common problem in elderly patients undergoing surgery. Standard delirium care is not available at all surgical wards. We determined the incidence, risk factors, and outcomes of postoperative delirium among patients undergoing elective/emergency aortoiliac surgery at a surgical ward with high-standard delirium care. A prospective descriptive survey in 107 patients was conducted. High-standard delirium care was given to patients above age 65, consisting of an extended focus on risk factors and intensive screening. The Delirium Observation Scale was used as a screening instrument for delirium. Patients were classified as having delirium if they met the DSM-IV criteria. The overall incidence of delirium was 23%. The incidence was 14% after elective surgery. Delirium occurred in 59% after emergency surgery and more often after open than after endovascular aneurysm repair (p < .01). Delirium was associated with age (p < .01) and emergency surgery (p = .01) and is an important and frequent complication after aortoiliac surgery.

A 76-year-old man was referred to the Emergency Department because of collapse, epigastric pain and nausea. The patient had been diagnosed with an infrarenal aneurysm of the abdominal aorta nine years earlier. His symptoms were attributed to an aortic-duodenal fistula originating from the aneurysm. The patient died despite placement of an aortic prosthesis. A hospital screening programme for chronic Q fever in patients with aortic aneurysm revealed chronic Q fever. Until recently, vascular infection with Coxiella burnetii was an unknown disease in the Netherlands. In view of the nonspecific clinical presentation, severity and therapeutic consequences of the disease, we advise screening for chronic Q fever in all symptomatic patients with an aortic aneurysm or prosthesis - whether or not with aspecific symptoms - in regions where the disease is endemic.

We report the clinical feasibility of fluoroscopic Roentgen stereophotogrammetric analysis (FRSA), a validated method to quantify real time three-dimensional (3D) dynamic motion of stent grafts and the first clinical results after abdominal and thoracic endovascular repair (EVAR). Stent graft motion was measured at 30 (stereo) frames per second, during the cardiac cycle and in the patient after abdominal EVAR, due to respiratory action. Translational motions of the center of mass, diameter change, and rotational and axial motion could be measured. Quantification of 3D motion was not available until now. FRSA can provide crucial information on the forces exerted on stent grafts and will, therefore, provide essential information for improvements in stent graft design.

The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.

Background and Purpose: Osseous pelvic tumors can be resected and reconstructed using massive bone allografts. Geometric accuracy of the conventional surgical procedure has not yet been documented. The aim of this experimental study was mainly to assess accuracy of tumoral resection with a 10-mm surgical margin, and also to evaluate the geometry of the host-graft reconstruction., Methods: An experimental model on plastic pelvises was designed to simulate tumor resection and reconstruction. 4 experienced surgeons were asked to resect 3 different tumors and to reconstruct pelvises. 24 resections and host-graft junctions were available for evaluation. Resection margins were measured. Several methods were created to evaluate geometric properties of the host-graft junction., Results: The probability of a surgeon obtaining a 10-mm surgical margin with a 5-mm tolerance above or below, was 52% (95% CI: 37-67). Maximal gap, gap volume, and mean gap between host and graft was 3.3 (SD 1.9) mm, 2.7 (SD 2.1) cm3 and 3.2 (SD 2.1) mm, respectively. Correlation between these 3 reconstruction measures and the degree of contact at the host-graft junction was poor., Interpretation: 4 experienced surgeons did not manage to consistently respect a fixed surgical margin under ideal working conditions. The complex 3-dimensional architecture of the pelvis would mainly explain this inaccuracy. Solutions to this might be to increase the surgical margin or to use computer- and robotic-assisted technologies in pelvic tumor resection. Furthermore, our attempt to evaluate geometry of the pelvic reconstruction using simple parameters was not satisfactory. We believe that there is a need to define new standards of evaluation.

