Brain cancer patient and support persons' experiences of psychosocial care: a mapping of research outputs.

BACKGROUND: People with brain cancer and their support persons (SPs) are critical sources of information on the components of care that contribute to psychosocial outcomes. AIMS: To determine the proportion of studies that examined (1) at least one of 14 nominated components of psychosocial cancer care and (2) more than one component of care. METHODS: Medline, The Cochrane Library, PsycINFO and Embase were electronically searched for publications from January 1999 to December 2019. Publications that met the inclusion criteria were coded according to the number and type of psychosocial care components assessed from 14 listed components, and whether patient and/or SPs' views about care were elicited. RESULTS: Of the 113 included publications, 61 publications included patient-reported data only (54%), 27 included both patient and SP-reported data (24%) and 25 included SP-reported data only (22%). Most assessed a single component of care (77% of patient-reported and 71% of SP-reported). No publications assessed all 14 components. The "Psychosocial" component was the most frequently assessed component of care for patient-reported (n = 80/88, 91%) and SP-reported publications (n = 46/52, 88%). CONCLUSIONS: Publications reporting on psychosocial care in brain cancer present a relatively narrow view of patient and support person experiences. The inclusion of both patient and support person perspectives and the assessment of multiple components of care are required in future research to optimize psychosocial outcomes in brain cancer.

Psychosocial well-being of brain cancer patients and support persons: A mapping review of study types over time.

INTRODUCTION: This review examined the: (1) number of publications exploring psychosocial outcomes of adults with brain cancer and/or support persons between 1999 and 2019 and whether there has been a change in the type of research over time; and (2) proportion of intervention studies meeting Cochrane Effective Practice and Organisation of Care (EPOC) research design criteria. METHODS: Embase, The Cochrane Library, Medline and PsycINFO databases were electronically searched January 1999 to December 2019. Articles were examined against inclusion/exclusion criteria and coded into measurement, descriptive or intervention categories. Intervention studies were assessed against the EPOC design criteria. RESULTS: 220 eligible publications were identified. The number of total publications significantly increased by an average of 1 each year (95%CI = 0.7-1.3; p < 0.001). There was no significant change in the proportion of publications by study type across three time periods. Descriptive research represented the majority within each time period. Of the 17 intervention studies, only 7(41%) met EPOC design criteria. CONCLUSIONS: Published literature on brain cancer psychosocial outcomes has increased significantly. However, descriptive research dominates research output. To increase high-level knowledge that can guide psychosocial care of people with brain cancer, there is a need to undertake methodologically rigorous intervention trials.

Australian GPs' perceptions of barriers and enablers to best practice palliative care: a qualitative study.

BACKGROUND: General Practitioners (GPs) often play an important role in caring for people at the end of life. While some international studies suggest that GPs experience a number of barriers to providing palliative care, little is known about views and experiences of GPs in Australia. This study explored Australian GPs' perceptions of barriers and enablers to the provision of palliative care and provides new insights into how to implement best practice care at the end of life. METHODS: This was a qualitative study using 25 semi-structured phone interviews conducted with GPs practising in metropolitan and non-metropolitan New South Wales, Australia. Data were analysed using qualitative content analysis. RESULTS: GPs reported difficulties with palliative care provision due to i) the complex and often emotional nature of doctor-family-interaction; ii) a lack of evidence to guide care; and iii) the need to negotiate roles and responsibilities within the healthcare team. GPs listed a number of strategies to help deal with their workload and to improve communication processes between healthcare providers. These included appropriate scheduling of appointments, locally tailored mentoring and further education, and palliative care guidelines which more clearly outline the roles and responsibilities within multidisciplinary teams. GPs also noted the importance of online platforms to facilitate their communication with patients, their families and other healthcare providers, and to provide centralised access to locally tailored information on palliative care services. GPs suggested that non-government organisations could play an important role by raising awareness of the key role of GPs in palliative care provision and implementing an "official visitor" program, i.e. supporting volunteers to provide peer support or respite to people with palliative care needs and their families. CONCLUSIONS: This study offers new insights into strategies to overcome well documented barriers to palliative care provision in general practice and help implement optimal care at the end of life. The results suggest that researchers and policy makers should adopt a comprehensive approach to improving the provision of palliative care which tackles the array of barriers and enablers identified in this study.

