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Objectives: Generative artificial intelligence (AI) has emerged as a promising tool to engage with patients. The objective of this study was to assess the quality of AI responses to common patient questions regarding vascular surgery disease processes., Methods: OpenAI's ChatGPT-3.5 and Google Bard were queried with 24 mock patient questions spanning seven vascular surgery disease domains. Six experienced vascular surgery faculty at a tertiary academic center independently graded AI responses on their accuracy (rated 1-4 from completely inaccurate to completely accurate), completeness (rated 1-4 from totally incomplete to totally complete), and appropriateness (binary). Responses were also evaluated with three readability scales., Results: ChatGPT responses were rated, on average, more accurate than Bard responses (3.08 ± 0.33 vs 2.82 ± 0.40, p < .01). ChatGPT responses were scored, on average, more complete than Bard responses (2.98 ± 0.34 vs 2.62 ± 0.36, p < .01). Most ChatGPT responses (75.0%, n = 18) and almost half of Bard responses (45.8%, n = 11) were unanimously deemed appropriate. Almost one-third of Bard responses (29.2%, n = 7) were deemed inappropriate by at least two reviewers (29.2%), and two Bard responses (8.4%) were considered inappropriate by the majority. The mean Flesch Reading Ease, Flesch-Kincaid Grade Level, and Gunning Fog Index of ChatGPT responses were 29.4 ± 10.8, 14.5 ± 2.2, and 17.7 ± 3.1, respectively, indicating that responses were readable with a post-secondary education. Bard's mean readability scores were 58.9 ± 10.5, 8.2 ± 1.7, and 11.0 ± 2.0, respectively, indicating that responses were readable with a high-school education ( p < .0001 for three metrics). ChatGPT's mean response length (332 ± 79 words) was higher than Bard's mean response length (183 ± 53 words, p < .001). There was no difference in the accuracy, completeness, readability, or response length of ChatGPT or Bard between disease domains ( p > .05 for all analyses)., Conclusions: AI offers a novel means of educating patients that avoids the inundation of information from "Dr Google" and the time barriers of physician-patient encounters. ChatGPT provides largely valid, though imperfect, responses to myriad patient questions at the expense of readability. While Bard responses are more readable and concise, their quality is poorer. Further research is warranted to better understand failure points for large language models in vascular surgery patient education., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Analyzing the relationship between cell morphology, rheological characteristics, and production dynamics of cultivations with filamentous microorganisms is a challenging task. The complex interdependencies and the commonly low reproducibility of heterogeneous cultivations hinder the bioprocess development of commercially relevant production systems. The present study aims to characterize process parameters in Actinomadura namibiensis shake flask cultures to gain insights into relationships between culture behavior and rheological characteristics during salt-enhanced labyrinthopeptin A1 production. Plate-plate (PP) and vane-cup rheometer measurements of viscous model fluids and culture broths are compared, revealing a more uniform distribution of broth when measured with the PP system. Additionally, rheological characteristics and culture performance of A. namibiensis cultures are evaluated using online data of the specific power input and the oxygen transfer rate. It is demonstrated that salt-enhancement labyrinthopeptin A1 production by the addition of 50 mM (NH 4 ) 2 SO 4 increases the apparent viscosity of the A. namibiensis culture by four-fold and significantly reduces the reproducibility of the culture resulting in a 46 h difference in lag-phase duration. This approach demonstrates that the culture behavior of complex filamentous cell morphologies is challenging to decipher, but online monitoring of rheology and oxygen transfer can provide valuable insights into the cultivation dynamics of filamentous microbial cultures., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Engineering in Life Sciences published by Wiley‐VCH GmbH.)

The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Semi-synthetic and grain-based diets are common rodent diets for biomedical research. Both diet types are considered nutritionally adequate to support breeding, growth, and long life, yet there are fundamental differences between them that may affect metabolic processes. We have characterized the effects of diet type on breeding outcomes, metabolic phenotype, and microbiota profile in adult mice. Healthy 8-week-old female and male C57BL/6J mice were fed a semi-synthetic or a grain-based diet for 12 weeks and changes in body weight and body composition were monitored. Breeding outcomes were determined. Body fat accumulation of female mice was lower on the semi-synthetic diet than on the grain-based diet. Pregnancy rate and newborn pup survival appeared to be lower in mice exposed to semi-synthetic diet compared to grain-based diet. Both female and male mice showed a profound change in fecal microbiota alpha and beta diversity depending on diet type. Our study shows that type of rodent diet may affect breeding outcomes whilst influencing metabolism and health of female laboratory mice. These factors have the potential to influence other experimental outcomes and the results suggest that semi-synthetic and grain-based diets are not interchangeable in research using rodent models. Careful consideration and increased understanding of the consequences of diet choice would lead to improvements in experimental design and reproducibility of study results., Competing Interests: “I have read the journal’s policy and the authors of this manuscript have the following competing interests: LS, ST, ET, JL, MR and LH are employees of the institution that funded the research or were at the time of the study (ET). This does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2024 Schipper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A patient with structural valve degeneration of an aortic bioprosthesis with stenosis stage 3 underwent valve-in-valve transcatheter aortic valve replacement (TAVR) at 29 weeks with improvement. This is the first reported TAVR in the third trimester. TAVR may be an alternative to preterm delivery in cases of symptomatic aortic stenosis., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

The ubiquitously expressed transmembrane enzyme Na,K-ATPase (NKA) is vital in maintaining functionality of cells. The association of α- and β-subunits is believed to be essential for forming a functional enzyme. In the large milkweed bug Oncopeltus fasciatus four α1-paralogs and four β-subunits exist that can associate into NKA complexes. This diversity raises the question of possible tissue-specific distribution and function. While the α1-subunits are known to modulate cardenolide-resistance and ion-transport efficiency, the functional importance of the β-subunits needed further investigation. We here characterize all four different β-subunits at the cellular, tissue, and whole organismal scales. A knockdown of different β-subunits heavily interferes with molting success resulting in strongly hampered phenotypes. The failure of ecdysis might be related to disrupted septate junction (SJ) formation, also reflected in β2-suppression-induced alteration in tracheal morphology. Our data further suggest the existence of isolated β-subunits forming homomeric or β-heteromeric complexes. This possible standalone and structure-specific distribution of the β-subunits predicts further, yet unknown pump-independent functions. The different effects caused by β knockdowns highlight the importance of the various β-subunits to fulfill tissue-specific requirements., (© 2022 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.)