Objectives: To determine the accuracy of bedside glucose strip assay on capillary blood and on whole blood and to identify factors predictive of discrepancies with the laboratory method., Patients and Methods: We conducted a prospective 3-month (July 1-September 30, 2003) study in 85 consecutive patients who required blood glucose monitoring. Values obtained with a glucose test strip on capillary blood and on whole blood were compared with those obtained in the laboratory during serial blood sampling (up to 4 samples per patient). The test strip values were considered to disagree significantly with the laboratory values when the difference exceeded 20%. Clinical and biological parameters and the perfusion index, based on percutaneous oxygen saturation monitoring, were recorded when each sample was obtained., Results: Capillary glucose values conflicted with laboratory reference values in 15% of samples. A low perfusion index was predictive of conflicting values (P=.04). Seven percent of values obtained with glucose strip on whole-blood samples conflicted with laboratory reference values; factors associated with these discrepancies were mean arterial hypotension (P=.007) and generalized mottling (P=.04)., Conclusion: Bedside blood glucose values must be interpreted with care in critically ill patients. A low perfusion index, reflecting peripheral hypoperfusion, is associated with poor glucose strip performance. Bedside measurements in whole blood seem to be most reliable, except in patients with arterial hypotension and generalized mottling.

Isolated inflammatory aneurysm of the common iliac artery is a rare condition. Previously reported cases presented with urologic complications owing to entrapment of the ureter in the perianeurysmal fibrosis. We report a case of a healthy young man who presented with acute abdominal pain in the right lower quadrant without urologic complications mimicking acute appendicitis. The pain was caused by an isolated inflammatory aneurysm of the right common iliac artery measuring 4 cm in diameter. Three years after open aneurysmal resection and graft interposition, the patient is doing well, with excellent peripheral circulation. The available literature on presentation, diagnosis, and treatment is reviewed.

Objective: To validate the use of fluoroscopic roentgenographic stereophotogrammetric analysis (FRSA) for its feasibility and accuracy for measuring the three-dimensional dynamic motion of stent grafts., Methods: A digital biplane fluoroscopy setup was calibrated (Siemens Axiom Artis dBc). Stereo images were acquired of a static aortic model with a stent graft in different axial positions, imposed by a micromanipulator. The three-dimensional measurement error of FRSA was determined by comparing FRSA measurements with the micromanipulator. An aortic model with a stent graft was constructed and connected to an artificial circulation with a physiological flow and pressure profile. Markers were added to the spine (tantalum spherical markers; diameter 1 mm) and stent (welding tin; diameter 1 mm). The three-dimensional measurement precision was determined by measuring the position of a single (stable) spine marker during two pulsatile cycles. Finally, three-dimensional stent marker motion was analyzed with a frame rate of 30 images per second, including three-dimensional marker position (change), diameter change, and center of circle position change., Results: The mean error of FRSA measurement of displacement was 0.003 mm (SD, 0.019 mm; maximum error, 0.058 mm). A very high precision of position measurement was found (SD, 0.009-0.015 mm). During pulsatile motion, the position (changes) of the markers could be assessed in the x, y, and z directions, as well as the stent diameter change and center of circle position change., Conclusions: FRSA has proven to be a method with very high accuracy and temporal resolution to measure three-dimensional stent-graft motion in a pulsatile environment. This technique has the potential to contribute significantly to the knowledge of stent-graft behavior after endovascular aneurysm repair and improvements in stent-graft design. The technique is ready for clinical testing.

Purpose: This study was conducted to clarify the effect of the direction of pressure measurement on the pressure readout in fibrinous thrombus of the abdominal aortic aneurysm., Methods: Three weights of 468 g (weight 1), 578 g (weight 2), and 675 g (weight 3) were molded. A specimen of human fibrinous thrombus was positioned under the weights. Because the surface area of the weights and the thrombus was 400 mm(2), weights 1, 2, and 3 caused pressures of 88, 108, and 127 mm Hg, respectively. Pressure measurements were performed at different angles between the sensor and the applied force (0 degrees , 22.5 degrees , 30 degrees , 45 degrees , 60 degrees , 67.5 degrees , 90 degrees ) Thrombi of 10 different patients were analyzed. Pressure measurements in the thrombi at different angles were statistically compared by a linear mixed model analysis., Results: The measurements at 90 degrees differed statistically from the measurements at 0 degrees , 22.5 degrees , 30 degrees , 45 degrees , 60 degrees , and 67.5 degrees (P < .001). The pressure readout was only similar to the applied pressure when the pressure sensor was positioned at 90 degrees to the applied force. Pressure measurements in other sensor positions resulted in lower pressure measurements. Pressure changes were detected in all sensor positions. There appeared to be no significant difference between the pressure measurements taken at same angles in the 10 thrombi (P > .05)., Conclusion: In fibrinous thrombus of abdominal aortic aneurysm, the direction of pressure measurement influenced the pressure readout.

