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Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal metabolites were measured using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gut microbiome using shotgun metagenomic sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HCs) with extensive clinical, biological and phenotype information. Data were analyzed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome–metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on fecal microbiome–metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome–metabolome signatures for IBS, associated with altered serotonin metabolism and unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS
Quambalaria shoot blight in Corymbia calophylla: Detection, pathogenicity, and host resistance
Quambalaria shoot blight (QSB) caused by the non-native pathogen Quambalaria pitereka has been recently introduced to south-west Western Australia (SWWA). It affects the leaves, buds, flowers, and fruits of the keystone tree species Corymbia calophylla (marri) and can lead to the death of young trees. This project examined the potential to establish a disease resistance program for marri to QSB by (1) developing qPCR assays for the rapid and sensitive detection of Q. pitereka from plant tissues, (2) investigating the pathogenicity of Q. pitereka isolates collected in SWWA; (3) screening for QSB resistance of 3-month-old seedlings under glasshouse conditions; and (4) estimating the genetic control of growth traits and QSB resistance in four-, and six-year old trees in two common garden trials containing 165 - 170 open-pollinated families from 18 provenances of marri from across its natural range. As disease expression in QSB is similar to myrtle rust (Austropuccinia psidii), in a glasshouse experiment, seedlings were also screened for resistance to myrtle rust to test whether resistance to both diseases is linked. A qPCR assay for the rapid and sensitive detection of Q. pitereka from plant tissues was developed. Inoculation of seedlings with several Q. pitereka isolates demonstrated that they varied in their pathogenicity ranging from those that caused no disease symptoms to ones that were highly pathogenic in seedlings. There were significant differences in resistance to both QSB and myrtle rust between seedling provenances but no significant correlation between resistance to QSB and myrtle rust. In the common garden field trials, narrow-sense heritability for all growth traits and QSB damage were low to moderate (h2 = 0.11 - 0.26). A correlation between QSB damage and growth traits indicated that fastgrowing provenances were less damaged by QSB disease. The genetic correlation between the same traits at four and six years was strong, and the Type-B correlations were strongly positive for all traits. Both disease incidence and disease severity were assessed and gave similar results, but disease incidence is the easiest to assess in older trees. There was poor correlation between the provenance resistance assessed at the seedling stage and trees at four and six years of age. Provenances from cooler wetter regions showed higher resistance in the field trials than those from warmer, drier areas. Results suggest that selection for QSB resistance cannot be assessed in seedlings but may be reliably undertaken by assessing disease incidence on four-year old trees at the earliest. The results of this study indicate a strong potential for a resistance breeding program to develop populations of genetically diverse and resistant trees
Balance on the Brain: a randomised controlled trial evaluating the effect of a multimodal exercise programme on physical performance, falls, quality of life and cognition for people with mild cognitive impairment—study protocol
Introduction: Exercise and physical activity have been shown to improve cognition for people living with mild cognitive impairment (MCI). There is strong evidence for the benefits of aerobic exercise and medium evidence for participating in regular strength training for people with MCI. However, people living with MCI fall two times as often as those without cognitive impairment and the evidence is currently unknown as to whether balance training for people with MCI is beneficial, as has been demonstrated for older people without cognitive impairment. The aim of this study is to determine whether a balance-focused multimodal exercise intervention improves balance and reduces falls for people with MCI, compared with a control group receiving usual care.
Methods and analysis: This single blind randomised controlled trial (Balance on the Brain) will be offered to 396 people with MCI living in the community. The multimodal exercise intervention consists of two balance programmes and a walking programme to be delivered by physiotherapists over a 6-month intervention period. All participants will be followed up over 12 months (for the intervention group, this involves 6-month intervention and 6-month maintenance). The primary outcomes are (1) balance performance and (2) rate of falls. Physical performance, levels of physical activity and sedentary behaviour, quality of life and cognition are secondary outcomes. A health economic analysis will be undertaken to evaluate the cost-effectiveness of the intervention compared with usual care.
