Dialysis for paediatric acute kidney injury in Cape Town, South Africa.

BACKGROUND: Dialysis is lifesaving for acute kidney injury (AKI), but access is poor in less resourced settings. A "peritoneal dialysis (PD) first" policy for paediatric AKI is more feasible than haemodialysis in low-resource settings. METHODS: Retrospective review of modalities and outcomes of children dialysed acutely at Red Cross War Memorial Children's Hospital between 1998 and 2020. RESULTS: Of the 593 children with AKI who received dialysis, 463 (78.1%) received PD first. Median age was 9.0 (range 0.03-219.3; IQR 13.0-69.6) months; 57.6% were < 1 year old. Weights ranged from 0.9 to 2.0 kg (median 7.0 kg, IQR 3.0-16.0 kg); 38.6% were < 5 kg. PD was used more in younger children compared to extracorporeal dialysis (ECD), with median ages 6.4 (IQR 0.9-30.4) vs. 73.9 (IQR 17.5-113.9) months, respectively (p = 0.001). PD was performed with Seldinger soft catheters (n = 480/578, 83%), predominantly inserted by paediatricians at the bedside (n = 412/490, 84.1%). Complications occurred in 127/560 (22.7%) children receiving PD. Overall, 314/542 (57.8%) children survived. Survival was significantly lower in neonates (< 1 month old, 47.5%) and infants (1-12 months old, 49.2%) compared with older children (> 1 year old, 70.4%, p < 0.0001). Survival was superior in the ECD (75.4%) than in the PD group (55.6%, p = 0.002). CONCLUSIONS: "PD First for Paediatric AKI" is a valuable therapeutic approach for children with AKI. It is feasible in low-resourced settings where bedside PD catheter insertion can be safely taught and is an acceptable dialysis modality, especially in settings where children with AKI would otherwise not survive.

Study protocol for a 15-week randomised controlled trial assessing the independent effects of high-cholesterol and high-saturated fat diets on LDL cholesterol.

INTRODUCTION: Previous research has associated high dietary cholesterol intake with raised low-density lipoprotein cholesterol (LDL-C) and thus increased risk for cardiovascular disease (CVD). Emerging research suggests that it is saturated fat, not dietary cholesterol, associated with increased CVD risk. Despite being high in cholesterol, eggs, low in saturated fat, are not adversely associated with blood lipids or CVD risk. This paper describes a randomised controlled counter-balanced, cross-over trial assessing the effects of a high-cholesterol/low-saturated fat (egg) diet and a low-cholesterol/high-saturated fat diet (egg free) on blood lipids and lipoproteins, while accounting for physical activity levels which can also influence these parameters. The primary aim is to demonstrate that high cholesterol intake (from eggs) within a healthy, low-saturated fat diet does not adversely affect blood lipid levels and lipoprotein profiles. Instead, we propose that adverse effects on these parameters are mediated by saturated fat intake. The secondary aim is to explore relationships between changes in blood lutein and zeaxanthin concentrations and alterations in physical activity, examining whether changes in physical activity mediate effects on blood lipids and lipoproteins. METHODS AND ANALYSIS: Fifty-two adults aged 18-60 years with LDL-C less than 3.5 mmol/L will be randomly allocated to three isocaloric diets for 5 weeks each: a high-cholesterol (600 mg)/low-saturated fat (6%) (egg) diet, a low-cholesterol (300 mg)/high-saturated fat (12%) (egg free) diet and a control diet that is high in both cholesterol (600 mg) and saturated fat (12%). Lipid and lipoprotein levels, lipoprotein size and concentrations, blood pressure, blood glucose, physical activity levels, and plasma lutein and zeaxanthin concentrations will be measured. Treatment effects will be analysed using linear mixed effects models. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of South Australia Human Research Ethics Committee no. 204 327. Results will be disseminated through peer-reviewed journals and national and international presentations. TRIAL REGISTRATION NUMBER: NCT05267522.

An Exome Capture-Based RNA-Sequencing Assay for Genome-Wide Identification and Prioritization of Clinically Important Fusions in Pediatric Tumors.

