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Clinical cardiology 45(4), 352-358 (2022). doi:10.1002/clc.23819, Published by Wiley, Weinheim [u.a.]

Plants can respond to insects that feed with stylet mouthparts using various processes that are initiated via the salicylic acid metabolic pathway. In Australia, scale insects of the genus Parthenolecanium can cause economic damage to grapevines as they feed on the vines and produce honeydew as a waste by-product, which supports the growth of black sooty mould on fruit and leaves, potentially affecting the plant growth and yield. Using rootlings of Sauvignon Blanc (SB, resistant) and Chardonnay (Char, susceptible), the growth and production of volatile organic compounds (VOCs) following exposure to scale insect infestations were measured under controlled greenhouse conditions. At harvest, the numbers of scale insects per five leaves were higher on plants infested at the start of the study compared with the control plants. Infested SB had increased dry root and shoot mass compared with the SB control, which was also the case with Char (control and infested). Leaf volatiles differed between cultivars in response to scale infestation. Benzyl alcohol decreased among infested SB plants compared with the other treatments. A change in the salicylic acid pathway as indicated by the change in benzyl alcohol may cause the increased growth in SB associated with the increased scale insect infestation.

Opioids efficiently alleviate pain and dyspnea. However, guidelines on symptom management with opioids differ, which may lead to an uncertainty concerning opioid indication and ethical implication among medical staff, especially when caring for COVID-19 patients.We aimed to examine the perception of members of the German Association for Palliative Medicine (DGP) concerning the administration of morphine as the gold standard opioid (subsequently termed M/O) for symptom control within and outside of a palliative care (PC) setting, including care for COVID-19 patients.DGP members received an anonymized online questionnaire (Survey Monkey®) containing questions regarding their perception of symptom management with M/O in general and in particular concerning COVID-19 patients. Participants were asked to rate their perception within and outside of a PC setting.Of the 6129 DGP members, N = 506 participated. DGP physicians and nurses perceived handling of M/O as "certain and confident" (98%) and "clearly regulated" within PC (95%) but rated it significantly lower for outside PC (48%/38%). When caring for COVID-19 patients, handling of M/O was even less often rated "certain and confident" (26%) or "clearly regulated" (23%) for outside PC. Dyspnea (99%/52%), relief from the dying process (62%/37%), restlessness (30%/15%) and fear or panic (27%/13%) were more frequently rated as general indications for morphine within versus outside PC. Most participants (89%) wished to involve palliative care consultation teams.DGP members perceived substantial uncertainty in the handling of M/O for medical fields outside PC. Uniform interdisciplinary guidelines for symptom control, more education, and involvement of a PC consultation team should be increasingly considered in the future.HINTERGRUND: Obwohl Opioide wirksam Schmerzen und Dyspnoe lindern, findet dies in Leitlinien zur Symptomkontrolle unterschiedliche Gewichtung. Dies kann zu Unsicherheiten bezüglich Indikationen und ethischer Implikationen im Umgang mit Opioiden auch bei COVID-19 führen.Wir untersuchten bei Mitgliedern der Deutschen Gesellschaft für Palliativmedizin (DGP) die persönliche Wahrnehmung des Umgangs mit Morphin/Opioiden (M/O) zur Symptomkontrolle innerhalb und außerhalb der Palliativmedizin (PM), auch bei der Betreuung COVID-19-Erkrankter.Mittels Survey Monkey® wurden DGP-Mitglieder anonymisiert nach ihrer eigenen Wahrnehmung des Umgangs mit M/O zur Symptomkontrolle befragt.Von den 6192 DGP-Mitgliedern nahmen N = 506 teil. Den Umgang mit M/O innerhalb der PM beschrieben 98 % der befragten Ärzt:innen und Pflegekräfte als „sicher und vertraut“ bzw. 95 % als „klar geregelt“, während dies für die Bereiche außerhalb der PM von weniger als der Hälfte angegeben wurde (48 %/38 %). Bei der Betreuung COVID-19-Erkrankter wurde der Umgang mit M/O außerhalb der PM noch seltener als „sicher und vertraut“ (26 %) oder „klar geregelt“ (23 %) wahrgenommen. Dyspnoe (99 %/52 %), Erleichterung des Sterbeprozesses (62 %/37 %), Unruhe (30 %/15 %) und Angst/Panik (27 %/13 %) wurden häufiger innerhalb als außerhalb der PM als allgemeine Indikationen genannt. 89 % der Befragten wünschten sich die Einbindung eines PM-Konsilteams.Mitglieder der DGP nahmen deutliche Unsicherheiten im Umgang mit M/O außerhalb der PM wahr. Einheitliche interdisziplinäre Leitlinien zur Symptomkontrolle etwa bei Dyspnoe, mehr Lehre und die Einbindung eines PM-Konsilteams sollten zukünftig mehr bedacht werden.

