Nontarget-site resistance due to rapid physiological response in 2,4-D resistant Conyza sumatrensis: reduced 2,4-D translocation and auxin-induced gene expression.

BACKGROUND: Resistance to 2,4-Dichlorophenoxyacetic acid (2,4-D) has been reported in several weed species since the 1950s; however, a biotype of Conyza sumatrensis showing a novel physiology of the rapid response minutes after herbicide application was reported in 2017. The objective of this research was to investigate the mechanisms of resistance and identify transcripts associated with the rapid physiological response of C. sumatrensis to 2,4-D herbicide. RESULTS: Differences were found in 2,4-D absorption between the resistant and susceptible biotypes. Herbicide translocation was reduced in the resistant biotype compared to the susceptible. In resistant plants 98.8% of [14 C] 2,4-D was found in the treated leaf, whereas ≈13% translocated to other plant parts in the susceptible biotype at 96 h after treatment. Resistant plants did not metabolize [14 C] 2,4-D and had only intact [14 C] 2,4-D at 96 h after application, whereas susceptible plants metabolized [14 C] 2,4-D into four detected metabolites, consistent with reversible conjugation metabolites found in other 2,4-D sensitive plant species. Pre-treatment with the cytochrome P450 inhibitor malathion did not enhance 2,4-D sensitivity in either biotype. Following treatment with 2,4-D, resistant plants showed increased expression of transcripts within plant defense response and hypersensitivity pathways, whereas both sensitive and resistant plants showed increased expression of auxin-response transcripts. CONCLUSION: Our results demonstrate that reduced 2,4-D translocation contributes to resistance in the C. sumatrensis biotype. The reduction in 2,4-D transport is likely to be a consequence of the rapid physiological response to 2,4-D in resistant C. sumatrensis. Resistant plants had increased expression of auxin-responsive transcripts, indicating that a target-site mechanism is unlikely. © 2023 Society of Chemical Industry.

Identification of a Novel 2,4-D Metabolic Detoxification Pathway in 2,4-D-Resistant Waterhemp (Amaranthus tuberculatus).

A 2,4-dichlorophenoxyactic acid (2,4-D)-resistant population of Amaranthus tuberculatus (common waterhemp) from Nebraska, USA, was previously found to have rapid metabolic detoxification of the synthetic auxin herbicide 2,4-D. We purified the main 2,4-D metabolites from resistant and susceptible plants, solved their structures by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS), and synthesized the metabolites to determine their in planta toxicity. Susceptible plants conjugated 2,4-D to aspartate to form 2,4-D-aspartic acid (2,4-D-Asp), while resistant plants had a unique metabolic profile where 2,4-D was hydroxylated into 5-OH-2,4-D, followed by conjugation into a sugar metabolite (2,4-D-5-O-d-glucopyranoside) and subsequent malonylation into 2,4-D-(6'-O-malonyl)-5-O-d-glucopyranoside. Toxicological studies on waterhemp and Arabidopsis thaliana confirmed that the hydroxylated metabolite lost its auxinic action and toxicity. In contrast, the 2,4-D-Asp metabolite found in susceptible plants retained some auxinic action and toxicity. These results demonstrate that 2,4-D-resistant A. tuberculatus evolved novel detoxification reactions not present in susceptible plants to rapidly metabolize 2,4-D, potentially mediated by cytochrome P450 enzymes that perform the initial 5-hydroxylation reaction. This novel mechanism is more efficient to detoxify 2,4-D and produces metabolites with lower toxicity compared to the aspartic acid conjugation found in susceptible waterhemp.

Com-On Questionnaire: Development and validation of a questionnaire for evaluating communication skills of oncologists.

OBJECTIVE: The present study aimed to develop and validate an instrument for assessing the communication skills of oncology physicians from a patient's point of view. METHODS: A first draft of the questionnaire was compiled based on skills reflecting good physician-patient communication identified in the literature. The questionnaire was critically revised by experts to ensure the validity of its contents. The revised questionnaire was completed by a sample of 153 cancer patients. The questionnaire was developed in German and later translated into English. RESULTS: After analysis using classical test theory and an exploratory factor analysis, four different factors could be extracted. These factors were labelled setting, patient-centeredness, empathy and consulting competencies. Unsuitable items were eliminated within the analysis. All remaining items hold an appropriate degree of selectivity, item difficulty and reliability/consistency. CONCLUSION: A novel questionnaire for evaluating communication skills of physicians was developed. It contains 36 items and is named 'Com-On Questionnaire: Questionnaire for the Evaluation of Physician's Communication Skills in Oncology'. PRACTICE IMPLICATIONS: The questionnaire is suitable for measuring both the strengths and deficits within the physician-patient communication in oncology from the patients' perspective.

Correction: ComOn-Coaching: The effect of a varied number of coaching sessions on transfer into clinical practice following communication skills training in oncology: Results of a randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0205315.].

Assessing Communication Skills in Real Medical Encounters in Oncology: Development and Validation of the ComOn-Coaching Rating Scales.

