Whole-genome sequencing facilitates patient-specific quantitative PCR-based minimal residual disease monitoring in acute lymphoblastic leukaemia, neuroblastoma and Ewing sarcoma.

BACKGROUND: Minimal residual disease (MRD) measurement is a cornerstone of contemporary acute lymphoblastic leukaemia (ALL) treatment. The presence of immunoglobulin (Ig) and T cell receptor (TCR) gene recombinations in leukaemic clones allows widespread use of patient-specific, DNA-based MRD assays. In contrast, paediatric solid tumour MRD remains experimental and has focussed on generic assays targeting tumour-specific messenger RNA, methylated DNA or microRNA. METHODS: We examined the feasibility of using whole-genome sequencing (WGS) data to design tumour-specific polymerase chain reaction (PCR)-based MRD tests (WGS-MRD) in 18 children with high-risk relapsed cancer, including ALL, high-risk neuroblastoma (HR-NB) and Ewing sarcoma (EWS) (n = 6 each). RESULTS: Sensitive WGS-MRD assays were generated for each patient and allowed quantitation of 1 tumour cell per 10-4 (0.01%)-10-5 (0.001%) mononuclear cells. In ALL, WGS-MRD and Ig/TCR-MRD were highly concordant. WGS-MRD assays also showed good concordance between quantitative PCR and droplet digital PCR formats. In serial clinical samples, WGS-MRD correlated with disease course. In solid tumours, WGS-MRD assays were more sensitive than RNA-MRD assays. CONCLUSIONS: WGS facilitated the development of patient-specific MRD tests in ALL, HR-NB and EWS with potential clinical utility in monitoring treatment response. WGS data could be used to design patient-specific MRD assays in a broad range of tumours.

Measurable residual disease analysis in paediatric acute lymphoblastic leukaemia patients with ABL-class fusions.

BACKGROUND: ABL-class fusions including NUP214-ABL1 and EBF1-PDGFRB occur in high risk acute lymphoblastic leukaemia (ALL) with gene expression patterns similar to BCR-ABL-positive ALL. Our aim was to evaluate new DNA-based measurable residual disease (MRD) tests detecting these fusions and IKZF1-deletions in comparison with conventional immunoglobulin/T-cell receptor (Ig/TCR) markers. METHODS: Precise genomic breakpoints were defined from targeted or whole genome next generation sequencing for ABL-fusions and BCR-ABL1. Quantitative PCR assays were designed and used to re-measure MRD in remission bone marrow samples previously tested using Ig/TCR markers. All MRD testing complied with EuroMRD guidelines. RESULTS: ABL-class patients had 46% 5year event-free survival and 79% 5year overall survival. All had sensitive fusion tests giving high concordance between Ig/TCR and ABL-class fusion results (21 patients, n = 257 samples, r2 = 0.9786, P < 0.0001) and Ig/TCR and IKZF1-deletion results (9 patients, n = 143 samples, r2 = 0.9661, P < 0.0001). In contrast, in BCR-ABL1 patients, Ig/TCR and BCR-ABL1 tests were discordant in 32% (40 patients, n = 346 samples, r2 = 0.4703, P < 0.0001) and IKZF1-deletion results were closer to Ig/TCR (25 patients, n = 176, r2 = 0.8631, P < 0.0001). CONCLUSIONS: MRD monitoring based on patient-specific assays detecting gene fusions or recurrent assays for IKZF1-deletions is feasible and provides good alternatives to Ig/TCR tests to monitor MRD in ABL-class ALL.

Fast and accurate HLA typing from short-read next-generation sequence data with xHLA.

The HLA gene complex on human chromosome 6 is one of the most polymorphic regions in the human genome and contributes in large part to the diversity of the immune system. Accurate typing of HLA genes with short-read sequencing data has historically been difficult due to the sequence similarity between the polymorphic alleles. Here, we introduce an algorithm, xHLA, that iteratively refines the mapping results at the amino acid level to achieve 99-100% four-digit typing accuracy for both class I and II HLA genes, taking only [Formula: see text]3 min to process a 30× whole-genome BAM file on a desktop computer.

Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma.

