Genomic Screening to Identify Food Trees Potentially Dispersed by Precolonial Indigenous Peoples.

Over millennia, Indigenous peoples have dispersed the propagules of non-crop plants through trade, seasonal migration or attending ceremonies; and potentially increased the geographic range or abundance of many food species around the world. Genomic data can be used to reconstruct these histories. However, it can be difficult to disentangle anthropogenic from non-anthropogenic dispersal in long-lived non-crop species. We developed a genomic workflow that can be used to screen out species that show patterns consistent with faunal dispersal or long-term isolation, and identify species that carry dispersal signals of putative human influence. We used genotyping-by-sequencing (DArTseq) and whole-plastid sequencing (SKIMseq) to identify nuclear and chloroplast Single Nucleotide Polymorphisms in east Australian rainforest trees (4 families, 7 genera, 15 species) with large (>30 mm) or small (<30 mm) edible fruit, either with or without a known history of use by Indigenous peoples. We employed standard population genetic analyses to test for four signals of dispersal using a limited and opportunistically acquired sample scheme. We expected different patterns for species that fall into one of three broadly described dispersal histories: (1) ongoing faunal dispersal, (2) post-megafauna isolation and (3) post-megafauna isolation followed by dispersal of putative human influence. We identified five large-fruited species that displayed strong population structure combined with signals of dispersal. We propose coalescent methods to investigate whether these genomic signals can be attributed to post-megafauna isolation and dispersal by Indigenous peoples.

Statistical analysis plan for the Prophylactic Melatonin for Delirium in Intensive Care (ProMEDIC): a randomised controlled trial.

RATIONALE: Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. METHODS AND DESIGN: The 'Prophylactic Melatonin for Delirium in Intensive Care' study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. RESULTS: This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications. DISCUSSION: The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647 , registration date: 06 April 2016. WHO Trial Number - U1111-1175-1814.

Effect of Vitamin B Supplementation on Cognitive Function in the Elderly: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin B deficiency and elevated total plasma homocysteine have been associated with cognitive impairment and dementia in later life, although it is unknown if treatment with these vitamins improves cognitive outcomes. OBJECTIVES: The objectives of this study were to examine the efficacy of treatment with vitamin B12, vitamin B6, or folic acid in slowing cognitive decline amongst older adults with and without cognitive impairment. METHODS: We summarized findings from previous systematic reviews of clinical trials and performed a new systematic review and meta-analysis of 31 English-language, randomized placebo-controlled trials of B-vitamin supplementation of individuals with and without existing cognitive impairment. RESULTS: Previous reviews have generally reported no effect of B vitamins on cognitive function in older adults with or without cognitive impairment at study entry, although these vitamins effectively lowered total plasma homocysteine levels in participants. Ten randomized placebo-controlled trials of 1925 participants with pre-existing cognitive impairment and 21 trials of 15,104 participants without cognitive impairment have been completed to date but these generally confirmed findings from previous reviews with the exception of two trials that showed a modest but clinically uncertain benefit for vitamins in people with elevated plasma homocysteine. B-vitamin supplementation did not show an improvement in Mini-Mental State Examination scores for individuals with (mean difference 0.16, 95% confidence interval - 0.18 to 0.51) and without (mean difference 0.04, 95% confidence interval - 0.10 to 0.18) cognitive impairment compared to placebo. CONCLUSIONS: Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocysteine using B vitamins. Existing trials vary greatly in the type of supplementation, population sampled, study quality, and duration of treatment, thereby making it difficult to draw firm conclusions from existing data. Findings should therefore be viewed in the context of the limitations of the available data and the lack of evidence of effect should not necessarily be interpreted as evidence of no effect.

Scaling leaf respiration with nitrogen and phosphorus in tropical forests across two continents.