Interaction between Digestive Strategy and Niche Specialization Predicts Speciation Rates across Herbivorous Mammals.

Biotic and abiotic factors often are treated as mutually exclusive drivers of diversification processes. In this framework, ecological specialists are expected to have higher speciation rates than generalists if abiotic factors are the primary controls on species diversity but lower rates if biotic interactions are more important. Speciation rate is therefore predicted to positively correlate with ecological specialization in the purely abiotic model but negatively correlate in the biotic model. In this study, I show that the positive relationship between ecological specialization and speciation expected from the purely abiotic model is recovered only when a species-specific trait, digestive strategy, is modeled in the terrestrial, herbivorous mammals (Mammalia). This result suggests a more nuanced model in which the response of specialized lineages to abiotic factors is dependent on a biological trait. I also demonstrate that the effect of digestive strategy on the ecological specialization-speciation rate relationship is not due to a difference in either the degree of ecological specialization or the speciation rate between foregut- and hindgut-fermenting mammals. Together, these findings suggest that a biological trait, alongside historical abiotic events, played an important role in shaping mammal speciation at long temporal and large geographic scales.

The role of ecological opportunity in shaping disparate diversification trajectories in a bicontinental primate radiation.

Exceptional species and phenotypic diversity commonly are attributed to ecological opportunity (EO). The conventional EO model predicts that rates of lineage diversification and phenotypic evolution are elevated early in a radiation only to decline later in response to niche availability. Foregut fermentation is hypothesized to be a key innovation that allowed colobine monkeys (subfamily Colobinae), the only primates with this trait, to successfully colonize folivore adaptive zones unavailable to other herbivorous species. Therefore, diversification rates also are expected to be strongly linked with the evolution of traits related to folivory in these monkeys. Using dated molecular phylogenies and a dataset of feeding morphology, I test predictions of the EO model to evaluate the role of EO conferred by foregut fermentation in shaping the African and Asian colobine radiations. Findings from diversification methods coupled with colobine biogeographic history provide compelling evidence that decreasing availability of new adaptive zones during colonization of Asia together with constraints presented by dietary specialization underlie temporal changes in diversification in the Asian but not African clade. Additionally, departures from the EO model likely reflect iterative diversification events in Asia.

Do estimated and actual species phylogenies match? Evaluation of East African cichlid radiations.

A large number of published phylogenetic estimates are based on a single locus or the concatenation of multiple loci, even though genealogies of single or concatenated loci may not accurately reflect the true history of species diversification (i.e., the species tree). The increased availability of genomic data, coupled with new computational methods, improves resolution of species relationships beyond what was possible in the past. Such developments will no doubt benefit future phylogenetic studies. It remains unclear how robust phylogenies that predate these developments (i.e., the bulk of phylogenetic studies) are to departures from the assumption of strict gene tree-species tree concordance. Here, we present a parametric bootstrap (PBST) approach that assesses the reliability of past phylogenetic estimates in which gene tree-species tree discord was ignored. We focus on a universal cause of discord-the random loss of gene lineages from genetic drift-and apply the method in a meta-analysis of East African cichlids, a group encompassing historical scenarios that are particularly challenging for phylogenetic estimation. Although we identify some evolutionary relationships that are robust to gene tree discord, many past phylogenetic estimates of cichlids are not. We discuss the utility of the PBST method for evaluating the robustness of gene tree-based phylogenetic estimations in general as well as for testing the clade-specific performance of species tree estimation methods and designing sampling strategies that increase the accuracy of estimated species relationships.

Relationships of diversity, disparity, and their evolutionary rates in squirrels (Sciuridae).

