Fungal quinones: diversity, producers, and applications of quinones from Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium.

Quinones represent an important group of highly structurally diverse, mainly polyketide-derived secondary metabolites widely distributed among filamentous fungi. Many quinones have been reported to have important biological functions such as inhibition of bacteria or repression of the immune response in insects. Other quinones, such as ubiquinones are known to be essential molecules in cellular respiration, and many quinones are known to protect their producing organisms from exposure to sunlight. Most recently, quinones have also attracted a lot of industrial interest since their electron-donating and -accepting properties make them good candidates as electrolytes in redox flow batteries, like their often highly conjugated double bond systems make them attractive as pigments. On an industrial level, quinones are mainly synthesized from raw components in coal tar. However, the possibility of producing quinones by fungal cultivation has great prospects since fungi can often be grown in industrially scaled bioreactors, producing valuable metabolites on cheap substrates. In order to give a better overview of the secondary metabolite quinones produced by and shared between various fungi, mainly belonging to the genera Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium, this review categorizes quinones into families such as emodins, fumigatins, sorbicillinoids, yanuthones, and xanthomegnins, depending on structural similarities and information about the biosynthetic pathway from which they are derived, whenever applicable. The production of these quinone families is compared between the different genera, based on recently revised taxonomy. KEY POINTS: • Quinones represent an important group of secondary metabolites widely distributed in important fungal genera such as Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium. • Quinones are of industrial interest and can be used in pharmacology, as colorants and pigments, and as electrolytes in redox flow batteries. • Quinones are grouped into families and compared between genera according to the revised taxonomy.

Collecting Validity Evidence for the Assessment of Mastery Learning in Simulation-Based Ultrasound Training.

PURPOSE: To collect validity evidence for the assessment of mastery learning on a virtual reality transabdominal ultrasound simulator. MATERIALS AND METHODS: We assessed the validity evidence using Messick's framework for validity. The study included 20 novices and 9 ultrasound experts who all completed 10 obstetric training modules on a transabdominal ultrasound simulator that provided automated measures of performance for each completed module (i. e., simulator metrics). Differences in the performance of the two groups were used to identify simulator metrics with validity evidence for the assessment of mastery learning. The novices continued to practice until they had attained mastery learning level. RESULTS: One-third of the simulator metrics discriminated between the two groups. The median simulator scores from a maximum of 40 metrics were 17.5 percent (range 0 - 45.0 percent) for novices and 90.0 percent (range 85.0 - 97.5) for experts, p < 0.001. Internal consistency was high, with a Cronbach's alpha value of 0.98. The test/retest reliability gave an intra-class correlation coefficient (ICC) of 0.62 for novices who reached the mastery learning level twice. Novices reached the mastery learning level within a median of 4 attempts (range 3 - 8) corresponding to a median of 252 minutes of simulator training (range 211 - 394 minutes). CONCLUSION: This study found that validity evidence for the assessment of mastery learning in simulation-based ultrasound training can be demonstrated and that ultrasound novices can attain mastery learning levels with less than 5 hours of training. Only one-third of the standard simulator metrics discriminated between different levels of competence.

Randomized trial to examine procedure-to-procedure transfer in laparoscopic simulator training.

BACKGROUND: Laparoscopic simulation has become a standard component of surgical training, but there is limited knowledge regarding skills transfer between procedural tasks. The objective was to investigate the specificity of procedural simulator training. METHODS: This was randomized single-centre educational superiority trial. Surgical novices practised basic skills on a laparoscopic virtual reality simulator. On reaching proficiency, participants were randomized to proficiency-based training. The intervention group practised two procedures on the simulator (appendicectomy followed by salpingectomy), whereas the control group trained on only one procedure (salpingectomy). The main outcomes were number of repetitions and time to proficiency for the second procedure. RESULTS: Ninety-six participants were randomized, of whom 74 per cent were women, with a median age of 26 years. The intervention group needed significantly fewer attempts than the control group to reach proficiency in the second procedure: median (i.q.r.) 22 (17-34) versus 32 (26-41) attempts, which corresponded to 24·1 per cent fewer attempts as assessed by multivariable analysis (P = 0·004). The intervention group required significantly less time than the control group to reach proficiency: median (i.q.r.) 88 (63-127) versus 131 (101-153) min respectively, corresponding to a difference of 31·1 min as assessed by multivariable analysis (P = 0·001). CONCLUSION: Practising two procedures, compared with only one, reduced the number of attempts and time to reach proficiency in the second procedure. Skills transfer is seen between two tasks in laparoscopic simulator training; however, task specificity is still present when practising procedures. REGISTRATION NUMBER: NCT02069951 (http://www.clinicaltrials.gov).