Ethics and dissemination: Ethics approval has been received from the South Metropolitan Health Service Human Research Ethics Committee (HREC), Curtin University HREC and the Western Australia Department of Health HREC; and approval has been received to obtain data for health costings from Services Australia. The results will be disseminated through peer-review publications, conference presentations and online platforms
Plasma lipid profiles change with increasing numbers of mild traumatic brain injuries in rats
Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable insight into the neuropathological state. This study used liquid chromatography-mass spectrometry (LC-MS) to examine plasma lipid concentrations at 11 days following sham (no injury), one (1×) or two (2×) mTBI in rats. Eighteen lipid species were identified that distinguished between sham, 1× and 2× mTBI. Three distinct patterns were found: (1) lipids that were altered significantly in concentration after either 1× or 2× F mTBI: cholesterol ester CE (14:0) (increased), phosphoserine PS (14:0/18:2) and hexosylceramide HCER (d18:0/26:0) (decreased), phosphoinositol PI(16:0/18:2) (increased with 1×, decreased with 2× mTBI); (2) lipids that were altered in response to 1× mTBI only: free fatty acid FFA (18:3 and 20:3) (increased); (3) lipids that were altered in response to 2× mTBI only: HCER (22:0), phosphoethanolamine PE (P-18:1/20:4 and P-18:0/20:1) (increased), lysophosphatidylethanolamine LPE (20:1), phosphocholine PC (20:0/22:4), PI (18:1/18:2 and 20:0/18:2) (decreased). These findings suggest that increasing numbers of mTBI induce a range of changes dependent upon the lipid species, which likely reflect a balance of damage and reparative responses
The Genome of the Acid Soil-Adapted Strain Rhizobium favelukesii OR191 Encodes Determinants for Effective Symbiotic Interaction With Both an Inverted Repeat Lacking Clade and a Phaseoloid Legume Host
Although Medicago sativa forms highly effective symbioses with the comparatively acid-sensitive genus Ensifer, its introduction into acid soils appears to have selected for symbiotic interactions with acid-tolerant R. favelukesii strains. Rhizobium favelukesii has the unusual ability of being able to nodulate and fix nitrogen, albeit sub-optimally, not only with M. sativa but also with the promiscuous host Phaseolus vulgaris. Here we describe the genome of R. favelukesii OR191 and genomic features important for the symbiotic interaction with both of these hosts. The OR191 draft genome contained acid adaptation loci, including the highly acid-inducible lpiA/acvB operon and olsC, required for production of lysine- and ornithine-containing membrane lipids, respectively. The olsC gene was also present in other acid-tolerant Rhizobium strains but absent from the more acid-sensitive Ensifer microsymbionts. The OR191 symbiotic genes were in general more closely related to those found in Medicago microsymbionts. OR191 contained the nodA, nodEF, nodHPQ, and nodL genes for synthesis of polyunsaturated, sulfated and acetylated Nod factors that are important for symbiosis with Medicago, but contained a truncated nodG, which may decrease nodulation efficiency with M. sativa. OR191 contained an E. meliloti type BacA, which has been shown to specifically protect Ensifer microsymbionts from Medicago nodule-specific cysteine-rich peptides. The nitrogen fixation genes nifQWZS were present in OR191 and P. vulgaris microsymbionts but absent from E. meliloti-Medicago microsymbionts. The ability of OR191 to nodulate and fix nitrogen symbiotically with P. vulgaris indicates that this host has less stringent requirements for nodulation than M. sativa but may need rhizobial strains that possess nifQWZS for N2-fixation to occur. OR191 possessed the exo genes required for the biosynthesis of succinoglycan, which is required for the Ensifer-Medicago symbiosis. However, 1H-NMR spectra revealed that, in the conditions tested, OR191 exopolysaccharide did not contain a succinyl substituent but instead contained a 3-hydroxybutyrate moiety, which may affect its symbiotic performance with Medicago hosts. These findings provide a foundation for the genetic basis of nodulation requirements and symbiotic effectiveness with different hosts
Penicillin allergy SHACK : Survey of hospital and community knowledge
Aim
Penicillin allergy accounts for the majority of all reported adverse drug reactions in adults and children. Foregoing first-line antibiotic therapy due to penicillin allergy label is associated with an increased prevalence of infections by resistant organisms and longer hospitalisation. Clinician awareness of allergy assessment, referral indications, management of allergy and anaphylaxis is therefore vital but globally lacking. We aim to assess the knowledge of penicillin allergy, assessment and management in Western Australian health professionals.
Methods
An anonymous survey was distributed to pharmacists, nurses and physicians within Western Australian paediatric and adult Hospitals, Community and General Practice.
Results
In total, 487/611 were completed and included in the statistical analysis. Only 62% (301/487) of respondents routinely assessed for patient medication allergies. Of those who assessed allergy, 9% (28/301) of respondents met the Australian standards for allergy assessment. Only 22% (106/487) of participants correctly cited all indications for management with adrenaline in anaphylaxis to antibiotics and 67% (197/292) of physicians rarely or never referred to an allergy service. Paediatric clinicians had an increased understanding of allergy assessment and anaphylaxis management. Recent penicillin allergy education within a 5-year period led to significant improvements in allergy knowledge.
Conclusion
Overall, knowledge, assessment and management of penicillin allergies among practitioners in Western Australia are currently inadequate in adults and paediatric clinicians to provide safe and effective clinical care. The implementation of a targeted education program for WA health professionals is urgently required and is expected to improve clinician knowledge and aid standardised penicillin assessment (de-labelling) practices
2022 Update of the consensus on the rational use of antithrombotics and thrombolytics in Veterinary Critical Care (CURATIVE) Domain 1‐ Defining populations at risk
Objectives
To expand the number of conditions and interventions explored for their associations with thrombosis in the veterinary literature and to provide the basis for prescribing recommendations.
Design
A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. The revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated in this iteration included heartworm disease (dogs and cats), immune-mediated hemolytic anemia (cats), protein-losing nephropathy (cats), protein-losing enteropathy (dogs and cats), sepsis (cats), hyperadrenocorticism (cats), liver disease (dogs), congenital portosystemic shunts (dogs and cats) and the following interventions: IV catheters (dogs and cats), arterial catheters (dogs and cats), vascular access ports (dogs and cats), extracorporeal circuits (dogs and cats) and transvenous pacemakers (dogs and cats).