Purpose: To evaluate the feasibility and accuracy of Roentgen stereophotogrammetric analysis (RSA) versus computed tomography (CT) for detecting stent-graft migration in an in vitro pulsatile circulation model and to study the feasibility of a nitinol endovascular clip (NEC) as an aortic wall reference marker for RSA., Methods: An aortic model with stent-graft was constructed and connected to an artificial circulation with a physiological flow and pressure profile. Tantalum markers and NECs were used as aortic reference markers for RSA analysis. Stent-graft migrations were measured during pulsatile circulation with RSA and CT. CT images acquired with 64 x 0.5-mm beam collimation were analyzed with Vitrea postprocessing software using a standard clinical protocol and central lumen line reconstruction. RSA in the model with the circulation switched off was used as the reference standard to determine stent-graft migration. The measurement errors of RSA and CT were determined during pulsatile circulation., Results: The mean measurement error +/- standard deviation (maximum) of RSA during pulsatile circulation using the tantalum markers was -0.5+/-0.16 (0.7) mm. Using the NEC, the mean (maximum) measurement error was -0.4+/-0.25 (1.1) mm. The mean (maximum) measurement error of CT was -1.1+/-1.17 (2.8) mm., Conclusion: RSA is an accurate and feasible tool to measure stent-graft migration in a pulsatile environment. Migration measurement with RSA was more accurate than CT in this experimental setup. The nitinol clip tested in this study is potentially feasible as an aortic reference marker in patients after endovascular repair.

Vertebrate gap junctions are constituted of connexin (Cx) proteins. In Xenopus laevis, only seven different Cxs have been described so far. Here, we identify two new Cxs from X. laevis. Cx28.6 displays > 60% amino acid identity with human Cx25, Cx29 displays strong homology with mouse Cx26 and Cx30. Cx29 is expressed throughout embryonic development. Cx28.6 mRNA is only transiently found from stage 22 to 26 of development. While no Cx28.6 expression could be detected by whole mount in situ hybridization, expression of Cx29 was found in the developing endoderm, lateral mesoderm, liver anlage, pronephros, and proctodeum. Ectopic expression of Cx28.6 failed to produce functional gap-junctions. In contrast, ectopic expression of full-length Cx29 in HEK293 and COS-7 cells resulted in the formation of gap junction-like structures at the cell-cell interfaces. Ectopic expression of Cx29 in communication deficient N2A cell pairs led to functional electrical coupling.

Purpose: To evaluate in an in vitro model the feasibility and accuracy of Roentgen stereophotogrammetric analysis (RSA) versus computed tomography (CT) for the ability to detect stent-graft migration., Methods: An aortic model was constructed from a 22-mm-diameter Plexiglas tube with 6-mm polytetrafluoroethylene inlays to mimic the renal arteries. Six tantalum markers were placed in the wall of the aortic tube proximal to the renal arteries. Another 6 markers were added to a Gianturco stent, which was cast in Plexiglas and placed inside the aorta and fixed to a micromanipulator to precisely control displacement of the stent along the longitudinal axis. Sixteen migrations were analyzed with RSA software and compared to the micromanipulator. Thirty-two migrations were measured by 3 observers from CT images acquired with 16x0.5-mm beam collimation and reconstructed with a 0.5-mm slice thickness and a 0.4-mm reconstruction interval. Measurements were made with Vitrea postprocessing software using a standard clinical protocol and central lumen line reconstruction. Results of CT were also compared to the micromanipulator., Results: The mean RSA measurement error compared to the micromanipulator was 0.002+/-0.044 mm, and the maximum error was 0.10 mm. There was no statistically significant interobserver variability for CT (p=0.17). The pooled mean (maximum) measurement error of CT was 0.14+/-0.29 (1.00) mm, which was significantly different from the RSA measurement error (p<0.0001)., Conclusion: Detection of endograft migration by RSA is feasible and was significantly more accurate than CT in this nonpulsatile in vitro model.

