Health outcomes of penicillin allergy testing in children: a systematic review.

BACKGROUND: Penicillin allergy labels are commonly acquired in childhood and lead to avoidance of first-line penicillin antibiotics. Understanding the health outcomes of penicillin allergy testing (PAT) can strengthen its place in antimicrobial stewardship efforts. OBJECTIVES: To identify and summarize the health outcomes of PAT in children. METHODS: Embase, MEDLINE, Web of Science, Cochrane Library, SCOPUS and CINAHL were searched from inception to 11 Oct 2021 (Embase and MEDLINE updated April 2022). Studies that utilized in vivo PAT in children (≤18 years old) and reported outcomes relevant to the study objectives were included. RESULTS: Thirty-seven studies were included in the review, with a total of 8411 participants. The most commonly reported outcomes were delabelling, subsequent penicillin courses, and tolerability to penicillin courses. Ten studies had patient-reported tolerability to subsequent penicillin use, with a median 93.6% (IQR 90.3%-97.8%) of children tolerating a subsequent course of penicillins. In eight studies, a median 97.3% (IQR 96.4%-99.0%) of children were reported as 'delabelled' after a negative PAT without further definition. Three separate studies verified delabelling by checking electronic or primary care medical records, where 48.0%-68.3% children were delabelled. No studies reported on outcomes relating to disease burden such as antibiotic resistance, mortality, infection rates or cure rates. CONCLUSIONS: Safety and efficacy of PAT and subsequent penicillin use was the focus of existing literature. Further research is required to determine the long-term impact of delabelling penicillin allergies on disease burden.