Genes encoding TRK are oncogenic drivers in multiple tumour types including infantile fibrosarcoma, papillary thyroid cancer and high-grade gliomas (HGG). TRK fusions have a critical role in tumourigenesis in 40% of infant HGG. Here we report the first case of a TRK fusion-driven HGG treated with larotrectinib-the first selective pan-TRK inhibitor in clinical development. This 3-year-old girl had failed multiple therapies including chemotherapy and radiotherapy. Tumour profiling confirmed an ETV6-NTRK3 fusion. Treatment with larotrectinib led to rapid clinical improvement with near total resolution of primary and metastatic lesions on MRI imaging. This is the first report of a TRK fusion glioma successfully treated with a TRK inhibitor.

Teledermatology: an evidence map of systematic reviews.

BACKGROUND: Although the number of teledermatology studies is increasing, not all variables have been researched in equal depth, so there remains a lack of robust evidence for some teledermatology initiatives. This review describes the landscape of teledermatology research and identifies knowledge gaps and research needs. This evidence map can be used to inform clinicians about the current knowledge about teledermatology and guide researchers for future studies. METHODS: Our evidence map was conducted according to the Campbell Collaboration checklist for evidence and gap maps. Eight databases were searched (CINAHL, Embase, PubMed, Scopus, Web of Science, Cochrane Library, JBI Database of Systematic Reviews and Implementation Reports, and OpenGray), and only included systematic reviews of teledermatology involving humans published in English; while excluding non-systematic reviews (i.e., abstracts, conference proceedings, editorials, commentaries, or letters). From 909 records, 14 systematic reviews published between 2004 and 2022 were included. Our analysis focused on the systematic reviews' characteristics, dermatological conditions studied, rate of overlap and quality assessment of primary studies reviewed, and main findings reported. RESULTS: Teledermatology was reportedly comparable with clinic dermatology and generally accepted by patients as a mode of care delivery for dermatological conditions. However, there are concerns about privacy, communication, completeness of information transmitted, familiarity with the technology, and technical problems. Healthcare professionals were generally satisfied with teledermatology but found telemedicine consultations longer than face-to-face consultations, and less confident in asynchronous teledermatology than conventional consultations. Teledermatology was reportedly more cost-effective than clinic dermatology; especially considering the distance traveled by patients, referral volume to teledermatology, and clinic dermatology costs. Although patients and providers are satisfied with teledermatology, face-to-face dermatology has higher diagnostic and management accuracy. Teledermatology was also used for training medical professionals. Regarding the validity and reliability of teledermatology outcome measures, no significant discussions were found. CONCLUSIONS: COVID-19 spotlighted telemedicine in clinical care, and we must ensure telemedicine continually improves with robust research. Further research is necessary for establishing a standardized outcome set, enhancing accuracy, concordance, cost-effectiveness, and safety, comparing teledermatology with non-dermatologist care, examining its effectiveness in non-Western low and middle-income countries, and incorporating patient involvement for improved study design. SYSTEMATIC REVIEW REGISTRATION: https://www.researchregistry.com/ (Unique Identifying Number: reviewregistry878).

Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome.

Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP. This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported.

Precision-guided treatment in high-risk pediatric cancers.

Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment (PGT). Here we report consecutive data from 384 patients with high-risk pediatric cancer (with an expected cure rate of less than 30%) who had at least 18 months of follow-up on the ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial. A total of 256 (67%) patients received PGT recommendations and 110 (29%) received a recommended treatment. PGT resulted in a 36% objective response rate and improved 2-year progression-free survival compared with standard of care (26% versus 12%; P = 0.049) or targeted agents not guided by molecular findings (26% versus 5.2%; P = 0.003). PGT based on tier 1 evidence, PGT targeting fusions or commenced before disease progression had the greatest clinical benefit. Our data show that PGT informed by comprehensive molecular profiling significantly improves outcomes for children with high-risk cancers. ClinicalTrials.gov registration: NCT03336931.

Introme accurately predicts the impact of coding and noncoding variants on gene splicing, with clinical applications.

Predicting the impact of coding and noncoding variants on splicing is challenging, particularly in non-canonical splice sites, leading to missed diagnoses in patients. Existing splice prediction tools are complementary but knowing which to use for each splicing context remains difficult. Here, we describe Introme, which uses machine learning to integrate predictions from several splice detection tools, additional splicing rules, and gene architecture features to comprehensively evaluate the likelihood of a variant impacting splicing. Through extensive benchmarking across 21,000 splice-altering variants, Introme outperformed all tools (auPRC: 0.98) for the detection of clinically significant splice variants. Introme is available at https://github.com/CCICB/introme .

