bluuebunny/crossref_metadata_2025 huggingface dataset:
Haemodynamic monitoring in the peri‐operative period: the past, the present and the future
Authors: Watson X. , Cecconi M.
Published: January 2017

Over recent years there has been an increase in the implementation of goal‐directed therapy using minimally invasive haemodynamic monitoring techniques to guide peri‐operative care. Since the introduction of the pulmonary artery flotation catheter in the 1980s, various haemodynamic monitors have been developed, each associated with their own benefits and limitations. Goal‐directed therapy has been well‐established as a standard of care in the peri‐operative period and has largely been associated with a reduction in morbidity and mortality. However, evidence over the last few years from major studies has led us to question: what is the future for goal‐directed therapy? Care of the peri‐operative patient has significantly evolved over the last decade and this needs to be taken into account when assessing the results of these studies. We should therefore not look at the effects of goal‐directed therapy in isolation but as part of a progressive care bundle. Additionally, other markers of haemodynamic status have also begun to be further appreciated and these are worthy of further investigation. We feel that the future for haemodynamic monitoring remains promising with new areas of interest continuously emerging, but further research is still required.
Conceptual and technical insights into the basis of neuromuscular monitoring
Authors: Naguib M. , Brull S. J. , Johnson K. B.
Published: January 2017

Unrecognised postoperative residual neuromuscular block remains a frequent occurrence in recovery rooms. Evidence indicates that current practice continues to perpetuate the status quo, in which 10–40% of patients experience postoperative residual weakness. A departure from the current practice requires small efforts on the clinicians’ part. This review addresses several selected core questions regarding neuromuscular blockade monitoring and provides a framework to rationally discuss and develop basic guidelines for the use of neuromuscular blocking agents in patient care.
The role and limitations of EEG‐based depth of anaesthesia monitoring in theatres and intensive care
Authors: Hajat Z. , Ahmad N. , Andrzejowski J.
Published: January 2017

In this article we will look at some of the principles in processed EEG monitoring as applied to bispectral index (BIS). We outline why BIS should be regarded as a ‘memory’ monitor which in most circumstances reflects the depth of sedation or anaesthesia in particular patients. Its limitation in paralysed and non‐paralysed patients must be understood in order for this monitor to be used safely. Finally, its emerging use in critical care will be explored.
Cerebral oximetry and its role in adult cardiac, non‐cardiac surgery and resuscitation from cardiac arrest
Authors: Green D. W. , Kunst G.
Published: January 2017

Monitors using near‐infra red spectroscopy to assess cerebral oxygenation levels non‐invasively in discrete areas of the brain have been used clinically for over 20 years. Interest has intensified recently, especially during cardiac surgery, and there are now five commercially available devices. Despite the attraction of being able to measure oxygen supply/demand in such a critical area, there has been only limited uptake of this technology in overall clinical anaesthetic practice. This narrative review aims to explore not only the rationale for using this technology but also the factors which have restricted its more widespread use.
An introduction to predictive modelling of drug concentration in anaesthesia monitors
Authors: DeCou J. , Johnson K.
Published: January 2017

A significant amount of anaesthetists’ work involves the prediction of drug effects and interactions to produce a smooth general anaesthetic that minimises drug side effects and promotes rapid emergence. Successfully managing this process requires a basic understanding of drug effects, experience and inevitably some guesswork, since it is difficult (and in some cases impossible) to anticipate all relevant patient and surgical factors. Although data are generally available to allow calculation of plasma drug and effect site concentrations, this is often difficult to apply in complex clinical contexts, particularly when multiple drug types are used.

In recent years, manufacturers have developed and incorporated into anaesthetic workstations technologies that use drug pharmacodynamic and pharmacokinetic data to predict drug effects and interactions. Such systems can predict the duration and effects of drugs during anaesthesia and assist the anaesthetist to understand complex drug interactions. With this information available, different drug types, doses and combinations may be tailored in a scientific way to maximise useful effects whilst minimising overdose and side‐effects, particularly in high‐risk patients. Examples are used to illustrate how such systems can be used in practice, and how drug effects and interactions can be simulated to “rehearse” an anaesthetic before any drugs are actually administered.

At present only a small number of anaesthetic workstations use this technology, and as yet they are not able to manage all drugs used in anaesthetic practice. However, such systems have the potential to help anaesthetists manage the complexity of their work, and to provide information on predicted drug effects in a way that is useful and relevant to both experienced anaesthetists and trainees.
Monitoring regional blockade
Authors: Ode K. , Selvaraj S. , Smith A. F.
Published: January 2017

This review attempts to draw on the published literature to address three practical clinical questions. First, what means of testing the degree of regional blockade pre‐operatively are available, and can eventual success or failure be determined soon after injection? Second, is it possible to predict if a block inserted after the induction of general anaesthesia will be effective when the patient wakes? Third, what features, and what duration, should cause concern when a block does not resolve as expected after surgery? Although the relevant literature is limited, we recommend testing of multiple sensory modalities before surgery commences; temperature and thermographic changes may offer additional early warning of success or failure. There are a number of existing methods of assessing nociception under general anaesthesia, but none has yet been applied to gauge the onset of a regional block. Finally, criteria for further investigation and neurological referral when block symptoms persist postoperatively are presented.
Monitoring the anaesthetist in the operating theatre – professional competence and patient safety
Authors: Larsson J.
Published: January 2017