Lantipeptides from bacterial sources are increasingly important as biopharmaceuticals because of their broad range of applications. However, the availability of most lantipeptides is low, and systematic approaches for downstream processing of this group of peptides is still lacking. Model-based development for chromatographic separations has proven to be a useful tool for developing reliable purification processes. One important compound of such a model is the adsorption behavior of the components of interest. In ion-exchange chromatography, the adsorption equilibrium between salt and proteins can be described using the steric mass action (SMA) formalism. Beyond, the model parameters may be related to the lanthipeptides physico-chemical properties. In this study, the antiviral lantipeptides labyrinthopeptin A1 and A2, purified from Actinomadura namibiensis culture broth, were characterized for their adsorption behavior in anion-exchange chromatography in the range from pH 5.0-7.4. The experiments necessary to determine the three SMA parameters were chosen in a way to limit the amount of peptides needed. Linear gradient elution was applied successfully to separate A1 and A2 and to determine the characteristic charge ν i and the equilibrium constant [Formula: see text] . Batch adsorption experiments using a robotic workstation for high throughput and accuracy provided non-linear adsorption isotherms and the steric factor σ i . Labyrinthopeptin A1 and A2 show a very different adsorption behavior even though the fundamental structure of the two peptides is similar. k eq of A1 ranging from 0.18 to 0.88 are approximately one order of magnitude smaller than that of A2 ranging from 3.44 to 9.73 indicating the higher affinity of A2 to the stationary phase. At pH 7.0 σ was 1.12 and 0.60 for A1 and A2, respectively which was expected based on the molecular weight of the peptides. The characteristic charge for both peptides was also theoretically estimated from the amino acids involved in electrostatic interactions which was in good agreement with experimental data. Thereby, this work provides an useful approach to estimate SMA parameters based on simple structural information that can be applied early in chromatographic ion-exchange process development for peptides and may help adapting the processes for future designed lanthipeptides., 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 © 2023. Published by Elsevier B.V.)

Background: Critical spinal epidural pathologies can cause paralysis or death if untreated. Although magnetic resonance imaging is the preferred modality for visualizing these pathologies, computed tomography (CT) occurs far more commonly than magnetic resonance imaging in the clinical setting., Objective: A machine learning model was developed to screen for critical epidural lesions on CT images at a large-scale teleradiology practice. This model has utility for both worklist prioritization of emergent studies and identifying missed findings., Materials and Methods: There were 153 studies with epidural lesions available for training. These lesions were segmented and used to train a machine learning model. A test data set was also created using previously missed epidural lesions. The trained model was then integrated into a teleradiology workflow for 90 days. Studies were sent to secondary manual review if the model detected an epidural lesion but none was mentioned in the clinical report., Results: The model correctly identified 50.0% of epidural lesions in the test data set with 99.0% specificity. For prospective data, the model correctly prioritized 66.7% of the 18 epidural lesions diagnosed on the initial read with 98.9% specificity. There were 2.0 studies flagged for potential missed findings per day, and 17 missed epidural lesions were found during a 90-day time period. These results suggest almost half of critical spinal epidural lesions visible on CT imaging are being missed on initial diagnosis., Conclusion: A machine learning model for identifying spinal epidural hematomas and abscesses on CT can be implemented in a clinical workflow., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: 2017 International and 2018 European guidelines are the most recent guidelines for intraductal papillary mucinous neoplasms management., Aim: to evaluate the diagnostic accuracy of these guidelines in identifying malignant IPMN., Methods: data from resected patients with IPMN were collected in two referral centers. Features of risk associated to cancerous degeneration described in International and European guidelines were retrospectively applied. Sensitivity, specificity, positive and negative predictive value in detecting malignant disease were calculated., Results: the study includes 627 resected patients. European guidelines suggest resection in any patient with at least one feature of moderate-risk. International guidelines suggest that patients with moderate-risk features undergo endoscopic ultrasound before surgery. European guidelines had a higher sensitivity (99.2% vs. 83%) but a lower positive predictive value (59.5% vs. 65.8%) and Specificity (2% vs. 37.5%). European guidelines detected almost all malignancies, but 40% of resected patients had low-grade dysplasia. 297 patients underwent endoscopic ultrasound before surgery. 31/116 (26.7%) tumors radiologically classified as "worrisome features" were reclassified as "high-risk stigmata" by endoscopic ultrasound and 24/31 were malignant IPMN., Conclusions: European and International guidelines have a relatively low diagnostic accuracy, being European guidelines more aggressive. Endoscopic ultrasound can improve guidelines accuracy in patients with moderate-risk features., Competing Interests: Declaration of Competing Interest No author has conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Ltd.)

Patients who are intubated with endotracheal tubes often receive chest x-ray (CXR) imaging to determine whether the tube is correctly positioned. When these CXRs are interpreted by a radiologist, they evaluate whether the tube needs to be repositioned and typically provide a measurement in centimeters between the endotracheal tube tip and carina. In this project, a large dataset of endotracheal tube and carina bounding boxes was annotated on CXRs, and a machine-learning model was trained to generate these boxes on new CXRs and to calculate a distance measurement between the tube and carina. This model was applied to a gold standard annotated dataset, as well as to all prospective data passing through our radiology system for two weeks. Inter-radiologist variability was also measured on a test dataset. The distance measurements for both the gold standard dataset (mean error = 0.70 cm) and prospective dataset (mean error = 0.68 cm) were noninferior to inter-radiologist variability (mean error = 0.70 cm) within an equivalence bound of 0.1 cm. This suggests that this model performs at an accuracy similar to human measurements, and these distance calculations can be used for clinical report auto-population and/or worklist prioritization of severely malpositioned tubes., (© 2021. Society for Imaging Informatics in Medicine.)

[Box: see text] With the support of the American College of Obstetricians and Gynecologists, the American Vein & Lymphatic Society, the American Venous Forum, the Canadian Society of Phlebology, the Cardiovascular and Interventional Radiology Society of Europe, the European Venous Forum, the International Pelvic Pain Society, the International Union of Phlebology, the Korean Society of Interventional Radiology, the Society of Interventional Radiology, and the Society for Vascular Surgery .

