Homeodomain‐interacting protein kinase (Hipk) phosphorylates the small SPOC family protein Spenito

The Drosophila homeodomain‐interacting protein kinase (Hipk) is a versatile regulator involved in a variety of pathways, such as Notch and Wingless signalling, thereby acting in processes including the promotion of eye development or control of cell numbers in the nervous system. In vertebrates, extensive studies have related its homologue HIPK2 to important roles in the control of p53‐mediated apoptosis and tumour suppression. Spenito (Nito) belongs to the group of small SPOC family proteins and has a role, amongst others, as a regulator of Wingless signalling downstream of Armadillo. In the present study, we show that both proteins have an enzyme–substrate relationship, adding a new interesting component to the broad range of Hipk interactions, and we map several phosphorylation sites of Nito. Furthermore, we were able to define a preliminary consensus motif for Hipk target sites, which will simplify the identification of new substrates of this kinase.     

From complex questionnaire and interviewing data to intelligent Bayesian network models for medical decision support

Objectives(1) To develop a rigorous and repeatable method for building effective Bayesian network (BN) models for medical decision support from complex, unstructured and incomplete patient questionnaires and interviews that inevitably contain examples of repetitive, redundant and contradictory responses; (2) To exploit expert knowledge in the BN development since further data acquisition is usually not possible; (3) To ensure the BN model can be used for interventional analysis; (4) To demonstrate why using data alone to learn the model structure and parameters is often unsatisfactory even when extensive data is available.MethodThe method is based on applying a range of recent BN developments targeted at helping experts build BNs given limited data. While most of the components of the method are based on established work, its novelty is that it provides a rigorous consolidated and generalised framework that addresses the whole life-cycle of BN model development. The method is based on two original and recent validated BN models in forensic psychiatry, known as DSVM-MSS and DSVM-P.ResultsWhen employed with the same datasets, the DSVM-MSS demonstrated competitive to superior predictive performance (AUC scores 0.708 and 0.797) against the state-of-the-art (AUC scores ranging from 0.527 to 0.705), and the DSVM-P demonstrated superior predictive performance (cross-validated AUC score of 0.78) against the state-of-the-art (AUC scores ranging from 0.665 to 0.717). More importantly, the resulting models go beyond improving predictive accuracy and into usefulness for risk management purposes through intervention, and enhanced decision support in terms of answering complex clinical questions that are based on unobserved evidence.ConclusionsThis development process is applicable to any application domain which involves large-scale decision analysis based on such complex information, rather than based on data with hard facts, and in conjunction with the incorporation of expert knowledge for decision support via intervention. The novelty extends to challenging the decision scientists to reason about building models based on what information is really required for inference, rather than based on what data is available and hence, forces decision scientists to use available data in a much smarter way.     

An expert system feedback tool improves the reliability of clinical gait kinematics for older adults with lower limb osteoarthritis

Recently, an expert system was developed to provide feedback to examiners with the aim of improving reliability of marker-based gait analysis. The purpose of the current study was to evaluate the effectiveness of this novel feedback tool in improving the reliability of gait analysis for individuals with lower limb osteoarthritis. Three-dimensional gait analysis was conducted for n = 27 individuals, at two different time points, and during each session the feedback tool was used to refine marker placement. Results for both discrete variables and support vector machine classifications demonstrated improved reliability of the data with the feedback tool.     

First International Consensus Report on Adnexal Masses: Management Recommendations