This article about competence and patient safety in anaesthesia was inspired by a statement in the 2015 AAGBI guidelines on monitoring during anaesthesia: ‘the presence of an appropriately trained and experienced anaesthetist is important for patient safety during anaesthesia’. The review starts with a structured description of competence, presenting five dimensions of it; the first two dimensions are identical with the two classical attributes of competence, practical skills and theoretical knowledge. Concerning skills, the value of aiming for a high level of proficiency early in a traning programme is pointed out, and deliberate practice is given as an example of a pedagogical model where aiming for excellence is a core idea. For theoretical knowledge, the value of a deep approach to learning physiology and basic sciences is stressed. The third dimension (anaesthetists’ non‐technical skills), represents skills necessary for good team‐work in the operating theatre. The two last dimensions of competence are the understanding of work and intuitive expert knowing. Understanding work means being aware of what the work is about, appreciating the different aspects of the anaesthetist's job. Intuitive expert knowing, lastly, concerns the tacit dimension of knowledge and skills, which enables professional experts to quickly find a working solution for most clinical problems. The final part of the review is about the ‘when’ and ‘how’ of competence assessment. The main message is the importance of assessing the competence of clinically active anaesthetists regularly during their whole career.
Monitoring teamwork: a narrative review
Authors: Rutherford J. S.
Published: January 2017

A narrative review was carried out to identify articles on monitoring of teamwork, with particular relevance to anaesthetists. The papers reviewed showed that team monitoring takes place both implicitly and explicitly in the anaesthetic environment. No single optimal model of teamwork monitoring for all situations was identified. Most of the studies identified were of a pre‐intervention, post‐intervention design, without randomisation or control group. Information shared during a formal briefing is more likely to be recalled, and provides a basis for a shared team mental model. A number of studies appeared to show that targeted teamwork training has a positive impact on both teamwork and patient safety.
Intravascular oxygen sensors with novel applications for bedside respiratory monitoring
Authors: Formenti F. , Farmery A. D.
Published: January 2017

Measurement allows us to quantify various parameters and variables in natural systems. In addition, by measuring the effect by which a perturbation of one part of the system influences the system as a whole, insights into the functional mechanisms of the system can be inferred. Clinical monitoring has a different role to that of scientific measurement. Monitoring describes measurements whose prime purpose is not to give insights into underlying mechanisms, but to provide information to ‘warn’ of imminent events. What is often more important is the description of trends in measured variables. In this article, we give some examples ‐ focussed around oxygen sensors ‐ of how new sensors can make important measurements and might in the future contribute to improved clinical management.
Letter: comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for noninvasive diagnosis of advanced fibrosis in biopsy‐proven NAFLD
Authors: Shi H. L. , Liu L. N. , Shao M.
Published: January 2017

Linked Content

This article is linked to Cui et al and Loomba papers. To view these articles visit https://doi.org/10.1111/apt.13196 and https://doi.org/10.1111/apt.13906.
Letter: HBsAg kinetics‐guided interferon therapy for chronic hepatitis D
Authors: Kao C.‐N. , Su T.‐H. , Kao J.‐H.
Published: January 2017

Linked Content

This article is linked to Niro et al papers. To view these articles visit https://doi.org/10.1111/apt.13734 and https://doi.org/10.1111/apt.13892.
Editorial: should the inappropriate use of proton pump inhibitors be a quality assurance issue in cirrhotic patients?
Authors: Shaw J. , Bajaj J. S.
Published: January 2017

Linked Content

This article is linked to Cole et al paper. To view this article visit https://doi.org/10.1111/apt.13827.
Letter: is body‐mass index really associated with fibrosis regression during long‐term nucleoside analogue therapy in chronic hepatitis B?
Authors: Huang R. , Wang G. , Liu Y. , Jia B. , Wu C.
Published: January 2017

Linked Content

This article is linked to Seto et al and Seto, Yuen papers. To view these articles visit https://doi.org/10.1111/apt.13804 and https://doi.org/10.1111/apt.13899.
Letter: HBsAg kinetics‐guided interferon therapy for chronic hepatitis D – authors’ reply
Authors: Niro G. A. , Smedile A. , Andriulli A. , Rizzetto M.
Published: January 2017

Linked Content

This article is linked to Niro et al and Kao et al papers. To view these articles visit https://doi.org/10.1111/apt.13734 and https://doi.org/10.1111/apt.13872.
Letter: is body‐mass index really associated with fibrosis regression during long‐term nucleoside analogue therapy in chronic hepatitis B? Authors’ reply
Authors: Seto W.‐K. , Yuen M.‐F.
Published: January 2017

Linked Content

This article is linked to Seto et al and Huang et al papers. To view these articles visit https://doi.org/10.1111/apt.13804 and https://doi.org/10.1111/apt.13885.
Letter: comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non‐invasive diagnosis of advanced fibrosis in biopsy‐proven NAFLD – author's reply
Authors: Loomba R.
Published: January 2017