This study reports the development of an exome capture-based RNA-sequencing assay to detect recurring and novel fusions in hematologic, solid, and central nervous system tumors. The assay used Twist Comprehensive Exome capture with either fresh or formalin-fixed samples and a bioinformatic platform that provides fusion detection, prioritization, and downstream curation. A minimum of 50 million uniquely mapped reads, a consensus read alignment/fusion calling approach using four callers (Arriba, FusionCatcher, STAR-Fusion, and Dragen), and custom software were used to integrate, annotate, and rank the candidate fusion calls. In an evaluation of 50 samples, the number of calls varied substantially by caller, from a mean of 24.8 with STAR-Fusion to 259.6 with FusionCatcher; only 1.1% of calls were made by all four callers. Therefore a filtering and ranking algorithm was developed based on multiple criteria, including number of supporting reads, calling consensus, genes involved, and cross-reference against databases of known cancer-associated or likely false-positive fusions. This approach was highly effective in pinpointing known clinically relevant fusions, ranking them first in 47 of 50 samples (94%). Detection of pathogenic gene fusions in three diagnostically challenging cases highlights the importance of a genome-wide and nontargeted method for fusion detection in pediatric cancer.

Optimizing Wearable Device and Testing Parameters to Monitor Running-Stride Long-Range Correlations for Fatigue Management in Field Settings.

PURPOSE: There are important methodological considerations for translating wearable-based gait-monitoring data to field settings. This study investigated different devices' sampling rates, signal lengths, and testing frequencies for athlete monitoring using dynamical systems variables. METHODS: Secondary analysis of previous wearables data (N = 10 runners) from a 5-week intensive training intervention investigated impacts of sampling rate (100-2000 Hz) and signal length (100-300 strides) on detection of gait changes caused by intensive training. Primary analysis of data from 13 separate runners during 1 week of field-based testing determined day-to-day stability of outcomes using single-session data and mean data from 2 sessions. Stride-interval long-range correlation coefficient α from detrended fluctuation analysis was the gait outcome variable. RESULTS: Stride-interval α reduced at 100- and 200- versus 300- to 2000-Hz sampling rates (mean difference: -.02 to -.08; P ≤ .045) and at 100- compared to 200- to 300-stride signal lengths (mean difference: -.05 to -.07; P < .010). Effects of intensive training were detected at 100, 200, and 400 to 2000 Hz (P ≤ .043) but not 300 Hz (P = .069). Within-athlete α variability was lower using 2-session mean versus single-session data (smallest detectable change: .13 and .22, respectively). CONCLUSIONS: Detecting altered gait following intensive training was possible using 200 to 300 strides and a 100-Hz sampling rate, although 100 and 200 Hz underestimated α compared to higher rates. Using 2-session mean data lowers smallest detectable change values by nearly half compared to single-session data. Coaches, runners, and researchers can use these findings to integrate wearable-device gait monitoring into practice using dynamic systems variables.

A Mediterranean Diet and Walking Intervention to Reduce Cognitive Decline and Dementia Risk in Independently Living Older Australians: The MedWalk Randomized Controlled Trial Experimental Protocol, Including COVID-19 Related Modifications and Baseline Characteristics.

BACKGROUND: Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias such as Alzheimer's disease. However, the ability to modify these behaviors longer term, to impact cognitive health has remained elusive. OBJECTIVE: The MedWalk trial's primary aim is to investigate whether longer-term adherence to a Mediterranean-style diet and regular walking, delivered through motivational interviewing and cognitive-behavioral therapy (MI-CBT), can reduce age-associated cognitive decline and other dementia risk factors in older, independently living individuals without cognitive impairment. METHODS: MedWalk, a one-year cluster-randomized controlled trial across two Australian states, recruited 60-90-year-old people from independent living retirement villages and the wider community. Participants were assigned to either the MedWalk intervention or a control group (maintaining their usual diet and physical activity). The primary outcome is 12-month change in visual memory and learning assessed from errors on the Paired Associates Learning Task of the Cambridge Neuropsychological Test Automated Battery. Secondary outcomes include cognition, mood, cardiovascular function, biomarkers related to nutrient status and cognitive decline, MI-CBT effectiveness, Mediterranean diet adherence, physical activity, quality of life, cost-effectiveness, and health economic evaluation.Progress and Discussion:Although COVID-19 impacts over two years necessitated a reduced timeline and sample size, MedWalk retains sufficient power to address its aims and hypotheses. Baseline testing has been completed with 157 participants, who will be followed over 12 months. If successful, MedWalk will inform interventions that could substantially reduce dementia incidence and ameliorate cognitive decline in the community. TRIAL REGISTRATION: Registered on the Australia New Zealand Clinical Trials Registry ANZCTR 12620000978965 (https://www.anzctr.org.au).