Complete removal of an aortic endograft with suprarenal fixation is difficult. We report the use of a simple device to extract a Zenith endograft. This device is made by cutting off the tip of the cylinder of a 20-mL syringe and rounding off the edges. The main body of the graft is resheathed by advancing the cylinder cranially while keeping the graft in a stable position. This way, the graft collapses and the hooks are withdrawn without tearing the wall of the aorta. The supraceliac clamping time in our patient was less than 2 minutes. This technique offers a safe and fast solution to the potentially hazardous removal of an aortic endograft with suprarenal fixation.

Purpose: To determine the effect of pulsatile motion of graft-attached pressure sensors on the accuracy of aneurysm sac pressure measurement., Methods: Pressure inside a pressure box was measured with a sensor attached to a stent-graft (Sensorgraft) facing a sensor in fixed position (Sensorbox). Maximum inter-sensor variation of Sensorgraft and Sensorbox was determined in static experiments. Experiments with pulsatile circulation were performed with a compliant and a noncompliant stent-graft at 120/80 mmHg and 160/95 mmHg. Pressure measurements in the box were repeated after the box pressure was increased from 0 to 120 mmHg. Sensorgraft motion was measured by ultrasound. Measurements with Sensorgraft were compared to those with Sensorbox using Pearson correlation coefficients to determine the concordance between the sensors., Results: The maximum inter-sensor variation was 4 mmHg. Increased box pressure induced progressive pulsatile graft and sensor motion during all experiments. During the experiments with the compliant graft at systemic pressures of 120/80 and 160/95 mmHg, the maximum inter-sensor variation was exceeded at box pressures of 65 and 75 mmHg, respectively. The sensor motion at these box pressures was 214+/-2.70 microm and 210+/-0.93 microm, respectively. Measurements of Sensorgraft were higher than Sensorbox, up to 13 mmHg at a box pressure of 120 mmHg. The Pearson correlation coefficients during these experiments were 0.99 and 1.00 (p < 0.001), respectively. In the experiments with the noncompliant graft, the maximum inter-sensor variation was not exceeded, and sensor motion was only 7 +/- 0.46 microm and 26 +/- 1.48 microm, respectively. The Pearson correlation coefficient during these experiments was 1.00 (p < 0.001)., Conclusion: Pulsatile sensor motion can influence the accuracy of pressure measurement. More compliant grafts are more susceptible to this phenomenon. Despite false high pressure measurements, stent-graft-attached pressure sensors seem appropriate to follow pressure trends in the aneurysm sac.

The physical and physiological behavior of sickle cell trait carriers (AS) is somewhat equivocal under strenuous conditions, although this genetic abnormality is generally considered to be a benign disorder. The occurrence of incidents and severe injuries in AS during exercise might be explained, in part, by the lactic acidosis due to a greater lactate influx into AS red blood cells (RBCs). In the present study, the RBC lactate transport activity via the different pathways was compared between AS and individuals with normal hemoglobin (AA). Sixteen Caribbean students, nine AS and seven AA, performed a progressive and maximal exercise test to determine maximal oxygen consumption. Blood samples were obtained at rest to assess haematological parameters and RBC lactate transport activity. Lactate influxes [total lactate influx and monocarboxylate transporter (MCT-1)-mediated lactate influx] into erythrocytes were measured at four external [14C]-labeled lactate concentrations (1.6, 8.1, 41, and 81.1 mM). The two groups had similar maximal oxygen consumption. Total lactate influx and lactate influx via the MCT-1 pathway were significantly higher in AS compared with AA at 1.6, 41, and 81.1 mM. The maximal lactate transport capacity for MCT-1 was higher in AS than in AA. Although AS and AA had the same maximal aerobic physical fitness, the RBCs from the sickle cell trait carriers took up more lactate at low and high concentrations than the RBCs from AA individuals. The higher MCT-1 maximal lactate transport capacity found in AS suggests greater content or greater activity of MCT-1 in AS RBC membranes.