In vivo loss of tumorigenicity in a patient-derived orthotopic xenograft mouse model of ependymoma.

Introduction: Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, a proportion of patients who survive treatment often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) EPN, derived from a metastatic cranial lesion. Methods: Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. Results: Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo. Discussion: Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenges of propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models.

Histone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes.

Diffuse midline gliomas (DMG) harbouring H3K27M mutation are paediatric tumours with a dismal outcome. Recently, a new subtype of midline gliomas has been described with similar features to DMG, including loss of H3K27 trimethylation, but lacking the canonical H3K27M mutation (H3-WT). Here, we report a cohort of five H3-WT tumours profiled by whole-genome sequencing, RNA sequencing and DNA methylation profiling and combine their analysis with previously published cases. We show that these tumours have recurrent and mutually exclusive mutations in either ACVR1 or EGFR and are characterised by high expression of EZHIP associated to its promoter hypomethylation. Affected patients share a similar poor prognosis as patients with H3K27M DMG. Global molecular analysis of H3-WT and H3K27M DMG reveal distinct transcriptome and methylome profiles including differential methylation of homeobox genes involved in development and cellular differentiation. Patients have distinct clinical features, with a trend demonstrating ACVR1 mutations occurring in H3-WT tumours at an older age. This in-depth exploration of H3-WT tumours further characterises this novel DMG, H3K27-altered sub-group, characterised by a specific immunohistochemistry profile with H3K27me3 loss, wild-type H3K27M and positive EZHIP. It also gives new insights into the possible mechanism and pathway regulation in these tumours, potentially opening new therapeutic avenues for these tumours which have no known effective treatment. This study has been retrospectively registered on clinicaltrial.gov on 8 November 2017 under the registration number NCT03336931 ( https://clinicaltrials.gov/ct2/show/NCT03336931 ).

High-Throughput Drug Screening of Primary Tumor Cells Identifies Therapeutic Strategies for Treating Children with High-Risk Cancer.

For one-third of patients with pediatric cancer enrolled in precision medicine programs, molecular profiling does not result in a therapeutic recommendation. To identify potential strategies for treating these high-risk pediatric patients, we performed in vitro screening of 125 patient-derived samples against a library of 126 anticancer drugs. Tumor cell expansion did not influence drug responses, and 82% of the screens on expanded tumor cells were completed while the patients were still under clinical care. High-throughput drug screening (HTS) confirmed known associations between activating genomic alterations in NTRK, BRAF, and ALK and responses to matching targeted drugs. The in vitro results were further validated in patient-derived xenograft models in vivo and were consistent with clinical responses in treated patients. In addition, effective combinations could be predicted by correlating sensitivity profiles between drugs. Furthermore, molecular integration with HTS identified biomarkers of sensitivity to WEE1 and MEK inhibition. Incorporating HTS into precision medicine programs is a powerful tool to accelerate the improved identification of effective biomarker-driven therapeutic strategies for treating high-risk pediatric cancers. SIGNIFICANCE: Integrating HTS with molecular profiling is a powerful tool for expanding precision medicine to support drug treatment recommendations and broaden the therapeutic options available to high-risk pediatric cancers.

A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer.

BACKGROUND: Molecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers. METHODS: We combined immunohistochemistry (IHC) with RNA sequencing and whole-genome sequencing across a diverse spectrum of high-risk paediatric cancers to develop an alternative, expression-based signature associated with CD8+ T-cell infiltration of the TIME. Furthermore, we explored transcriptional features of immune archetypes and T-cell receptor sequencing diversity, assessed the relationship between CD8+ and CD4+ abundance by IHC and deconvolution predictions and assessed the common adult biomarkers such as neoantigen load and TMB. RESULTS: A novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), was identified. Using this signature, we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. In addition, we showed that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression and TMB and neoantigen load are not predictive of T-cell infiltration in paediatrics. Furthermore, deconvolution algorithms are only weakly correlated with IHC measurements of T-cells. CONCLUSIONS: Our data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in high-risk paediatric cancer will require individualised analysis of the TIME.

Cloning, purification and preliminary X-ray data analysis of the human ID2 homodimer.