Almonds vs. carbohydrate snacks in an energy-restricted diet: Weight and cardiometabolic outcomes from a randomized trial.

OBJECTIVE: This study evaluated weight and cardiometabolic outcomes after a 3-month energy-restricted diet (-30%) containing almonds (almond-enriched diet [AED]) or containing carbohydrate-rich snacks (nut-free control diet [NFD]) (Phase 1), followed by 6 months of weight maintenance (Phase 2). METHODS: Participants (25-65 years old) with overweight or obesity (BMI 27.5-34.9 kg/m2 ) were randomly allocated to AED (n = 68) or NFD (n = 72). RESULTS: Both groups lost weight during Phase 1 (p < 0.001) (mean [SE], -7.0 [0.5] kg AED vs. -7.0 [0.5] kg NFD, p = 0.858) and Phase 2 (p = 0.009) (-1.1 [0.5] kg AED vs. -1.3 [0.6] NFD, p = 0.756), with improvements in percentage lean mass after Phase 2 (4.8% [0.3%], p < 0.001). Reductions occurred in fasting glucose (-0.2 [0.07] mmol/L, p = 0.003), insulin (-8.1 [4.0] pmol/L, p = 0.036), blood pressure (-4.9 [0.8] mm Hg systolic, -5.0 [0.5] mm Hg diastolic, p < 0.001), total cholesterol (-0.3 [0.1] mmol/L), low-density lipoprotein (LDL) (-0.2 [0.1] mmol/L), very low-density lipoprotein (-0.1 [0.03] mmol/L), and triglycerides (-0.3 [0.06] mmol/L) (all p < 0.001), and high-density lipoprotein increased (0.1 [0.02] mmol/L, p = 0.011) by the end of Phase 2 in both groups. There were group by time interactions for lipoprotein particle concentrations: very small triglyceride-rich (-31.0 [7.7] nmol/L AED vs. -4.8 [7.9] nmol/L NFD, p = 0.007), small LDL (-109.3 [40.5] nmol/L AED vs. -20.7 [41.6] nmol/L NFD, p = 0.017), and medium LDL (-24.4 [43.4] nmol/L AED vs. -130.5 [44.4] nmol/L NFD, p = 0.045). CONCLUSIONS: An energy-restricted AED resulted in weight loss and weight loss maintenance comparable to an energy-restricted NFD, and both diets supported cardiometabolic health. The AED resulted in greater improvements in some lipoprotein subfractions, which may enhance reductions in cardiovascular risk.

Lessons learned from regional training of paediatric nephrology fellows in Africa.

BACKGROUND: Access to care for children with kidney disease is limited in less well-resourced regions of the world and paediatric nephrology (PN) workforce development with good practical skills is critical. METHODS: Retrospective review of a PN training program and trainee feedback from 1999 to 2021, based at Red Cross War Memorial Children's Hospital (RCWMCH), University of Cape Town. RESULTS: A regionally appropriate 1-2-year training program enrolled 38 fellows with an initial 100% return rate to their country of origin. Program funding included fellowships from the International Pediatric Nephrology Association (IPNA), International Society of Nephrology (ISN), International Society of Peritoneal Dialysis (ISPD), and the African Paediatric Fellowship Program (APFP). Fellows were trained on both in- and out-patient management of infants and children with kidney disorders. "Hands-on skills" training included examination, diagnosis and management skills, practical insertion of peritoneal dialysis catheters for management of acute kidney injury and kidney biopsies. Of 16 trainees who completed > 1 year of training, 14 (88%) successfully completed subspecialty exams and 9 (56%) completed a master's degree with a research component. PN fellows reported that their training was appropriate and enabled them to make a difference in their respective communities. CONCLUSIONS: This training program has successfully equipped African physicians with the requisite knowledge and skills to provide PN services in resource-constrained areas for children with kidney disease. The provision of funding from multiple organizations committed to paediatric kidney disease has contributed to the success of the program, along with the fellows' commitment to build PN healthcare capacity in Africa. A higher resolution version of the Graphical abstract is available as Supplementary information.

Eggs and Cardiovascular Disease Risk: An Update of Recent Evidence.