As the importance of pelvic venous disorders (PeVD) has been increasingly recognized, progress in the field has been limited by the lack of a valid and reliable classification instrument. Misleading historical nomenclature, such as the May-Thurner, pelvic congestion, and nutcracker syndromes, often fails to recognize the interrelationship of many pelvic symptoms and their underlying pathophysiology. Based on a perceived need, the American Vein and Lymphatic Society convened an international, multidisciplinary panel charged with the development of a discriminative classification instrument for PeVD. This instrument, the Symptoms-Varices-Pathophysiology ("SVP") classification for PeVD, includes three domains-Symptoms (S), Varices (V), and Pathophysiology (P), with the pathophysiology domain encompassing the Anatomic (A), Hemodynamic (H), and Etiologic (E) features of the patient's disease. An individual patient's classification is designated as SVP A,H,E . For patients with pelvic origin lower extremity signs or symptoms, the SVP instrument is complementary to and should be used in conjunction with the Clinical-Etiologic-Anatomic-Physiologic (CEAP) classification. The SVP instrument accurately defines the diverse patient populations with PeVD, an important step in improving clinical decision making, developing disease-specific outcome measures and identifying homogenous patient populations for clinical trials., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In this work it is shown a precise way to optimize the heat generation in high viscosity magnetic colloids, by adjusting the Néel relaxation time in core/shell bimagnetic nanoparticles, for magnetic fluid hyperthermia (MFH) applications. To pursue this goal, Fe 3 O 4 /Zn x Co 1-x Fe 2 O 4 core/shell nanoparticles were synthesized with 8.5 nm mean core diameter, encapsulated in a shell of ∼1.1 nm of thickness, where the Zn atomic ratio (Zn/(Zn + Co) at%) changes from 33 to 68 at%. The magnetic measurements are consistent with a rigid interface coupling between the core and shell phases, where the effective magnetic anisotropy systematically decreases when the Zn concentration increases, without a significant change of the saturation magnetization. Experiments of MFH of 0.1 wt% of these particles dispersed in water, in Dulbecco modified Eagles minimal essential medium, and a high viscosity butter oil, result in a large specific loss power (SLP), up to 150 W g -1 , when the experiments are performed at 571 kHz and 200 Oe. The SLP was optimized adjusting the shell composition, showing a maximum for intermediate Zn concentration. This study shows a way to maximize the heat generation in viscous media like cytosol, for those biomedical applications that require smaller particle sizes.

The concept of phenoptosis (or programmed organismal death) is problematic with respect to most species (including humans) since it implies that dying of old age is an adaptation, which contradicts the established evolutionary theory. But can dying ever be a strategy to promote fitness? Given recent developments in our understanding of the evolution of altruism, particularly kin and multilevel selection theories, it is timely to revisit the possible existence of adaptive death. Here, we discuss how programmed death could be an adaptive trait under certain conditions found in organisms capable of clonal colonial existence, such as the budding yeast Saccharomyces cerevisiae and, perhaps, the nematode Caenorhabditis elegans. The concept of phenoptosis is only tenable if consistent with the evolutionary theory; this accepted, phenoptosis may only occur under special conditions that do not apply to most animal groups (including mammals).

Aortic dissections and ruptures are life-threatening injuries that must be immediately treated. Our national radiology practice receives dozens of these cases each month, but no automated process is currently available to check for critical pathologies before the images are opened by a radiologist. In this project, we developed a convolutional neural network model trained on aortic dissection and rupture data to assess the likelihood of these pathologies being present in prospective patients. This aortic injury model was used for study prioritization over the course of 4 weeks and model results were compared with clinicians' reports to determine accuracy metrics. The model obtained a sensitivity and specificity of 87.8% and 96.0% for aortic dissection and 100% and 96.0% for aortic rupture. We observed a median reduction of 395 s in the time between study intake and radiologist review for studies that were prioritized by this model. False-positive and false-negative data were also collected for retraining to provide further improvements in subsequent versions of the model. The methodology described here can be applied to a number of modalities and pathologies moving forward.

Salt-enhanced cultivation as a morphology engineering tool for the filamentous actinomycete Actinomadura namibiensis was evaluated in 500-mL shaking flasks (working volume 100 mL) with the aim of increasing the concentration of the pharmaceutically interesting peptide labyrinthopeptin A1. Among the inorganic salts added to a complex production medium, the addition of (NH 4 ) 2 SO 4 led to the highest amount of labyrinthopeptin A1 production. By using 50 mM (NH 4 ) 2 SO 4 , the labyrinthopeptin A1 concentration increased up to sevenfold compared to the non-supplemented control, resulting in 325 mg L -1 labyrinthopeptin A1 after 10 days of cultivation. The performance of other ammonium- and sulfate-containing salts (e.g., NH 4 Cl, K 2 SO 4 ) was much lower than the performance of (NH 4 ) 2 SO 4 . A positive correlation between the uptake of glycerol as one of the main carbon sources and nongrowth-associated labyrinthopeptin productivity was found. The change in the cell morphology of A. namibiensis in conjunction with increased osmolality by the addition of 50 mM (NH 4 ) 2 SO 4 , was quantified by image analysis. A. namibiensis always developed a heterogeneous morphology with pellets and loose mycelia present simultaneously. In contrast to the non-supplemented control, the morphology of (NH 4 ) 2 SO 4 -supplemented cultures was characterized by smaller and circular pellets that were more stable against disintegration in the stationary production phase., Competing Interests: The authors have declared no conflict of interest., (© 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Cancer vaccines are designed to promote systemic antitumor immunity and tumor eradication. Cancer vaccination may be more efficacious in combination with additional interventions that may build on or amplify their effects., Methods: Based on our previous clinical and in vitro studies, we designed an antigen-engineered DC vaccine trial to promote a polyclonal CD8 + and CD4 + T cell response against three shared melanoma antigens. The 35 vaccine recipients were then randomized to receive one month of high-dose IFNα or observation., Results: The resulting clinical outcomes were 2 partial responses, 8 stable disease and 14 progressive disease among patients with measurable disease using RECIST 1.1, and, of 11 surgically treated patients with no evidence of disease (NED), 4 remain NED at a median follow-up of 3 years. The majority of vaccinated patients showed an increase in vaccine antigen-specific CD8 + and CD4 + T cell responses. The addition of IFNα did not appear to improve immune or clinical responses in this trial. Examination of the DC vaccine profiles showed that IL-12p70 secretion did not correlate with immune or clinical responses. In depth immune biomarker studies support the importance of circulating Treg and MDSC for development of antigen-specific T cell responses, and of circulating CD8 + and CD4 + T cell subsets in clinical responses., Conclusions: DC vaccines are a safe and reliable platform for promoting antitumor immunity. This combination with one month of high dose IFNα did not improve outcomes. Immune biomarker analysis in the blood identified several predictive and prognostic biomarkers for further analysis, including MDSC., Trial Registration: NCT01622933 .