One of the challenges in research on teaching physician-patient communication is how to assess communication, necessary for evaluating training, the learning process, and for feedback. Few instruments have been validated for real physician-patient consultations. Real consultations involve unique contexts, different persons, and topics, and are difficult to compare. The aim of this study is to develop and validate a rating scale for assessment of such consultations. For the evaluation study of a communication skills training for physicians in oncology, real consultations were recorded in three assessment points. Based on earlier work and on current studies, a new instrument was developed for assessment of these consultations. Two psychologists were trained in using the instrument and assessed 42 consultations. For inter-rater reliability, interclass correlation (ICC) was calculated. The final version of the rating scales consists of 13 items evaluated on a 5-point scale. The items are grouped in seven areas: "Start of conversation," "assessment of the patient's perspective," "structure of conversation," "emotional issues," "end of conversation," "general communication skills," and "overall evaluation." ICC coefficients for the domains ranged from .44 to .77. An overall coefficient of all items resulted in an ICC of .66. The ComOn-Coaching Rating Scales are a short, reliable, and applicable instrument for the assessment of real physician-patient consultations in oncology. If adapted, they could be used in other areas. They were developed for research and teaching purposes and meet the required methodological criteria. Rater training should be considered more deeply by further research.

ComOn-Coaching: The effect of a varied number of coaching sessions on transfer into clinical practice following communication skills training in oncology: Results of a randomized controlled trial.

OBJECTIVE: To investigate the effect of the number of coaching sessions after communication skills training on the medical communicative performance of oncologists in clinical practice. METHODS/DESIGN: The training, consisting of a workshop and one (control group) vs. four (intervention group) sessions of individual coaching, was evaluated in a randomized controlled trial. Eligible participants included physicians working in any setting where patients with oncological diseases were treated. Real medical consultations were video recorded at three time points: before the workshop (t0), after the workshop (t1) and after completion of coaching (t2). The 1.5-day workshop was based on role-playing in small groups; in the coaching sessions, the videos recorded at t1 were analyzed in detail by both the trainer and the physician. The coaching sessions were manualized and based on the physician's learning goals. The primary hypothesis was that the intervention group would improve to a higher extent than the control group, as assessed by external raters using rating scales specially developed for this project. Physicians were stratified for sex and setting and randomized by an independent statistician. The group assignment was revealed for physicians and trainers at the end of the workshop, while the raters were blinded to group assignments and assessment points. RESULTS: A total of 72 physicians participated in one of 8 workshops and could be allocated to either the control or intervention group. The intervention group showed a statistically significant improvement (ES d = 0.41, p<.01) in the All items domain of the rating scales between t1 and t2 and showed a significant advantage compared with the CG (ES = .41, p = .04). The impact on diverse specified skills was heterogeneous; a larger sample is necessary for more detailed analysis. CONCLUSIONS: The training achieved some observable and significant changes in the communicative behavior of oncologists in clinical practice. The four coaching sessions showed some significant advantages compared to the single coaching session. Considerable effort is necessary to achieve sustained changes in communication in clinical every-day practice. Thus, our coaching concept is a promising method for this purpose.

Fluid-Attenuated Inversion Recovery Vascular Hyperintensities in Patients with Transient Ischemic Attack.

BACKGROUND: Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) are common in patients with acute ischemic stroke, possibly representing impaired hemodynamics in the ischemic territory due to intracranial steno-occlusive disease. There are few reports on FVHs in patients with transient ischemic attack (TIA). AIMS: We investigated the prevalence of FVHs and its clinical correlations in patients with TIA. METHODS: We evaluated consecutive patients admitted with TIA from February 2009 to June 2012 who had undergone magnetic resonance imaging within 30 hours of symptoms onset and intracranial and extracranial vascular imaging. Two independent neuroradiologists determined the presence of FVHs. We assessed the relationship between FVHs, clinical presentation, vascular risk factors, neuroimaging characteristics, and the presence of large artery stenosis or occlusion. RESULTS: Seventy-two patients with TIA were evaluated. FVHs were present in 12 (16.7%) patients. The overall agreement between examiners was good (κ = .67). There were no differences in the frequency of intracranial or cervical arterial stenosis in patients with and without FVH. In a multivariate logistic regression analysis including atrial fibrillation (AF), congestive heart failure, and diabetes, only AF remained in the final model. CONCLUSIONS: FVH signals on FLAIR images occur in patients with TIA and might correlate with clinical variables like AF and not only with large vessel occlusion. The presence of FVH in patients with TIA and AF might be a surrogate marker for a large vessel occlusion spontaneously recanalized or for impaired autoregulation in a previously ischemic vascular territory.

ComOn Coaching: Study protocol of a randomized controlled trial to assess the effect of a varied number of coaching sessions on transfer into clinical practice following communication skills training.