Several theories predict that rapidly diversifying clades will also rapidly diverge phenotypically; yet, there are also reasons for suspecting that diversification and divergence might not be correlated. In the widely distributed squirrel clade (Sciuridae), we test for correlations between per lineage speciation rates, species richness, disparity, and a time-invariant measure of disparity that allows for comparing rates when evolutionary modes differ, as they do in squirrels. We find that species richness and speciation rates are not correlated with clade age or with each other. Disparity appears to be positively correlated with clade age because young, rapidly diversifying Nearctic grassland clades are strongly pulled to a single stable optimum but older, slowly diversifying Paleotropical forest clades contain lineages that diverge along multiple ecological and morphological lines. That contrast is likely due to both the environments they inhabit and their phylogenetic community structure. Our results argue against a shared explanation for diversity and disparity in favor of geographically mediated modes of speciation and ecologically mediated modes of phenotypic evolution.

Cholinoceptive properties of respiratory neurones in the rat medulla.

The effects of iontophoretically applied acetylcholine, the acetylcholine agonists nicotine and muscarine, and the antagonists atropine, dihydro-beta-erythroidine (DH beta E) and mecamylamine, together with the excitatory amino acids, glutamate and D,L-homocysteic acid (DLH) were examined on the activity of respiratory-related neurones in the rat medulla and were compared with effects on non-respiratory brain stem neurones. Most neurones were excited by acetylcholine and no inhibitory responses were seen. Glutamate and DLH also excited but there was a trend for the phasic activity of respiratory neurones to be converted to a tonic discharge. Nicotine also excited most neurones to which it was applied and these responses were blocked by DH beta E but not by atropine. Muscarine also caused excitation and these responses were blocked by atropine but not by DH beta E. Both antagonists blocked acetylcholine-induced excitation but had no effect on responses to glutamate or DLH. Mecamylamine was without effect. It is concluded that the proportion of cholinoceptive respiratory neurones in the rat brain stem is similar to that for non-respiratory neurones. It seems likely that both nicotinic and muscarinic receptors are present on the majority of respiratory neurones and that both contribute to the response produced by iontophoretically-applied acetylcholine.

Susceptibility of Brassica species to cauliflower mosaic virus infection is related to a specific stage in the virus multiplication cycle.

The relative susceptibilities and symptom responses of different Brassica species to infection by cauliflower mosaic virus (CaMV) have been compared and related to molecular events of the virus multiplication cycle. Variants of B. rapa (genome descriptor aa) were highly susceptible to infection by CaMV strain Cabb B-JI and contained relatively large amounts of virus; B. oleracea (cc) variants showed low susceptibility and contained small amounts of virus. B. nigra (bb) and allotetraploid species. B. juncea (aabb), B. napus (aacc) and B. carinata (bbcc), showed moderate responses to CaMV. CaMV unencapsidated DNA forms were isolated from different Brassica plants and examined by two-dimensional gel electrophoresis and blot hybridization. Viral RNA was estimated by dot blot analysis. These analyses showed differences in accumulation of key viral replication cycle intermediates within the broad range of host plants studied. The most susceptible species contained relatively small amounts of supercoiled (SC) DNA, a component of the CaMV mini-chromosome, but abundant viral transcripts and reverse transcription replication products. Tolerant plant hosts contained high levels of SC DNA but low levels of viral transcripts and reverse transcription DNA products. Allotetraploids contained SC DNA, RNA transcripts and replication product levels which were generally intermediate between those of their respective progenitor species. Evidence is presented that accumulation of CaMV SC DNA in the less susceptible host species is probably not due to autonomous DNA replication or tissue-specific expression. We conclude that a major component of the susceptibility of Brassica plants (and probably all CaMV host species) to CaMV infection is the level of viral minichromosome expression, influenced directly by the host genotype.

Suppression of post-transcriptional gene silencing by a plant viral protein localized in the nucleus.

Post-transcriptional gene silencing (PTGS) is a homology-dependent RNA degradation process that may target RNA exclusively in the cytoplasm. In plants, PTGS functions as a natural defense mechanism against viruses. We reported previously that the 2b protein encoded by cucumber mosaic cucumovirus (CMV) is a virulence determinant and a suppressor of PTGS initiation in transgenic Nicotiana benthamiana. By fusion with the green fluorescent protein, we now show that the CMV 2b protein localizes to the nuclei of tobacco suspension cells and whole plants via an arginine-rich nuclear localization signal, (22)KRRRRR(27). We further demonstrate that the nuclear targeting of the 2b protein is required for the efficient suppression of PTGS, indicating that PTGS may be blocked in the nucleus. In addition, our data indicate that the PTGS suppressor activity is important, but not sufficient, for virulence determination by the 2b protein.

