Identification of Streptococcus pneumoniae genes associated with hypothiocyanous acid tolerance through genome-wide screening.

Streptococcus pneumoniae is a commensal bacterium and invasive pathogen that causes millions of deaths worldwide. The pneumococcal vaccine offers limited protection, and the rise of antimicrobial resistance will make treatment increasingly challenging, emphasizing the need for new antipneumococcal strategies. One possibility is to target antioxidant defenses to render S. pneumoniae more susceptible to oxidants produced by the immune system. Human peroxidase enzymes will convert bacterial-derived hydrogen peroxide to hypothiocyanous acid (HOSCN) at sites of colonization and infection. Here, we used saturation transposon mutagenesis and deep sequencing to identify genes that enable S. pneumoniae to tolerate HOSCN. We identified 37 genes associated with S. pneumoniae HOSCN tolerance, including genes involved in metabolism, membrane transport, DNA repair, and oxidant detoxification. Single-gene deletion mutants of the identified antioxidant defense genes sodA, spxB, trxA, and ahpD were generated and their ability to survive HOSCN was assessed. With the exception of ΔahpD, all deletion mutants showed significantly greater sensitivity to HOSCN, validating the result of the genome-wide screen. The activity of hypothiocyanous acid reductase or glutathione reductase, known to be important for S. pneumoniae tolerance of HOSCN, was increased in three of the mutants, highlighting the compensatory potential of antioxidant systems. Double deletion of the gene encoding glutathione reductase and sodA sensitized the bacteria significantly more than single deletion. The HOSCN defense systems identified in this study may be viable targets for novel therapeutics against this deadly pathogen. IMPORTANCE Streptococcus pneumoniae is a human pathogen that causes pneumonia, bacteremia, and meningitis. Vaccination provides protection only against a quarter of the known S. pneumoniae serotypes, and the bacterium is rapidly becoming resistant to antibiotics. As such, new treatments are required. One strategy is to sensitize the bacteria to killing by the immune system. In this study, we performed a genome-wide screen to identify genes that help this bacterium resist oxidative stress exerted by the host at sites of colonization and infection. By identifying a number of critical pneumococcal defense mechanisms, our work provides novel targets for antimicrobial therapy.

Relationship between attentional bias and stimulus control: An observational study of real-world eating patterns.

BACKGROUND: Attentional bias towards food related stimuli has been proposed as a potential target for dieting intervention, however the evidence supporting a relationship between attentional bias and food intake is mixed. Theory holds that food related attentional bias should be positively associated with measures of stimulus-controlled eating, and that implicit processes such as impulsivity moderate this association. The aim of the present study was to examine whether the proposed relationship between food-related attentional bias and stimulus control exists, and whether it is moderated by impulsivity. METHOD: A community sample of 68 participants completed a food-related attentional bias task and impulsiveness scale during a laboratory visit, after which they recorded their real-world eating in real-time over 14 days using Ecological Momentary Assessment (EMA). During this time, participants also responded to 4-5 randomly timed assessments per day. Food outlet presence (e.g., fast food restaurants, cafes, corner stores etc.) was assessed during both eating and non-eating assessments. EMA data was then used to determine levels of stimulus controlled eating for each participant. FINDINGS: Substantial variation was seen in both our measure of both food-related attentional bias (Range: 33.9 to 80.0) and in the degree to which the participant's eating could be categorised as being under stimulus control (Range: 0.50 to 0.93). However, food-related attentional bias scores were not a significant independent predictor of stimulus control and nor was this relationship moderated by impulsivity. CONCLUSION: Contrary to theoretical predictions, we found no evidence that of an association between attentional bias, impulsivity, and stimulus control. More work is needed to better understand the implicit processes underlying eating behaviour in the real-world.

Psychological Outcomes and Mechanisms of Mindfulness-Based Training for Generalised Anxiety Disorder: A Systematic Review and Meta-Analysis.