BACKGROUND: Communication skills training has proven to be an effective means to enhance communication of health care professionals in oncology. These effects are well studied in standardized settings. The question of transferring these skills into clinical consultations remains open. We build up on a previous developed training concept consisting of a workshop and coaching. This training achieved a medium effect size in two studies with standardized patients. In the current study, we expanded and manualized the coaching concept, and we will evaluate effects of a varied number of coaching sessions on real clinical consultations. Our aim is to determine how much coaching oncologists need to transfer communication skills into clinical practice. METHODS/DESIGN: Physicians of two German medical centers will participate in a workshop for communication skills and will be randomized to either a group with one coaching session or a group with four coaching sessions following the workshop. The participation is voluntary and the physicians will receive medical education points. Consultations held by the participating physicians with actual patients who gave their informed consent will be filmed at three time points. These consultations will be evaluated by blinded raters using a checklist based on the training content (primary outcome). Secondary outcomes will be the self-evaluated communication competence by physicians and an evaluation of the consultations by both physicians and patients. DISCUSSION: We will evaluate our communication training concept on three levels - rater, physician and patient - and concentrate on the transfer of communication skills into real life situations. As we emphasize the external validity in this study design, limitations will be expected due to heterogeneity of data. With this study we aim to gain data on how to improve communication skills training that will result in better patient outcomes. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004385 .

Score for atrial fibrillation detection in acute stroke and transient ischemic attack patients in a Brazilian population: The acute stroke atrial fibrillation scoring system

OBJECTIVE: Atrial fibrillation is a common arrhythmia that increases the risk of stroke by four- to five-fold. We aimed to establish a profile of patients with atrial fibrillation from a population of patients admitted with acute ischemic stroke or transient ischemic attack using clinical and echocardiographic findings. METHODS: We evaluated patients consecutively admitted to a tertiary hospital with acute ischemic stroke or transient ischemic attack. Subjects were divided into an original set (admissions from May 2009 to October 2010) and a validation set (admissions from November 2010 to April 2013). The study was designed as a cohort, with clinical and echocardiographic findings compared between patients with and without atrial fibrillation. A multivariable model was built, and independent predictive factors were used to produce a predictive grading score for atrial fibrillation (Acute Stroke AF Score-ASAS). RESULTS: A total of 257 patients were evaluated from May 2009 to October 2010 and included in the original set. Atrial fibrillation was diagnosed in 17.5% of these patients. Significant predictors of atrial fibrillation in the multivariate analysis included age, National Institutes of Health Stroke Scores, and the presence of left atrial enlargement. These predictors were used in the final logistic model. For this model, the area under the receiver operating characteristic curve was 0.79. The score derived from the logistic regression analysis was The model developed from the original data set was then applied to the validation data set, showing the preserved discriminatory ability of the model (c statistic = 0.76). CONCLUSIONS: Our risk score suggests that the individual risk for atrial fibrillation in patients with acute ischemic stroke can be assessed using simple data, including age, National Institutes of Health Stroke Scores at admission, and the presence of left atrial enlargement. .

Acute stroke: postprocedural care and management of complications.

Endovascular treatment for acute ischemic stroke is an important alternative to thrombolysis with recombinant tissue plasminogen activator (rt-PA) for patients who present beyond the thrombolysis time window, those who are ineligible for rt-PA, or those who do not improve after intravenous rt-PA. These patients generally require special attention in the postprocedural period because, although not frequent, complications of endovascular procedures in acute ischemic stroke have the potential to be devastating. Neurocritical care is essential to reduce and appropriately treat complications after endovascular procedures. Neurointensivists and neurocritical care nurses are experts in both critical care and neurologic disorders and have special training to recognize early physiological derangements in patients presenting with acute stroke. Close attention to the serial neurological examination, blood pressure control, adequate management of glucose, temperature, and immediate identification of complications such as reocclusion and hemorrhagic transformation are key elements that exemplify the importance of postprocedural neurocritical care in acute ischemic stroke.

Specific training program improves oncologists' palliative care communication skills in a randomized controlled trial.

PURPOSE: The aim of the study was to demonstrate that COM-ON-p, concise and individualized communication skills training (CST), improves oncologists' communication skills in consultations focusing on the transition to palliative care. METHODS: Forty-one physicians were randomly assigned to a control (CG) or intervention group (IG). At t(0), all physicians held two video-recorded consultations with actor-patient pairs. Afterward, physicians in the IG participated in COM-ON-p. Five weeks after t(0), a second assessment took place (t(1)). COM-ON-p consists of an 11-hour workshop (1.5 days), pre- and postassessment (2 hours), and coaching (0.5 hours). Physicians focused on practicing individual learning goals with actor patients in small groups. To evaluate the training, blinded raters assessed communication behavior of the physicians in video-recorded actor-patient consultations using a specific checklist. Data were analyzed using a mixed model with baseline levels as covariates. RESULTS: Participants in the IG improved significantly more than those in the CG in all three sections of the COM-ON-Checklist: skills specific to the transition to palliative care, global communication skills, and involvement of significant others (all P < .01). Differences between the CG and IG on the global items of communication skills and involvement of significant others were also significant (P < .01). Effect sizes were medium to large, with a 0.5-point improvement on average on a five-point rating scale. CONCLUSION: Physicians can be trained to meet better core challenges during the transition to palliative care through developed concise CST. Generalization and transfer into clinical practice must be proven in additional studies.