Objectives: To determine whether missing the HepB birth dose vaccine is a risk factor for incomplete vaccination later in childhood., Methods: This was a retrospective cohort study of infants born over one year at an academic medical center. The "not vaccinated at birth" group consisted of all infants who did not receive the HepB birth dose vaccine by seven days of life, while the "vaccinated at birth" group included infants who did receive the birth dose. The primary outcome was vaccination status at 18 months of age, determined from the state vaccination registry., Results: Infants "not vaccinated at birth" had lower vaccination rates. At 18 months, 44% of the "vaccinated at birth" group received all recommended vaccines, compared with 23% of the "not vaccinated at birth" group (p < 0.001); at 24 months, rates were 65% and 45%, respectively (p < 0.001). Over 80% of the variability in vaccination completions were related to a single latent variable, which is most likely vaccine hesitancy/refusal., Conclusions: Infants who miss the HepB birth dose vaccine are at risk for under-immunization by 18 and 24 months of age. This suggests that parents likely form opinions about vaccines long before the birth of their child; therefore, efforts to influence attitudes must begin earlier., (Copyright © 2018. Published by Elsevier Ltd.)

Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impact of this vaccine as well as the subsequent systemic delivery of high-dose interferon-α2b (HDI) on the circulatory NK cell profile in melanoma patients. At baseline, patient NK cells, particularly those isolated from high-risk patients with no measurable disease, showed altered distribution of CD56 dim CD16 + and CD56 dim CD16 - NK cell subsets, as well as elevated serum levels of immune suppressive MICA, TN5E/CD73 and tactile/CD96, and perforin. Surprisingly, patient NK cells displayed a higher level of activation than those from healthy donors as measured by elevated CD69, NKp44 and CCR7 levels, and enhanced K562 killing. Elevated cytolytic ability strongly correlated with increased representation of CD56 dim CD16 + NK cells and amplified CD69 expression on CD56 dim CD16 + NK cells. While intradermal DC immunizations did not significantly impact circulatory NK cell activation and distribution profiles, subsequent HDI injections enhanced CD56 bright CD16 - NK cell numbers when compared to patients that did not receive HDI. Phenotypic analysis of tumor-infiltrating NK cells showed that CD56 dim CD16 - NK cells are the dominant subset in melanoma tumors. NanoString transcriptomic analysis of melanomas resected at baseline indicated that there was a trend of increased CD56 dim NK cell gene signature expression in patients with better clinical response. These data indicate that melanoma patient blood NK cells display elevated activation levels, that intra-dermal DC immunizations did not effectively promote systemic NK cell responses, that systemic HDI administration can modulate NK cell subset distributions and suggest that CD56 dim CD16 - NK cells are a unique non-cytolytic subset in melanoma patients that may associate with better patient outcome.

Guideline 1.1: Compression after thermal ablation or stripping of the saphenous veins. When possible, we suggest compression (elastic stockings or wraps) should be used after surgical or thermal procedures to eliminate varicose veins. [GRADE - 2; LEVEL OF EVIDENCE - C] Guideline 1.2: Dose of compression after thermal ablation or stripping of the varicose veins. If compression dressings are to be used postprocedurally in patients undergoing ablation or surgical procedures on the saphenous veins, those providing pressures >20 mm Hg together with eccentric pads placed directly over the vein ablated or operated on provide the greatest reduction in postoperative pain.[GRADE - 2; LEVEL OF EVIDENCE - B] Guideline 2.1: Duration of compression therapy after thermal ablation or stripping of the saphenous veins. In the absence of convincing evidence, we recommend best clinical judgment to determine the duration of compression therapy after treatment. [BEST PRACTICE] Guideline 3.1: Compression therapy after sclerotherapy. We suggest compression therapy immediately after treatment of superficial veins with sclerotherapy to improve outcomes of sclerotherapy. [GRADE - 2; LEVEL OF EVIDENCE - C] Guideline 3.2: Duration of compression therapy after sclerotherapy. In the absence of convincing evidence, we recommend best clinical judgment to determine the duration of compression therapy after sclerotherapy. [BEST PRACTICE] Guideline 4.1: Compression after superficial vein treatment in patients with a venous leg ulcer. In a patient with a venous leg ulcer, we recommend compression therapy over no compression therapy to increase venous leg ulcer healing rate and to decrease the risk of ulcer recurrence. [GRADE - 1; LEVEL OF EVIDENCE - B] Guideline 4.2: Compression after superficial vein treatment in patients with a mixed arterial and venous leg ulcer. In a patient with a venous leg ulcer and underlying arterial disease, we suggest limiting the use of compression to patients with ankle-brachial index exceeding 0.5 or if absolute ankle pressure is >60 mm Hg. [GRADE - 2; LEVEL OF EVIDENCE - C]., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

An experimental measurement of the wave electric field vector provides important data that can be used to directly compare against 3D full-wave simulations. This direct comparison yields the fastest approach toward identifying missing physics in computational models and providing a high fidelity validation platform. In this paper, we present a diagnostic that is capable of imaging the Electron Cyclotron (EC) wave electric field vector by acquiring filtered images of polarized D β spectral satellites. The diagnostic is designed to have a spatial and temporal resolution on the order of 100 μ m and 100 μ s, respectively. The diagnostic purpose is to provide experimental data for the direct validation of full-wave codes used to predict EC beam propagation and absorption and to provide real-time monitoring of EC waves.