Pulmonary rehabilitation for interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is characterised by reduced functional capacity, dyspnoea and exercise-induced hypoxia. Pulmonary rehabilitation is often used to improve symptoms, health-related quality of life and functional status in other chronic lung conditions. There is accumulating evidence for comparable effects of pulmonary rehabilitation in people with ILD. However, further information is needed to clarify the long-term benefit and to strengthen the rationale for pulmonary rehabilitation to be incorporated into standard clinical management of people with ILD. This review updates the results reported in 2014. OBJECTIVES: To determine whether pulmonary rehabilitation in people with ILD has beneficial effects on exercise capacity, symptoms, quality of life and survival compared with no pulmonary rehabilitation in people with ILD. To assess the safety of pulmonary rehabilitation in people with ILD. SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO) and PEDro from inception to April 2020. We searched the reference lists of relevant studies, international clinical trial registries and respiratory conference abstracts to look for qualifying studies. SELECTION CRITERIA: We included randomised controlled trials and quasi-randomised controlled trials in which pulmonary rehabilitation was compared with no pulmonary rehabilitation or with other therapy in people with ILD of any origin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias. We contacted study authors to request missing data and information regarding adverse effects. We specified a priori subgroup analyses for participants with idiopathic pulmonary fibrosis (IPF) and participants with severe lung disease (low diffusing capacity or desaturation during exercise). There were insufficient data to perform the prespecified subgroup analysis for type of exercise training modality. MAIN RESULTS: For this update, we included an additional 12 studies resulting in a total of 21 studies. We included 16 studies in the meta-analysis (356 participants undertook pulmonary rehabilitation and 319 were control participants). The mean age of participants ranged from 36 to 72 years and included people with ILD of varying aetiology, sarcoidosis or IPF (with mean transfer factor of carbon dioxide (TLCO) % predicted ranging from 37% to 63%). Most pulmonary rehabilitation programmes were conducted in an outpatient setting, with a small number conducted in home-based, inpatient or tele-rehabilitation settings. The duration of pulmonary rehabilitation ranged from three to 48 weeks. There was a moderate risk of bias due to the absence of outcome assessor blinding and intention-to-treat analyses and the inadequate reporting of randomisation and allocation procedures in 60% of the studies. Pulmonary rehabilitation probably improves the six-minute walk distance (6MWD) with mean difference (MD) of 40.07 metres, 95% confidence interval (CI) 32.70 to 47.44; 585 participants; moderate-certainty evidence). There may be improvements in peak workload (MD 9.04 watts, 95% CI 6.07 to 12.0; 159 participants; low-certainty evidence), peak oxygen consumption (MD 1.28 mL/kg/minute, 95% CI 0.51 to 2.05; 94 participants; low-certainty evidence) and maximum ventilation (MD 7.21 L/minute, 95% CI 4.10 to 10.32; 94 participants; low-certainty evidence). In the subgroup of participants with IPF, there were comparable improvements in 6MWD (MD 37.25 metres, 95% CI 26.16 to 48.33; 278 participants; moderate-certainty evidence), peak workload (MD 9.94 watts, 95% CI 6.39 to 13.49; low-certainty evidence), VO2 (oxygen uptake) peak (MD 1.45 mL/kg/minute, 95% CI 0.51 to 2.40; low-certainty evidence) and maximum ventilation (MD 9.80 L/minute, 95% CI 6.06 to 13.53; 62 participants; low-certainty evidence). The effect of pulmonary rehabilitation on maximum heart rate was uncertain. Pulmonary rehabilitation may reduce dyspnoea in participants with ILD (standardised mean difference (SMD) -0.36, 95% CI -0.58 to -0.14; 348 participants; low-certainty evidence) and in the IPF subgroup (SMD -0.41, 95% CI -0.74 to -0.09; 155 participants; low-certainty evidence). Pulmonary rehabilitation probably improves health-related quality of life: there were improvements in all four domains of the Chronic Respiratory Disease Questionnaire (CRQ) and the St George's Respiratory Questionnaire (SGRQ) for participants with ILD and for the subgroup of people with IPF. The improvement in SGRQ Total score was -9.29 for participants with ILD (95% CI -11.06 to -7.52; 478 participants; moderate-certainty evidence) and -7.91 for participants with IPF (95% CI -10.55 to -5.26; 194 participants; moderate-certainty evidence). Five studies reported longer-term outcomes, with improvements in exercise capacity, dyspnoea and health-related quality of life still evident six to 12 months following the intervention period (6MWD: MD 32.43, 95% CI 15.58 to 49.28; 297 participants; moderate-certainty evidence; dyspnoea: MD -0.29, 95% CI -0.49 to -0.10; 335 participants; SGRQ Total score: MD -4.93, 95% CI -7.81 to -2.06; 240 participants; low-certainty evidence). In the subgroup of participants with IPF, there were improvements at six to 12 months following the intervention for dyspnoea and SGRQ Impact score. The effect of pulmonary rehabilitation on survival at long-term follow-up is uncertain. There were insufficient data to allow examination of the impact of disease severity or exercise training modality. Ten studies provided information on adverse events; however, there were no adverse events reported during rehabilitation. Four studies reported the death of one pulmonary rehabilitation participant; however, all four studies indicated this death was unrelated to the intervention received. AUTHORS' CONCLUSIONS: Pulmonary rehabilitation can be performed safely in people with ILD. Pulmonary rehabilitation probably improves functional exercise capacity, dyspnoea and quality of life in the short term, with benefits also probable in IPF. Improvements in functional exercise capacity, dyspnoea and quality of life were sustained longer term. Dyspnoea and quality of life may be sustained in people with IPF. The certainty of evidence was low to moderate, due to inadequate reporting of methods, the lack of outcome assessment blinding and heterogeneity in some results. Further well-designed randomised trials are needed to determine the optimal exercise prescription, and to investigate ways to promote longer-lasting improvements, particularly for people with IPF.

High intensity interval training versus moderate intensity continuous training for people with interstitial lung disease: protocol for a randomised controlled trial.