Results
Of the diseases evaluated in this iteration, a high risk for thrombosis was defined as heartworm disease or protein-losing enteropathy. Low risk for thrombosis was defined as dogs with liver disease, cats with immune-mediated hemolytic anemia, protein-losing nephropathy, sepsis, or hyperadrenocorticism.
Conclusions
Associations with thrombosis are outlined for various conditions and interventions and provide the basis for management recommendations. Numerous knowledge gaps were identified that represent opportunities for future studies
Bathymetry derivatives and habitat data from hyperspectral imagery establish a high-resolution baseline for managing the Ningaloo Reef, Western Australia
The Ningaloo Reef, Australia’s longest fringing reef, is uniquely positioned in the NW region of the continent, with clear, oligotrophic waters, relatively low human impacts, and a high level of protection through the World Heritage Site and its marine park status. Non-invasive optical sensors, which seamlessly derive bathymetry and bottom reflectance, are ideally suited for mapping and monitoring shallow reefs such as Ningaloo. Using an existing airborne hyperspectral survey, we developed a new, geomorphic layer for the reef for depths down to 20 m, through an object-oriented classification that combines topography and benthic cover. We demonstrate the classification approach using three focus areas in the northern region of the Muiron Islands, the central part around Point Maud, and Gnaraloo Bay in the south. Topographic mapping combined aspect, slope, and depth into 18 classes and, unsurprisingly, allocated much of the area into shallow, flat lagoons, and highlighted narrow, deeper channels that facilitate water circulation. There were five distinct geomorphic classes of coral-algal mosaics in different topographic settings. Our classifications provide a useful baseline for stratifying ecological field surveys, designing monitoring programmes, and assessing reef resilience from current and future threats
Livestock guardian dog protection of free-range poultry from the red fox
Context: Predation of layer chickens is a major issue for free-range egg producers. Using livestock guardian dogs (LGD) to protect free-ranging poultry is a possible option for producers, although there is little published literature regarding how the dogs protect chickens.
Aims: This case study was conducted at a free-range egg production farm in Western Australia, where red foxes (Vulpes vulpes) were a common predator of chickens prior to introducing Maremma LGD. We investigated LGD responses to experimental cues that might indicate fox incursion (fox urine and calls).
Methods: Four dogs were GPS tracked and monitored using camera traps. Over the first week, experimental fox cues were set out around the paddock boundaries, alternating with ‘non-cue’ experimental control nights. We recorded whether the LGD altered (1) their space use, (2) activity patterns (movement speed), or (3) behaviour in response to these cues. We also recorded (4) distances between LGD from known sightings of foxes.
Key results: The Maremmas appeared to work independently of each other, covering separate areas. There was no significant difference in overnight home range area by experimental fox cue treatment, but there was a significant (P < 0.001) treatment × dog interaction term for distance moved. Three dogs spent most of their time at night around the chicken shelters and generally increased distances moved on experimental fox cue nights. The fourth dog was more bonded to people and did not alter its movements. Paradoxically, dogs rested more and barked less on experimental fox cue nights; however, we recorded foxes on camera traps placed around the chicken shelters on 17 of the 23 nights of monitoring, and the high background activity level of foxes on this property compromised our experimental control (nights without experimental fox cues). The dogs did not move towards known fox sightings.
Conclusions: The Maremmas in this trial closely guarded the chicken shelters rather than maintaining the entire paddock as a predator-exclusion zone.
Implications: Understanding how guardian dogs behave when challenged by potential predators will help increase producers’ confidence in the efficacy of these dogs as a viable method to protect livestock from predation threat
The effect of an evidence-based Tai chi intervention on the fatigue-sleep disturbance-depression symptom cluster in breast cancer patients: A preliminary randomised controlled trial
Purpose
To explore the potential effects of Tai chi on the fatigue-sleep disturbance-depression symptom cluster (FSDSC) among breast cancer (BC) patients.
Methods
This study was conducted as a preliminary randomized controlled trial among 72 BC patients (36 Tai chi and 36 control participants). All the participants were provided with routine care, while participants in the Tai chi group received an additional 8-week Tai chi intervention. Participants' fatigue, sleep disturbance and depression were assessed by the Brief Fatigue Inventory, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale-Depression. Participants’ quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy-Breast. Both covariates-unadjusted and adjusted GEE models were run to assess the effects of Tai chi intervention on the FSDSC and QoL and the relevant impacts of the covariates.
Results
Sixty-nine participants completed this study. In the unadjusted GEE model, compared with the control group and baseline, participants in the Tai chi group showed significant reductions in fatigue (p < 0.001), sleep disturbance (p < 0.001) and depression (p = 0.006), as well as a significant improvement in QoL (p = 0.032) at immediately post-intervention and four-week follow-up. The positive regression coefficients of the adjusted GEE model showed fatigue, sleep disturbance and depression can have impacts on each other (all at p < 0.05).
Conclusion
Tai chi as an adjuvant intervention to routine care could relieve the symptom cluster of fatigue, sleep disturbance and depression and improve QoL among BC patients