Background Terpene rich leaves are a characteristic of Myrtaceae. There is significant qualitative variation in the terpene profile of plants within a single species, which is observable as “chemotypes”. Understanding the molecular basis of chemotypic variation will help explain how such variation is maintained in natural populations as well as allowing focussed breeding for those terpenes sought by industry. The leaves of the medicinal tea tree, Melaleuca alternifolia, are used to produce terpinen-4-ol rich tea tree oil, but there are six naturally occurring chemotypes; three cardinal chemotypes (dominated by terpinen-4-ol, terpinolene and 1,8-cineole, respectively) and three intermediates. It has been predicted that three distinct terpene synthases could be responsible for the maintenance of chemotypic variation in this species. Results We isolated and characterised the most abundant terpene synthases (TPSs) from the three cardinal chemotypes of M. alternifolia. Functional characterisation of these enzymes shows that they produce the dominant compounds in the foliar terpene profile of all six chemotypes. Using RNA-Seq, we investigated the expression of these and 24 additional putative terpene synthases in young leaves of all six chemotypes of M. alternifolia. Conclusions Despite contributing to the variation patterns observed, variation in gene expression of the three TPS genes is not enough to explain all variation for the maintenance of chemotypes. Other candidate terpene synthases as well as other levels of regulation must also be involved. The results of this study provide novel insights into the complexity of terpene biosynthesis in natural populations of a non-model organism. Electronic supplementary material The online version of this article (10.1186/s12870-017-1107-2) contains supplementary material, which is available to authorized users.

To explore and compare the impact of socio-economic deprivation on the occurrence of the major rheumatic and musculoskeletal diseases (RMDs) and health care costs.Data on diagnoses, socio-demographics and health care costs of the entire adult population of the Basque Country (Spain) was used. Area deprivation index included five categories (1 to 5 (most deprived)). Cost categories included primary and specialist care, emergency room, hospitalisations, and drug prescriptions. Twenty-nine RMDs were grouped into seven groups: Rheumatoid Arthritis, Spondyloarthritis, Crystal Arthropathies, Osteoarthritis, Soft Tissue Diseases, Connective Tissue Diseases, and Vasculitis. The relations between the deprivation and the occurrence of RMD and costs were explored in regression models adjusted for relevant confounders.Data from 1,923,156 adults were analysed. Mean age was 49.9 (SD18.4) years, 49% were males. Soft tissue diseases were the most prevalent RMD (5.5%, n=105,656), followed by osteoarthritis (2.2%, n=41,924). Socio-economic deprivation was associated with higher likelihood to have any of the 29 RMDs. The strongest socio-economic gradient was seen for the soft tissue diseases (OR 1.82 [95%CI 1.78;1.85], most vs. least deprived), followed by osteoarthritis (OR 1.59 [1.54;1.64]). Deprivation was also associated with higher costs across the majority of the conditions however patterns were more blurred, and inverse relationship was observed for connective tissue diseases, gout, hip osteoarthritis and undifferentiated (poly)arthritis.Socio-economic deprivation is associated with increased occurrence of all RMDs, and in most cases more deprived patients incur higher health care costs.