BACKGROUND: Interstitial lung disease is a debilitating condition associated with significant dyspnoea, fatigue, and poor exercise tolerance. Pulmonary rehabilitation is an effective and key intervention in people with interstitial lung disease. However, despite the best efforts of patients and clinicians, many of those who participate are not achieving clinically meaningful benefits. This assessor-blinded, multi-centre, randomised controlled trial aims to compare the clinical benefits of high intensity interval exercise training versus the standard pulmonary rehabilitation method of continuous training at moderate intensity in people with fibrotic interstitial lung disease. METHODS: Eligible participants will be randomised to either a standard pulmonary rehabilitation group using moderate intensity continuous exercise training or high intensity interval exercise training. Participants in both groups will undertake an 8-week pulmonary rehabilitation program of twice-weekly supervised exercise training including aerobic (cycling) and strengthening exercises. In addition, participants in both groups will be prescribed a home exercise program. Outcomes will be assessed at baseline, upon completion of the intervention and at six months following the intervention by a blinded assessor. The primary outcome is endurance time on a constant work rate test. Secondary outcomes are functional capacity (6-min walk distance), health-related quality of life (Chronic Respiratory Disease Questionnaire (CRQ), St George's Respiratory Questionnaire idiopathic pulmonary fibrosis specific version (SGRQ-I), breathlessness (Dyspnoea 12, Modified Medical Research Council Dyspnoea Scale), fatigue (fatigue severity scale), anxiety (Hospital Anxiety and Depression Scale), physical activity level (GeneActiv), skeletal muscle changes (ultrasonography) and completion and adherence to pulmonary rehabilitation. DISCUSSION: The standard exercise training strategies used in pulmonary rehabilitation may not provide an optimal exercise training stimulus for people with interstitial lung disease. This study will determine whether high intensity interval training can produce equivalent or even superior changes in exercise performance and symptoms. If high intensity interval training proves effective, it will provide an exercise training strategy that can readily be implemented into clinical practice for people with interstitial lung disease. Trial registration ClinicalTrials.gov Registry (NCT03800914). Registered 11 January 2019, https://clinicaltrials.gov/ct2/show/NCT03800914 Australian New Zealand Clinical Trials Registry ACTRN12619000019101. Registered 9 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376050&isReview=true.

Overexpression of NDRG2 in skeletal muscle does not ameliorate the effects of stress in vivo.

NEW FINDINGS: What is the central question of this study? Do elevated levels of the stress-response protein NDRG2 protect against fasting and chronic disease in mouse skeletal muscle? What is the main finding and its importance? NDRG2 levels increased in the tibialis anterior muscle in response to fasting and the effects of motor neurone disease. No alleviation of the stress-related and proteasomal pathways, mitochondrial dysfunction or muscle mass loss was observed even with the addition of exogenous NDRG2 indicating that the increase in NDRG2 is a normal adaptive response. ABSTRACT: Skeletal muscle mass loss and dysfunction can arise from stress, which leads to enhanced protein degradation and metabolic impairment. The expression of N-myc downstream-regulated gene 2 (NDRG2) is induced in response to different stressors and is protective against the effects of stress in some tissues and cell types. Here, we investigated the endogenous NDRG2 response to the stress of fasting and chronic disease in mice and whether exogenous NDRG2 overexpression through adeno-associated viral (AAV) treatment ameliorated the response of skeletal muscle to these conditions. Endogenous levels of NDRG2 increased in the tibialis anterior muscle in response to 24 h fasting and with the development of the motor neurone disease, amyotrophic lateral sclerosis, in SOD1G93A transgenic mice. Despite AAV-induced overexpression and increased expression with fasting, NDRG2 was unable to protect against the activation of proteasomal and stress pathways in response to fasting. Furthermore, NDRG2 was unable to reduce muscle mass loss, mitochondrial dysfunction and elevated oxidative and endoplasmic reticulum stress levels in SOD1G93A mice. Conversely, elevated NDRG2 levels did not exacerbate these stress responses. Overall, increasing NDRG2 levels might not be a useful therapeutic strategy to alleviate stress-related disease pathologies in skeletal muscle.

Placental membrane grafts for urethral replacement in a rabbit model: a pilot study.

PURPOSE: Several graft materials are available for use in the treatment of urethral stricture disease. Placental membrane is being used in a variety of settings as a graft in wound healing and tissue repair. We aim to evaluate the effect of implanting decellularized human placental membrane into rabbit urethras. METHODS: Dorsal onlay graft urethroplasty using prepared human placental membrane was performed in 10 New Zealand White rabbits (Oryctolagus cuniculus). After 3 months, the rabbits underwent cystourethroscopy to evaluate urethral patency. The rabbits were then euthanized and the urethras examined for pathological findings. RESULTS: All urethroplasties were performed without complication. There were no observed episodes of urinary retention, infection, or renal failure. Urethral patency was achieved in all rabbits 3 months postoperatively. Urothelial replacement of the placental membrane graft was observed in all rabbits without malignant transformation. CONCLUSION: Dorsal onlay urethroplasty using decellularized human placental membrane can safely be performed in a rabbit model. This pilot study demonstrated urothelial replacement of human placental membrane in the rabbit urethra without stricture formation. Placental membrane is a promising biomaterial for urethral reconstruction.