Leaf dark respiration (Rdark ) represents an important component controlling the carbon balance in tropical forests. Here, we test how nitrogen (N) and phosphorus (P) affect Rdark and its relationship with photosynthesis using three widely separated tropical forests which differ in soil fertility. Rdark was measured on 431 rainforest canopy trees, from 182 species, in French Guiana, Peru and Australia. The variation in Rdark was examined in relation to leaf N and P content, leaf structure and maximum photosynthetic rates at ambient and saturating atmospheric CO2 concentration. We found that the site with the lowest fertility (French Guiana) exhibited greater rates of Rdark per unit leaf N, P and photosynthesis. The data from Australia, for which there were no phylogenetic overlaps with the samples from the South American sites, yielded the most distinct relationships of Rdark with the measured leaf traits. Our data indicate that no single universal scaling relationship accounts for variation in Rdark across this large biogeographical space. Variability between sites in the absolute rates of Rdark and the Rdark  : photosynthesis ratio were driven by variations in N- and P-use efficiency, which were related to both taxonomic and environmental variability.

The Healthy Heart-Mind trial: melatonin for prevention of delirium following cardiac surgery: study protocol for a randomized controlled trial.

BACKGROUND: Delirium is a common occurrence in patients undergoing major cardiac surgery and is associated with a number of adverse consequences for the individual, their family and the health system. Current approaches to the prevention of delirium include identifying those at risk together with various non-pharmacological and pharmacological strategies, although the efficacy of these is often modest. Emerging evidence suggests that melatonin may be biologically implicated in the development of delirium and that melatonin supplementation may be beneficial in reducing the incidence of delirium in medical and surgical patients. We designed this trial to determine whether melatonin reduces the incidence of delirium following cardiac surgery compared with placebo. METHODS/DESIGN: The Healthy Heart-Mind trial is a randomized, double-blind, placebo-controlled clinical trial of 3 mg melatonin or matching placebo administered on seven consecutive days for the prevention of delirium following cardiac surgery. We will recruit 210 adult participants, aged 50 and older, undergoing elective or semi-elective cardiac surgery with the primary outcome of interest for this study being the difference in the incidence of delirium between the groups within 7 days of surgery. Secondary outcomes of interest include the difference between groups in the severity and duration of delirious episodes, hospital length of stay and referrals to mental health services during admission. In addition, we will assess differences in depressive and anxiety symptoms, as well as cognitive performance, at discharge and 3 months after surgery. DISCUSSION: The results of this trial will clarify whether melatonin reduces the incidence of delirium following cardiac surgery. TRIAL REGISTRATION: The trial is registered with the Australian Clinical Trials Registry, trial number ACTRN12615000819527 (10 August 2015).

The Leaf Essential Oil of Eugenia reinwardtiana Growing in Australia.

The leaf essential oils of the two chemotypes of Eugenia reinwardtiana (Blume) DC growing in Australia have been investigated. Chemotype 1, isolated in 0.2% yield, w/w, dry weight, contained major amounts of α-pinene (10-26%), limonene (1-15%), ß-caryophyllene (0.7-11%), α-humulene (0.9-16%) and bicyclogermacrene (1-23%). The second chemotype, found only on coastal dunes SW of Lockerbie Qld, and isolated in 0.4-0.6% (w/w, dry weight), contained α-pinene (tr-8.5%) ß-caryophyllene (12-27%) and α-humulene (1-17%) as the major terpenes. This chemotype also contained the novel aliphatic diketone, 2-butyl-2,4,4-trimethyl-5-methoxycyclohex-5-en-1,3-dione (18-33%), whose structure determination is reported herein.

Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression.