Plant terpenes play many roles in natural systems, from altering plant–animal interactions, to altering the local abiotic environment. Additionally, many industries depend on terpenes. For example, commercially used essential oils, including tea tree oil and lavender oil, are a mixture of terpenes. Many species of the family Myrtaceae form a key resource for these industries due to the high concentration of terpenes found predominately in their leaves. The frequency of chemotypic differences within many species and populations can lead to costly errors in industry. Terpene diversity in Myrtaceae is driven by variation in the terpene synthase enzymes, which catalyse the conversion a few common substrates into thousands of terpene structures. We review terpene diversity within and between species of Myrtaceae and relate this to variation in the terpene synthase enzymes to reconstruct the evolution of foliar terpene diversity in Myrtaceae. We found that (1) high inter- and intra-species variation exists in terpene profile and that α-pinene the most likely ancestral foliar terpene, and (2) that high concentration of 1,8-cineole (a compound which is regarded as the signature compound of Myrtaceae) is limited to just four Myrtaceae sub-families. We suggest that the terpene synthase enzymes do not limit terpene diversity in this family and variation in these enzymes suggests a mode of enzymatic evolution that could lead to high 1,8-cineole production. Our analysis highlights the need to standardise methods for collecting and reporting foliar terpene data, and we discuss some methods and issues here. Although there are many gaps in the published data, our large scale analysis using the results of many studies, shows the value of a family wide analysis for understanding both the evolution and industrial potential of terpene-producing plants.

Sociodemographic and clinical characteristics for employed population by country and high and low gross domestic product (GDP). (DOCX 16Â kb)

Overview of odds ratios for each country index (in fully adjusted models) and results of likelihood ratio chi-square (LR chi2) tests comparing models with and without country index variables for the sample age ≤60 years. (DOCX 17 kb)

Characteristics of study population with paid work ≤ 65 years (DOCX 14 kb)

Association of multimorbidity of 2 or ≥3 diseases in- and excluding musculoskeletal disease with work status compared to ‘being employed’, comparison of odds of work disability, dependence on living allowances and unemployment between multimorbidity patterns including a musculoskeletal disease and multimorbidity patterns without a musculoskeletal disease. (DOCX 14 kb)

Association of individual sociodemographic and clinical characteristics and gross domestic product (GDP) with absenteeism and presenteeism (total sample). (DOCX 13Â kb)

Missing values, n (%) in variables by country; n (%). (DOCX 15Â kb)

Sociodemographic and lifestyle characteristics in subjects with and without missing data in the outcome variables. (DOCX 13Â kb)

Association of individual sociodemographic and clinical characteristics with being employed stratified by gross domestic product (GDP) (total sample). (DOCX 14Â kb)

Association of specific disease combinations in- and excluding musculoskeletal disease with work status compared to â being employedâ , odds of work disability, dependence on living allowances and unemployment for musculoskeletal disease, cardiovascular disease, diabetes, respiratory disease, mental disease, cancer, skin disease, bowel disease, migraine, combinations of the latter eight diseases with musculoskeletal disease, any two diseases other than musculoskeletal and combinations of 3 diseases with and without MSKD. (DOCX 16Â kb)

Association of multimorbidity of 2 or ≥3 diseases in- and excluding musculoskeletal disease with sick leave in the past 12 months in employed population ≤65 years, comparison of odds of sick leave between multimorbidity patterns including a musculoskeletal disease and multimorbidity patterns without a musculoskeletal disease. (DOCX 14 kb)

Overview of the countries in the categories of each country index and overlap between categories. (DOCX 1591Â kb)

Characteristics of the study sample and general Dutch population (DOCX 16Â kb)

