Antiviral activities and applications of ribosomally synthesized and post-translationally modified peptides (RiPPs)

The emergence and re-emergence of viral epidemics and the risks of antiviral drug resistance are a serious threat to global public health. New options to supplement or replace currently used drugs for antiviral therapy are urgently needed. The research in the field of ribosomally synthesized and post-translationally modified peptides (RiPPs) has been booming in the last few decades, in particular in view of their strong antimicrobial activities and high stability. The RiPPs with antiviral activity, especially those against enveloped viruses, are now also gaining more interest. RiPPs have a number of advantages over small molecule drugs in terms of specificity and affinity for targets, and over protein-based drugs in terms of cellular penetrability, stability and size. Moreover, the great engineering potential of RiPPs provides an efficient way to optimize them as potent antiviral drugs candidates. These intrinsic advantages underscore the good therapeutic prospects of RiPPs in viral treatment. With the aim to highlight the underrated antiviral potential of RiPPs and explore their development as antiviral drugs, we review the current literature describing the antiviral activities and mechanisms of action of RiPPs, discussing the ongoing efforts to improve their antiviral potential and demonstrate their suitability as antiviral therapeutics. We propose that antiviral RiPPs may overcome the limits of peptide-based antiviral therapy, providing an innovative option for the treatment of viral disease

Biphasic positive airway pressure ventilation (PeV+) in children

BACKGROUND: Biphasic positive airway pressure (BIPAP) (also known as PeV+) is a mode of ventilation with cycling variations between two continuous positive airway pressure levels. In adults this mode of ventilation is effective and is being accepted with a decrease in need for sedatives because of the ability to breathe spontaneously during the entire breathing cycle. We studied the use of BIPAP in infants and children. METHODS: We randomized 18 patients with respiratory failure for ventilation with either BIPAP (n = 11) or assisted spontaneous breathing (ASB) (n = 7) on Evita 4. Lorazepam and, if necessary, morphine were used as sedatives and adjusted in accordance with the Comfort scale. We compared number of randomized mode failure, duration and complications of ventilation and number and dosages of sedatives administered. RESULTS: No differences in patient characteristics, ventilatory parameters, complications of ventilation or use of sedatives were noted. Ten out of eleven patients that we intended to ventilate with BIPAP were successfully ventilated with BIPAP. Four out of seven patients that we intended to ventilate with ASB could not be ventilated adequately with ASB but were successfully crossed over to BIPAP without the need for further sedatives. CONCLUSIONS: BIPAP is an effective, safe and easy to use mode of ventilation in infants and children

Driving lesson or driving test?:A metaphor to help faculty separate feedback from assessment

Although there is consensus in the medical education world that feedback is an important and effective tool to support experiential workplace-based learning, learners tend to avoid the feedback associated with direct observation because they perceive it as a high-stakes evaluation with significant consequences for their future. The perceived dominance of the summative assessment paradigm throughout medical education reduces learners’ willingness to seek feedback, and encourages supervisors to mix up feedback with provision of ‘objective’ grades or pass/fail marks. This eye-opener article argues that the provision and reception of effective feedback by clinical supervisors and their learners is dependent on both parties’ awareness of the important distinction between feedback used in coaching towards growth and development (assessment for learning) and reaching a high-stakes judgement on the learner’s competence and fitness for practice (assessment of learning). Using driving lessons and the driving test as a metaphor for feedback and assessment helps supervisors and learners to understand this crucial difference and to act upon it. It is the supervisor’s responsibility to ensure that supervisor and learner achieve a clear mutual understanding of the purpose of each interaction (i.e. feedback or assessment). To allow supervisors to use the driving lesson—driving test metaphor for this purpose in their interactions with learners, it should be included in faculty development initiatives, along with a discussion of the key importance of separating feedback from assessment, to promote a feedback culture of growth and support programmatic assessment of competence

The objective burden in partners of heart failure patients; development and initial validation of the Dutch objective burden inventory