Most travel medical care is provided by patients' primary care physicians; only 10% of international travelers visit a travel clinic. The main purposes for travel include vacationing, visiting friends and family, business, and for educational purposes. The purposes of the pretravel consultation are to estimate risk and provide recommendations to mitigate risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Camera-based photoplethysmography (cbPPG) is a measurement technique which enables remote vital sign monitoring by using cameras. To obtain valid plethysmograms, proper regions of interest (ROIs) have to be selected in the video data. Most automated selection methods rely on specific spatial or temporal features limiting a broader application. In this work, we present a new method which overcomes those drawbacks and, therefore, allows cbPPG to be applied in an intraoperative environment., Methods: We recorded 41 patients during surgery using an RGB and a near-infrared (NIR) camera. A Bayesian skin classifier was employed to detect suitable regions, and a level set segmentation approach to define and track ROIs based on spatial homogeneity., Results: The results show stable and homogeneously illuminated ROIs. We further evaluated their quality with regards to extracted cbPPG signals. The green channel provided the best results where heart rates could be correctly estimated in 95.6% of cases. The NIR channel yielded the highest contribution in compensating false estimations., Conclusions: The proposed method proved that cbPPG is applicable in intraoperative environments. It can be easily transferred to other settings regardless of which body site is considered.

This study examined the factors that influence Latina mothers' decisions to initiate breastfeeding, formula feeding, or both, and when a given neonatal feeding method is decided, in order to assess the optimum time for healthcare providers to discuss nutrition decisions. A Spanish-speaking health care provider orally administered a 24-question survey to self-identified Latina mothers in the Newborn Nursery at North Carolina Children's Hospital after delivery. A total of 152 Latina mothers, aged 17 to 43 years, were interviewed from September 2014 to September 2015. Three decisive factors resulted from multivariate analysis regarding a participant's decision to exclusively breastfeed: age (27.3 years or younger); deciding about feeding method before pregnancy; and believing that exclusively breastfeeding is best for an infant's growth and development. Overall, 95% of Latina mothers made their decision regarding their infant's nutrition before delivery. Newborn nurseries have trended toward the allocation of substantial resources to the mission of enhancing the likelihood of breastfeeding initiation and success in the newborn period. Perhaps a reallocation of some of these resources for educational interventions earlier in pregnancy should be considered.

Objective: To evaluate the implementation of early screening for critical congenital heart defects (CCHDs) in the neonatal intensive care unit (NICU) and potential exclusion of sub-populations from universal screening., Study Design: Prospective evaluation of CCHD screening at multiple time intervals was conducted in 21 NICUs across five states (n=4556 infants)., Results: Of the 4120 infants with complete screens, 92% did not have prenatal CHD diagnosis or echocardiography before screening, 72% were not receiving oxygen at 24 to 48 h and 56% were born ⩾2500 g. Thirty-seven infants failed screening (0.9%); none with an unsuspected CCHD. False positive rates were low for infants not receiving oxygen (0.5%) and those screened after weaning (0.6%), yet higher among infants born at <28 weeks (3.8%). Unnecessary echocardiograms were minimal (0.2%)., Conclusion: Given the majority of NICU infants were ⩾2500 g, not on oxygen and not preidentified for CCHD, systematic screening at 24 to 48 h may be of benefit for early detection of CCHD with minimal burden.

Preclinical and clinical research supports a role for neuroactive steroids in the pathophysiology of posttraumatic stress disorder (PTSD). We investigated ganaxolone (a synthetic 3β-methylated derivative of allopregnanolone, a GABAergic neuroactive steroid) for treatment of PTSD in a proof-of-concept, multisite, double-blind, placebo-controlled trial. Veteran and non-veteran participants (n = 112) were randomized to ganaxolone or placebo at biweekly escalating doses of 200, 400, and 600 mg twice daily for 6 weeks. During an open-label 6-week extension phase, the initial ganaxolone group continued ganaxolone, while the placebo group crossed over to ganaxolone. Eighty-six and 59 participants, respectively, completed the placebo-controlled and open-label phases. A modified intent-to-treat mixed model repeated measures analysis revealed no significant differences between the effects of ganaxolone and placebo on Clinician Administered PTSD Symptom (CAPS) scores, global well-being, negative mood, or sleep. Dropout rates did not differ between groups, and ganaxolone was generally well tolerated. Trough blood levels of ganaxolone at the end of the double-blind phase were, however, lower than the anticipated therapeutic level of ganaxolone in >35% of participants on active drug. Pharmacokinetic profiling of the ganaxolone dose regimen used in the trial and adverse event sensitivity analyses suggest that under-dosing may have contributed to the failure of ganaxolone to out-perform placebo. Future investigations of ganaxolone may benefit from higher dosing, rigorous monitoring of dosing adherence, a longer length of placebo-controlled testing, and targeting of treatment to PTSD subpopulations with demonstrably dysregulated pre-treatment neuroactive steroid levels. Clinicaltrials.gov identifier: NCT01339689.

Toads are chemically defended by bufadienolides, which are lethal to most predators. These toxins exert their lethal effects by binding to and disabling the Na + /K + -ATPases of cell membranes. Many species of snakes exhibit resistance to the effects of bufadienolides due to target-site insensitivity of the Na + /K + -ATPase. Mutations that confer resistance have previously been identified in ATP1a3, the gene that codes for the Na + /K + -ATPase α-3 paralog. We have found that this mutant gene is expressed at a significantly elevated level in heart tissue compared to gut, kidney, and liver of the bufadienolide-resistant snake, Thamnophis elegans. Furthermore, we found that exposure to bufadienolides elicits a significant increase in the expression levels of ATP1a3 in the heart, but not in the kidneys, liver, or gut 1h after exposure. We suggest that upregulation of ATP1a3 in the heart plays an important role in the physiological processes involved in tolerance of bufadienolides among genetically resistant snakes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Thomson scattering produces n e profiles from measurement of scattered laser beam intensity. Rayleigh scattering provides a first calibration of the relation n e ∝ I TS , which depends on many factors (e.g., laser alignment and power, optics, and measurement systems). On DIII-D, the n e calibration is adjusted against an absolute n e from the density-driven cutoff of the 48 channel 2nd harmonic X-mode electron cyclotron emission system. This method has been used to calibrate Thomson n e from the edge to near the core (r/a > 0.15). Application of core electron cyclotron heating improves the quality of cutoff and depth of its penetration into the core, and also changes underlying MHD activity, minimizing crashes which confound calibration. Less fueling is needed as "ECH pump-out" generates a plasma ready to take up gas. On removal of gyrotron power, cutoff penetrates into the core as channels fall successively and smoothly into cutoff.