Linked Content

This article is linked to Cui et al and Shi et al papers. To view these articles visit https://doi.org/10.1111/apt.13196 and https://doi.org/10.1111/apt.13871.
Feasibility of umbilical loop ileostomy in overweight and obese patients with rectal cancer during laparoscopic surgery: Preliminary results
Authors: Ishiguro Seiji , Komatsu Shunichiro , Ando Keiichi , Osawa Takaaki , Yasui Kohei , Arikawa Takashi , Ohashi Norifumi , Miyachi Masahiko , Sano Tsuyoshi
Published: January 2017

We examined the feasibility of umbilical diverting ileostomy for overweight and obese patients with rectal cancer undergoing laparoscopic surgery. Four patients who were overweight or obese (BMI > 27 kg/m2) were initially scheduled for the creation of a conventional loop ileostomy. Intraoperatively, however, this was considered too complicated because of thick subcutaneous fat, bulky mesentery, or both. Instead, patients received a diverting ileostomy with the placement of an umbilical stoma. All patients had protruding umbilical ileostomies. No severe stoma‐related complications were encountered. One patient had minor skin dehiscence, and another had paralytic ileus but resumed oral intake after a short time. Performing a temporary loop ileostomy at the umbilicus was safe and feasible in this small group of overweight and obese patients. This stoma placement may avoid the problems inherent to conventional loop ileostomy in obese subjects.
Secure, low‐cost technique for laparoscopic hepatic resection using the crush‐clamp method with a bipolar sealer
Authors: Yamamoto Takatsugu , Uenishi Takahiro , Kaneda Kazuhisa , Okawa Masato , Tanaka Shogo , Kubo Shoji
Published: January 2017

Introduction

Laparoscopic hepatectomy is difficult because surgeons must perform the transection using many (four and more) energy devices and without direct manual maneuvers. Here we introduce hepatic transection by the classical method with a few (two or three) energy devices.

Materials and Surgical Technique

We performed laparoscopic hepatectomy for 40 patients with hepatic tumor and liver dysfunction. For parenchymal transection, we used bipolar radiofrequency coagulation forceps connected to a voltage‐controlled electrosurgical generator and ultrasonic dissector. The demarcation of the liver surface was made by an ultrasonic dissector. Along the demarcation line, the blades of a BiClamp were opened slightly and inserted into the hepatic parenchyma. We clamped slowly, softly, and gradually, and a small amount of hepatic parenchyma was consequently coagulated and fractured. After the crush, the small vessels and intrahepatic bile duct that were sealed were left as atrophic strings, and the strings were divided by an ultrasonic dissector. Large vessels and Glisson's sheaths were left because of the small clamp. Large Glisson's sheaths and hepatic veins were ligated with a titanium clip or autosutures, and cut without bile leakage or bleeding. The mean operation time of the procedure was 196.9 min, mean blood loss was 69.9 mL, and mean postoperative hospitalization was 9.5 days. No blood transfusions were needed. Two cases had perioperative complications—one involving right shoulder pain and the other involving ascites due to liver dysfunction—but there were no serious postoperative complications.

Discussion

The present results appear to demonstrate that this simple and safe method helps decrease intraoperative bleeding and shorten hospital stay.
Percutaneous endoscopic transpedicle approach for herniated nucleus pulposus in the lumbar hidden zone
Authors: Wang Dong , Pan Hao , Hu Qinfeng , Zhu Hang , Zhu Li , He Yongjiang , Wang Jian , Jia Gaoyong
Published: January 2017

Introduction

Although endoscopic procedures for lumbar disc diseases have improved greatly, treating migrated disc herniation is still a challenging task. Because of anatomic limitations, a rigid endoscope cannot effectively reach the herniated nucleus pulposus (HNP) in the hidden zone. The purpose of this study was to describe the transpedicle approach for HNP in the hidden zone using the percutaneous endoscopic lumbar discectomy system and to demonstrate the clinical results.

Materials and Surgical Technique: Under fluoroscopy, the percutaneous endoscopic lumbar discectomy cannula is placed on the superior articular process, and a trephine with a diameter of 7.3 mm is used to make a bone hole. Through the bone hole, an HNP in the hidden zone can be detected with a rongeur for percutaneous endoscopic lumbar discectomy, the HNP can be removed, and then the decompressed nerve root is verified. We have treated two cases of hidden‐zone HNP using the transpedicle approach. In all cases, the HNP was successfully removed, as confirmed by postoperative MRI. Clinical outcomes were acceptable.

Discussion

The percutaneous endoscopic transpedicle approach is an effective technique for managing HNP in the lumbar hidden zone.
Usefulness of a CT‐guided hookwire marking in laparoscopic partial hepatectomy for hepatocellular carcinoma invisible on ultrasonography
Authors: Monden Kazuteru , Sadamori Hiroshi , Hioki Masayoshi , Nakano Kanyu , Asami Shinya , Ohno Satoshi , Sasaki Kyo , Ueki Toru , Yabushita Kazuhisa , Uka Mayu , Hyodo Tsuyoshi , Sakaguchi Kousaku , Takakura Norihisa
Published: January 2017

Introduction

The intra‐operative detection of hepatocellular carcinoma (HCC) by ultrasonography is indispensable for laparoscopic partial hepatectomy. However, it is occasionally difficult to localize an HCC on an ultrasound in chronic liver disease. Two cases of partial hepatectomy using hookwire marking under CT guidance are presented.