Objective: Inhibition of 2,3-oxidosqualene:lanosterol cyclase (OSC), an enzyme in the cholesterol synthesis pathway, has the unique ability to inhibit cholesterol synthesis while simultaneously enhancing oxysterol synthesis. Our objectives were to determine, in vivo, if a novel OSC inhibitor reduced low-density lipoprotein (LDL) cholesterol and to define the mechanism(s) involved., Methods and Results: Miniature pigs received the OSC inhibitor RO0717625 or placebo and a diet containing fat (34% of energy) and 400 mg per day of cholesterol. Treatment decreased plasma total cholesterol (-20%) and LDL cholesterol (-29%). Apolipoprotein B (apoB) kinetic parameters were determined. Very low-density lipoprotein (VLDL) apoB pool size decreased 22% because of inhibition of VLDL production (-43%). LDL apoB pool size decreased 22% because of a 1.5-fold increase in fractional catabolic rate (FCR). The increased FCR was associated with a 2-fold increase in hepatic LDL receptor mRNA. Hepatic total and microsomal cholesterol were reduced by 16% and 27%, respectively. Plasma lathosterol concentrations decreased 57%, reflecting inhibition of hepatic cholesterol synthesis. Treatment reduced plasma plant sterols and decreased postprandial cholesterol transport in chylomicrons., Conclusions: A novel OSC inhibitor, RO0717625, decreased VLDL and LDL apoB100 through decreased VLDL production and enhanced LDL clearance. Thus, OSC represents a potential therapeutic target for dyslipidemia.

Objective: To clarify the effect of intraluminal thrombus on pressure transmission., Methods: A saccular aneurysm was inserted into an artificial circulation system. Subsequently, the saccular aneurysm was filled with eight different human aortic aneurysm thrombus samples. Starch solution in an empty aneurysm was used as a control. A pressure sensor measured the pressure in the circulation, and a second piezoelectric sensor measured the pressure in the saccular aneurysm at 3, 2, and 1 cm from the endoluminal surface (23 locations). The influence of the elastic characteristics of the aneurysm wall on the extent of pressure reduction was evaluated by experiments performed with aneurysms made of rubber and paraffin., Results: The pressures measured in the empty aneurysm were identical to those measured in circulation (P > .05). The pressure measured in the thrombus was significantly lower than the pressure measured in the circulation (P < .05). The mean pressure ratio between the systolic thrombus pressure and systolic circulation pressure at 1, 2, and 3 cm was 0.90 +/- 0.09, 0.86 +/- 0.10, and 0.81 +/- 0.09, respectively. However, there was a clear correlation between the pressure in the circulation and in the thrombus (Pearson correlation coefficient: mean, r = 0.997; range, 0.975-0.999; P < .01). The change in circulatory pressure was followed by an almost identical change in thrombus pressure (regression coefficient: mean, beta = .997; range, .983-1.000; P < .01). In stiff aneurysms, the pressure reduction is less than in more compliant ones (P < .05)., Conclusions: In an in vitro model, pressure in the aneurysmal sac is reduced by fibrinous thrombus., Clinical Relevance: Endovascular aneurysm repair (EVAR) aims at reducing the pressure in the aneurysmal sac. Therefore, it seems attractive to use pressure monitoring in the aneurysmal sac as a follow-up after EVAR. This study contributes to the development of the rationale of pressure monitoring in the aneurysmal sac as a follow-up method after EVAR. The aneurysmal sac is filled with thrombus. To interpret pressure measurements in the thrombus, we have to learn about the effect of the thrombus on pressure transmission and on the pressure measurements themselves. Our study demonstrates that reduction of pressure occurs as it is transmitted through a human aortic thrombus.