Sacral dimples are common physical examination findings among newborns and are rarely associated with spinal dysraphism. Screening ultrasonography for simple sacral dimples in the absence of other physical findings leads to unnecessary health care costs and undue stress on families. This study was a retrospective chart review of infants with a sacral dimple on examination who underwent spinal ultrasonography in the first week of life. The documented indication for ultrasonography was compared to standard guidelines. Among 151 infants in the study, 80% had a normal spinal ultrasound. Of infants with abnormal ultrasonography, 7 (5%) had abnormal spinal magnetic resonance imaging and 2 infants (1%) required neurosurgical intervention. Our study revealed that nearly one-third of infants who underwent spinal ultrasonography had a simple sacral dimple and low likelihood of spinal dysraphism according to existing guidelines. Among patients who underwent spinal ultrasonography in accordance with guidelines, only a small percentage required neurosurgical intervention indicating that guidelines may need to be revised. Larger studies involving multiple centers are necessary to assess this need., (© The Author(s) 2016.)

Nonrotating ("locked") magnetic islands often lead to complete losses of confinement in tokamak plasmas, called major disruptions. Here locked islands were suppressed for the first time, by a combination of applied three-dimensional magnetic fields and injected millimeter waves. The applied fields were used to control the phase of locking and so align the island O point with the region where the injected waves generated noninductive currents. This resulted in stabilization of the locked island, disruption avoidance, recovery of high confinement, and high pressure, in accordance with the expected dependencies upon wave power and relative phase between the O point and driven current.

Background: Human umbilical cord vein endothelial cells (HUVECs) are commonly chosen over freshly isolated endothelial cells from glioblastomas (GECs) due to accessibility and costs., Materials and Methods: To test their suitability for in vitro studies, we comprehensively compared the transcriptomes and responses to major angiogenic cytokines of HUVECs (n=2) and GECs (n=5). Purity of GEC cultures was confirmed by uptake of acetylated low-density protein and immunostaining., Results: Unsupervised analysis revealed a distinct grouping. We identified 854 differentially expressed genes. Pathway and gene ontology enrichment analyses pointed to clear differences in angiogenesis and leukocyte transmigration. Comparing the expression of cell adhesion molecules in five major angiogenic cytokines revealed that HUVECs in contrast to GECs did not exhibit a previously described down-regulation of cell adhesion molecules upon incubation with transforming growth factor betas, but rather with basic fibroblast growth factor., Conclusion: Given our findings, we strongly recommend the use of GECs as model cells for brain tumor endothelium for experiments investigating angiogenesis and immunobiology., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Hand-foot-and-mouth disease (HFMD) is a common self-limited viral illness seen in the United States and around the world. Its classic features are easily recognizable; however, nail changes are not well known or characterized. This case demonstrates onychomadesis and Beau lines in a child following clinical diagnosis of hand-foot-and-mouth disease. In this setting, nail dystrophies should be reassuring to pediatricians and families.

Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, and renal and vertebral anomalies. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported. Since the description of autosomal dominant Robinow Syndrome (ADRS; OMIM 180700) in 1969 by Meinhard Robinow and colleagues, the molecular etiology remained elusive until only recently. WNT5A was proposed to be the candidate gene for ADRS, as mutations were found in two affected families, one of those being the originally described index family. We report three families with RS caused by novel heterozygous WNT5A mutations, which were confirmed in the first family by whole exome sequencing, and in all by Sanger sequencing. To our knowledge, this is the largest number of published families with ADRS in whom a WNT5A mutation was identified. Families 1 and 2 are the first cases showing de novo inheritance in the affected family members and thus strengthen the evidence for WNT5A as the causative gene in ADRS. Finally, we propose WNT5A mutation specificity in ADRS, which may affect interactions with other proteins in the Wnt pathway., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance and proliferation of cancer cells by inhibiting disulfide reductases. Here, we report on the antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold chloride thio-β-d-glucose tetraacetate (GoPI-sugar), which exhibits antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines. Compared to carmustine (BCNU), an established nitrosourea compound for the treatment of glioblastomas that inhibits the proliferation of these glioma cell lines with an IC50 of 430μM, GoPI-sugar is more effective by two orders of magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6 glioma rat model and significantly reduces tumor volume while being well tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly and potently inhibits thioredoxin reductase (IC50 4.3nM) and human glutathione reductase (IC50 88.5nM). However, treatment with GoPI-sugar did not significantly alter redox parameters in the brain tissue of treated animals. This might be due to compensatory upregulation of redox-related enzymes but might also indicate that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA interaction and inhibition of topoisomerase I than on the disturbance of redox equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well tolerated, it represents a most promising lead for drug development. This article is part of a Special Issue entitled: Thiol-Based Redox Processes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Glioblastomas are highly aggressive brain tumours and are characterised by substantial cellular heterogeneity within a single tumour. A sub-population of glioblastoma stem-like cells (GSCs) that shares properties with neural precursor cells has been described, exhibiting resistance to therapy and therefore being considered responsible for the high recurrence rate in glioblastoma. To elucidate the underlying cellular processes we investigated the role of phosphatases in the GSC phenotype, using an in vitro phosphatome-wide RNA interference screen. We identified a set of genes, the knockdown of which induces a significant decrease in the glioma stem cell marker CD133, indicating a role in the glioblastoma stem-like phenotype. Among these genes, the ecto-nucleotidase ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) was found to be highly expressed in GSCs compared with normal brain and neural stem cells. Knockdown of ENPP1 in cultured GSCs resulted in an overall downregulation of stem cell-associated genes, induction of differentiation into astrocytic cell lineage, impairment of sphere formation, in addition to increased cell death, accumulation of cells in G1/G0 cell cycle phase and sensitisation to chemotherapeutic treatment. Genome-wide gene expression analysis and nucleoside and nucleotide profiling revealed that knockdown of ENPP1 affects purine and pyrimidine metabolism, suggesting a link between ENPP1 expression and a balanced nucleoside-nucleotide pool in GSCs. The phenotypic changes in E-NPP1-deficient GSCs are assumed to be a consequence of decreased transcriptional function of E2F1. Together, these results reveal that E-NPP1, by acting upstream of E2F1, is indispensable for the maintenance of GSCs in vitro and hence required to keep GSCs in an undifferentiated, proliferative state.