Is there rationale for the cuff pressures prescribed for blood flow restriction exercise? A systematic review.

BACKGROUND: Blood flow restriction exercise has increasingly broad applications among healthy and clinical populations. Ensuring the technique is applied in a safe, controlled, and beneficial way for target populations is essential. Individualized cuff pressures are a favored method for achieving this. However, there remains marked inconsistency in how individualized cuff pressures are applied. OBJECTIVES: To quantify the cuff pressures used in the broader blood flow restriction exercise literature, and determine whether there is clear justification for the choice of pressure prescribed. METHODS: Studies were included in this review from database searches if they employed an experimental design using original data, involved either acute or chronic exercise using blood flow restriction, and they assessed limb or arterial occlusion pressure to determine an individualized cuff pressure. Methodologies of the studies were evaluated using a bespoke quality assessment tool. RESULTS: Fifty-one studies met the inclusion criteria. Individualized cuff pressures ranged from 30% to 100% arterial occlusion pressure. Only 7 out of 52 studies attempted to justify the individualized cuff pressure applied during exercise. The mean quality rating for all studies was 11.1 ± 1.2 out of 13. CONCLUSIONS: The broader blood flow restriction exercise literature uses markedly heterogeneous prescription variables despite using individualized cuff pressures. This is problematic in the absence of any clear justification for the individualized cuff pressures selected. Systematically measuring and reporting all relevant acute responses and training adaptations to the full spectrum of BFR pressures alongside increased clarity around the methodology used during blood flow restriction exercise is paramount.

The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester.

Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27-40 weeks' gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A & cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings; total creatine content of PE placentae was 38% higher than controls (p < 0.01). mRNA expression of GATM (p < 0.001), GAMT (p < 0.001), SLC6A8 (p = 0.021) and BBCK (p < 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.

Home-based or remote exercise testing in chronic respiratory disease, during the COVID-19 pandemic and beyond: A rapid review.

OBJECTIVES: To identify exercise tests that are suitable for home-based or remote administration in people with chronic lung disease. METHODS: Rapid review of studies that reported home-based or remote administration of an exercise test in people with chronic lung disease, and studies reporting their clinimetric (measurement) properties. RESULTS: 84 studies were included. Tests used at home were the 6-minute walk test (6MWT, two studies), sit-to-stand tests (STS, five studies), Timed Up and Go (TUG, 4 studies) and step tests (two studies). Exercise tests administered remotely were the 6MWT (two studies) and step test (one study). Compared to centre-based testing the 6MWT distance was similar when performed outdoors but shorter when performed at home (two studies). The STS, TUG and step tests were feasible, reliable (intra-class correlation coefficients >0.80), valid (concurrent and known groups validity) and moderately responsive to pulmonary rehabilitation (medium effect sizes). These tests elicited less desaturation than the 6MWT, and validated methods to prescribe exercise were not reported. DISCUSSION: The STS, step and TUG tests can be performed at home, but do not accurately document desaturation with walking or allow exercise prescription. Patients at risk of desaturation should be prioritised for centre-based exercise testing when this is available.

Placental creatine metabolism in cases of placental insufficiency and reduced fetal growth.