This systematic review aimed to identify 1) the effect of mindfulness training on pre-post measures of anxiety and attention among adults experiencing high levels of generalised anxiety; and 2) the impact of predictors, mediators and moderators on post-intervention changes in anxiety or attention. Trait mindfulness and distress measures were included as secondary outcomes. A systematic search was conducted in November 2021 in electronic databases using relevant search terms. Eight articles comprising four independent studies were included (N = 334). All studies included participants diagnosed with generalised anxiety disorder (GAD) who participated in an 8-week manualised program. The meta-analysis indicated that mindfulness training had a large effect on anxiety symptoms (g = -1.92, 95%CI[-3.44, -0.40]) when compared to inactive (i.e., care as usual, waitlist) or non-specified (i.e., condition not defined) controls. However, a significant effect was not found when compared to active controls. Effects for depression, worry and trait mindfulness did not reach statistical significance, despite small-large effect sizes favouring mindfulness compared to inactive/non-specified controls. Our narrative review found evidence that changes in aspects of trait mindfulness mediate anxiety reduction following mindfulness training. However, a small number of studies were available for inclusion in the review, with high risk of bias and low certainty of evidence present. Overall, the findings support the use of mindfulness training programs for GAD and indicate mechanisms that may differ from those involved in other cognitive therapy approaches. Further RCTs with evidence-based controls are needed to clarify techniques most beneficial for generalised anxiety to support individually tailored treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04695-x.

Exploring the Patient Experience with Patient-Reported Outcomes: A Qualitative, Multistakeholder Study.

OBJECTIVES: Although the literature provides guidance regarding patient-reported outcome (PRO) implementation barriers, patients' perspectives are underreported. This study aimed to improve the understanding of patient experiences with PRO tools through examining perceptions of and attitudes toward PROs and expectations of data use after collection. METHODS: Ethnographic human-centered design approaches were used to conduct free-form interviews. Two case studies of existing PRO use in clinics also were examined. Unstructured thematic analyses were performed using notes taken during these interviews. RESULTS: Patients generally reported a good understanding of the need for PRO collection, both for research and clinical use. Many expected that results would be acted upon by the clinicians promptly. Thematic analyses identified the following patient perception topics: transparency, individualization to patient needs, timely response, different "identities" while accessing care locally compared with at a destination center, and preference for brief PROs. CONCLUSIONS: Design and implementation of PRO assessments into patient care should include the patients as key end users. Transparency of the purpose for data collection is critical for broader patient adoption. Ensuring that only necessary and sufficient data are collected for clinical action, and associated research may help minimize burden and maximize patient participation.

A Tn-seq Screen of Streptococcus pneumoniae Uncovers DNA Repair as the Major Pathway for Desiccation Tolerance and Transmission.

Streptococcus pneumoniae is an opportunistic pathogen that is a common cause of serious invasive diseases such as pneumonia, bacteremia, meningitis, and otitis media. Transmission of this bacterium has classically been thought to occur through inhalation of respiratory droplets and direct contact with nasal secretions. However, the demonstration that S. pneumoniae is desiccation tolerant and, therefore, environmentally stable for extended periods of time opens up the possibility that this pathogen is also transmitted via contaminated surfaces (fomites). To better understand the molecular mechanisms that enable S. pneumoniae to survive periods of desiccation, we performed a high-throughput transposon sequencing (Tn-seq) screen in search of genetic determinants of desiccation tolerance. We identified 42 genes whose disruption reduced desiccation tolerance and 45 genes that enhanced desiccation tolerance. The nucleotide excision repair pathway was the most enriched category in our Tn-seq results, and we found that additional DNA repair pathways are required for desiccation tolerance, demonstrating the importance of maintaining genome integrity after desiccation. Deletion of the nucleotide excision repair gene uvrA resulted in a delay in transmission between infant mice, indicating a correlation between desiccation tolerance and pneumococcal transmssion. Understanding the molecular mechanisms that enable pneumococcal persistence in the environment may enable targeting of these pathways to prevent fomite transmission, thereby preventing the establishment of new colonization and any resulting invasive disease.

Secondary biogenic amine deficiencies: genetic etiology, therapeutic interventions, and clinical effects.