Materials and Surgical Technique

The location of the HCC was identified by CT scan, and the puncture site was determined. A hookwire system, made of a stainless steel hook, was used to localize the HCC. The hookwire was placed percutaneously close to the HCC, and then the patient was taken to the operating room as soon as possible. After identification of the hookwire marker, the cutting line was determined on the liver surface to ensure a sufficient surgical margin in laparoscopic partial hepatectomy.

Discussion

Two cases underwent these procedures with easy intra‐operative marking of the resection area. This technique facilitates safe laparoscopic partial hepatectomy for an HCC that is invisible on ultrasound.
Safe approach to the splenic hilum by first mobilizing the pancreatic tail in laparoscopic splenectomy
Authors: Sakamoto Katsunori , Honda Goro , Kurata Masanao , Homma Yuki , Shinya Satoshi , Honjo Masahiko
Published: January 2017

Introduction

We employed a safe approach during laparoscopic splenectomy by first mobilizing the pancreatic tail and then dissecting the splenic vessels at the splenic hilum before mobilizing the spleen.

Materials and Surgical Technique

Patients were placed in the lithotomy position, and only the upper body was twisted to the right side. Five trocars were placed. After the bursa omentalis was opened, an avascular layer was identified behind the pancreas. This avascular layer was bluntly dissected, and the pancreatic tail was isolated from the retroperitoneum. The tissue surrounding the splenic hilum was dissected by a handling tape that was placed around the pancreatic tail. Because the spleen remained connected to the retroperitoneum with the splenorenal ligament, a good operative view of the splenic hilum was obtained with proper extension. After sufficient space was secured between the pancreatic tail and the spleen, the splenic vessels were divided with a linear stapler. The spleen was detached in the final stage.

Discussion

The current standardized procedure is highly recommended for a safe laparoscopic splenectomy.
Serosal and muscular layers incision technique in laparoscopic surgery for gastric gastrointestinal stromal tumors
Authors: Fujishima Hajime , Etoh Tsuyoshi , Hiratsuka Takahiro , Akagi Tomonori , Tajima Masaaki , Shibata Tomotaka , Ueda Yoshitake , Tojigamori Manabu , Shiroshita Hidefumi , Shiraishi Norio , Kitano Seigo , Inomata Masafumi
Published: January 2017

Introduction

To minimize the resection of stomach tissue, especially for lesions close to the esophagogastric junction or pyloric ring, we developed laparoscopic wedge resection with the serosal and muscular layers incision technique (SAMIT) for gastric gastrointestinal stromal tumors.

Materials and Surgical Technique

SAMIT involves resection of the mucosal and submucosal layers and then an incision in serosal and muscular layers around the tumor. SAMIT is simple and does not require special devices. The data of 13 patients who underwent laparoscopic wedge resection with SAMIT for primary gastric gastrointestinal stromal tumors were reviewed. No intraoperative complications were observed, and postoperative stenosis occurred in only one case of a middle stomach lesion. Adequate oncological resection was performed in all cases.

Discussion

Laparoscopic wedge resection with SAMIT is technically and oncologically safe. It is useful for treating gastric gastrointestinal stromal tumors, including those close to the esophagogastric junction or pyloric ring.
Global Research Trends in Lithium Toxicity from 1913 to 2015: A Bibliometric Analysis
Authors: Zyoud Sa'ed H. , Waring W. Stephen , Sweileh Waleed M. , Al‐Jabi Samah W.
Published: January 2017

Lithium salts have been used to treat psychiatric disorders since the 1940s and are currently used in prophylaxis and treatment of depression and bipolar disorder. Therefore, we conducted this study to assess lithium toxicity‐related publications using bibliometric approaches from a health point of view to assess global research trends in the lithium toxicity field to offer guidance to future research in this field. The data were retrieved from the online version of Scopus database on 6 August 2016. All records with the term ‘lithium’ in the title were retrieved, and those related to lithium toxicity were evaluated. There were a total of 1241 publications related to lithium toxicity published from 1913 to 2016. Articles (971 or 78.2%) were the most common type, followed by letters (179 or 14.4%) and reviews (61 or 4.9%). The annual publication of articles increased slightly after 1950 and the total number of publications related to lithium toxicity fluctuated with three peaks occurred in 1978, 1985 and 2014. The USA was the predominant country (25.38%), followed by the UK (7.82%), France (6.85%) and Canada (3.55%). Denmark had the highest productivity of publication after standardization by gross domestic product and population size. The average number of citations per article was 9.24, and the h‐index for all publications in the field of lithium toxicity was 46. The highest h‐index value was achieved by the USA (31) followed by the UK (21) and Canada (13). The Lancet was the highest ranked journal with 27 articles, followed by American Journal of Psychiatry with 23 articles. This study provides a bibliometric analysis on the global research trends in lithium toxicity studies during 1913–2015. There has been a progressive increase in the number of publications related to lithium toxicity published in the last decade, and most of the studies related to lithium toxicity arose from the USA and the UK.
Clinical Pharmacology Research Internships at the Interface between Academia and Industry: Students’ Perceptions and Scientific Output
Authors: Goulooze Sebastiaan C. , Franson Kari L. , Cohen Adam F. , Rissmann Robert
Published: January 2017