To determine the origin and gene diversity of the Chinese and Mongolian domestic sheep, a partial fragment of mitochondrial DNA D-loop was sequenced for total number of 314 individuals from nine Chinese sheep populations and 11 Mongolian sheep populations. The results show no difference in nucleotide composition between Chinese and Mongolian sheep mtDNA D-loop sequences. However, more variables were identified in Mongolian sheep (26.85% of the sites) than that in Chinese sheep (24.22%). In China, mtDNA haplotype diversity was the highest in Qinghai Tibetan sheep, followed then by Gansu Tibetan sheep, Gansu Alpine Merino, Qinghai Merino, Gannan Tibetan sheep, Small-tailed Han sheep, Tan sheep, Hu sheep and Minxian Black Fur sheep. In Mongolian sheep, mtDNA haplotype diversity was the highest in Bayad and Baidrag populations and the lowest in the Gobi-Altai population. In general, Mongolian sheep have a richer genetic diversity than the Chinese ones with larger number of haplotypes (86.06% (142/165) versus 78.83% (108/137)), higher haplotype diversity (Hd; 0.976 versus 0.936), higher nucleotide diversity (Pi (pi); 0. 036 versus 0.034) and higher average number of nucleotide differences (k; 23.50 versus 22.48). Phylogenetic analysis of the 217 haplotypes identified in both Mongolian and Chinese sheep supported the same origin of their domestication with three distinct maternal lineages defined as major haplotypes A, B and C, of which haplotype A are the commonest in all Chinese sheep populations and in the majority of Mongolian sheep populations (9/11) with an average frequency of 58.73%, followed by haplotype B present in eight of Chinese population and in all Mongolian sheep populations with an average frequency of 24.68%, and haplotype C present in eight Chinese and in 10 Mongolian sheep populations with an average frequency of 16.59%. Further network analysis of the phylogenetic relationship of the 87 haplotypes identified from 91 sequences retrieved from GenBank together with the 217 haplotypes detected in this study reveals clearly four distinct lineages with the European mouflon (O. musimon) mixed into one of the lineages (haplotype B). There is no evidence of contribution of Argali sheep (O. ammon), O. vignei bochariensis and/or O. ammon nigrimontana to the maternal origin of both Mongolian and Chinese domestic sheep.

Connexin-containing gap junctions play an essential role in vertebrate development. More than 20 connexin isoforms have been identified in mammals. However, the number identified in Xenopus trails with only six isoforms described. Here, identification of a new connexin isoform from Xenopus laevis is described. Connexin40.4 was found by screening expressed sequence tag databases and carrying out polymerase chain reaction on genomic DNA. This new connexin has limited amino acid identity with mammalian (<50%) connexins, but conservation is higher (approximately 62%) with fish. During Xenopus laevis development, connexin40.4 was first expressed after the mid-blastula transition. There was prominent expression in the presomitic paraxial mesoderm and later in the developing somites. In adult frogs, expression was detected in kidney and stomach as well as in brain, heart, and skeletal muscle. Ectopic expression of connexin40.4 in HEK293 cells, resulted in formation of gap junction like structures at the cell interfaces. Similar ectopic expression in neural N2A cells resulted in functional electrical coupling, displaying mild, asymmetric voltage dependence. We thus cloned a novel connexin from Xenopus laevis, strongly expressed in developing somites, with no apparent orthologue in mammals.

The monotopic integral membrane protein 2,3-oxidosqualene cyclase (OSC) catalyzes the formation of lanosterol the first sterol precursor of cholesterol in mammals. Therefore, it is an important target for the development of new hypocholesterolemic drugs. Here, we report the overexpression and purification of functional human OSC (hOSC) in Pichia pastoris. The obtained IC(50) for the reference inhibitor Ro 48-8071 is nearly identical for the recombinant hOSC compared to OSC from human liver microsomes. The correlation of analytical ultracentrifugation data and activity measurements showed the highest enzymatic activity for the monomeric hOSC indicating that this would be the natural form. Furthermore, these data helped us to identify the detergent for a successful crystallization of the protein. The availability of this active recombinant human membrane protein is a very important step on the way to a more detailed functional and structural characterization of OSCs.

Oxysterols are key regulators of lipid metabolism and regulate gene expression by activating the liver X receptor (LXR). LXR plays a vital role in macrophage foam cell formation, a central event in atherosclerosis. It is known that addition of exogenous oxysterols to cultured macrophages activates LXR, leading to increased expression of ABCA1 and cholesterol efflux. In this study, we tested the novel hypothesis that stimulation of endogenous oxysterol synthesis would block foam cell formation induced by atherogenic lipoproteins. Macrophage synthesis of 24(S),25-epoxycholesterol, a potent LXR ligand, increased 60-fold by partial inhibition of 2,3-oxidosqualene:lanosterol cyclase (OSC), a microsomal enzyme in both the cholesterol biosynthetic pathway and the alternative oxysterol synthetic pathway. When macrophages were challenged with human hypertriglyceridemic VLDL (HTG-VLDL), cellular cholesteryl ester accumulation increased 12-fold. This was reduced dramatically, by 65%, after preincubation with an OSC inhibitor (OSCi). The HTG-VLDL-induced accumulation of macrophage TG (70-fold) was unaffected by the OSCi or exogenous 24(S),25-epoxycholesterol, an effect associated with suppression of SREBP-1 processing. By contrast, TO901317, a synthetic LXR agonist, increased cellular TG significantly and markedly increased SREBP-1 processing. OSC inhibition decreased HTG-VLDL uptake through downregulation of LDL-receptor expression, despite substantial inhibition of cholesterol synthesis. Furthermore, OSC inhibition significantly upregulated ABCA1 and ABCG1 expression, which led to enhanced macrophage cholesterol efflux, an effect mediated through LXR activation. Therefore, increased macrophage synthesis of endogenous oxysterols represents a new mechanism for the dual regulation of LXR- and SREBP-responsive genes, an approach that inhibits foam cell formation without detrimental effect on TG synthesis.