Creatine is a metabolite involved in cellular energy homeostasis. In this study, we examined placental creatine content, and expression of the enzymes required for creatine synthesis, transport and the creatine kinase reaction, in pregnancies complicated by low birthweight. We studied first trimester chorionic villus biopsies (CVBs) of small for gestational age (SGA) and appropriately grown infants (AGA), along with third trimester placental samples from fetal growth restricted (FGR) and healthy gestation-matched controls. Placental creatine and creatine precursor (guanidinoacetate-GAA) levels were measured. Maternal and cord serum from control and FGR pregnancies were also analyzed for creatine concentration. mRNA expression of the creatine transporter (SLC6A8); synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT); mitochondrial (mtCK) and cytosolic (BBCK) creatine kinases; and amino acid transporters (SLC7A1 & SLC7A2) was assessed in both CVBs and placental samples. Protein levels of AGAT (arginine:glycine aminotransferase), GAMT, mtCK and BBCK were also measured in placental samples. Key findings; total creatine content of the third trimester FGR placentae was 43% higher than controls. The increased creatine content of placental tissue was not reflected in maternal or fetal serum from FGR pregnancies. Tissue concentrations of GAA were lower in the third trimester FGR placentae compared to controls, with lower GATM and GAMT mRNA expression also observed. No differences in the mRNA expression of GATM, GAMT or SLC6A8 were observed between CVBs from SGA and AGA pregnancies. These results suggest placental creatine metabolism in FGR pregnancies is altered in late gestation. The relevance of these changes on placental bioenergetics should be the focus of future investigations.

Lower body blood flow restriction training may induce remote muscle strength adaptations in an active unrestricted arm.

PURPOSE: We examined the concurrent characteristics of the remote development of strength and cross-sectional area (CSA) of upper body skeletal muscle in response to lower body resistance training performed with an applied blood flow restriction (BFR). METHODS: Males allocated to an experimental BFR group (EXP; n = 12) or a non-BFR control group (CON; n = 12) completed 7-weeks of resistance training comprising three sets of unilateral bicep curls [50% 1-repetition maximum (1-RM)], then four sets of bilateral knee extension and flexion exercises (30% 1-RM). EXP performed leg exercises with an applied BFR (60% limb occlusion pressure). 1-RM strength was measured using bilateral leg exercises and unilateral bicep curls in both trained and untrained arms. Muscle CSA was measured via peripheral quantitative computed tomography in the dominant leg and both arms. RESULTS: 1-RM in the trained arm increased more in EXP (2.5 ± 0.4 kg; mean ± SEM) than the contralateral untrained arm (0.8 ± 0.4 kg), and the trained arm of CON (0.6 ± 0.3 kg, P < 0.05). The increase in knee extension 1-RM was twofold that of CON (P < 0.01). Knee flexion 1-RM, leg CSA, and trained arm CSA increased similarly between groups (P > 0.05), while untrained arm CSA did not change (P > 0.05). CONCLUSION: Lower limb BFR training increased trained arm strength more than the contralateral untrained arm, and the trained arm of controls. However, there was no additional effect on muscle CSA. These findings support evidence for a BFR training-derived remote strength transfer that may be relevant to populations with localised movement disorders.

Characterization of the Testicular Toxicity of 3-Nitro-1,2,4-Triazol-5-One and 2,4-Dinitroanisole in Rats ( Rattus norvegicus).

Nitrotriazolone (3-nitro-1,2,4-triazol-5-one; NTO) and dinitroanisole (2,4-dinitroanisole; DNAN), insensitive energetic materials used in explosive formulations, have induced testicular toxicity and oligospermia in repeated-dose oral toxicity tests. To identify the target site of testicular toxicity of NTO and DNAN, Sprague Dawley rats were orally dosed with NTO (500 mg/kg/d) or DNAN (50 or 100 mg/kg/d) in corn oil for 1, 3, 7, or 14 days. Degeneration of germinal epithelium occurred in multiple tubule stages on days 7 and 14 in treated rats. Degeneration increased in severity with time and was characterized by degeneration/apoptosis of pachytene spermatocytes and round and elongating spermatids, depletion of step 19 spermatids, luminal spermatogenic cell sloughing, multinucleate cells, and pronounced Sertoli cell vacuolation. Serum luteinizing hormone and follicle-stimulating hormone did not differ between NTO- and DNAN-treated and control rats on any sampling day. Serum testosterone levels reduced only in rats given 50 mg/kg/d DNAN for 7 days. These results suggest that the initial site of testicular injury for both NTO and DNAN is the Sertoli cell.

Rhesus macaque and mouse models for down-selecting circumsporozoite protein based malaria vaccines differ significantly in immunogenicity and functional outcomes.