Sustained effect of simulation-based ultrasound training on clinical performance: a randomized trial.

OBJECTIVE: To study the effect of initial simulation-based transvaginal sonography (TVS) training compared with clinical training only, on the clinical performance of residents in obstetrics and gynecology (Ob-Gyn), assessed 2 months into their residency. METHODS: In a randomized study, new Ob-Gyn residents (n = 33) with no prior ultrasound experience were recruited from three teaching hospitals. Participants were allocated to either simulation-based training followed by clinical training (intervention group; n = 18) or clinical training only (control group; n = 15). The simulation-based training was performed using a virtual-reality TVS simulator until an expert performance level was attained, and was followed by training on a pelvic mannequin. After 2 months of clinical training, one TVS examination was recorded for assessment of each resident's clinical performance (n = 26). Two ultrasound experts blinded to group allocation rated the scans using the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale. RESULTS: During the 2 months of clinical training, participants in the intervention and control groups completed an average ± SD of 58 ± 41 and 63 ± 47 scans, respectively (P = 0.67). In the subsequent clinical performance test, the intervention group achieved higher OSAUS scores than did the control group (mean score, 59.1% vs 37.6%, respectively; P < 0.001). A greater proportion of the intervention group passed a pre-established pass/fail level than did controls (85.7% vs 8.3%, respectively; P < 0.001). CONCLUSION: Simulation-based ultrasound training leads to substantial improvement in clinical performance that is sustained after 2 months of clinical training. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Development of knowledge tests for multi-disciplinary emergency training: a review and an example.

BACKGROUND: The literature is sparse on written test development in a post-graduate multi-disciplinary setting. Developing and evaluating knowledge tests for use in multi-disciplinary post-graduate training is challenging. The objective of this study was to describe the process of developing and evaluating a multiple-choice question (MCQ) test for use in a multi-disciplinary training program in obstetric-anesthesia emergencies. METHODS: A multi-disciplinary working committee with 12 members representing six professional healthcare groups and another 28 participants were involved. Recurrent revisions of the MCQ items were undertaken followed by a statistical analysis. The MCQ items were developed stepwise, including decisions on aims and content, followed by testing for face and content validity, construct validity, item-total correlation, and reliability. RESULTS: To obtain acceptable content validity, 40 out of originally 50 items were included in the final MCQ test. The MCQ test was able to distinguish between levels of competence, and good construct validity was indicated by a significant difference in the mean score between consultants and first-year trainees, as well as between first-year trainees and medical and midwifery students. Evaluation of the item-total correlation analysis in the 40 items set revealed that 11 items needed re-evaluation, four of which addressed content issues in local clinical guidelines. A Cronbach's alpha of 0.83 for reliability was found, which is acceptable. CONCLUSION: Content and construct validity and reliability were acceptable. The presented template for the development of this MCQ test could be useful to others when developing knowledge tests and may enhance the overall quality of test development.

Which factors are associated with trainees' confidence in performing obstetric and gynecological ultrasound examinations?

OBJECTIVE: To explore the association between clinical training characteristics and trainees' level of confidence in performing ultrasound scans independently. METHODS: A cross-sectional e-survey was distributed to members of the national societies of junior obstetricians/gynecologists in Denmark, Sweden and Norway (n = 973). Multiple linear regression models were used to explore the effect that amount of time spent in specialized ultrasound units and clinical experience had on trainees' confidence in performing ultrasonography independently. Exploratory factor analysis was used to identify factors that contributed to trainees' confidence in performing ultrasonography. Trainees' ultrasound confidence was finally compared with their expected levels of performance. RESULTS: Of the 682 respondents (response rate 70.1%), 621 met the inclusion criteria. Clinical experience and time spent in specialized ultrasound units were predictors of trainees' confidence in performing ultrasonography independently (P < 0.001). Trainees required more than 24 months of clinical experience and 12-24 days of training in specialized ultrasound units in order to feel confident about performing transvaginal and transabdominal ultrasound scans independently. Three factors were related to ultrasound confidence: technical aspects, image perception and integration of scan into patient care. There were significant differences between trainees' level of confidence and their expected levels of performance (P < 0.001). CONCLUSIONS: Clinical experience and time spent in specialized ultrasound units were predictors of trainees' confidence in performing ultrasonography independently. Discrepancies between trainees' confidence and their expected levels of performance raised concerns about the adequacy of current ultrasound training programs.

Reliable and valid assessment of ultrasound operator competence in obstetrics and gynecology.