Monoamine neurotransmitter disorders present predominantly with neurologic features, including dystonic or dyskinetic cerebral palsy and movement disorders. Genetic conditions that lead to secondary defects in the synthesis, catabolism, transport, and metabolism of biogenic amines can lead to neurotransmitter abnormalities, which can present with similar features. Eleven patients with secondary neurotransmitter abnormalities were enrolled between 2011 and 2015. All patients underwent research-based whole exome and/or whole genome sequencing (WES/WGS). A trial of treatment with levodopa/carbidopa and 5-hydroxytryptophan was initiated. In six families with abnormal neurotransmitter profiles and neurological phenotypes, variants in known disease-causing genes (KCNJ6, SCN2A, CSTB in 2 siblings, NRNX1, KIF1A and PAK3) were identified, while one patient had a variant of uncertain significance in a candidate gene (DLG4) that may explain her phenotype. In 3 patients, no compelling candidate genes were identified. A trial of neurotransmitter replacement therapy led to improvement in motor and behavioral symptoms in all but two patients. The patient with KCNJ6 variant did not respond to L-dopa therapy, but rather experienced increased dyskinetic movements even at low dose of medication. The patient's symptoms harboring the NRNX1 deletion remained unaltered. This study demonstrates the utility of genome-wide sequencing in further understanding the etiology and pathophysiology of neurometabolic conditions, and the potential of secondary neurotransmitter deficiencies to serve as novel therapeutic targets. As there was a largely favorable response to therapy in our case series, a careful trial of neurotransmitter replacement therapy should be considered in patients with cerebrospinal fluid (CSF) monoamines below reference range.

Cannabinoid polymorphisms interact with plasma endocannabinoid levels to predict fear extinction learning.

BACKGROUND: The endocannabinoid system is gaining increasing attention as a favorable target for improving posttraumatic stress disorder (PTSD) treatments. Exposure therapy is the gold-standard treatment for PTSD, and fear extinction learning is a key concept underlying successful exposure. METHODS: This study examined the role of genetic endocannabinoid polymorphisms in a fear extinction paradigm with PTSD compared to healthy participants (N = 220). Participants provided saliva for genotyping, completed a fear conditioning and extinction task, with blood samples taken before and after the task (n = 57). Skin conductance was the outcome and was analyzed using mixed models. RESULTS: Results for cannabinoid receptor type 1 polymorphisms suggested that minor alleles of rs2180619 and rs1049353 were associated with poorer extinction learning in PTSD participants. The minor allele of the fatty acid amide hydrolase (FAAH) polymorphism rs324420 was associated with worse extinction in PTSD participants. Subanalysis of healthy participants (n = 57) showed the FAAH rs324420 genotype effect was dependent on plasma arachidonoyl ethanolamide (AEA) level, but not oleoylethanolamide or 2-arachidonoyl glycerol. Specifically, higher but not lower AEA levels in conjunction with the minor allele of FAAH rs324420 were associated with better extinction learning. CONCLUSIONS: These findings provide translational evidence that cannabinoid receptor 1 and AEA are involved in extinction learning in humans. FAAH rs324420's effect on fear extinction is moderated by AEA plasma level in healthy controls. These findings imply that FAAH inhibitors may be effective for targeting anxiety in PTSD, but this effect needs to be explored further in clinical populations.

Transcription and translation of the sigG gene is tuned for proper execution of the switch from early to late gene expression in the developing Bacillus subtilis spore.