PURPOSE OF REVIEW: This review summarizes recent evidence published since a previous review in 2018 on the association between egg consumption and risk of cardiovascular disease (CVD) mortality, CVD incidence, and CVD risk factors. RECENT FINDINGS: No recent randomized controlled trials were identified. Evidence from observational studies is mixed, with studies reporting either an increased risk or no association of highest egg consumption with CVD mortality, and a similar spread of increased risk, decreased risk, or no association between egg intake and total CVD incidence. Most studies reported a reduced risk or no association between egg consumption and CVD risk factors. Included studies reported low and high egg intake as between 0 and 1.9 eggs/week and 2 and ≥14 eggs/week, respectively. Ethnicity may influence the risk of CVD with egg consumption, likely due to differences in how eggs are consumed in the diet rather than eggs themselves. Recent findings are inconsistent regarding the possible relationship between egg consumption and CVD mortality and morbidity. Dietary guidance should focus on improving the overall quality of the diet to promote cardiovascular health.

Effects of Cold-Water Immersion Compared with Other Recovery Modalities on Athletic Performance Following Acute Strenuous Exercise in Physically Active Participants: A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Studies investigating the effects of common recovery modalities following acute strenuous exercise have reported mixed results. OBJECTIVES: This systematic review with meta-analysis and meta-regression compared the effects of cold-water immersion (CWI) against other common recovery modalities on recovery of athletic performance, perceptual outcomes, and creatine kinase (CK) following acute strenuous exercise in physically active populations. STUDY DESIGN: Systematic review, meta-analysis, and meta-regression. METHODS: The MEDLINE, SPORTDiscus, Scopus, Web of Science, Cochrane Library, EmCare, and Embase databases were searched up until September 2022. Studies were included if they were peer reviewed, published in English, included participants who were involved in sport or deemed physically active, compared CWI with other recovery modalities following an acute bout of strenuous exercise, and included measures of performance, perceptual measures of recovery, or CK. RESULTS: Twenty-eight studies were meta-analysed. CWI was superior to other recovery methods for recovering from muscle soreness, and similar to other methods for recovery of muscular power and flexibility. CWI was more effective than active recovery, contrast water therapy and warm-water immersion for most recovery outcomes. Air cryotherapy was significantly more effective than CWI for the promotion of recovery of muscular strength and the immediate recovery of muscular power (1-h post-exercise). Meta-regression revealed that water temperature and exposure duration were rarely exposure moderators. CONCLUSION: CWI is effective for promoting recovery from acute strenuous exercise in physically active populations compared with other common recovery methods. PROTOCOL REGISTRATION: Open Science Framework: https://doi.org/10.17605/OSF.IO/NGP7C.

Acute feeding with almonds compared to a carbohydrate-based snack improves appetite-regulating hormones with no effect on self-reported appetite sensations: a randomised controlled trial.

PURPOSE: Early satiety has been identified as one of the mechanisms that may explain the beneficial effects of nuts for reducing obesity. This study compared postprandial changes in appetite-regulating hormones and self-reported appetite ratings after consuming almonds (AL, 15% of energy requirement) or an isocaloric carbohydrate-rich snack bar (SB). METHODS: This is a sub-analysis of baseline assessments of a larger parallel-arm randomised controlled trial in overweight and obese (Body Mass Index 27.5-34.9 kg/m2) adults (25-65 years). After an overnight fast, 140 participants consumed a randomly allocated snack (AL [n = 68] or SB [n = 72]). Appetite-regulating hormones and self-reported appetite sensations, measured using visual analogue scales, were assessed immediately before snack food consumption, and at 30, 60, 90 and 120 min following snack consumption. A sub-set of participants (AL, n = 49; SB, n = 48) then consumed a meal challenge buffet ad libitum to assess subsequent energy intake. An additional appetite rating assessment was administered post buffet at 150 min. RESULTS: Postprandial C-peptide area under the curve (AUC) response was 47% smaller with AL compared to SB (p < 0.001). Glucose-dependent insulinotropic polypeptide, glucagon and pancreatic polypeptide AUC responses were larger with AL compared to SB (18%, p = 0.005; 39% p < 0.001; 45% p < 0.001 respectively). Cholecystokinin, ghrelin, glucagon-like peptide-1, leptin and polypeptide YY AUCs were not different between groups. Self-reported appetite ratings and energy intake following the buffet did not differ between groups. CONCLUSION: More favourable appetite-regulating hormone responses to AL did not translate into better self-reported appetite or reduced short-term energy consumption. Future studies should investigate implications for longer term appetite regulation. ANZCTR REFERENCE NUMBER: ACTRN12618001861246 2018.