It is becoming increasingly easy to generate genotypic data but much harder to gather an equivalent amount of phenotypic information, particularly for chemical traits. In this study of Eucalyptus globulus ssp. globulus, we measured about 60 chemical leaf traits of trees growing in a common garden to address the following questions: (1) how much variation is there between geographic regions, populations within regions and within populations? (2) How do chemical traits vary over the species’ geographic range? (3) If so, does E. globulus ssp. globulus exhibit distinct chemotypes – plants that are morphologically similar but which differ chemically? (4) Are the affinities between E. globulus ssp. globulus and closely related subspecies apparent in the chemical variation? Variation among trees within populations contributed most variation in leaf chemistry followed by variation between geographic regions. For many traits, variation among populations within proposed races and variation among proposed races within geographic regions explained little of the total variation. There was a cline in the concentration of secondary chemicals with the lowest concentrations in Tasmanian populations and the highest in those from eastern Victoria, with intermediate concentrations in populations from Bass Strait Islands. We identified three chemotypes, characterised by specific terpenes and formylated phloroglucinol compounds. The frequency of occurrence of these chemotypes showed a geographic pattern also, with “chemotype 1” predominating in Tasmania, while “chemotypes 2 and 3” occurred at highest frequency in eastern Victoria. We suggest that the chemotypes reflect introgression between E. globulus ssp. globulus and the three closely related subspecies – E. globulus ssp. bicostata, E. globulus ssp. maidenii and E. globulus ssp. pseudoglobulus. Although the formation of land-bridges with fluctuating sea levels has no doubt shaped the evolutionary history of all four subspecies, we propose that the migratory swift parrot (Lathamus discolor), an important pollinator and a species closely associated with E. globulus, has helped shape the evolution of the four tree subspecies.

Melaleuca quinquenervia (Cav) S.T. Blake (broadleaf paperbark) is an Australian tree that has become a serious weed in many places around the world. Two insects Oxyops vitiosa (the melaleuca weevil), and Boreioglycaspis melaleucae (the melaleuca psyllid), which were introduced to Florida as part of a biological control programme, have been very effective in reducing survival and reproduction of this weed. There are two terpene chemotypes of M. quinquenervia; one rich in the sesquiterpene E-nerolidol whereas the other is rich in viridiflorol. Viridiflorol is a strong feeding deterrent for the melaleuca weevil and retards larval development. The larvae therefore avoid the viridiflorol-rich chemotype, in contrast, female melaleuca psyllids prefer to oviposit on these leaves. To identify the molecular basis of these preferences, we isolated and characterised two terpene synthases from the viridiflorol-rich chemotype, both of which utilise farnesyl pyrophosphate and have the same product profile. Chemotypic variation in terpenes in M. quinquenervia is under strong genetic control and the reproductive potential of each chemotype is limited by a different insect. These insects could, therefore, be selective agents for the maintenance of chemotypic variation in M. quinquenervia.

Myrtaceae is one of the chemically most variable and most significant essential oil yielding plant families. Despite an abundance of chemical information, very little work has focussed on the biochemistry of terpene production in these plants. We describe 70 unique partial terpene synthase transcripts and eight full-length cDNA clones from 21 myrtaceous species, and compare phylogenetic relationships and leaf oil composition to reveal clades defined by common function. We provide further support for the correlation between function and phylogenetic relationships by the first functional characterisation of terpene synthases from Myrtaceae: a 1,8-cineole synthase from Eucalyptus sideroxylon and a caryophyllene synthase from Eucalyptusdives.

Chronic diseases are increasingly prevalent and often occur as multimorbidity. This study compares the impact of musculoskeletal disorders (MSKDs) on health and health care costs with other chronic diseases, and assesses the additional impact of MSKDs on these outcomes when occurring as part of multimorbidity.A household survey in a random Dutch population sample (n = 8,904) yielded information on sociodemographics, presence of 9 physician-confirmed chronic diseases (i.e., musculoskeletal, migraine, diabetes mellitus, cardiovascular, cancer, respiratory, skin, mental, and gastrointestinal), physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 12 health survey, and health care utilization. The independent influence of different diseases and the role of MSKDs with increasing number of morbidities on PCS/MCS and 3-month societal health care costs were explored through multivariable linear and zero-inflated negative binomial regressions, respectively.Twenty percent of all subjects and 56% of those with multimorbidity had an MSKD. MSKDs had the largest impact on PCS (β = -8.37 [95% confidence interval (95% CI) -8.84, -7.89]) but no significant impact on MCS. When MSKDs occurred as part of multimorbidity, an amplification of the adverse effect on PCS but not on MCS was seen, irrespective of the number of comorbidities. MSKDs were responsible for a 2-fold increase in costs (Exp [β] = 2.27 [95% CI 2.08, 2.51]), which was the second highest cost increase of all diseases (after cancer). Significant amplification of costs was seen when MSKDs co-occurred with mental diseases.MSKDs often co-occur with other chronic diseases. In the context of multimorbidity, presence of an MSKD amplifies the impact on physical health, and to a lesser extent on health care costs, but not on mental health.