A cascade of alternative sigma factors directs developmental gene expression during spore formation by the bacterium Bacillus subtilis. As the spore develops, a tightly regulated switch occurs in which the early-acting sigma factor σF is replaced by the late-acting sigma factor σG. The gene encoding σG (sigG) is transcribed by σF and by σG itself in an autoregulatory loop; yet σG activity is not detected until σF-dependent gene expression is complete. This separation in σF and σG activities has been suggested to be due at least in part to a poorly understood intercellular checkpoint pathway that delays sigG expression by σF. Here we report the results of a careful examination of sigG expression during sporulation. Unexpectedly, our findings argue against the existence of a regulatory mechanism to delay sigG transcription by σF and instead support a model in which sigG is transcribed by σF with normal timing, but at levels that are very low. This low-level expression of sigG is the consequence of several intrinsic features of the sigG regulatory and coding sequence-promoter spacing, secondary structure potential of the mRNA, and start codon identity-that dampen its transcription and translation. Especially notable is the presence of a conserved hairpin in the 5' leader sequence of the sigG mRNA that occludes the ribosome-binding site, reducing translation by up to 4-fold. Finally, we demonstrate that misexpression of sigG from regulatory and coding sequences lacking these features triggers premature σG activity in the forespore during sporulation, as well as inappropriate σG activity during vegetative growth. Altogether, these data indicate that transcription and translation of the sigG gene is tuned to prevent vegetative expression of σG and to ensure the precise timing of the switch from σF to σG in the developing spore.

Brain-derived neurotropic factor and cortisol levels negatively predict working memory performance in healthy males.

There is now significant literature suggesting that increasing brain-derived neurotropic factor (BDNF) signalling may improve memory-related disorders such as Alzheimer's disease. However, the effects of BDNF on short-term and working memory are not clear and existing evidence is inconsistent. Here we measured plasma BDNF and salivary cortisol levels, as well as working memory, on an N-Back task before and after mixed psychosocial/physiological stress induction in healthy males (N = 29). Stress induction was associated with higher circulating cortisol, but not BDNF levels. Higher cortisol and BDNF levels were significantly associated with poorer accuracy before and after stress induction. There was also a significant interaction, such that higher BDNF was associated with a buffering effect on the negative association between high cortisol and working memory. Future studies should replicate this data in larger samples, with emphasis on cortisol/BDNF interactions in determining working memory performance.

Atypical cerebral palsy: genomics analysis enables precision medicine.

PURPOSE: The presentation and etiology of cerebral palsy (CP) are heterogeneous. Diagnostic evaluation can be a prolonged and expensive process that might remain inconclusive. This study aimed to determine the diagnostic yield and impact on management of next-generation sequencing (NGS) in 50 individuals with atypical CP (ACP). METHODS: Patient eligibility criteria included impaired motor function with onset at birth or within the first year of life, and one or more of the following: severe intellectual disability, progressive neurological deterioration, other abnormalities on neurological examination, multiorgan disease, congenital anomalies outside of the central nervous system, an abnormal neurotransmitter profile, family history, brain imaging findings not typical for cerebral palsy. Previous assessment by a neurologist and/or clinical geneticist, including biochemical testing, neuroimaging, and chromosomal microarray, did not yield an etiologic diagnosis. RESULTS: A precise molecular diagnosis was established in 65% of the 50 patients. We also identified candidate disease genes without a current OMIM disease designation. Targeted intervention was enabled in eight families (~15%). CONCLUSION: NGS enabled a molecular diagnosis in ACP cases, ending the diagnostic odyssey, improving genetic counseling and personalized management, all in all enhancing precision medicine practices.

Factors Associated With Nonaccidental Trauma Evaluation Among Patients Below 36 Months Old Presenting With Femur Fractures at a Level-1 Pediatric Trauma Center.