OBJECTIVES: To explore the reliability and validity of a recently developed instrument for assessment of ultrasound operator competence, the Objective Structured Assessment of Ultrasound Skills (OSAUS). METHODS: Three groups of 10 doctors with different levels of ultrasound experience in obstetrics and gynecology were included. The novices had less than 1 month of experience, the intermediate group had 12-60 months of experience and the senior participants were all consultants. Fifteen participants performed transabdominal fetal biometry and the other 15 participants performed systematic transvaginal gynecological ultrasound scans. All scans were video-recorded and assessed by two blinded consultants using the OSAUS scale. The OSAUS scores were compared between the groups using the Kruskal-Wallis test, and pass/fail scores were determined using the contrasting-groups method of standard setting. RESULTS: For the transabdominal fetal biometry examinations, the mean ± SD OSAUS scores of the novices, intermediates and senior participants were 1.5 ± 0.4, 3.3 ± 0.6 and 4.4 ± 0.4, respectively (P = 0.003). For the systematic transvaginal scans, the mean ± SD OSAUS scores of the novices, intermediates and senior participants were 1.8 ± 0.2, 3.1 ± 0.1 and 3.9 ± 0.5, respectively (P = 0.003). Post-hoc comparisons showed significant differences between each of the groups for both types of scans. The pass/fail score was 2.5 for the transvaginal scan and 3.0 for the transabdominal biometry examinations. The inter-rater reliability was 0.89. CONCLUSIONS: Ultrasound competence can be assessed in a reliable and valid way using the OSAUS scale. The pass/fail scores may be used to help determine when trainees are qualified for independent practice.

Fusarin C acts like an estrogenic agonist and stimulates breast cancer cells in vitro.

Fusarin C is a mycotoxin produced by several Fusarium species and has been associated with esophageal cancer due to its carcinogenic effects. Here, we report that fusarin C stimulates growth of the breast cancer cell line MCF-7. This suggests that fusarin C can act as an estrogenic agonist and should be classified as a mycoestrogen. MCF-7 cells were stimulated in the range between 0.1 and 20µM and inhibited when the concentration exceeded 50µM. The toxicity of fusarin C is comparable to other mycoestrogens such as zearalenone, but the chemical structure of fusarin C is very different from other known estrogen agonists. Furthermore, the toxicity of fusarin C was tested in five additional human cell lines Caco 2, U266, PC3, MDA-MB-231 and MCF-10a which were all inhibited when the concentration of fusarin C exceeded 10µM. To the best of our knowledge this is the first report on the mycoestrogenic properties of fusarin C.

Evaluation and impact of cardiotocography training programmes: a systematic review.

BACKGROUND: The interpretation and management of cardiotocography (CTG) tracings are often criticised in obstetric malpractice cases. As a consequence, regular CTG training has been recommended, even though little is known about the effect of CTG training. OBJECTIVES: To perform a systematic review of the existing literature on studies on CTG training in order to assess educational strategies, evaluation of training programmes, and impact of training programmes. SEARCH STRATEGY: The Medline database was searched to identify studies describing and/or evaluating CTG training programmes. The literature search resulted in 409 citations. SELECTION CRITERIA: Twenty studies describing and evaluating CTG training programmes were included. There was no restriction on study design. DATA COLLECTION AND ANALYSIS: Data regarding study design, study quality, educational strategies used for training in CTG interpretation and decision making, target groups, number of participants, methods used for evaluation, quality of evaluation, level of evaluation and results of training was extracted from 20 articles, and analysed using Kirkpatrick's four-level model for the evaluation of education. MAIN RESULTS: Training was associated with improvements on all Kirkpatrick levels, resulting in increased CTG knowledge and interpretive skills, higher interobserver agreement, better management of intrapartum CTG, and improved quality of care. Computer-based training (CBT) might be less time-consuming than classroom teaching. Clinical skills seem to decrease faster than theoretical knowledge. AUTHOR'S CONCLUSIONS: Training can improve CTG competence and clinical practise. Further research on CBT, test-enhanced learning and long-term retention, evaluation of training and impact on clinical outcomes is recommended.

Objective assessment of gynecologic laparoscopic skills using the LapSimGyn virtual reality simulator.