BACKGROUND: Non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. Transgenic rodent parasites expressing genes of human Plasmodium are now routinely used for efficacy studies of human malaria vaccines. Mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are sufficient to move a vaccine candidate into the clinic. METHODS: A comparison of immunogenicity, fine-specificity and functional activity of two Alum-adjuvanted Plasmodium falciparum circumsporozoite protein (CSP)-based vaccines was conducted in mouse and rhesus models. One vaccine was a soluble recombinant protein (CSP) and the other was the same CSP covalently conjugated to the Qß phage particle (Qß-CSP). RESULTS: Mice showed different kinetics of antibody responses and different sensitivity to the NANP-repeat and N-terminal epitopes as compared to rhesus. While mice failed to discern differences between the protective efficacy of CSP versus Qß-CSP vaccine following direct challenge with transgenic Plasmodium berghei parasites, rhesus serum from the Qß-CSP-vaccinated animals induced higher in vivo sporozoite neutralization activity. CONCLUSIONS: Despite some immunologic parallels between models, these data demonstrate that differences between the immune responses induced in the two models risk conflicting decisions regarding potential vaccine utility in humans. In combination with historical observations, the data presented here suggest that although murine models may be useful for some purposes, non-human primate models may be more likely to predict the human response to investigational vaccines.

Haemodynamics of aerobic and resistance blood flow restriction exercise in young and older adults.

PURPOSE: Light-load blood flow restriction exercise (BFRE) may provide a novel training method to limit the effects of age-related muscle atrophy in older adults. Therefore, the purpose of this study was to compare the haemodynamic response to resistance and aerobic BFRE between young adults (YA; n = 11; 22 ± 1 years) and older adults (OA; n = 13; 69 ± 1 years). METHOD: On two occasions, participants completed BFRE or control exercise (CON). One occasion was leg press (LP; 20 % 1-RM) and the other was treadmill walking (TM; 4 km h(-1)). Haemodynamic responses (HR, Q, SV and BP) were recorded during baseline and exercise. RESULT: At baseline, YA and OA were different for some haemodynamic parameters (e.g. BP, SV). The relative responses to BFRE were similar between YA and OA. Blood pressures increased more with BFRE, and also for LP over TM. Q increased similarly for BFRE and CON (in both LP and TM), but with elevated HR and reduced SV (TM only). CONCLUSION: While BFR conferred slightly greater haemodynamic stress than CON, this was lower for walking than leg-press exercise. Given similar response magnitudes between YA and OA, these data support aerobic exercise being a more appropriate BFRE for prescription in older adults that may contribute to limiting the effects of age-related muscle atrophy.

The Effect of Palmitoylethanolamide (PEA) on Skeletal Muscle Hypertrophy, Strength, and Power in Response to Resistance Training in Healthy Active Adults: A Double-Blind Randomized Control Trial.

BACKGROUND: Palmitoylethanolamide (PEA) has analgesic/anti-inflammatory properties that may be a suitable alternative to over-the-counter (OTC) non-steroidal analgesics/anti-inflammatories. While OTC pain medications can impair strength training adaptations, the mechanism of action of PEA is distinct from these and it may not negatively affect skeletal muscle adaptations to strength training. METHODS: The primary aim of this study was to investigate the effects of daily PEA supplementation (350 mg Levagen + equivalent to 300 mg PEA) combined with 8-weeks of resistance training on lean body mass with secondary aims addressing strength, power, sleep, and wellbeing compared to placebo (PLA) in young, healthy, active adults. In a randomized, controlled, double-blinded trial, 52 untrained, recreationally active participants aged 18-35 y were allocated to either the PEA or PLA groups. Participants consumed either 2 × 175 mg Levagen + PEA or identically matched maltodextrin capsules during an 8-week period of whole-body resistance training. This trial assessed the pre- to post- changes in total and regional lean body mass, muscular strength (1-RM bench, isometric mid-thigh pull), muscular power [countermovement jump (CMJ), bench throw], pain associated with exercise training, sleep, and wellbeing compared with the PEA or PLA condition. RESULTS: 48 Participants were included in the final intention to treat (ITT) analysis and we also conducted per protocol (PP) analysis (n = 42). There were no significant between-group differences for total or regional lean muscle mass post-intervention. There was a significantly higher jump height (CMJ) at week 10 in the PEA group compared to the PLA (Adjusted mean difference [95% CI] p-value; ITT: - 2.94 cm [- 5.15, - 0.74] p = 0.010; PP: - 2.93 cm [- 5.31, - 0.55] p = 0.017). The PLA group had higher 1-RM bench press post-intervention compared with the PEA group (ITT: 2.24 kg [0.12, 4.37] p = 0.039; PP: 2.73 kg [0.40, 5.06] p = 0.023). No significant treatment effects were noted for any of the other outcomes. CONCLUSION: PEA supplementation, when combined with 8 weeks of strength training, did not impair lean mass gains and it resulted in significantly higher dynamic lower-body power when compared with the PLA condition. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).