Plants show a high degree of intraspecific variation in several traits including plant secondary metabolites. This variation can be influenced by genetic and environmental factors that result in geographical structure in their distribution. By growing plants from several populations in a controlled environment, we studied variation in foliar terpenes in Eucalyptus camaldulensis, which is the widest distributed eucalypt, with a large range both latitudinally and longitudinally. We found that the concentration of terpenes is highly variable among subspecies. We identified four chemotypes dominated by 1,8-cineole, γ-terpinene, α- and β-phellandrene. While the 1,8-cineole chemotype is abundant in all populations, the other three chemotypes are rare in the central area and the north-east of Australia. The γ-terpinene chemotype is mainly restricted to the north and west of Australia, whereas the α- and β-phellandrene chemotypes show an opposite distribution in the north and south of the continent. The annual mean temperature and humidity of the source populations correlate with the abundance of the dominant terpenes. We also tested the effects of elevated CO2 concentrations on the terpene concentration and found that elevated CO2 atmosphere reduces the overall accumulation of foliar terpenes. The results suggest that variation in terpene composition in E. camaldulensis can be influenced by environmental variables, mainly favouring the 1,8-cineole chemotype in arid locations.

Australian members of the Myrtaceae produce large quantities of ecologically and economically important terpenes and display abundant diversity in both yield and composition of their oils. In a survey of the concentrations of leaf terpenes in Eucalyptus tricarpa (L.A.S. Johnson) L.A.S. Johnson & K.D. Hill, which were previously known from few samples, exceptional variability was found in composition. The aim was to characterize the patterns of variation and covariation among terpene components in this species and to use this information to enhance our understanding of their biosynthesis. There were marked discontinuities in the distributions of numerous compounds, including the overall proportions of mono- and sesquiterpenes, leading us to delineate three distinct chemotypes. Overall, positive covariation predominated, but negative covariation suggested competitive interactions involved in monoterpene synthesis. Two groups of covarying monoterpenes were found, each of which was positively correlated with a group of sesquiterpenes and negatively correlated with the alternate sesquiterpene group. These results imply substantial cross-talk between mono- and sesquiterpene biosynthesis pathways. However, only those compounds hypothesized to share final carbocation intermediates or post-processing steps were strongly positively correlated within chemotypes. This suggests that the broader patterns of covariation among groups of compounds may result from co-regulation of multiple biosynthetic genes, controlling the complex terpene profiles of the chemotypes of Eucalyptus.

Mosaic trees contain more than one phenotype. The two Eucalyptus mosaic trees studied here (E. melliodora and E. sideroxylon) are predominantly susceptible to insect herbivory, with the leaves on a single large branch on each tree resisting herbivory. We used gas chromatography-mass spectrometry and high-pressure liquid chromatography to analyze the chemical profile of leaves of the mosaic trees, as well as leaves of adjacent non-mosaic con-specifics. We show that the leaves of the two phenotypes are distinctly different. Compared to the susceptible (S) leaves on the same tree, the resistant (R) leaves on the mosaic trees had low concentrations of sesquiterpenes (E. melliodora: 2 vs. 24 mg·g(-1) dry matter; E. sideroxylon: 8 vs. 22 mg·g(-1) dry matter), high concentrations of FPCs (E. melliodora: 5.4 vs. 0.3 mg·g(-1) dry matter; E. sideroxylon: 9.8 vs. 0.2 mg·g(-1) dry matter) but similar concentrations of nitrogen (E. melliodora: 15.4 vs. 16.8 mg·g(-1) dry matter; E. sideroxylon: 13.1 vs. 14.0 mg·g(-1) dry matter). The only difference between the two mosaic trees was in the levels of monoterpenes. The R leaves from the mosaic E. melliodora contained higher concentrations of monoterpenes compared to the S leaves (12 vs. 6 mg·g(-1) dry matter). In contrast, the leaves from the E. sideroxylon mosaic contained much higher concentrations of monoterpenes with a reversed pattern (R: 26 vs. S: 45 mg·g(-1) dry matter). There were qualitative differences too on the mosaic trees. The R leaves of both species contained much higher concentrations of the monoterpene, 1,8-cineole, whereas the S chemotype of E. sideroxylon only had high concentrations of phellandrenes. Furthermore, the chemical differences between leaves on the R and S branches of the mosaic trees resembled those between the leaves of R and S con-specific trees in the same population. We use these data and knowledge of secondary metabolite biosynthesis to propose that high-level transcriptional differences may control the profile of specialized metabolites in eucalypts.