The Centre for Human Drug Research (CHDR) is a non‐profit clinical research institute at the interface between academia and the pharmaceutical industry. CHDR hosts a research internship programme for undergraduate (bio)medical students. The aim of this study was (i) to investigate the student perceptions of the undergraduate research internship and (ii) to quantify the scientific output related to these internships. We surveyed former interns at the CHDR from the year 2007 to 2014 and quantified their scientific output with a PubMed search. There was a response rate to the survey of 61%, with a good overall rating of the internships. Many students considered their internship at CHDR to be (much) more broad (55%) and with a (much) stricter planning (48%), compared to previous internships at academic research groups. In turn, there were many aspects reported to be similar to academic research internships such as focus on research methodology and ‘outcome‐drivenness’. Twenty‐four per cent of the internships resulted in a co‐authorship on papers published in peer‐reviewed journals with an average impact factor of 3.3. In conclusion, with appropriate management and supervision, effective research electives are possible in the more commercial environment of a clinical research organization.
Tumor‐derived spheroids: Relevance to cancer stem cells and clinical applications
Authors: Ishiguro Tatsuya , Ohata Hirokazu , Sato Ai , Yamawaki Kaoru , Enomoto Takayuki , Okamoto Koji
Published: January 2017

Recently, many types of in vitro 3‐D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3‐D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2‐D monolayer cultures, and include tumor‐derived organoids, tumor‐derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3‐D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals. Tumor‐derived spheroids are unique because they are purposed for the enrichment of cancer stem cells (CSCs) or cells with stem cell‐related characteristics. These spheroids are grown as floating spheres and have been used as surrogate systems to evaluate the CSC‐related characteristics of solid tumors in vitro. Because eradication of CSCs is likely to be of clinical importance due to their association with the malignant nature of cancer cells, such as tumorigenicity or chemoresistance, the investigation of tumor‐derived spheroids may provide invaluable clues to fight against cancer. Spheroid cultures have been established from cancers including glioma, breast, colon, ovary, and prostate cancers, and their biological and biochemical characteristics have been investigated by many research groups. In addition to the investigation of CSCs, tumor‐derived spheroids may prove to be instrumental for a high‐throughput screening platform or for the cultivation of CSC‐related tumor cells found in the circulation or body fluids.
Hepatocyte growth factor/MET in cancer progression and biomarker discovery
Authors: Matsumoto Kunio , Umitsu Masataka , De Silva Dinuka M. , Roy Arpita , Bottaro Donald P.
Published: January 2017

Signaling driven by hepatocyte growth factor (HGF) and MET receptor facilitates conspicuous biological responses such as epithelial cell migration, 3‐D morphogenesis, and survival. The dynamic migration and promotion of cell survival induced by MET activation are bases for invasion–metastasis and resistance, respectively, against targeted drugs in cancers. Recent studies indicated that MET in tumor‐derived exosomes facilitates metastatic niche formation and metastasis in malignant melanoma. In lung cancer, gene amplification‐induced MET activation and ligand‐dependent MET activation in an autocrine/paracrine manner are causes for resistance to epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors. Hepatocyte growth factor secreted in the tumor microenvironment contributes to the innate and acquired resistance to RAF inhibitors. Changes in serum/plasma HGF, soluble MET (sMET), and phospho‐MET have been confirmed to be associated with disease progression, metastasis, therapy response, and survival. Higher serum/plasma HGF levels are associated with therapy resistance and/or metastasis, while lower HGF levels are associated with progression‐free survival and overall survival after treatment with targeted drugs in lung cancer, gastric cancer, colon cancer, and malignant melanoma. Urinary sMET levels in patients with bladder cancer are higher than those in patients without bladder cancer and associated with disease progression. Some of the multi‐kinase inhibitors that target MET have received regulatory approval, whereas none of the selective HGF‐MET inhibitors have shown efficacy in phase III clinical trials. Validation of the HGF‐MET pathway as a critical driver in cancer development/progression and utilization of appropriate biomarkers are key to development and approval of HGF‐MET inhibitors for clinical use.
Vasohibin‐2 is required for epithelial–mesenchymal transition of ovarian cancer cells by modulating transforming growth factor‐β signaling
Authors: Norita Rie , Suzuki Yasuhiro , Furutani Yutaka , Takahashi Kazuki , Yoshimatsu Yasuhiro , Podyma‐Inoue Katarzyna A. , Watabe Tetsuro , Sato Yasufumi
Published: January 2017