Longitudinal haematological responses to training load and heat acclimation preceding a male team pursuit cycling world record.

This study evaluated relationships between changes in training load, haematological responses, and endurance exercise performance during temperate and heat acclimation (HA) training preceding a male team cycling pursuit world record (WR). Haemoglobin mass (Hbmass) and concentration ([Hb]), plasma volume (PV) and blood volume (BV) were assessed in nine male track endurance cyclists (∼3 occasions per month) training in temperate conditions (247-142 days prior to the WR) to establish responses to differing acute (ATL) and chronic (CTL) training loads. Testing was performed again pre- and post-HA (22-28 days prior to the WR). Endurance performance (V̇O2max, 4MMP, lactate threshold 1 and 2) was assessed on three occasions (238-231, 189-182 and 133-126 days prior to the WR). In temperate conditions, CTL was associated with Hbmass (B = 0.62, P = 0.02), PV (B = 4.49, P = 0.01) and BV (B = 6.51, P = 0.04) but not [Hb] (B = -0.01, P = 0.17). ATL was associated with PV (B = 2.28, P < 0.01), BV (B = 2.63, P = 0.04) and [Hb] (B = -0.01, P = 0.04) but not Hbmass (B = 0.10, P = 0.41). During HA, PV increased 8.2% (P < 0.01), while Hbmass, CTL and ATL were unchanged. Hbmass and [Hb] were associated with all performance outcomes (P < 0.05), except V̇O2max. PV and BV were not associated with performance outcomes. During temperate training, changes in Hbmass were most strongly associated with changes in CTL. Both CTL and ATL were associated with changes in PV, but HA was associated with increased PV and maintenance of Hbmass without increasing ATL or CTL. In practical terms, maintaining high CTL and high Hbmass might be beneficial for improving endurance performance.HIGHLIGHTSChanges in haemoglobin mass were associated with endurance exercise performance and changes in chronic training load in temperate conditions.Heat acclimation increased plasma volume and maintained haemoglobin mass independently of chronic training load.Chronic training loads and haemoglobin mass should be increased to improve endurance exercise performance.Heat acclimation may optimise haematological adaptations when training load is reduced.

Potential methylation-regulated genes and pathways in hepatocellular neoplasm, not otherwise specified.

Background and Aims: The molecular basis of hepatocellular neoplasm, not otherwise specified (HCN-NOS) is unknown. We aimed to identify gene expression patterns, potential methylation-regulated genes and pathways that characterize the tumor, and its possible relationship to hepatoblastoma and hepatocellular carcinoma (HCC). Approach & Results: Parallel genome-wide profiling of gene expression (RNAseq) and DNA methylation (EPIC850) was performed on 4 pairs of pre-treatment HCN-NOS tumors and adjacent non-tumor controls. 2530 significantly differentially expressed genes (DEGs) were identified between tumors and controls. Many of these DEGs were associated with hepatoblastoma and/or HCC. Analysis Match in Ingenuity Pathway Analysis determined that the gene expression profile of HCN-NOS was unique but significantly similar to that of both hepatoblastoma and HCC. A total of 27,195 CpG sites (CpGs) were significantly differentially methylated (DM) between tumors and controls, with a global hypomethylation pattern and predominant CpG island hypermethylation in promotor regions. Aberrant DNA methylation predominated in Developmental Process and Molecular Function Regulator pathways. Embryonic stem cell pathways were significantly enriched. In total, 1055 aberrantly methylated (at CpGs) and differentially expressed genes were identified, including 25 upstream regulators and sixty-one potential CpG island methylation-regulated genes. Eight methylation-regulated genes (TCF3, MYBL2, SRC, HMGA2, PPARGC1A, SLC22A1, COL2A1 and MYCN) had highly consistent gene expression patterns and prognostic value in patients with HCC, based on comparison to publicly available datasets. Conclusions: HCN-NOS has a unique, stem-cell like gene expression and DNA methylation profile related to both hepatoblastoma and HCC but distinct therefrom. Further, 8 methylation-regulated genes associated with prognosis in HCC were identified.

Mitochondrial DNA haplogroup, genetic ancestry, and susceptibility to Ewing sarcoma.

