Metaeffector interactions modulate the type III effector-triggered immunity load of Pseudomonas syringae.

The bacterial plant pathogen Pseudomonas syringae requires type III secreted effectors (T3SEs) for pathogenesis. However, a major facet of plant immunity entails the recognition of a subset of P. syringae's T3SEs by intracellular host receptors in a process called Effector-Triggered Immunity (ETI). Prior work has shown that ETI-eliciting T3SEs are pervasive in the P. syringae species complex raising the question of how P. syringae mitigates its ETI load to become a successful pathogen. While pathogens can evade ETI by T3SE mutation, recombination, or loss, there is increasing evidence that effector-effector (a.k.a., metaeffector) interactions can suppress ETI. To study the ETI-suppression potential of P. syringae T3SE repertoires, we compared the ETI-elicitation profiles of two genetically divergent strains: P. syringae pv. tomato DC3000 (PtoDC3000) and P. syringae pv. maculicola ES4326 (PmaES4326), which are both virulent on Arabidopsis thaliana but harbour largely distinct effector repertoires. Of the 529 T3SE alleles screened on A. thaliana Col-0 from the P. syringae T3SE compendium (PsyTEC), 69 alleles from 21 T3SE families elicited ETI in at least one of the two strain backgrounds, while 50 elicited ETI in both backgrounds, resulting in 19 differential ETI responses including two novel ETI-eliciting families: AvrPto1 and HopT1. Although most of these differences were quantitative, three ETI responses were completely absent in one of the pathogenic backgrounds. We performed ETI suppression screens to test if metaeffector interactions contributed to these ETI differences, and found that HopQ1a suppressed AvrPto1m-mediated ETI, while HopG1c and HopF1g suppressed HopT1b-mediated ETI. Overall, these results show that P. syringae strains leverage metaeffector interactions and ETI suppression to overcome the ETI load associated with their native T3SE repertoires.

Preparedness for practice of newly qualified dental professionals in Australia - educator, employer, and consumer perspectives.

BACKGROUND: Limited data regarding the perspectives of other observers (i.e. those who educate, employ or receive care from) of new graduates' preparedness to practice is available. The present study aimed to explore perceptions of different observers regarding the preparedness to practice and work readiness of newly qualified dental professionals. This broader range of perspectives is crucial to inform the development of educational programs, including continuing professional development, for newly qualified dental professionals, by clarifying the skills, knowledge and behaviours expected by the dental profession and wider public. RESULTS: Nineteen individual qualitative interviews were undertaken. Interview participants included clinical demonstrators (n = 9; 2 Oral Health Therapists; 5 Dentists; and 2 Prosthetists), dental course convenors (n = 4), representatives of large employers (n = 2), and consumers (n = 4). According to this diverse group of respondents, dental students receive adequate theoretical and evidence-based information in their formal learning and teaching activities, which prepares them for practice as dental professionals. There were no specific clinical areas or procedures where preparedness was highlighted as a major concern. Notwithstanding this, specific graduate skills which would benefit from further training and consolidation were identified, including areas where higher levels of experience would be beneficial. Nonetheless, respondents indicated that new graduates were aware of their limitations and had developed self-discipline and ethics that would allow them to identify conditions/situations where they would not have the experience or expertise to provide care safely. CONCLUSIONS: From an observer perspective, dental students appeared to have gained adequate theoretical and evidence-based information in their formal learning and teaching activities to prepared them to commence practicing safely as dental professionals. Areas were identified in which new graduates were underprepared and when transitional support may be required.

Preparedness for practice of newly qualified dental practitioners in the Australian context: an exploratory study.