Objective: This report summarizes the findings of the consensus panel based on the results of the comprehensive questionnaire of US American College of Phlebology annual congress attendees and results of the systematic meta-analysis of the literature and provides quality improvement guidelines for the use of endovenous foam sclerotherapy (EFS) for the treatment of venous disorders, as well as identifies areas of needed research., Methods: Based on the above data, quality improvement guidelines were developed and reviewed by the ten US consensus panel members and approved by their respective societies., Results: EFS is effective for the treatment of truncal and tributary varicose veins, both as primary treatment and for treatment of recurrence. It may improve the signs and symptoms associated with varicose veins including pain and swelling. EFS is contraindicated in patients who have experienced an allergic reaction to previous treatment with foam or liquid sclerosant, and in patients with acute venous thrombosis events secondary to EFS., Conclusion: These guidelines for the use of EFS in the treatment of venous disorders provide an initial framework for the safe and efficacious use of this therapy, and the impetus to promote the evaluation of the questions remaining regarding the use of EFS through well-designed randomized and cohort studies.

Mild traumatic brain injury (MTBI) is a vulnerability factor for the development of pain-related conditions above and beyond those related to comorbid traumatic and emotional symptoms. We acquired functional magnetic resonance imaging (fMRI) on a validated pain anticipation task and tested the hypotheses that individuals with a reported history of MTBI, compared with healthy comparison subjects, would show increased brain response to pain anticipation and ineffective pain modulation after controlling for psychiatric symptoms. Eighteen male subjects with a reported history of blast-related MTBI related to combat, and eighteen healthy male subjects with no reported history of MTBI (healthy controls) underwent fMRI during an event-related experimental pain paradigm with cued high or low intensity painful heat stimuli. No subjects in either group met diagnostic criteria for current mood or anxiety disorder. We found that relative to healthy comparison subjects, after controlling for traumatic and depressive symptoms, participants with a reported history of MTBI showed significantly stronger activations within midbrain periaqueductual grey (PAG), right dorsolateral prefrontal cortex and cuneus during pain anticipation. Furthermore, we found that brain injury was a significant moderator of the relationship between anticipatory PAG activation and reported subjective pain. Our results suggest that a potentially disrupted neurocognitive anticipatory network may result from damage to the endogenous pain modulatory system and underlie difficulties with regulatory pain processing following MTBI. In other words, our findings are consistent with a notion that brain injury makes it more difficult to control acute pain. Understanding these mechanisms of dysfunctional acute pain processing following MTBI may help shed light on the underlying causes of increased vulnerability for the development of pain-related conditions in this population.

Objective: Previous studies in acromegaly and growth hormone deficiency observed inverse associations between insulin-like growth factor-I (IGF-I) levels and inflammatory biomarkers including high-sensitive C-reactive protein (hsCRP), interleukin-6 or fibrinogen. We aimed to assess the relations between IGF-I or IGF binding protein 3 (IGFBP-3) levels and hsCRP, interleukin-6, fibrinogen and white blood cell count (WBC) in a population-based sample., Design and Patients: Data from 3480 subjects from the population-based Study of Health in Pomerania (SHIP) were used. IGF-I, IGFBP-3 and inflammatory biomarkers were measured. Analysis of variance (anova), quantile regression models and logistic regression models, adjusted for age, smoking, diabetes mellitus and waist circumference, were performed., Measurements and Results: anova and/or quantile regression showed inverse associations between IGF-I and hsCRP as well as positive associations between IGF-I and fibrinogen among both sexes. Furthermore, the odds of elevated fibrinogen levels increased with increasing IGF-I levels (per SD IGF-I increase: men: odds ratio (OR) 1·35 [95% confidence interval (CI) 1·04, 1·55]; women: OR 1·44 [95% CI 1·21, 1·71]) in both sexes, whereas the odds of increased hsCRP (women: OR 0·46 [95% CI 0·36, 0·58]) and interleukin-6 (men: odds ratio (OR) 0·77 [95% CI 0·61, 0·96]; women: OR 0·69 [95% CI 0·55, 0·86]) decreased., Conclusion: Serum IGF-I levels are associated with inflammatory biomarkers including hsCRP, interleukin-6 and fibrinogen. Further experimental studies are needed to elucidate the mechanisms underlying the relation between the GH/IGF axis and the inflammatory system., (© 2013 John Wiley & Sons Ltd.)

Rationale: To improve outcomes for patients undergoing extinction-based therapies (e.g., exposure therapy) for anxiety disorders such as post-traumatic stress disorder (PTSD), there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall. Oxytocin (OT) is a mammalian neuropeptide that modulates activation of fear extinction-based neural circuits and fear responses. Little is known, however, about the effects of OT treatment on conditioned fear responding and extinction in humans., Objectives: The purpose of the present study was to assess the effects of OT in a fear-potentiated startle task of fear conditioning and extinction., Methods: A double-blind, placebo-controlled study of 44 healthy human participants was conducted. Participants underwent a conditioned fear acquisition procedure, after which they were randomized to treatment group and delivered OT (24 IU) or placebo via intranasal (IN) spray. Forty-five minutes after treatment, participants underwent extinction training. Twenty-four hours later, subjects were tested for extinction recall., Results: Relative to placebo, the OT group showed increased fear-potentiated startle responding during the earliest stage of extinction training relative to placebo; however, all treatment groups showed the same level of reduced responding by the end of extinction training. Twenty-four hours later, the OT group showed significantly higher recall of extinction relative to placebo., Conclusions: The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans. These results support further study of OT as a potential adjunctive treatment for extinction-based therapies in fear-related disorders.

Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.