BACKGROUND: In 2009, the American Academy of Orthopedic Surgeons published clinical practice guidelines (CPGs) on the treatment of pediatric diaphyseal femur fractures, which recommended a nonaccidental trauma (NAT) evaluation for all patients below 36 months of age. A recent study of these guidelines found <50% clinical compliance with this treatment recommendation. We aimed to identify areas for improvement in compliance with this guideline. METHODS: A retrospective review was performed of all patients presenting to a single pediatric tertiary care hospital with a diaphyseal femur fracture from January 2007 to June 2013 who were below 36 months old. Medical records were reviewed for documentation of a NAT evaluation, patient characteristics, presence of other fractures or injuries, and hospital of presentation. Radiographs were reviewed for fracture pattern. Statistical analysis was performed to assess for differences overall and before and after CPG publication. RESULTS: During the study period, 281 children below 36 months presented with femur fractures; 41% were evaluated for NAT. Overall, the following factors were significantly associated with receipt of a NAT evaluation: younger age (P<0.001), transfer from an outside facility (P=0.027), and identification of another fracture (P=0.004). Before publication of the CPG, nonwhite patients were much more likely to undergo NAT evaluation compared with white patients (43% vs. 19%; P=0.014). After publication of the CPGs, this differential disappeared (43% vs. 47%; P=0.685). Fracture pattern and patient sex did not influence receipt of NAT evaluation. CONCLUSIONS: We found poor utilization of NAT evaluation for patients below 36 months old presenting with femur fracture. Despite CPG publication, only modest improvements in this evaluation occurred over the study period, with less than half of all patients being evaluated. Younger children, patients transferred from other institutions, and patients presenting with concomitant fractures were more likely to undergo NAT evaluation. Compliance with the CPG may be improved by focusing on older children, patients who initially present to tertiary care centers, and those with an isolated femur fracture. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review.

Many inborn errors of metabolism (IEMs) are amenable to treatment; therefore, early diagnosis and treatment is imperative. Despite recent advances, the genetic basis of many metabolic phenotypes remains unknown. For discovery purposes, whole exome sequencing (WES) variant prioritization coupled with clinical and bioinformatics expertise is the primary method used to identify novel disease-causing variants; however, causation is often difficult to establish due to the number of plausible variants. Integrated analysis of untargeted metabolomics (UM) and WES or whole genome sequencing (WGS) data is a promising systematic approach for identifying disease-causing variants. In this review, we provide a literature-based overview of UM methods utilizing liquid chromatography mass spectrometry (LC-MS), and assess approaches to integrating WES/WGS and LC-MS UM data for the discovery and prioritization of variants causing IEMs. To embed this integrated -omics approach in the clinic, expansion of gene-metabolite annotations and metabolomic feature-to-metabolite mapping methods are needed.

Using the Severity of Dependence Scale to screen for DSM-5 khat use disorder.

OBJECTIVE: This study aimed to determine the efficacy of the Severity of Dependence Scale (SDS) as a screening tool for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-defined khat use disorder. METHODS: Cross-sectional, purposive sample of past-year khat consumers aged 16 and above were recruited from khat markets and cafes from university and general community in Adama, Ethiopia. Participants self-completed a survey comprising current substance use disorder. RESULTS: The SDS formed a unifactorial structure, consistent with the dependence construct. Almost three quarters (73%) of the sample were identified as experiencing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition khat use disorder. The SDS demonstrated excellent discrimination (area under the curve = 0.92) and an optimal cut-off as a score of 3 or greater, with sensitivity of 81% and specificity of 96%. This classification validly identified a group with more frequent and higher dose khat use than participants that did not screen positive. CONCLUSION: Although khat is a mild stimulant, there is clear evidence that some consumers are both concerned with their use and experience problems associated with their use. Consistent with its application for other drugs, the SDS is a brief and simple screening tool that appears to validly identify individuals experiencing a khat use disorder syndrome and experiencing high rates of adverse consequences in association with use.

ERP correlates of attentional processing in spider fear: evidence of threat-specific hypervigilance.

Attentional bias towards threat can be demonstrated by enhanced processing of threat-related targets and/or greater interference when threat-related distractors are present. These effects are argued to reflect processing within the orienting and executive control networks of the brain respectively. This study investigated behavioural (RT) and electrophysiological correlates of early selective attention and top-down attentional control among females with high (n = 16) or low (n = 16) spider fear (Mean age = 22 years). Participants completed a novel flanker go/nogo task in which a central schematic flower or spider stimulus was flanked by either congruent or incongruent distractors. Participants responded to green stimuli (go trials) and withheld response to yellow stimuli (nogo trials). High fear participants demonstrated significantly shorter reaction times and greater P1 amplitude to spider targets, suggesting specific hypervigilance towards threat-relevant stimuli. In contrast to predictions, there was little evidence for behavioural interference effects or differences in N2 amplitude when distractor stimuli were threat-relevant.