New orally active non-terpenoic inhibitors of human 2,3-oxidosqualene cyclase (hOSC) are reported. The starting point for the optimization process was a set of compounds derived from a fungicide project, which in addition to showing high affinity for OSC from Candida albicans showed also high affinity for human OSC. Common structural elements of these inhibitors are an amine residue and an electrophilic carbonyl C atom embedded in a benzophenone system, which are at a distance of about 10.7 A. Considering that the keto moiety is in a potentially labile position, modifications of the substitution pattern at the benzophenone as well as annelated heteroaryl systems were explored. Our approach combined testing of the compounds first for increased binding affinity and for increased stability in vitro. Most promising compounds were then evaluated for their efficacy in lowering plasma total cholesterol (TC) and plasma low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic hamsters. In this respect, the most promising compounds are the benzophenone derivative 1.fumarate and the benzo[d]isothiazol 24.fumarate, which lowered TC by 40% and 33%, respectively.

Background: There are little comparative data on Carpentier-Edwards supraannular and pericardial second-generation bioprostheses. The aim of this work was to compare their hemodynamic and clinical outcomes in patients with aortic stenosis., Methods: We conducted a retrospective study including 150 patients operated on for aortic stenosis between 1989 and 1993. Patients undergoing aortic valve replacement with either a Carpentier-Edwards supraannular or pericardial prosthesis were matched for sex (49% male), age (72 +/- 8 years), body surface area, valve size, associated procedures, and left ventricular ejection fraction., Results: Mean follow-up was 6.5 +/- 3.3 years, giving a total follow-up of 983 patient-years. Thirty-day mortality and 10-year actuarial survival were, respectively, 8% and 51% in the supraannular group and 6.7% and 43.4% in the pericardial group. At 10 years, freedom from thromboembolism, structural failure, and all valve-related events were, respectively, 88.7%, 88.9%, and 68.7% in the supraannular group and 85%, 100%, and 82.2% in the pericardial group. There were four (5.3%) structural failures, and four (5.3%) reoperations for degeneration (n = 3) and endocarditis (n = 1) in the supraannular group. Freedom from structural dysfunction or reoperation was 87.3% in the supraannular group and 100% (p < 0.05) in the pericardial group. Echocardiographic review of 62 of 76 survivors (81.5%) demonstrated a trend toward a better hemodynamic profile of pericardial valves at the end of follow-up., Conclusions: Ten years after aortic valve replacement for aortic stenosis, Carpentier-Edwards pericardial prostheses give comparable and probably better results than Carpentier-Edwards supraannular prostheses.

At one time, benzodiazepines were the number one prescription drug in the United States and the world. While the use of benzodiazepines has declined since the Journal published an article about the use and misuse in 1989, benzodiazepines still have clinical efficacy and clinical misuse. This article details current epidemiology, indications, and precautions to prevent abuse.

Eighty prostheses, including 46 humeral prostheses and 34 total ones, have been laid for complex injuries of the shoulder. In 56 cases, these were recent fractures, mainly of the head and tubercle of the humerus, in subject ages 65 in average. In 34 cases, the injuries were older and comprised malunion or epiphyseal necrosis. Five cases of subluxation and six of secondary displacement of the tubercles were noted. Pain was suppressed in most cases, but mobility was less satisfactory (37% exceeding 90 degrees active elevation). The humeral sealing evolved in a reassuring way, but a poorly evolutive glenoid rim was often observed. Finally, upper subluxation may occur during the evolution, which suggests the possibility of secondary ruptures in the rotator cuff.