BACKGROUND: The current study explored the perspectives of preparedness for dental practice from a range of relevant stakeholders (i.e., educators, employers, final-year students, graduates, practitioners, and professional associations) using an anonymous online survey in which participants described either their preparedness for practice, or the preparedness of graduates they have encountered, across six domains. RESULTS: A total of 120 participants completed the survey. Participants were from several Australian states and territories; regional, rural, and urban locations; and working in the public and private sector. Students and new graduates generally felt prepared for activities in all the identified domains. Stakeholders reported consistently that the knowledge of dental profession graduates was at the required level to enter practice in Australia in a safe way. Activities involving the knowledge of clinical entrepreneurship and financial solvency were the dimensions where students and graduates felt least prepared (e.g., explaining fees, negotiating finances). In the domains involving clinical and technical competencies, students and new graduates self-assessed as less prepared around managing dental trauma and medical emergencies. On the other hand, activities around social and community orientation, and to a lesser extent professional attitudes and ethical judgements, were the dimensions where students and graduates felt the most prepared. CONCLUSIONS: Present findings indicate that there appear to be good standards of preparedness for practice for graduate dental professionals. This exploratory study provides insights into the nature of preparedness for Australian dental professionals and provides a basis for targeting education and professional development to address areas of need.

A Case Report of Biventricular Arrhythmogenic Cardiomyopathy in a Middle-Aged Female.

Arrhythmogenic cardiomyopathy is an inherited disease in which the normal myocardium is replaced by fibroadipose infiltrates. It is increasingly being recognized as a separate entity to arrhythmogenic right ventricular cardiomyopathy though is rarely diagnosed. We report a 47-year-old female who presented to her local emergency department with a history of presyncope while driving. Electrocardiograph revealed inferolateral ST changes and right bundle branch block. A high burden of premature ventricular contractions and non-sustained ventricular tachycardia was seen on telemetry. Echocardiography showed reduced left ventricular systolic function and cardiac magnetic resonance imaging demonstrated extensive fibrosis involving the left ventricle and the septum of the right ventricle. An inherited cardiac disease genetic panel, including desmosomal gene mutations, was non-contributary. Extensive workup for other potential causes of cardiac fibrosis and reduced left ventricle function including cardiac positron emission tomography (PET) was negative. Based on the presentation and these findings, a diagnosis of biventricular arrhythmogenic cardiomyopathy was made. The patient's condition was complicated by third-degree heart block two weeks after initiation of pharmacological treatment that included amiodarone. An implantable cardiac defibrillator was implanted. She was referred to a tertiary centre specializing in inherited cardiac conditions for familial screening.

The Arabidopsis effector-triggered immunity landscape is conserved in oilseed crops.

The bacterial phytopathogen Pseudomonas syringae causes disease on a wide array of plants, including the model plant Arabidopsis thaliana and its agronomically important relatives in the Brassicaceae family. To cause disease, P. syringae delivers effector proteins into plant cells through a type III secretion system. In response, plant nucleotide-binding leucine-rich repeat proteins recognize specific effectors and mount effector-triggered immunity (ETI). While ETI is pervasive across A. thaliana, with at least 19 families of P. syringae effectors recognized in this model species, the ETI landscapes of crop species have yet to be systematically studied. Here, we investigated the conservation of the A. thaliana ETI landscape in two closely related oilseed crops, Brassica napus (canola) and Camelina sativa (false flax). We show that the level of immune conservation is inversely related to the degree of evolutionary divergence from A. thaliana, with the more closely related C. sativa losing ETI responses to only one of the 19 P. syringae effectors tested, while the more distantly related B. napus loses ETI responses to four effectors. In contrast to the qualitative conservation of immune response, the quantitative rank order is not as well-maintained across the three species and diverges increasingly with evolutionary distance from A. thaliana. Overall, our results indicate that the A. thaliana ETI profile is qualitatively conserved in oilseed crops, but quantitatively distinct.

ZAR1: Guardian of plant kinases.