Assessment of the ExAC data set for the presence of individuals with pathogenic genotypes implicated in severe Mendelian pediatric disorders.

PurposeWe analyzed the Exome Aggregation Consortium (ExAC) data set for the presence of individuals with pathogenic genotypes implicated in Mendelian pediatric disorders.MethodsClinVar likely/pathogenic variants supported by at least one peer-reviewed publication were assessed within the ExAC database to identify individuals expected to exhibit a childhood disorder based on concordance with disease inheritance modes: heterozygous (for dominant), homozygous (for recessive) or hemizygous (for X-linked recessive conditions). Variants from 924 genes reported to cause Mendelian childhood disorders were considered.ResultsWe identified ExAC individuals with candidate pathogenic genotypes for 190 previously published likely/pathogenic variants in 128 genes. After curation, we determined that 113 of the variants have sufficient support for pathogenicity and identified 1,717 ExAC individuals (~2.8% of the ExAC population) with corresponding possible/disease-associated genotypes implicated in rare Mendelian disorders, ranging from mild (e.g., due to SCN2A deficiency) to severe pediatric conditions (e.g., due to FGFR1 deficiency).ConclusionLarge-scale sequencing projects and data aggregation consortia provide unprecedented opportunities to determine the prevalence of pathogenic genotypes in unselected populations. This knowledge is crucial for understanding the penetrance of disease-associated variants, phenotypic variability, somatic mosaicism, as well as published literature curation for variant classification procedures and predicted clinical outcomes.

Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction.

Clinical and laboratory data were collected from three Finnish patients including a sibling pair and another unrelated child with unexplained childhood hypoglycemia. Transient elevation of alanine transaminase, lactate and tricarboxylic acid cycle intermediates, especially fumarate, were noticed in urine organic acid analysis. Exome sequencing was performed for the patients and their parents. A novel homozygous PCK1 c.925G>A (p.G309R) mutation was detected in all affected individuals. COS-1 cells transfected with mutant PCK1 transcripts were used to study the pathogenic nature of the detected variant. The COS-1 transfected cells showed the mutant gene to be incapable of producing a normally functioning cytosolic phosphoenolpyruvate carboxykinase (PEPCK) enzyme. This report further delineates the clinical phenotype of isolated cytosolic PEPCK deficiency and offers a metabolic pattern helping to recognize these patients. Cytosolic PEPCK deficiency should be considered in the differential diagnosis of children presenting with hypoglycemia, hepatic dysfunction and elevated tricarboxylic acid intermediates in urinary organic acid analysis.

Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?

We describe neurotransmitter abnormalities in two patients with drug-resistant epilepsy resulting from deleterious de novo mutations in sodium channel genes. Whole exome sequencing identified a de novo SCN2A splice-site mutation (c.2379+1G>A, p.Glu717Gly.fs*30) resulting in deletion of exon 14, in a 10-year old male with early onset global developmental delay, intermittent ataxia, autism, hypotonia, epileptic encephalopathy and cerebral/cerebellar atrophy. In the cerebrospinal fluid both homovanillic acid and 5-hydroxyindoleacetic acid were significantly decreased; extensive biochemical and genetic investigations ruled out primary neurotransmitter deficiencies and other known inborn errors of metabolism. In an 8-year old female with an early onset intractable epileptic encephalopathy, developmental regression, and progressive cerebellar atrophy, a previously unreported de novo missense mutation was identified in SCN8A (c.5615G>A; p.Arg1872Gln), affecting a highly conserved residue located in the C-terminal of the Nav1.6 protein. Aside from decreased homovanillic acid and 5-hydroxyindoleacetic acid, 5-methyltetrahydrofolate was also found to be low. We hypothesize that these channelopathies cause abnormal synaptic mono-amine metabolite secretion/uptake via impaired vesicular release and imbalance in electrochemical ion gradients, which in turn aggravate the seizures. Treatment with oral 5-hydroxytryptophan, l-Dopa/Carbidopa, and a dopa agonist resulted in mild improvement of seizure control in the male case, most likely via dopamine and serotonin receptor activated signal transduction and modulation of glutamatergic, GABA-ergic and glycinergic neurotransmission. Neurotransmitter analysis in other sodium channelopathy patients will help validate our findings, potentially yielding novel treatment opportunities.