Host regulation of the cauliflower mosaic virus multiplication cycle.

The DNA genome of cauliflower mosaic virus (CaMV) replicates in the cytoplasm of infected plant cells by reverse transcription of an RNA template. Viral RNA is generated in the nucleus by transcription of an episomal minichromosome containing supercoiled DNA. We have assessed the relative activities of the nuclear and cytoplasmic phases of the CaMV multiplication cycle by monitoring unencapsidated viral DNA forms and polyadenylylated RNAs in different organs of one host plant and in different host species. Systemically infected leaves of a highly susceptible host, turnip (Brassica rapa), contained abundant 35S RNA and 19S RNA transcripts and unencapsidated reverse transcription products but relatively little supercoiled DNA. In contrast, supercoiled DNA accumulated in roots and other tissues of turnip plants but without significant amounts of steady-state viral RNA. Infected but asymptomatic leaves of a less susceptible CaMV host, kohlrabi (Brassica oleracea), contained supercoiled DNA almost exclusively but negligible viral RNA and DNA products of reverse transcription. An allotetraploid species, rape (Brassica napus), exhibited infection characteristics and minichromosome expression levels intermediate between the other two species from which it was derived. We conclude that expression of the CaMV minichromosome is a key phase of the virus multiplication cycle, which is regulated differentially in organs of a highly susceptible host species. Furthermore, this regulation exhibits genetic variation among different Brassica species and controls host susceptibility to CaMV infection.

A single amino acid change in the coat protein of Maize streak virus abolishes systemic infection, but not interaction with viral DNA or movement protein.

Summary Functional coat protein (CP) is important for host plant infection by monopartite geminiviruses. We identified a proline-cysteine-lysine (PCK) motif at amino acids 180-182 of the maize streak virus (MSV) CP that is conserved in most of the cereal-infecting Mastreviruses. Substitution of the lysine (K) with a valine (V) in the CP of MSV to produce mutant MSVCP182V abolished systemic infection in maize plants, although the mutant replicated around the inoculation site and, unlike other MSV CP mutants, enabled single-stranded (ss) DNA accumulation in suspension cells. The stability of the mutant protein, CP182V, in infected cells was confirmed by immunoblotting, but virions could not be detected. Like the wild-type (wt) CP, CP182V localized to the nucleus when expressed in insect and tobacco cells, and the Escherichia coli-expressed protein bound both ss and double-stranded DNA and interacted with movement protein in vitro. Taken together, these data suggest that mutation of amino acid 182 affects virion formation of MSV, either by affecting encapsidation per se or by affecting particle stability, and that virions are necessary for the long-distance movement of MSV in maize plants.

Strong host resistance targeted against a viral suppressor of the plant gene silencing defence mechanism.

The 2b protein encoded by cucumber mosaic cucumovirus (Cmv2b) acts as an important virulence determinant by suppressing post-transcriptional gene silencing (PTGS), a natural plant defence mechanism against viruses. We report here that the tomato aspermy cucumovirus 2b protein (Tav2b), when expressed from the unrelated tobacco mosaic tobamovirus (TMV) RNA genome, activates strong host resistance responses to TMV in tobacco which are typical of the gene-for-gene disease resistance mechanism. Domain swapping between Cmv2b, which does not elicit these responses, and Tav2b, revealed functional domains in Tav2b critical for triggering virus resistance and hypersensitive cell death. Furthermore, substitution of two amino acids from Tav2b by those found at the same positions in Cmv2b, Lys21-->Val and Arg28-->Ser, abolished the ability to induce hypersensitive cell death and virus resistance. However, in Nicotiana benthamiana, a species related to tobacco, Tav2b functions as a virulence determinant and suppresses PTGS. Thus, a viral suppressor of the host gene silencing defence mechanism is the target of another independent host resistance mechanism. Our results provide new insights into the complex molecular strategies employed by viruses and their hosts for defence, counter-defence and counter counter-defence.