The First International Consensus Conference on Adnexal Masses was convened to thoroughly examine the state of the science and to formulate recommendations for clinical assessment and management. The panel included representatives of societies in the fields of gynecology, gynecologic oncology, radiology, and pathology and clinicians from Europe, Canada, and the United States. In the United States, there are approximately 9.1 surgeries per malignancy compared to the European International Ovarian Tumor Analysis center trials, with only 2.3 (oncology centers) and 5.9 (other centers) reported surgeries per malignancy, suggesting that there is room to improve our preoperative assessments. The American College of Obstetricians and Gynecologists Practice Bulletin on “Management of Adnexal Masses,” reaffirmed in 2015 (Obstet Gynecol 2007; 110:201–214), still states, “With the exception of simple cysts on a transvaginal ultrasound finding, most pelvic masses in postmenopausal women will require surgical intervention.” The panel concluded that patients would benefit not only from a more conservative approach to many benign adnexal masses but also from optimization of physician referral patterns to a gynecologic oncologist in cases of suspected ovarian malignancies. A number of next‐step options were offered to aid in management of cases with sonographically indeterminate adnexal masses. This process would provide an opportunity to improve risk stratification for indeterminate masses via the provision of alternatives, including but not limited to evidence‐based risk‐assessment algorithms and referral to an “expert sonologist” or to a gynecologic oncologist. The panel believed that these efforts to improve clinical management and preoperative triage patterns would ultimately improve patient care.     

The risky shift

Currently, there seems to be a great hurry to develop guidelines for the clinical management of everything. Many evolving guidelines are proffered to be consensus decisions, which means, in most cases, that the guidelines were agreed on by multidisciplinary groups or committees. There is an unfortunate tendency to assume that consensus decisions are, a priori, correct and constitute the best and only way to address different problems.     

临床分离金黄色葡萄球菌对20种抗菌药物耐药性及耐药机制分析

目的 了解临床分离金黄色葡萄球菌对常用抗菌药物耐药性及产生机制。方法 42株金黄色葡萄球菌先用PCR检测mecA基因，再用VITEK2高级专家系统(AES)检测并分析对20种抗菌药物耐药性及耐药机制。结果 19株金黄色葡萄球菌mecA基因检测阳性，23株阴性；VITEK2 AES耐药机制分析，对β-内酰胺类耐药涉及青霉素结合蛋白(PBP)改变、获得性青霉素酶；氨基糖苷类耐药包括磷酸转移酶(2″) 乙酰转移酶(6′)双功能酶、磷酸转移酶(3′)-Ⅲ、腺苷转移酶(4′)(4″)；大环内酯类／林可霉胺类／链阳菌素B(MLSB)与MLSB固有耐药或诱导耐药有关；对四环素类耐药包括TETK蛋白导致药物外排和(或)TETM蛋白导致靶位改变；利福霉素类耐药主要为高水平耐药；MRSA对喹诺酮类均耐药，而MSSA除1株外均敏感；其余抗菌药物如呋喃妥因、糖肽类(万古霉素、替考拉宁)、复方新诺明、夫西地酸等均敏感。结论 临床分离金黄色葡萄球菌，尤其是MRSA具有多种耐药机制，因而对常用抗菌药物产生多重耐药性，VITEK2AES能可靠推测分析耐药菌所具有的耐药机制，将为临床抗感染治疗提供更加准确的依据。     

Subchronic oral toxicity of turmeric oleoresin in pigs

Turmeric oleoresin was fed for 102-109 days to groups of eight pigs (males and females) at dietary levels providing intakes of 60, 296 and 1551 mg/kg body weight/day. Twelve pigs served as controls. The highest dose group showed a reduction in weight gain and in food-conversion efficiency. Statistically significant dose-related increases in the weight of the liver and the thyroid were recorded at all dose levels. Pericholangitis, hyperplasia of the thyroid and epithelial changes in the kidney and urinary bladder were observed in the two higher dose groups. It is questionable whether a no-adverse-effect level can be established on the basis of the observations in this experiment. Further studies should be initiated to elucidate the mechanism of action of turmeric.     

Knowledge based expert systems for medical diagnosis

Knowledge based expert systems' have been developed in the last decade for many different applications by adopting artificial intelligence techniques. The paper discusses the main characteristics of the expert systems devoted to medical diagnosis (knowledge representation, explanation capability, inexact reasoning) and addresses some of the limitations (mainly system validation and knowledge acquisition). Finally the paper sketches the overall organization of an expert system devoted to the evaluation of liver function.