The ID proteins are named for their role as inhibitors of DNA binding and differentiation. They contain a helix-loop-helix (HLH) domain but lack a basic DNA-binding domain. In complex with basic HLH (bHLH) transcription factors, gene expression is regulated by DNA-binding inactivation. Although the HLH domain is highly conserved and shares a similar topology, the IDs preferentially bind class I bHLH-group members such as E47 (TCF3) but not the class III bHLH member Myc. A structure of an ID protein could potentially shed light on its mechanism. Owing to their short half-lives in vivo and reported in vitro instability, this paper describes the strategies that went into expressing sufficient soluble and stable ID2 to finally obtain diffraction-quality crystals. A 2.1 Šresolution data set was collected from a crystal belonging to space group P3(1)21 with unit-cell parameters a=b=51.622, c=111.474 Å, α=ß=90, γ=120° that was obtained by hanging-drop vapour diffusion in a precipitant solution consisting of 0.1 M MES pH 6.5, 2.0 M potassium acetate. The solvent content was consistent with the presence of one or two molecules in the asymmetric unit.

The Effect of a 14-Day gymnema sylvestre Intervention to Reduce Sugar Cravings in Adults.

Gymnemic-acids (GA) block lingual sweet taste receptors, thereby reducing pleasantness and intake of sweet food. Objective: To examine whether a 14-day gymnema-based intervention can reduce sweet foods and discretionary sugar intake in free-living adults. Healthy adults (n = 58) were randomly allocated to either the intervention group (INT) or control group (CON). The intervention comprised of consuming 4 mg of Gymnema sylvestre containing 75% gymnema acids, a fibre and vitamin supplement, and an associated healthy-eating guide for 14 days; participants in the CON group followed the same protocol, replacing the GA with a placebo mint. Amount of chocolate bars eaten and sensory testing were conducted before and after the 14-day intervention (post-GA or placebo dosing on days zero and 15, respectively). Food frequency questionnaires were conducted on days zero, 15 and after a 28-day maintenance period to examine any changes in intake of sweet foods. A range of statistical procedures were used to analyse the data including Chi square, t-test and two-way analysis of variance. Post dosing, INT consumed fewer chocolates (2.65 ± 0.21 bars) at day zero than CON (3.15 ± 0.24 bars; p = 0.02); there were no differences between groups at day 15 (INT = 2.77 ± 0.22 bars; CON = 2.78 ± 0.22 bars; p = 0.81). At both visits, a small substantive effect (r < 0.3) was observed in the change in pleasantness and desire ratings, with INT showing a slight increase while CON showed a small decrease over the 14-day period. No differences were found in the intake of 9 food categories between groups at any timepoint. There were no differences in consumption of low sugar healthy foods between visits, or by group. The 14-day behavioural intervention reduced pleasantness and intake of chocolate in a laboratory setting. There was no habituation to the mint over the 14-day period. This study is the first to investigate the effect of longer-term gymnema acid consumption on sweet food consumption outside of a laboratory setting; further research is needed to assess how long the effect of the 14-day intervention persists.

Unscrambling cancer genomes via integrated analysis of structural variation and copy number.

Complex somatic genomic rearrangements and copy number alterations are hallmarks of nearly all cancers. We have developed an algorithm, LINX, to aid interpretation of structural variant and copy number data derived from short-read, whole-genome sequencing. LINX classifies raw structural variant calls into distinct events and predicts their effect on the local structure of the derivative chromosome and the functional impact on affected genes. Visualizations facilitate further investigation of complex rearrangements. LINX allows insights into a diverse range of structural variation events and can reliably detect pathogenic rearrangements, including gene fusions, immunoglobulin enhancer rearrangements, intragenic deletions, and duplications. Uniquely, LINX also predicts chained fusions that we demonstrate account for 13% of clinically relevant oncogenic fusions. LINX also reports a class of inactivation events that we term homozygous disruptions that may be a driver mutation in up to 9% of tumors and may frequently affect PTEN, TP53, and RB1.

In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.

Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid high-throughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high-risk pediatric cancer patients.

Consumption of salmon v. salmon oil capsules: effects on n-3 PUFA and selenium status.