Vasohibin‐2 (VASH2) is a homolog of VASH1, an endothelium‐derived angiogenesis inhibitor. Vasohibin‐2 is mainly expressed in cancer cells, and has been implicated in the progression of cancer by inducing angiogenesis and tumor growth. Although VASH2 has been recently reported to be involved in epithelial–mesenchymal transition (EMT), its precise roles are obscure. The aim of the present study was to clarify the role of VASH2 in the EMT of cancer cells in relation to transforming growth factor‐β (TGF‐β) signaling, which is a major stimulator of EMT. Decreased expression of VASH2 in ovarian cancer cells significantly repressed the expression of TGF‐β type I receptor, namely activin receptor‐like kinase 5. Transforming growth factor‐β1‐induced phosphorylation of Smad2 and Smad3 was markedly decreased in VASH2 knockdown cells while the expression of Smad2 and Smad3 was unchanged. Accordingly, the responses to TGF‐β1 shown by promoter assay and plasminogen activator inhibitor type 1 expression were significantly attenuated in VASH2 knockdown cells. Furthermore, knockdown of VASH2 in cancer cells abrogated the TGF‐β1‐induced reduced expression of epithelial markers including E‐cadherin, and the elevated expression of mesenchymal markers including fibronectin, ZEB2, and Snail2, suggesting that endogenous VASH2 is required for TGF‐β1‐induced EMT. In accordance with these results, the effects of TGF‐β1 on cell morphology, migration, invasion, and MMP2 expression were also abrogated when VASH2 was knocked down. These results indicate that VASH2 played a significant role in the EMT by modulating the TGF‐β signaling. We propose that VASH2 would be a novel molecular target for the prevention of EMT in cancers.
Panel of autoantibodies against multiple tumor‐associated antigens for detecting gastric cancer
Authors: Hoshino Isamu , Nagata Matsuo , Takiguchi Nobuhiro , Nabeya Yoshihiro , Ikeda Atsushi , Yokoi Sana , Kuwajima Akiko , Tagawa Masatoshi , Matsushita Kazuyuki , Satoshi Yajima , Hideaki Shimada
Published: January 2017

Gastric cancer is the second leading cause of cancer death in the world, and effective diagnosis is extremely important for good outcome. We assessed the diagnostic potential of an autoantibody panel that may provide a novel tool for the early detection of gastric cancer. We analyzed data from patients with gastric cancer and normal controls in test and validation cohorts. Autoantibody levels were measured against a panel of six tumor‐associated antigens (TAAs) by ELISA: p53, heat shock protein 70, HCC‐22‐5, peroxiredoxin VI, KM‐HN‐1, and p90 TAA. We assessed serum autoantibodies in 100 participants in the test cohort. The validation cohort comprised 248 participants. Autoantibodies to at least one of the six antigens showed a sensitivity/specificity of 49.0% (95% confidence interval [CI], 39.2–58.8%)/92.4% (95% CI, 87.2–97.6%), and 52.0% (95% CI, 42.2–61.8%)/90.5% (95% CI, 84.8–96.3%) in the test and validation cohorts, respectively. In the validation cohort, no significant differences were seen when patients were subdivided based on age, sex, depth of tumor invasion, lymph node metastasis, distant metastasis, peritoneal dissemination, or TNM stage. Patients who were positive for more than two antibodies in the panel tended to have a worse prognosis than those who were positive for one or no antibody. Measurement of autoantibody response to multiple TAAs in an optimized panel assay to discriminate patients with early stage gastric cancer from normal controls may aid in the early detection of gastric cancer.
MicroRNA‐181b‐5p, ETS1, and the c‐Met pathway exacerbate the prognosis of pancreatic ductal adenocarcinoma after radiation therapy
Authors: Tomihara Hideo , Yamada Daisaku , Eguchi Hidetoshi , Iwagami Yoshifumi , Noda Takehiro , Asaoka Tadafumi , Wada Hiroshi , Kawamoto Koichi , Gotoh Kunihito , Takeda Yutaka , Tanemura Masahiro , Mori Masaki , Doki Yuichiro
Published: January 2017

Preoperative chemoradiation therapy (CRT) for pancreatic ductal adenocarcinoma (PDAC) has emerged as a reasonable strategy that shows good prognostic impact. However, after preoperative CRT, resected specimens show remnant tumor cells, which indicate that some tumor cells had acquired or were selected for resistance to CRT. Recently, two oncological mechanisms, the EMT and the presence of CSCs, were reported to be associated with resistance in various cancers. Previous reports showed that HGF could induce EMT in PDAC cells; moreover, the HGF receptor, c‐Met, was identified as a dominant pancreatic CSC marker. However, the clinical significance of c‐Met expression remains unclear. So, we hypothesized that remnant PDAC tissue after CRT might harbor cells with high c‐Met expression, and these cells may exacerbate patients’ prognosis. In the immunohistochemical analysis, we showed that preoperative CRT was significantly associated with high c‐Met expression; moreover, high c‐Met expression was a significant marker of a dismal prognosis. Next, we investigated mechanisms of c‐Met upregulation in PDAC cells. We established GEM‐resistant and radioresistant PDAC cells to analyze the transcriptome involved in c‐Met expression. The microarray data for the established radiation‐resistant PDAC cells indicated miR‐181b‐5p downregulation, which targets ETS1, one of the transcription factors for c‐Met, and it was shown that radiation exposure induced c‐Met expression through ETS1 increase by the suppression of miR‐181b‐5p. These results suggested that targeting these mechanisms may promote the development of a novel multidisciplinary treatment strategy for improving preoperative CRT efficiency.
Trajectories of Violent Behavior Among Females and Males
Authors: Cauffman Elizabeth , Fine Adam , Thomas April G. , Monahan Kathryn C.
Published: January 2017