Background: Schizophrenic patients treated with antipsychotic drugs (AP) have an increased frequency of glucose-lipid metabolic abnormalities and diabetes. Pioglitazone has been shown to be effective in the treatment of glucose and lipid abnormalities in diabetes and decreasing longer-term conversion of impaired glucose tolerance to frank diabetes. Some studies also suggest possible pro-cognitive and antidepressant effects of pioglitazone. We studied the effects of pioglitazone on potential metabolic, symptomatic and cognitive benefits in schizophrenic patients treated with AP., Methods: 54 schizophrenic patients with at least both a)impaired glucose and b) triglycerides≥120mg/dL and/or low HDL levels, participated in a double-blind placebo controlled study of 3month treatment with Pioglitazone (30-45mg/day) or matched placebo, at 5 sites (4 U.S., 1 China). Fasting glucose and lipid parameters, and psychopathology (PANSS scale) were assessed monthly, and patients had a glucose tolerance test and cognitive testing (RBANS and CPT) at baseline and at the end of study. Statistical analysis used mixed model repeated measures analysis, supplemented by completer and LOCF analysis., Results: In the total sample there was an overall effect (P's<.05 to <.01) of pioglitazone on preventing deterioration in fasting glucose and improving HDL and PANSS depression scores; in the pioglitazone group comparison of baseline vs 3month values also showed significant (P<.05) decreases in fasting insulin, 2h glucose in GTT and insulin resistance (HOMA-IR). However there were marked differences between the responses of patients in the U.S. sites vs the China site. In the U.S. sample, patients treated with pioglitazone, when compared to placebo treated patents, had significantly lower fasting glucose (F=3.99, P=0.02), improved insulin sensitivity (lower H0MA-IR, F=6.24, P=.002), lower triglycerides (F=2.68, P=.06) and increased HDL (F=6.50, P=.001). By the end of the study 52% of the pioglitazone treated patients compared to 15% of the placebo patients had fasting glucose in the normal range (Fisher's exact test P=.02). Pioglitazone also significantly improved PANSS depression factor scores (F=2.82, P=0.05). It did not improve cognitive performance on the RBANS or CPT tasks. Pioglitazone did not increase weight or produce any other significant side-effects. In the small mainland China site sample, pioglitazone treatment, as compared to placebo, did not show greater improvement in metabolic parameters or psychopathology ratings., Conclusions: In the sample of patients from the U.S., pioglitazone was an efficacious and safe treatment for glucose and lipid metabolic abnormalities in schizophrenic patients treated with AP, and it may also have beneficial effects on depressive symptoms. It may be particularly useful in patients whose weight gain effects from antipsychotics have plateaued and where weight loss is not the primary goal. The risk vs. benefits of longer term treatment with pioglitazone has to be carefully evaluated for individual patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Genes in the Wnt (wingless)/ β -catenin signaling pathway have been implicated in schizophrenia pathogenesis. No study has examined this pathway in the broader context of psychosis symptom severity. We investigated the association between symptom severity scores and expression of 25 Wnt pathway genes in blood from 19 psychotic patients. Significant correlations between negative symptom scores and deshivelled 2 (DVL2) (r adj = -0.70; P = 0.0008) and glycogen synthase kinase 3 beta (GSK3B) (r adj = 0.48; P = 0.039) were observed. No gene expression levels were associated with positive symptoms. Our findings suggest that the Wnt signaling pathway may harbor biomarkers for severity of negative but not positive symptoms.

Background and Objectives: Aversion of contaminants is important for several psychiatric disorders, particularly contamination-based obsessive-compulsive disorder (OCD). Recent theoretical models have proposed that the ability to control one's attention, especially when processing affectively laden information, is important in the etiology of pathological anxiety. The present study tested the relations between attentional control, affective arousal, and behavioral approach toward contaminants (contamination aversion)., Methods: Thirty-three non-selected (undergraduate university students) participants completed a measure of trait attentional control and three behavioral approach tasks, which measured emotional reactivity and approach toward contaminants., Results: Preliminary analyses showed that poorer attentional control and greater affective arousal predicted less behavioral approach toward contaminants. Modeling of direct and indirect relations showed that poor attentional shifting ability and greater subjective disgust were related to less behavioral approach. Moreover, disgust fully mediated the relation between attentional shifting and behavioral approach., Limitations: The present study used a convenience sample, which is not representative of the general population or individuals with OCD; therefore, research using clinical samples is necessary before making clinical interpretations. Moreover, the present study utilized subjective measures of attentional control and affective arousal. The use of objective measures of attention and affective arousal would provide a more valid test of the role of attentional control in contamination aversion., Conclusions: These findings suggest that attentional shifting abilities may serve as a vulnerability to affective arousal/regulation and behavioral avoidance of contaminants, but the latter relation only operated indirectly via disgust. These findings have clear implications for the etiology of contamination-related OCD., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Individuals with mental health problems may face barriers to accessing effective psychotherapies. Videoconferencing technology, which allows audio and video information to be shared concurrently across geographical distances, offers an alternative that may improve access. We conducted a systematic literature review of the use of videoconferencing psychotherapy (VCP), designed to address 10 specific questions, including therapeutic types/formats that have been implemented, the populations with which VCP is being used, the number and types of publications related to VCP, and available satisfaction, feasibility, and outcome data related to VCP. After electronic searches and reviews of reference lists, 821 potential articles were identified, and 65 were selected for inclusion. The results indicate that VCP is feasible, has been used in a variety of therapeutic formats and with diverse populations, is generally associated with good user satisfaction, and is found to have similar clinical outcomes to traditional face-to-face psychotherapy. Although the number of articles being published on VCP has increased in recent years, there remains a need for additional large-scale clinical trials to further assess the efficacy and effectiveness of VCP.

Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02(+) glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8(+) T cells in vitro. In vivo, glioblastoma-specific CD8(+) T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastoma.

Purpose: To assess practice patterns of endovenous foam sclerotherapy (EFS) use in the USA., Methods: A multidisciplinary panel of US experts was convened and developed a questionnaire to assess use of EFS. US attendees at the American College of Phlebology 2009 Annual Congress were asked to complete the questionnaire., Results: Of 776 questionnaires distributed, 239 were completed (31%). The majority of respondents (87%) reported using EFS for the treatment of venous disorders. Foam sclerotherapy was used by a wide variety of specialists in every region of the USA. The most common indication was sclerosis of recurrent truncal or tributary veins of the leg. There was variation among practitioners in the indications for use, pre- and postprocedural evaluation and procedure methodology., Conclusions: The results of this questionnaire show widespread usage of EFS and are important in the development of national quality improvement guidelines for the performance of EFS.