BACKGROUND: Measures on objective caregiver burden in partners of Heart Failure patients are hardly available and never include HF specific aspects. AIM: The main objective of our study was to develop an inventory that assesses the objective caregiver burden of partners of HF patients, including the full range of potential care giving demands. METHODS: To develop the inventory, six domains of caregiving demands were identified. Items for the domains were generated from the literature, expert opinion and existing scales. The original 50-items self-report inventory was administered to 321 partners of HF patients. Demographic data of HF partners were collected by questionnaire. Clinical data of the HF patients were collected by chart review. RESULTS: Component analysis led to exclusion of 12 original items and to a meaningful four-factor solution with a total explained variance of 43%. The components reflected four different kinds of care giving tasks; personal care, emotional, motivational and practical (treatment related) support. They demonstrated good internal consistency and initial validity was supported by a pattern of meaningful associations with external variables. CONCLUSION: The Objective Burden Inventory is a promising inventory to assess objective care giving tasks performed by HF partners, including emotional and motivational support. It provides information on the caregiver situation that may help to develop effective intervention

Impact of deliberate practice on evidence-based medicine attitudes and behaviours of health care professionals

Introduction Although evidence-based medicine (EBM) teaching activities may improve short-term EBM knowledge and skills, they have little long-term impact on learners' EBM attitudes and behaviour. This study examined the effects of learning EBM through stand-alone workshops or various forms of deliberate EBM practice. Methods We assessed EBM attitudes and behaviour with the evidence based practice inventory questionnaire, in paediatric health care professionals who had only participated in a stand-alone EBM workshop (controls), participants with a completed PhD in clinical research (PhDs), those who had completed part of their paediatric residency at a department (Isala Hospital) which systematically implemented EBM in its clinical and teaching activities (former Isala residents), and a reference group of paediatric professionals currently employed at Isala's paediatric department (current Isala participants). Results Compared to controls (n = 16), current Isala participants (n = 13) reported more positive EBM attitudes (p < 0.01), gave more priority to using EBM in decision making (p = 0.001) and reported more EBM behaviour (p = 0.007). PhDs (n = 20) gave more priority to using EBM in medical decision making (p < 0.001) and reported more EBM behaviour than controls (p = 0.016). Discussion Health care professionals exposed to deliberate practice of EBM, either in the daily routines of their department or by completing a PhD in clinical research, view EBM as more useful and are more likely to use it in decision making than their peers who only followed a standard EBM workshop. These findings support the use of deliberate practice as the basis for postgraduate EBM educational activities

Health-related quality of life and anemia in hospitalized patients with heart failure

AbstractBackgroundAnemia is a serious and highly prevalent co-morbidity in chronic heart failure (HF) patients. Its influence on health-related quality of life (HR-QoL) has rarely been studied, and no data is available regarding the role it plays in hospitalized HF patients.MethodsBaseline data from the COACH study (Coordinating study evaluating Outcomes of Advising and Counselling in Heart Failure) were used. HR-QoL was assessed by means of generic and disease-specific questionnaires. Analyses were performed using ANOVA and ANCOVA, with covariates of age, gender, eGFR, diabetes, and NYHA class.ResultsIn total, 1013 hospitalized patients with a mean age of 71 (SD 11) years were included; 70% of these patients had no anemia (n=712), 14% had mild anemia (n=141), and 16% had moderate-to-severe anemia (n=160). Independent associations were found between anemia and physical functioning (p=0.019), anemia and role limitations due to physical functioning (p=0.002), anemia and general health (p=0.024), and anemia and global well-being (p=0.003).ConclusionIn addition to the burden of HF itself, anemia is an important factor which influences HR-QoL in hospitalized HF patients, and one that is most pronounced in the domain related to physical functioning and general health

Urinary 1-Hydroxypyrene Levels in Workers Exposed to Polycyclic Aromatic Hydrocarbon from Rubber Wood Burning