Both the psychological and criminological fields have long hypothesized the mechanisms that influence desistance from violent offending, but few studies have focused on violent females. This study identifies patterns of violent behavior across 7 years among 172 females and 172 matched males ages 15–24, testing if heterogeneity in violent offending is linked to (a) developmental change in impulse control and (b) attainment of adult milestones. Fewer females persist in violence (25%) than males (46%); 19% of males increase in violent behavior. Females who develop impulse control and are employed are more likely to desist from violence. Violent offending is unrelated to other adult milestones. Developmental increases in impulse control may trigger desistance, while employment may maintain desistance from violence.
Students' Reports of Severe Violence in School as a Tool for Early Detection and Prevention
Authors: Yablon Yaacov B.
Published: January 2017

Early detection of severe violence is a significant challenge for many schools. Three studies were conducted on samples of 6th, 8th, and 10th graders (12–16 years old). The first study, based on paired reports of teachers and students (n = 130), showed that a high percentage of both victims and perpetrators of severe violence are not identified by teachers but are known to students. The second and third studies were based on qualitative (n = 30) and quantitative methods (n = 524) and revealed the factors that explain students' willingness to report or seek help from their teachers. The findings highlight the role of victims as a source of information regarding perpetrators and suggest a new perspective for early identification of severe violence in schools.
Early Childhood Predictors of Severe Youth Violence in Low‐Income Male Adolescents
Authors: Sitnick Stephanie L. , Shaw Daniel S. , Weaver Chelsea M. , Shelleby Elizabeth C. , Choe Daniel E. , Reuben Julia D. , Gilliam Mary , Winslow Emily B. , Taraban Lindsay
Published: January 2017

Using a cohort of 310 low‐income male adolescents living in an urban community and followed prospectively from 18 months through adolescence (ages 15–18 years), the current study examined whether individual, family, and community risk factors from ages 18 to 42 months were associated with adolescents' violent behavior, as indexed by juvenile petitions. Results of multivariate analyses indicated that although family income was the only factor to discriminate those with no arrest record from those with nonviolent arrests, rejecting parenting, child oppositional behavior, emotion regulation, and minority status during the toddler period contributed unique variance in distinguishing male adolescents arrested for violent behavior compared to those never arrested and those arrested for nonviolent behavior. Implications for prevention efforts are discussed.
Severe Violence During Adolescence and Early Adulthood and Its Relation to Anticipated Rewards and Costs
Authors: Shulman Elizabeth P. , Monahan Kathryn C. , Steinberg Laurence
Published: January 2017

This report compares the effects (concurrent and lagged) of the anticipated rewards and costs of violent crime on engagement in severe violence in a sample of male juvenile offenders (N = 1,170; 42.1% black, 34.0% Hispanic, 19.2% white, and 4.6% other; ages 14–18 at baseline). Anticipated rewards (social approval, thrill) are more predictive of concurrent severe violence than are anticipated costs (social disapproval, risk of punishment). The analysis finds no evidence that perceptions of the rewards and costs of violent crime influence engagement in severe violence 6 months later. The results support the view that adolescence is a time of heightened reward salience but raise doubt about the longitudinal predictive validity of perceptions about crime during this time of life.
Prevention of Targeted School Violence by Responding to Students' Psychosocial Crises: The NETWASS Program
Authors: Leuschner Vincenz , Fiedler Nora , Schultze Martin , Ahlig Nadine , Göbel Kristin , Sommer Friederike , Scholl Johanna , Cornell Dewey , Scheithauer Herbert
Published: January 2017

The standardized, indicated school‐based prevention program “Networks Against School Shootings” combines a threat assessment approach with a general model of prevention of emergency situations in schools through early intervention in student psychosocial crises and training teachers to recognize warning signs of targeted school violence. An evaluation study in 98 German schools with 3,473 school staff participants (Mage = 46.2 years) used a quasi‐experimental comparison group design with three measurement points (pre, post, and 7 months followup) with schools randomly allocated to implementation conditions. The study found increases in teachers' expertise and evaluation skills, enhanced abilities to identify students experiencing a psychosocial crisis, and positive secondary effects (e.g., teacher–student interaction, feelings of safety).
Severe Youth Violence: Developmental Perspectives Introduction to the Special Section
Authors: Malti Tina , Averdijk Margit
Published: January 2017

In this article, the authors introduce the special section on severe youth violence (SYV). As severe violence has significant negative consequences and youth commit more violence than other age groups, a developmental science approach is important to (a) understand pathways to SYV, (b) guide attempts to screen and assess SYV risk, and (c) inform novel, developmentally sensitive practices and policies to prevent and reduce SYV. The authors establish the theoretical and empirical contexts for the articles in this special section and explain how this developmental research on SYV can inform new lines of theoretical and empirical inquiry and innovative approaches to detect and respond to the risk of SYV.
Developmental Relations Among Behavioral Inhibition, Anxiety, and Attention Biases to Threat and Positive Information
Authors: White Lauren K. , Degnan Kathryn A. , Henderson Heather A. , Pérez‐Edgar Koraly , Walker Olga L. , Shechner Tomer , Leibenluft Ellen , Bar‐Haim Yair , Pine Daniel S. , Fox Nathan A.
Published: January 2017