Salmon provides long-chain (LC) n-3 PUFA and Se, which are well recognised for their health benefits. The n-3 and Se status of the New Zealand population is marginal. The objective of the present study was to compare the effects of consuming salmon v. supplementation with salmon oil on LC n-3 and Se status. Healthy volunteers (n 44) were randomly assigned to one of four groups consuming 2 × 120 g servings of salmon/week or 2, 4 or 6 salmon oil capsules/d for 8 weeks. Linear regression analysis predictive models were fitted to the capsule data to predict changes in erythrocyte LC n-3 levels with intakes of LC n-3 from capsules in amounts equivalent to that consumed from salmon. Changes in Se status (plasma Se and whole-blood glutathione peroxidase) were compared between the groups consuming salmon and capsules (three groups combined). Salmon, 2, 4 and 6 capsules provided 0·82, 0·24, 0·47 and 0·69 g/d of LC n-3 fatty acids. Salmon provided 7 µg/d and capsules < 0·02 µg/d of Se. The predictive model (r(2) 0·31, P = 0·001) showed that increases in erythrocyte LC n-3 levels were similar when intakes of 0·82 g/d LC n-3 from salmon or capsules (1·92 (95 % CI 1·35, 2·49) v. 2·32 (95 % 1·76, 2·88) %) were consumed. Plasma Se increased significantly more with salmon than with capsules (12·2 (95 % CI 6·18, 18·12) v. 1·57 (95 % CI - 2·32, 5·45) µg/l, P = 0·01). LC n-3 status was similarly improved with consumption of salmon and capsules, while consuming salmon had the added benefit of increasing Se status. This is of particular relevance to the New Zealand population that has marginal LC n-3 and Se status.

Direct catalytic asymmetric synthesis of α-chiral bicyclo[1.1.1]pentanes.

Bicyclo[1.1.1]pentanes (BCPs) are important motifs in contemporary drug design as linear spacer units that improve pharmacokinetic profiles. The synthesis of BCPs featuring adjacent stereocenters is highly challenging, but desirable due to the fundamental importance of 3D chemical space in medicinal chemistry. Current methods to access these high-value chiral molecules typically involve transformations of pre-formed BCPs, and can display limitations in substrate scope. Here we describe an approach to synthesize α-chiral BCPs involving the direct, asymmetric addition of simple aldehydes to [1.1.1]propellane, the predominant BCP precursor. This is achieved by combining a photocatalyst and an organocatalyst to generate a chiral α-iminyl radical cation intermediate, which installs a stereocenter simultaneously with ring-opening of [1.1.1]propellane. The reaction proceeds under mild conditions, displays broad scope, and provides an array of α-chiral BCPs in high yield and enantioselectivity. We also present a theoretical model for stereoinduction in this mode of photoredox organocatalysis.

Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption.

BACKGROUND: Nitrate (NO3 -)-rich beetrAs BR juice can naturally contain both NO3 In four separate treatments, 11 healthy adults consumed 250 mL of BR containing one of the following: (i) high NO3 Ingestion of the HL and MM BR increased plasma [NO2 Inorganic NO3 - consumptio

Effect of SunGold Kiwifruit and Vitamin C Consumption on Ameliorating Exercise-Induced Stress Response in Women.

INTRODUCTION: Markers of oxidative and psychological stress are elevated during high-intensity exercise. Additionally, when energy intake does not match expenditure, women who actively participate in sports and exercise are at risk of developing menstrual dysfunction, infertility, and osteoporosis. Vitamin C is known to reduce exercise-induced stress. Here, this study investigates the efficacy of consuming vitamin C from SunGold kiwifruit compared to in isolation, in ameliorating exercise-induced stress in recreationally active women. METHODS AND RESULTS: Ten eumenorrheic women are recruited in this crossover study and attended three exercise and one rest trial. In the exercise trials, participants consumed 300 mg vitamin C from kiwifruit or drink, or have a placebo drink, followed by 30-min exercise on a cycle ergometer at 60% power. During rest visit, participants sat quietly and consumed a placebo drink. Salivary uric acid (oxidative stress) and cortisol (psychological stress) are measured before and immediately after exercise for 2 h. Both vitamin C and kiwifruit reduced exercise-induced uric acid, immediately after exercise. Vitamin C drink continued to decrease uric acid for a further 30 min and slightly attenuated exercise-induced cortisol. CONCLUSIONS: Consuming liquid vitamin C prior to high-intensity cycling appears more effective than eating kiwifruit, in ameliorating exercise-induced stress in recreationally active women of reproductive age.