"A little bit of hope goes a long way": Exploring the role of peer workers in alcohol and other drug rehabilitation services.

INTRODUCTION: Peer workers operating within health care settings can offer unique perspectives based on their own lived experience. Within alcohol and other drug (AOD) rehabilitation services, the potential value of peer work is becoming increasingly recognised. This qualitative study aimed to evaluate a newly implemented peer worker program located across three rehabilitation services in Tasmania, Australia. METHODS: Online interviews were conducted with eight clients, seven peer workers, and five non-peer worker employees with varied experience with peer worker programs. All interviews were audio-recorded and transcribed verbatim. RESULTS: Guided by an overarching exploratory-descriptive methodological framework, thematic analysis generated three overarching themes: 1) Enhancing and supporting client experiences (what peer workers did in their role to improve client experiences, 2) Changing experiences with AOD rehabilitation (the unique benefits and changes that peer work brings to AOD rehabilitation services) and 3) Finding organizational value (how defining peer work and the feasibility of the peer worker role was challenged by different organizational factors). Overall, peer work was viewed as a positive addition to all rehabilitation services that was able to enhance client experiences through various mechanisms, such as by sharing their own stories, assisting with understanding, and creating safety. Peer work was also able to create change in AOD services, by instilling hope and reducing stigma. However, ongoing challenges with defining the peer worker role in a way that offers organizational recognition and financial security remain. CONCLUSION: Peer workers offer a unique and valuable perspective when working within rehabilitation services. Through their own lived experience peer workers were able to support clients and assist them in their recovery. These findings highlight the potential benefit of peer work programs within AOD rehabilitation services.

Psychological and attentional outcomes following acute mindfulness induction among high anxiety individuals: A systematic review and meta-analysis.

BACKGROUND: Training outcomes of mindfulness interventions for anxiety have been extensively researched. Less is known about the acute effects of mindfulness induction and associated mechanisms. This systematic review aimed to identify 1) the effect of mindfulness induction on pre-post measures of state anxiety and attention among adults experiencing high levels of anxiety; and 2) the impact of predictors, mediators and moderators on post-induction changes in anxiety and attention. State distress and mindfulness were included as secondary outcomes. METHODS: A systematic search was conducted in November 2021 in electronic databases using relevant search terms. Five studies (four randomised controlled trials and one non-randomised controlled trial) were included, comprising a total of 277 participants with elevated trait/generalised anxiety. Each study used a brief audio-based mindfulness induction exercise. RESULTS: The meta-analysis indicated mindfulness induction had medium and large effects on state anxiety (k = 3, n = 100, g = -0.60, 95%CI [-1.04, -0.16]; p = .008) and state mindfulness (k = 2, n = 110, g = 0.91, 95%CI [0.52, 1.30], p < .001), respectively, when compared with non-therapeutic control conditions. Furthermore, two studies showed small and moderate effects of mindfulness on state anxiety when compared to therapeutic active controls, but were not pooled in a meta-analysis. While results could not be pooled for attention, there was limited evidence of behavioural improvements on tasks measuring aspects of attention following mindfulness induction. However, one study found an increase in Low Beta to High Beta ratio and a reduction in Beta activity in the Anterior Cingulate Cortex following mindfulness induction. Moreover, another study found aspects of state mindfulness mediated reductions in state anxiety. LIMITATIONS: A small number of studies were included in the review, with high risk of bias and low certainty of evidence present. CONCLUSION: The findings support the use of mindfulness induction to reduce state anxiety in anxious individuals but suggest gains in state mindfulness may be a more realistic expected outcome. Further controlled trials are needed to delineate the relative effects of objectively assessed anxiety outcomes from mindfulness induction in clinically defined samples.