BACKGROUND: Safe realistic training and unbiased quantitative assessment of technical skills are required for laparoscopy. Virtual reality (VR) simulators may be useful tools for training and assessing basic and advanced surgical skills and procedures. This study aimed to investigate the construct validity of the LapSimGyn VR simulator, and to determine the learning curves of gynecologists with different levels of experience. METHODS: For this study, 32 gynecologic trainees and consultants (juniors or seniors) were allocated into three groups: novices (0 advanced laparoscopic procedures), intermediate level (>20 and <60 procedures), and experts (>100 procedures). All performed 10 sets of simulations consisting of three basic skill tasks and an ectopic pregnancy program. The simulations were carried out on 3 days within a maximum period of 2 weeks. Assessment of skills was based on time, economy of movement, and error parameters measured by the simulator. RESULTS: The data showed that expert gynecologists performed significantly and consistently better than intermediate and novice gynecologists. The learning curves differed significantly between the groups, showing that experts start at a higher level and more rapidly reach the plateau of their learning curve than do intermediate and novice groups of surgeons. CONCLUSION: The LapSimGyn VR simulator package demonstrates construct validity on both the basic skills module and the procedural gynecologic module for ectopic pregnancy. Learning curves can be obtained, but to reach the maximum performance for the more complex tasks, 10 repetitions do not seem sufficient at the given task level and settings. LapSimGyn also seems to be flexible and widely accepted by the users.

Gender differences among HIV-positive methadone maintenance patients enrolled in a medication adherence trial.

This study examined baseline gender differences among HIV-positive methadone maintenance outpatients currently prescribed antiretroviral medications. Participants were enrolled in a larger clinical trial, which included a 4-week observation period using electronic monitors to track medication adherence. Contrary to previous literature, no significant differences were detected between men (n = 42) and women (n = 36) on medication adherence or depression. Both groups showed remarkably poor adherence during baseline (M = 56% of doses taken on time), high overall prevalence of depression (47%) and illicit cocaine use (47%). Women reported significantly more medication side effects (M = 21.4 vs. 14.9), higher severity of ASI psychiatric problems (M = 0.50 vs. 0.40), and lower SF-36 health-related quality of life in physical (M = 42.1 vs. 63.3) and emotional functioning (M = 26.9 vs. 58.9) than men. Women tested positive for opioids at higher rates than men (53% vs. 29%, respectively), whereas men were more likely to be positive for benzodiazepines than women (26% vs. 6%, respectively). Findings suggest that gender differences between male and female methadone maintenance patients have relevance to treatment providers. Extensive assessment, specialized medical care and mental health services may be warranted in the treatment of HIV-positive female drug abusers.

Predictors of medical service utilization among individuals with co-occurring HIV infection and substance abuse disorders.

This study examined factors affecting medical service use among HIV-infected persons with a substance abuse disorder. The sample comprised 190 participants enrolled in a randomized trial of a case management intervention. Participants were interviewed about their backgrounds, housing status, income, alcohol and drug use problems, health status and depressive symptoms at study entry. Electronic medical records were used to assess medical service use. Poisson regression models were tested to determine the effects of need, enabling and predisposing factors on the dependent variables of emergency department visits, inpatient admissions and ambulatory care visits. During a two-year period, 71% were treated in the emergency department, 64% had been hospitalized and the sample averaged 12.9 ambulatory care visits. Homelessness was associated with higher utilization of emergency department and inpatient services; drug use severity was associated with higher inpatient and ambulatory care service use; and alcohol use severity was associated with greater use of emergency medical services. Homelessness and substance abuse exacerbate the health care needs of HIV-infected persons and result in increased use of emergency department and inpatient services. Interventions are needed that target HIV-infected persons with substance abuse disorders, particularly those that increase entry and retention in outpatient health care and thus decrease reliance on acute hospital-based services.

Nondestructive identification of cold and extremely localized single molecular ions.

We demonstrate a simple and nondestructive method for identification of a single molecular ion sympathetically cooled by a single laser cooled atomic ion in a linear Paul trap. The technique is based on a precise nondestructive determination of the molecular ion mass through a measurement of the eigenfrequency of a common motional mode of the two ions. The demonstrated mass resolution is sufficiently high that molecular ion mass doublets can potentially be distinguished from each other. The obtained results represent an important step towards single molecule gas phase chemical physics.

Entanglement and quantum teleportation with multi-atom ensembles.

Atomic ensembles containing a large number of atoms have been proved to be an effective medium for quantum-state (quantum information) engineering and processing via their coupling with multi-photon light pulses. The general mechanism of this coupling, which involves continuous quantum variables for light and atoms, is described. The efficient quantum interface between light and atoms has led to the recent demonstration of an entangled state of two macroscopic atomic objects, more precisely two caesium gas samples. Based on this result, a proposal for teleportation of an entangled state of two atomic samples (entanglement swapping) is presented.

Recording quantum properties of light in a long-lived atomic spin state: towards quantum memory.