A key facet of innate immunity in plants entails the recognition of pathogen "effector" virulence proteins by host Nucleotide-Binding Leucine-Rich Repeat Receptors (NLRs). Among characterized NLRs, the broadly conserved ZAR1 NLR is particularly remarkable due to its capacity to recognize at least six distinct families of effectors from at least two bacterial genera. This expanded recognition spectrum is conferred through interactions between ZAR1 and a dynamic network of two families of Receptor-Like Cytoplasmic Kinases (RLCKs): ZED1-Related Kinases (ZRKs) and PBS1-Like Kinases (PBLs). In this review, we survey the history of functional studies on ZAR1, with an emphasis on how the ZAR1-RLCK network functions to trap diverse effectors. We discuss 1) the dynamics of the ZAR1-associated RLCK network; 2) the specificity between ZRKs and PBLs; and 3) the specificity between effectors and the RLCK network. We posit that the shared protein fold of kinases and the switch-like properties of their interactions make them ideal effector sensors, enabling ZAR1 to act as a broad spectrum guardian of host kinases.

The ETS-ETI cycle: evolutionary processes and metapopulation dynamics driving the diversification of pathogen effectors and host immune factors.

The natural diversity of pathogen effectors and host immune components represents a snapshot of the underlying evolutionary processes driving the host-pathogen arms race. In plants, this arms race is manifested by an ongoing cycle of disease and resistance driven by pathogenic effectors that promote disease (effector-triggered susceptibility; ETS) and plant resistance proteins that recognize effector activity to trigger immunity (effector-triggered immunity; ETI). Here we discuss how this ongoing ETS-ETI cycle has shaped the natural diversity of both plant resistance proteins and pathogen effectors. We focus on the evolutionary forces that drive the diversification of the molecules that determine the outcome of plant-pathogen interactions and introduce the concept of metapopulation dynamics (i.e., the introduction of genetic variation from conspecific organisms in different populations) as an alternative mechanism that can introduce and maintain diversity in both host and pathogen populations.

Antibiotic prophylaxis for dental treatment after prosthetic joint replacement: exploring the orthopaedic surgeon's opinion.

BACKGROUND: Antibiotic prophylaxis before dental treatment is routinely recommended by orthopaedic surgeons to prevent prosthetic joint infection (PJI). This recommendation is at odds with current guidelines. METHODS: A postal survey of 9 checkbox or short-answer questions was completed by 633 orthopaedic surgeons. RESULTS: The majority of respondents (n = 186 of 260, 72%) believe that antibiotic prophylaxis is required indefinitely for dental treatment. A small number (n = 43, 15%) seek a dentist's opinion before elective joint replacement. The surgeons reported low numbers of PJIs, although 24% (n = 68 of 280) believed that they were associated with dental treatment. CONCLUSIONS: Australian orthopaedic surgeons continue to recommend antibiotic prophylaxis for dental treatment. The recording of PJI in relation to dental procedures into clinical registries would enable the development of consistent guidelines between professional groups responsible for the care of this patient group.

Clinical deterioration in established heart failure: what is the value of BNP and weight gain in aiding diagnosis?

BACKGROUND: Weight gain and increase in B-Type Natriuretic Peptide have been advocated as means of aiding diagnosis of heart failure. However, there are few data to support the use of these criteria in diagnosing clinical deterioration in patients with established disease. AIMS: This prospective study examines the sensitivity and specificity of absolute and relative changes in BNP and weight in determining the early onset of clinical deterioration in patients with established heart failure. METHODS: All patients who presented to the outpatient clinic with completed self-reported daily weight books, baseline BNP measurement, outpatient BNP measurement and assessment by a cardiologist blinded to BNP and weight were included. Each patient was determined as clinically stable (CS) or in clinical deterioration (CD). Receiver operating characteristic (ROC) curves and sensitivity and specificity calculations for various absolute and relative BNP and weight changes were carried out. RESULTS: Weight and BNP changes were examined in 34 CS presentations (mean age 69.5+/-16.1 years) and 43 CD presentations (mean age 70.0+/-10.6 years). ROC analysis demonstrated that neither weight nor BNP changes in absolute or relative values predicted clinical deterioration in this study population adequately (AUC values ranging from 0.64 to 0.66). CONCLUSIONS: These data demonstrate that increase in body weight and BNP in isolation are not sensitive in assessing clinical deterioration in established heart failure. These observations may need to be emphasized in patient education and to physicians involved in assessment of heart failure patients.