The variation of foliar monoterpenes in the Australian Tea Tree (Melaleuca alternifolia) has been of significant interest both to the essential oil industry as well as to ecologists. The majority of studies on leaf chemistry have been aimed directly towards obtaining oil of higher quality or quantity. In the current study, we aimed to understand how molecular mechanisms contribute to the chemical variability of this species, based on chemical analysis of the leaf oils from a biochemical perspective. Correlations between monoterpenes across the species as well as within chemotypes show strong, persistent patterns, which enable us to establish groups based on possible common biosynthetic origins. We found that three distinct enzymes corresponding to these groups: a sabinene-hydrate synthase, a 1,8-cineole synthase, and a terpinolene synthase may be sufficient to explain all six chemotypes in M. alternifolia.

Background Long-lived trees can accumulate mutations throughout their lifetimes that may influence biotic and abiotic interactions. For example, some Eucalyptus trees display marked variation in herbivore defence within a single canopy. These “mosaic” trees support foliage with distinct chemotypes which are differentially favoured by insect and vertebrate herbivores, resulting in susceptible and resistant branches within a single canopy. These mosaic trees provide a unique opportunity to explore the biosynthesis and genetic regulation of chemical defences in the foliage. The biosynthesis of the principal defence compounds, terpenoid-dominated essential oils, is well understood. However, the regulation of the genes involved and thus the control of phenotypic variation within a single tree canopy remains a mystery. Results We sequenced the transcriptomes of the leaves of the two different chemotypes of a chemically mosaic Eucalyptus melliodora tree using 454 pyrosequencing technology. We used gene set enrichment analysis to identify differentially expressed transcripts and found the proportion of differentially expressed genes in the resistant and susceptible foliage similar to the transcript difference between functionally distinct tissues of the same organism, for example roots and leaves. We also investigated sequence differences in the form of single nucleotide polymorphisms and found 10 nucleotides that were different between the two branches. These are likely true SNPs and several occur in regulatory genes. Conclusion We found three lines of evidence that suggest changes to a ‘master switch’ can result in large scale phenotypic changes: 1. We found differential expression of terpene biosynthetic genes between the two chemotypes that could contribute to chemical variation within this plant. 2. We identified many genes that are differentially expressed between the two chemotypes, including some unique genes in each branch. These genes are involved in a variety of processes within the plant and many could contribute to the regulation of secondary metabolism, thus contributing to the chemical variation. 3. We identified 10 SNPs, some of which occur in regulatory genes that could influence secondary metabolism and thus contribute to chemical variation. Whilst this research is inherently limited by sample size, the patterns we describe could be indicative of other plant genetic mosaics.

The terpenoid-dominated essential oils in Australian Myrtaceae mediate many ecological interactions and are important industrially. Of all the significant essential oil-producing families, Myrtaceae is the only one for which there is no molecular information on terpene biosynthesis. Here we summarise available knowledge on terpene biosynthesis and its relevance to the Myrtaceae to provide a foundation for ecological and genetic studies of chemical diversity. There are several steps in the terpene biosynthesis pathway that have potential for influencing the oil yield, profile and composition of leaf oils in Myrtaceae. The biochemical steps that influence oil yield in Myrtaceae probably occur in the steps of the pathway leading up to the synthesis of the terpene backbone. Qualitative differences in oil profiles are more likely to be due to variation in terpene synthases and terpene-modifying enzymes. Most of the information on molecular variation in terpene biosynthesis is based on the analysis of artificially derived mutants but Australian Myrtaceae can provide examples of the same mechanisms in an ecological context.