We report an experiment on mapping a quantum state of light onto the ground state spin of an ensemble of Cs atoms with the lifetime of 2 ms. Recording of one of the two quadrature phase operators of light is demonstrated with vacuum and squeezed states of light. The sensitivity of the mapping procedure at the level of approximately 1 photon/sec per Hz is shown. The results pave the road towards complete (storing both quadrature phase observables) quantum memory for Gaussian states of light. The experiment also sheds new light on fundamental limits of sensitivity of the magneto-optical resonance method.

[Ogilvie syndrome after Cesarean section]. / Ogilvies syndrom efter sectio.

INTRODUCTION: Ogilvie's syndrome, acute pseudo-obstruction of the colon, can lead to perforation of the caecum and death. The syndrome is not well known and diagnosis can be difficult to make in time. METHODS: We analysed seven cases of Ogilvie's syndrome with the aim of improving diagnostics. RESULTS: All had prolonged labour before cesarean section, which was complicated by bleeding. All were treated with syntocinon, a hormone that may influence gastrointestinal motility. All patients developed abdominal meteorism within a few days of operation, which increased despite the passing of flatus and stool. Five cases resulted in caecum perforation before the correct diagnosis and treatment were made. Perforation occurred on days 3-4, day 5, or probably days 8-10 after the operation. One of these patients, who suffered from severe adipositas, died. CONCLUSION: It is very important to make an early diagnosis, as the condition can progress quickly. Diagnosis should be made on the history, clinical assessment, and abdominal X-ray. Intermittent flatus and stool are characteristic of this truly non-obstructive condition and should not therefore delay a diagnostic X-ray.

[Problem-based learning in medical education. Experiences from a department of gynecology]. / Problembaseret laering på medicinstudiet. Erfaringer fra en gynaekologisk afdeling.

INTRODUCTION: Problem-based learning (PBL) is an educational method based on a clinical problem, where students define their learning objectives, research these objectives, and report back. The aim of the present study was to compare PBL with other learning methods during a pregraduate clinical course. METHODS: PBL was applied to six groups of students (n = 35) during a pregraduate clinical course in obstetrics and gynaecology and compared with other learning methods, such as traditional lectures, participation in the clinical work of the department, and a training course in communication and clinical skills with simulated patients and phantoms. The learning methods were scored on a scale from zero to five. RESULTS: The educational methods were evaluated differently (p < 0.01). PBL reached a score of at least four more often (33/35) than did traditional lectures (25/34), p < 0.05. Most of the students enjoyed PBL, although they found it time consuming. Twenty-one preferred the mixture of PBL and lectures, whereas 13 preferred more PBL and one solely preferred lectures. DISCUSSION: The present study shows that it is possible to implement PBL sessions in clinical courses and the method is positively evaluated by both students and teachers.

Synthesis of novel gamma-aminobutyric acid (GABA) uptake inhibitors. 5.(1) Preparation and structure-activity studies of tricyclic analogues of known GABA uptake inhibitors.

On the basis of the SAR of a series of known gamma-aminobutyric acid (GABA) uptake inhibitors, including 4 (SKF 89976), new tricyclic analogues have been prepared. These novel compounds are derivatives of nipecotic acid, guvacine, and homo-beta-proline, substituted at the nitrogen of these amino acids by various lipophilic moieties such as (10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)alkoxyalkyl or (10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)alkoxyalkyl. The in vitro values for inhibition of [(3)H]-GABA uptake in rat synaptosomes was determined for each compound in this new series, and it was found that several of the novel compounds showed a high potency comparable with that of the reference compounds 4, 5 (tiagabine), and 6 (CI-966). Several of the novel compounds were also evaluated for their ability in vivo to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). One compound, (R)-1-(2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-piperidinecarboxylic acid (23), was selected for further biological investigations and showed a protective index comparable to or slightly better than that of the recently launched anticonvulsant product 5 ((R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid).

Differences between methamphetamine users and cocaine users in treatment.

To better understand the distinguishing characteristics of methamphetamine users versus cocaine users, we conducted a retrospective chart review of the 345 patients admitted to an outpatient stimulant treatment program during 1995--1997. Analyses revealed an increase in methamphetamine patients over the 3-year period, and that these patients were more likely than cocaine patients to be male, Caucasian, and gay or bisexual. Methamphetamine patients were also more likely to be HIV-positive, engage in behaviors such as using and sharing needles that place them at high risk for HIV transmission, have a psychiatric diagnosis, and be on psychiatric medications. The two populations did not differ in treatment adherence, as measured by clinic attendance, drug-free urines, and successful completion of treatment. These findings suggest that highly specialized substance abuse treatments for methamphetamine patients may not be needed. Resources may be directed toward addressing their medical and psychiatric diagnostic issues by providing ancillary services to stimulant treatment programs.