Based on current studies, the incidence of Ewing sarcoma (ES) varies significantly by race and ethnicity, with the disease being most common in patients of European ancestry. However, race/ethnicity has generally been self-reported rather than formally evaluated at a population level using DNA evidence. Additionally, mitochondrial dysfunction is a hallmark of ES, yet there have been no reported studies of mitochondrial genetics in ES. Thus, we evaluated both the mitochondrial and nuclear ancestries of 420 pediatric ES patients in the United States using whole-genome sequencing. We found that the mitochondrial DNA (mtDNA) genomes of only six (1.4 %) patients belonged to African L haplogroups, while those of 90 % of the patients belonged to macrohaplogroup R, which includes haplogroup H, the most common maternal lineage in Europe. Compared to the general US population, European haplogroups were significantly enriched in ES patients (p < 2.2e-16) and the African haplogroups are significantly impoverished (p < 4.6e-16). Using the ancestry informative markers defined in a National Genographic study, the vast majority of patients exhibited significant nuclear ancestry originating from the Mediterranean, Northern Europe, and Southwest Asia, including all six patients with African L mtDNAs. Very few had primarily African nuclear ancestry. This is the first genomic epidemiology study to simultaneously interrogate the mitochondrial and nuclear ancestries of ES patients. While supporting previous findings of enriched European ancestry in ES patients, these results also suggest alternative hypotheses for the significant contribution of mitochondrial ancestry in ES patients, as well as the protective role of African ancestry.

A Food Relief Charter for South Australia-Towards a Shared Vision for Pathways Out of Food Insecurity.

Chronic food insecurity persists in high-income countries, leading to an entrenched need for food relief. In Australia, food relief services primarily focus on providing food to meet immediate need. To date, there has been few examples of a vision in the sector towards client outcomes and pathways out of food insecurity. In 2016, the South Australian Government commissioned research and community sector engagement to identify potential policy actions to address food insecurity. This article describes the process of developing a co-designed South Australian Food Relief Charter, through policy-research-practice collaboration, and reflects on the role of the Charter as both a policy tool and a declaration of a shared vision. Methods used to develop the Charter, and resulting guiding principles, are discussed. This article reflects on the intentions of the Charter and suggests how its guiding principles may be used to guide collective actions for system improvement. Whilst a Charter alone may be insufficient to create an integrated food relief system that goes beyond the provision of food, it is a useful first step in enabling a culture where the sector can have a unified voice to advocate for the prevention of food insecurity.

Sport Participation and Subjective Outcomes of Health in Middle-Aged Men: A Scoping Review.

Although sport participation is intrinsically motivating and improves the physical health of middle-aged men, its influence on subjective health measures, such as health-related quality of life, self-rated health, or well-being is unclear. The purpose of this scoping review was to describe the existing literature that has assessed male sport participants and their subjective health. MEDLINE, Embase, Emcare, PsycInfo, SPORTDiscus, Cochrane Library, and Web of Science were searched, and reference lists of included studies were pearled. Included were original peer-reviewed studies reporting a marker of subjective health in males, 35 to 54 years (average), who participated in sport. The search identified 21 eligible articles, 18 quantitative, 2 mixed-methods, and 1 qualitative, from 13 different countries. Eighteen studies were cross-sectional. A broad range of outcomes were assessed, with the most common being quality of life/health-related quality of life (n = 6) and self-rated health (n = 6). Most studies assessing quality of life, health-related quality of life, or self-rated health demonstrated a positive association with sport participation, while sport participation was not related to measures of life satisfaction, flourishing, happiness or global well-being; however, limited studies examined these latter outcomes. Sport participation appears to be related to better select subjective health outcomes in middle-aged men. However, most available data are cross-sectional and thus causation cannot be determined. Randomized intervention trials are required to determine whether sport participation improves the subjective health of middle-aged men.Open Science Framework registration: https://osf.io/zypds.

Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis.

Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT scans from patients with metastatic castration-resistant PC (mCRPC). CTCs from 22 patients were enumerated, stained for PC-relevant markers, and clustered based on morphometric and immunofluorescent features using machine learning. DNA from single CTCs, matched cfDNA, and buffy coats was sequenced using a targeted amplicon cancer hotspot panel. Radiomic analysis was performed on bone metastases identified on CT scans from the same patients. CTCs were detected in 77% of patients and clustered reproducibly. cfDNA sequencing had high sensitivity (98.8%) for germline variants compared to WBC. Shared and unique somatic variants in PC-related genes were detected in cfDNA in 45% of patients (MAF > 0.1%) and in CTCs in 92% of patients (MAF > 10%). Radiomic analysis identified a signature that strongly correlated with CTC count and plasma cfDNA level. Integration of cellular, molecular, and radiomic data in a multi-parametric approach is feasible, yielding complementary profiles that may enable more comprehensive non-invasive disease modeling and prediction.