BACKGROUND: Folate and vitamin B12 insufficiencies have been associated with increased risk of depression. This systematic review aimed to clarify if, compared with placebo, treatment with folate and/or vitamin B12 reduces depression scale scores, increases remission, and prevents the onset of clinically significant symptoms of depression in people at risk. METHODS: This systematic review searched the PubMed, PsychInfo, Embase, and Cochrane databases from inception to 6 June 2014, using the following terms and strategy: (vitamin B12 or vitamin B9 or folate or folic acid or cobalamin or cyanocobalamin) and (depression or depressive disorder or depressive symptoms) and (randomized controlled trial or RCT). The electronic search was supplemented by manual search. Two independent reviewers assessed all papers retrieved for eligibility and bias, and extracted crude data. Review Manager 5 was used to manage and analyze the data. RESULTS: Two hundred and sixty-nine manuscripts were identified, of which 52 were RCTs and 11 fulfilled criteria for review. We found that the short-term use of vitamins (days to a few weeks) does not contribute to improve depressive symptoms in adults with major depression treated with antidepressants (5 studies, standardized mean difference = -0.12, 95% confidence interval--95% CI = -0.45, 0.22), but more prolonged consumption (several weeks to years) may decrease the risk of relapse (1 study, odds ratio (OR) = 0.33, 95% CI = 0.12, 0.94) and the onset of clinically significant symptoms in people at risk (2 studies, risk ratio = 0.65, 95% CI = 0.43, 0.98). CONCLUSIONS: The number of available trials remains small and heterogeneity between studies high. The results of these meta-analyses suggest that treatment with folate and vitamin B12 does not decrease the severity of depressive symptoms over a short period of time, but may be helpful in the long-term management of special populations.

Homocysteine, depression and cognitive function in older adults.

BACKGROUND: Depression and high total plasma homocysteine (tHcy) are independently associated with cognitive impairment in older adults. We designed this study to determine if high tHcy is a mediator of cognitive performance in older adults with major depression. METHODS: We recruited 358 community-dwelling older adults experiencing depressive symptoms, 236 (65.9%) of who met DSM-IV-TR criteria for major depression. Assessment included the Montgomery Asberg Depression Rating Scale (MADRS), fasting tHcy and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. RESULTS: Individuals with major depression and high tHcy had significantly worse immediate verbal and delayed visual recall. Non-depressed participants with high tHcy had lower MMSE, immediate and delayed recall scores than those with normal tHcy. The odds of cognitive inefficiency for those with high tHcy was nearly doubled for the MMSE (OR 1.9, 95%CI 1.1-3.3), immediate (OR 1.9, 95%CI 1.1-3.5) and delayed (OR 1.9, 95%CI 1.1-3.4) word recall after adjusting for age, gender, IHD and MADRS score. LIMITATIONS: The presence of sub-syndromal depressive symptoms in our non-depressed group and exclusion of participants with established cognitive impairment may limit the generalizability of this study. CONCLUSIONS: Elevated tHcy was associated with weaker performance in tests of immediate and delayed memory and global cognitive performance when compared to those with normal tHcy independent of the presence of major depression or the severity of depressive symptoms. Homocysteine lowering B-vitamin supplementation may offer a potential therapeutic target to try and mitigate the often-disabling impact of cognitive deficits found in this population.

Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis.

BACKGROUND AND PURPOSE: High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously. METHODS: A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 µg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score<24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up. RESULTS: A total of 3089 participants (38%) voluntarily undertook the MMSE>6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 µmol/L versus 14.2 µmol/L; P<0.001) but no change from baseline in the mean MMSE score (-0.22 points versus -0.25 points; difference, 0.03; 95% confidence interval, -0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855). CONCLUSIONS: Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN74743444; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00097669.

Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials.

Elevated total plasma homocysteine has been linked to the development of cognitive impairment and dementia in later life and this can be reliably lowered by the daily supplementation of vitamin B6, B12, and folic acid. We performed a systematic review and meta-analysis of 19 English language randomized, placebo-controlled trials of homocysteine lowering B-vitamin supplementation of individuals with and without cognitive impairment at the time of study entry. We standardized scores to facilitate comparison between studies and to enable us to complete a meta-analysis of randomized trials. In addition, we stratified our analyses according to the folate status of the country of origin. B-vitamin supplementation did not show an improvement in cognitive function for individuals with (SMD = 0.10, 95%CI -0.08 to 0.28) or without (SMD = -0.03, 95%CI -0.1 to 0.04) significant cognitive impairment. This was irrespective of study duration (SMD = 0.05, 95%CI -0.10 to 0.20 and SMD = 0, 95%CI -0.08 to 0.08), study size (SMD = 0.05, 95%CI -0.09 to 0.19 and SMD = -0.02, 95%CI -0.10 to 0.05), and whether participants came from countries with low folate status (SMD = 0.14, 95%CI -0.12 to 0.40 and SMD = -0.10, 95%CI -0.23 to 0.04). Supplementation of vitamins B12, B6, and folic acid alone or in combination does not appear to improve cognitive function in individuals with or without existing cognitive impairment. It remains to be established if prolonged treatment with B-vitamins can reduce the risk of dementia in later life.