This study examined relations between behavioral inhibition (BI) assessed in toddlerhood (n = 268) and attention biases (AB) to threat and positive faces and maternal‐reported anxiety assessed when children were 5‐ and 7‐year‐old. Results revealed that BI predicted anxiety at age 7 in children with AB toward threat, away from positive, or with no bias, at age 7; BI did not predict anxiety for children displaying AB away from threat or toward positive. Five‐year AB did not moderate the link between BI and 7‐year anxiety. No direct association between AB and BI or anxiety was detected; moreover, children did not show stable AB across development. These findings extend our understanding of the developmental links among BI, AB, and anxiety.
Spasticity: the need for objective assessment
Authors: Skalsky Andrew
Published: January 2017

This commentary is on the original article by Sloot et al. on pages 145–151 of this issue.
Aims and Exclusivity
Authors: Sullivan‐Bissett Ema
Published: January 2017

If belief has anaimby being a (quasi) intentional activity, then it ought to be the case that the aim of belief can beweighedagainst other aims one might have. However, this is not so with the putative truth aim of belief: from the first‐person perspective, one can only be motivated by truth considerations in deliberation over what to believe (exclusivity). From this perspective then, the aim cannot be weighed. This problem is captured by David Owens's Exclusivity Objection to belief having an aim (2003). Conor McHugh (2012; 2013) has responded to this problem by denying the phenomenon of exclusivity and replacing it with something weaker: demandingness. If deliberation over what to believe is characterised bydemandingnessand notexclusivity, this allows for the requisite weighing of the truth aim. I argue against such a move by suggesting that where non‐evidential considerations play a role in affecting what we believe, these considerations merely change the standards required for believing in a particular context, they donotprovide non‐evidential reasons for forming or withholding belief, which are consideredas suchfrom the deliberative perspective. Exclusivity thus remains, and so too does Owens's objection.
Depression screening tools in persons with epilepsy: A systematic review of validated tools
Authors: Gill Stephanie J. , Lukmanji Sara , Fiest Kirsten M. , Patten Scott B. , Wiebe Samuel , Jetté Nathalie
Published: January 2017

Objective

Depression affects approximately 25% of epilepsy patients. However, the optimal tool to screen for depression in epilepsy has not been definitively established. The purpose of this study was to systematically review the literature on the validity of depression‐screening tools in epilepsy.

Methods

MEDLINE, EMBASE, and PsycINFO were searched until April 4, 2016 with no restriction on dates. Abstract, full‐text review and data abstraction were conducted in duplicate. We included studies that evaluated the validity of depression‐screening tools and reported measures of diagnostic accuracy (e.g., sensitivity, specificity, and negative and positive predictive values) in epilepsy. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies Version 2. Medians and ranges for estimates of diagnostic accuracy were calculated when appropriate.

Results

A total of 16,070 abstracts were screened, and 38 articles met eligibility criteria. Sixteen screening tools were validated in 13 languages. The most commonly validated screening tool was the Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E) (n = 26). The Mini International Neuropsychiatric Interview (MINI) (n = 19) was the most common reference standard used. At the most common cutpoint of >15 (n = 12 studies), the NDDI‐E had a median sensitivity of 80.5% (range 64.0–100.0) and specificity of 86.2 (range 81.0–95.6). Meta‐analyses were not possible due to variability in cutpoints assessed, reference standards used, and lack of confidence intervals reported.

Significance

A number of studies validated depression screening tools; however, estimates of diagnostic accuracy were inconsistently reported. The validity of scales in practice may have been overestimated, as cutpoints were often selected post hoc based on the study sample. The NDDI‐E, which performed well, was the most commonly validated screening tool, is free to the public, and is validated in multiple languages and is easy to administer, although selection of the best tool may vary depending on the setting and available resources.
Integration of cellular ubiquitin and membrane traffic systems: focus on deubiquitylases
Authors: Clague Michael J. , Urbé Sylvie
Published: January 2017

The cell is comprised of integrated multilevel protein networks or systems. The ubiquitin, protein homeostasis and membrane trafficking systems are highly integrated. Here, we look at the influence of reversible ubiquitylation on membrane trafficking and organelle dynamics. We review the regulation of endocytic sorting, selective autophagy and the secretory pathway by ubiquitin signals, with a particular focus on detailing the contribution of deubiquitylating enzymes.
The membrane activity of BOK involves formation of large, stable toroidal pores and is promoted by cBID
Authors: Fernández‐Marrero Yuniel , Bleicken Stephanie , Das Kushal Kumar , Bachmann Daniel , Kaufmann Thomas , Garcia‐Saez Ana J.
Published: January 2017

The BCL‐2 family members are key regulators of the intrinsic apoptotic pathway, which is defined by permeabilization of the mitochondrial outer membrane by members of the BAX‐like subfamily. BOK is classified as a BAX‐like protein; however, its (patho‐)physiological role remains largely unclear. We therefore assessed the membrane permeabilization potential of C‐terminally truncated recombinant BOK, BOK∆C. We show that BOK∆C can permeabilize liposomes mimicking the composition of mitochondrial outer membrane, but not of endoplasmic reticulum, forming large and stable pores over time. Importantly, pore formation was enhanced by the presence of cBID and refractory to the addition of antiapoptotic BCL‐XL. However, isolated mitochondria from Bax−/−Bak−/− cells were resistant to BOK‐induced cytochrome c release, even in the presence of cBID. Taken together, we show that BOK∆C can permeabilize liposomes, and cooperate with cBID, but its role in directly mediating mitochondrial permeabilization is unclear and may underlie a yet to be determined negative regulation.