Impact of Cold-Water Immersion Compared with Passive Recovery Following a Single Bout of Strenuous Exercise on Athletic Performance in Physically Active Participants: A Systematic Review with Meta-analysis and Meta-regression.

BACKGROUND: Studies investigating the effects of cold-water immersion (CWI) on the recovery of athletic performance, perceptual measures and creatine kinase (CK) have reported mixed results in physically active populations. OBJECTIVES: The purpose of this systematic review was to investigate the effects of CWI on recovery of athletic performance, perceptual measures and CK following an acute bout of exercise in physically active populations. STUDY DESIGN: Systematic review with meta-analysis and meta-regression. METHODS: A systematic search was conducted in September 2021 using Medline, SPORTDiscus, Scopus, Web of Science, Cochrane Library, EmCare and Embase databases. Studies were included if they were peer reviewed and published in English, included participants who were involved in sport or deemed physically active, compared CWI with passive recovery methods following an acute bout of strenuous exercise and included athletic performance, athlete perception and CK outcome measures. Studies were divided into two strenuous exercise subgroups: eccentric exercise and high-intensity exercise. Random effects meta-analyses were used to determine standardised mean differences (SMD) with 95% confidence intervals. Meta-regression analyses were completed with water temperature and exposure durations as continuous moderator variables. RESULTS: Fifty-two studies were included in the meta-analyses. CWI improved the recovery of muscular power 24 h after eccentric exercise (SMD 0.34 [95% CI 0.06-0.62]) and after high-intensity exercise (SMD 0.22 [95% CI 0.004-0.43]), and reduced serum CK (SMD - 0.85 [95% CI - 1.61 to - 0.08]) 24 h after high-intensity exercise. CWI also improved muscle soreness (SMD - 0.89 [95% CI - 1.48 to - 0.29]) and perceived feelings of recovery (SMD 0.66 [95% CI 0.29-1.03]) 24 h after high-intensity exercise. There was no significant influence on the recovery of strength performance following either eccentric or high-intensity exercise. Meta-regression indicated that shorter time and lower temperatures were related to the largest beneficial effects on serum CK (duration and temperature dose effects) and endurance performance (duration dose effects only) after high-intensity exercise. CONCLUSION: CWI was an effective recovery tool after high-intensity exercise, with positive outcomes occurring for muscular power, muscle soreness, CK, and perceived recovery 24 h after exercise. However, after eccentric exercise, CWI was only effective for positively influencing muscular power 24 h after exercise. Dose-response relationships emerged for positively influencing endurance performance and reducing serum CK, indicating that shorter durations and lower temperatures may improve the efficacy of CWI if used after high-intensity exercise. FUNDING: Emma Moore is supported by a Research Training Program (Domestic) Scholarship from the Australian Commonwealth Department of Education and Training. PROTOCOL REGISTRATION: Open Science Framework: 10.17605/OSF.IO/SRB9D.

Minimal changes in telomere length after a 12-week dietary intervention with almonds in mid-age to older, overweight and obese Australians: results of a randomised clinical trial.

Diet is a modifiable risk factor for chronic disease and a potential modulator of telomere length (TL). The study aim was to investigate associations between diet quality and TL in Australian adults after a 12-week dietary intervention with an almond-enriched diet (AED). Participants (overweight/obese, 50-80 years) were randomised to an AED (n 62) or isoenergetic nut-free diet (NFD, n 62) for 12 weeks. Diet quality was assessed using a Dietary Guideline Index (DGI), applied to weighed food records, that consists of ten components reflecting adequacy, variety and quality of core food components and discretionary choices within the diet. TL was measured by quantitative PCR in samples of lymphocytes, neutrophils, and whole blood. There were no significant associations between DGI scores and TL at baseline. Diet quality improved with AED and decreased with NFD after 12 weeks (change from baseline AED + 9·8 %, NFD - 14·3 %; P < 0·001). TL increased in neutrophils (+9·6 bp, P = 0·009) and decreased in whole blood, to a trivial extent (-12·1 bp, P = 0·001), and was unchanged in lymphocytes. Changes did not differ between intervention groups. There were no significant relationships between changes in diet quality scores and changes in lymphocyte, neutrophil or whole blood TL. The inclusion of almonds in the diet improved diet quality scores but had no impact on TL mid-age to older Australian adults. Future studies should investigate the impact of more substantial dietary changes over longer periods of time.