Phylogeny of Celastraceae tribe Euonymeae inferred from morphological characters and nuclear and plastid genes.

The phylogeny of Celastraceae tribe Euonymeae (≈ 230 species in eight genera in both the Old and New Worlds) was inferred using morphological characters together with plastid (matK, trnL-F) and nuclear (ITS and 26S rDNA) genes. Tribe Euonymeae has been defined as those genera of Celastraceae with generally opposite leaves, isomerous carpels, loculicidally dehiscent capsules, and arillate seeds (except Microtropis). Euonymus is the most diverse (129 species) and widely cultivated genus in the tribe. We infer that tribe Euonymeae consists of at least six separate lineages within Celastraceae and that a revised natural classification of the family is needed. Microtropis and Quetzalia are inferred to be distinct sister groups that together are sister to Zinowiewia. The endangered Monimopetalum chinense is an isolated and early derived lineage of Celastraceae that represents an important component of phylogenetic diversity within the family. Hedraianthera is sister to Brassiantha, and we describe a second species (Brassiantha hedraiantheroides A.J. Ford) that represents the first reported occurrence of this genus in Australia. Euonymus globularis, from eastern Australia, is sister to Menepetalum, which is endemic to New Caledonia, and we erect a new genus (Dinghoua R.H. Archer) for it. The Madagascan species of Euonymus are sister to Pleurostylia and recognized as a distinct genus (Astrocassine ined.). Glyptopetalum, Torralbasia, and Xylonymus are all closely related to Euonymus sensu stricto and are questionably distinct from it. Current intrageneric classifications of Euonymus are not completely natural and require revision.

The B-VITAGE trial: a randomized trial of homocysteine lowering treatment of depression in later life.

BACKGROUND: Depression is a leading cause of disability worldwide and depressive symptoms are common in later life. Observational evidence suggests that depression is more prevalent among people with high plasma homocysteine (tHcy), but the results of randomized trials to date have been unable to show that lowering tHcy through the supplementation of vitamins B6, B12 and folate benefits depressive symptoms. We designed the B-VITAGE trial to determine whether adjunctive treatment with vitamins B6, B12 and folate increases the efficacy of standard antidepressant treatment. METHODS/DESIGN: The B-VITAGE trial is a 12-month randomized, double-blind, placebo-controlled trial of daily citalopram (20 to 40 mg) plus B12(0.5 mg), B6 (25 mg) and folic acid (2 mg) or citalopram (20 to 40 mg) plus placebo for the treatment of depression in later life. The trial aims to recruit over 300 older adults with major depression (DSM-IV) and has been powered to detect the impact of an intervention associated with moderate effect size. Depressive symptoms will be rated with the Montgomery-Asberg Depression Rating Scale (MADRS). The trial has two main outcomes of interest: a reduction of 50% or more in the MADRS total score between baseline and week 12 and the remission of the depressive episode at weeks 12, 26 and 52 according to DSM-IV criteria. We hypothesize that subjects randomly allocated to the vitamin arm of the study will be more likely to show a clinically significant improvement and achieve and maintain remission of symptoms at 12, 26 and 52 weeks. Secondary outcomes of interest include compliance with treatment, reduction in the severity of depressive symptoms, switching to different antidepressants, the use of non-pharmacological antidepressant treatments, response to treatment according to MTHFRC677T genotype, and changes in cognitive function over 52 weeks. CONCLUSIONS: The results of this trial will clarify whether the systematic use of B-vitamins improves the response of older adults to standard antidepressant treatment. We anticipate that our findings will have implications for clinical practice and health policy development. TRIAL REGISTRATION: The trial is registered with the Australian Clinical Trials Registry, trial number (())ACTRN12609000256279.