AbstractBackgroundUrinary 1-hydroxypyrene (1-OHP) was selected as a biomarker of polycyclic aromatic hydrocarbons (PAHs) to explore the accumulation level in the bodies of workers at rubber smoke sheet factories in southern Thailand.MethodsSpot urine samples were taken from four groups of workers from June 2006 to November 2007. The nonexposure or control groups included habitual cigarette smokers and nonsmokers. The other two groups were workers exposed to particle-bound PAHs from rubber wood smoke and they were nonsmokers. All spot urine samples were analyzed for 1-OHP and creatinine levels.ResultsThe mean ± standard deviation urinary 1-OHP in the control group of habitual smokers and the nonsmokers was 0.24 ± 0.16 μmol/mol creatinine and not-detected to 0.14 μmol/mol creatinine, respectively. In the workers, the 1-OHP levels on workdays had no significant difference from the 1-OHP levels on the days off. The yearly average 1-OHP level was 0.76 ± 0.41 μmol/mol creatinine whereas the average 1-OHP level during 10 consecutive workdays was 1.06 ± 0.29 μmol/mol creatinine (p > 0.05).ConclusionThe urinary 1-OHP levels of workers exposed to PAHs were high. The accumulation of 1-OHP in the body was not clear although the workers had long working hours with few days off during their working experience. Therefore, a regular day off schedule and rotation shift work during high productive RSS should be set for RSS workers

Explicit teaching in the operating room:Adding the why to the what

CONTEXT: Residents need their supervisors in the operating room to inform them on how to use their expertise in present and future occasions. A few studies hint at such explicit teaching behaviour, however without explaining its underlying mechanisms. Understanding and improving explicit teaching becomes more salient nowadays, as access of residents to relevant procedures is decreasing, while end-terms of training programs remain unchanged: high quality patient care. OBJECTIVES: A structured analysis of 1. The practices supervisors use for explicit teaching and 2. How supervisors introduce explicit teaching in real time during surgical procedures. METHODS: An observational qualitative collection study in which all actions of nine supervisor-resident dyads during a total hip replacement procedure were videotaped. Interactions in which supervisors explicitly or implicitly inform residents how to use their expertise now and in future occasions were included for further analysis, using the iterative inductive process of conversation analysis. RESULTS: 1. Supervisors used a basic template of if/then rules for explicit teaching, which they regularly customized by adding metaphors, motivations, and information about preference, prevalence and consequence. 2. If/then rules are introduced by supervisors to solve a (potential) problem in outcome for the present patient in reaction to local circumstances, e.g. what residents said, did or were about to do. CONCLUSIONS: If/then rules add the why to the what. Supervisors upgrade residents' insights in surgical procedures (professional vision) and teach the degree of individual freedom and variation of their expert standards for future occasions. These insights can be beneficial in improving supervisors' teaching skills

Patient and professional factors that impact the perceived likelihood and confidence of healthcare professionals to discuss Implantable Cardioverter Defibrillator deactivation in advanced heart failure: Results from an international factorial survey

Background: Rate of implantable cardioverter defibrillator (ICD) implantations is increasing in patients with advanced heart failure. Despite clear guideline recommendations, discussions addressing deactivation occur infrequently. Aim: The aim of this article is to explore patient and professional factors that impact perceived likelihood and confidence of healthcare professionals to discuss ICD deactivation. Methods and Results: Between 2015 and 2016, an international sample of 262 healthcare professionals (65% nursing, 24% medical) completed an online factorial survey, encompassing a demographic questionnaire and clinical vignettes. Each vignette had 9 randomly manipulated and embedded patient-related factors, considered as independent variables, providing 1572 unique vignettes for analysis. These factors were determined through synthesis of a systematic literature review, a retrospective case note review, and a qualitative exploratory study. Results showed that most healthcare professionals agreed that deactivation discussions should be initiated by a cardiologist (95%, n = 255) or a specialist nurse (81%, n = 215). In terms of experience, 84% of cardiologists (n = 53) but only 30% of nurses (n = 50) had previously been involved in a deactivation decision. Healthcare professionals valued patient involvement in deactivation decisions; however, only 50% (n = 130) actively involved family members. Five of 9 clinical factors were associated with an increased likelihood to discuss deactivation including advanced age, severe heart failure, presence of malignancy, receipt of multiple ICD shocks, and more than 3 hospital admissions during the previous year. Furthermore, nationality and discipline significantly influenced likelihood and confidence in decision making. Conclusions: Guidelines recommend that healthcare professionals discuss ICD deactivation; however, practice is suboptimal with multifactorial factors impacting on decision making. The role and responsibility of nurses in discussing deactivation require clarity and improvement.Funding Agencies|HFA Nurse Fellowship training grant; Public Health Agency NI (Research &amp; Development Division)</p