Heart-Rate Acceleration Is Linearly Related to Anaerobic Exercise Performance.

PURPOSE: To prescribe training loads to improve performance, one must know how an athlete is responding to loading. The maximal rate of heart-rate increase (rHRI) during the transition from rest to exercise is linearly related to changes in endurance exercise performance and can be used to infer how athletes are responding to changes in training load. Relationships between rHRI and anaerobic exercise performance have not been evaluated. The objective of this study was to evaluate relationships between rHRI and anaerobic exercise performance. METHODS: Eighteen recreational strength and power athletes (13 male and 5 female) were tested on a cycle ergometer for rHRI, 6-second peak power output, anaerobic capacity (30-s average power), and blood lactate concentration prior to (PRE), and 1 (POST1) and 3 (POST3) hours after fatiguing high-intensity interval cycling. RESULTS: Compared with PRE, rHRI was slower at POST1 (effect size [ES] = -0.38, P = .045) but not POST3 (ES = -0.36, P = .11). PPO was not changed at POST1 (ES = -0.12, P = .19) but reduced at POST3 (ES = -0.52, P = .01). Anaerobic capacity was reduced at POST1 (ES = -1.24, P < .001) and POST3 (ES = -0.83, P < .001), and blood lactate concentration was increased at POST1 (ES = 1.73, P < .001) but not at POST3 (ES = 0.75, P = .11). rHRI was positively related to PPO (B = 0.19, P = .03) and anaerobic capacity (B = 0.14, P = .005) and inversely related to blood lactate concentration (B = -0.22, P = .04). CONCLUSIONS: rHRI is linearly related to acute changes in anaerobic exercise performance and may indicate how athletes are responding to training to guide the application of training loads.

Effect of food sources of nitrate, polyphenols, L-arginine and L-citrulline on endurance exercise performance: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Increasing nitric oxide bioavailability may induce physiological effects that enhance endurance exercise performance. This review sought to evaluate the performance effects of consuming foods containing compounds that may promote nitric oxide bioavailability. METHODS: Scopus, Web of Science, Ovid Medline, EMBASE and SportDiscus were searched, with included studies assessing endurance performance following consumption of foods containing nitrate, L-arginine, L-citrulline or polyphenols. Random effects meta-analysis was conducted, with subgroup analyses performed based on food sources, sex, fitness, performance test type and supplementation protocol (e.g. duration). RESULTS: One hundred and eighteen studies were included in the meta-analysis, which encompassed 59 polyphenol studies, 56 nitrate studies and three L-citrulline studies. No effect on exercise performance following consumption of foods rich in L-citrulline was identified (SMD=-0.03, p=0.24). Trivial but significant benefits were demonstrated for consumption of nitrate and polyphenol-rich foods (SMD=0.15 and 0.17, respectively, p<0.001), including performance in time-trial, time-to-exhaustion and intermittent-type tests, and following both acute and multiple-day supplementation, but no effect of nitrate or polyphenol consumption was found in females. Among nitrate-rich foods, beneficial effects were seen for beetroot, but not red spinach or Swiss chard and rhubarb. For polyphenol-rich foods, benefits were found for grape, (nitrate-depleted) beetroot, French maritime pine, Montmorency cherry and pomegranate, while no significant effects were evident for New Zealand blackcurrant, cocoa, ginseng, green tea or raisins. Considerable heterogeneity between polyphenol studies may reflect food-specific effects or differences in study designs and subject characteristics. Well-trained males (V̇O2max ≥65 ml.kg.min-1) exhibited small, significant benefits following polyphenol, but not nitrate consumption. CONCLUSION: Foods rich in polyphenols and nitrate provide trivial benefits for endurance exercise performance, although these effects may be food dependent. Highly trained endurance athletes do not appear to benefit from consuming nitrate-rich foods but may benefit from polyphenol consumption. Further research into food sources, dosage and supplementation duration to optimise the ergogenic response to polyphenol consumption is warranted. Further studies should evaluate whether differential sex-based responses to nitrate and polyphenol consumption are attributable to physiological differences or sample size limitations. OTHER: The review protocol was registered on the Open Science Framework ( https://osf.io/u7nsj ) and no funding was provided.