A randomised controlled trial assessing the potential of palmitoylethanolamide (PEA) to act as an adjuvant to resistance training in healthy adults: a study protocol.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics are used frequently by athletes either prophylactically for the prevention of pain, or to accelerate recovery following an injury. However, these types of pain management strategies have been shown to inhibit signalling pathways (e.g., cyclooxygenase-2) that may hinder muscular adaptations such as hypertrophy and strength. Nutraceuticals such as palmitoylethanolamide (PEA) have analgesic properties that act via different mechanisms to NSAIDS/analgesics. Furthermore, PEA has been shown to have a positive effect on sleep and may contribute positively to muscle hypertrophy via PKB activation. Although PEA has not been widely studied in the athletic or recreationally active population, it may provide an alternative solution for pain management if it is found not to interfere with, or enhance training adaptations. Therefore, the study aim is to investigate the effects of daily PEA supplementation (Levagen + ®) with resistance training on lean body mass, strength, power and physical performance and outcomes of recovery (e.g., sleep) compared to placebo. METHODS: This double-blind, randomised controlled study will take place over an 11-week period (including 8-weeks of progressive resistance training). Participants for this study will be 18-35 years old, healthy active adults that are not resistance trained. Participants will attend a familiarisation (week 0), pre-testing (week 1) and final-testing (week 11). At the pre-testing and final-testing weeks, total lean body mass (dual-energy X-ray absorptiometry; DXA), total mid-thigh cross sectional area (pQCT), maximal muscular strength (1 repetition maximum bench press, isometric mid-thigh pull) and power (countermovement jump and bench throw) will be assessed. Additionally, circulating inflammatory cytokines and anabolic hormones, sleep quality and quantity (ActiGraph), pain and subjective wellbeing (questionnaires) will also be examined. DISCUSSION: This study is designed to investigate the effects that PEA may have on pre-to post intervention changes in total body and regional lean muscle mass, strength, power, sleep, subjective wellbeing, and pain associated with resistance training and menstruation compared with the placebo condition. Unlike other NSAIDs and analgesics, which may inhibit muscle protein synthesis and training adaptations, PEA which provides analgesia via alternative mechanisms may provide an alternative pain management solution. It is therefore important to determine if this analgesic compound interferes with or enhances training adaptations so that athletes and active individuals can make an informed decision on their pain management strategies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).

Muscle Adaptations to Heavy-Load and Blood Flow Restriction Resistance Training Methods.

Resistance-based blood flow restriction training (BFRT) improves skeletal muscle strength and size. Unlike heavy-load resistance training (HLRT), there is debate as to whether strength adaptations following BFRT interventions can be primarily attributed to concurrent muscle hypertrophy, as the magnitude of hypertrophy is often minor. The present study aimed to investigate the effect of 7 weeks of BFRT and HLRT on muscle strength and hypertrophy. The expression of protein growth markers from muscle biopsy samples was also measured. Male participants were allocated to moderately heavy-load training (HL; n = 9), low-load BFRT (LL + BFR; n = 8), or a control (CON; n = 9) group to control for the effect of time. HL and LL + BFR completed 21 training sessions (3 d.week-1) comprising bilateral knee extension and knee flexion exercises (HL = 70% one-repetition maximum (1-RM), LL + BFR = 20% 1-RM + blood flow restriction). Bilateral knee extension and flexion 1-RM strength were assessed, and leg muscle CSA was measured via peripheral quantitative computed tomography. Protein growth markers were measured in vastus lateralis biopsy samples taken pre- and post the first and last training sessions. Biopsy samples were also taken from CON at the same time intervals as HL and LL + BFR. Knee extension 1-RM strength increased in HL (19%) and LL + BFR (19%) but not CON (2%; p < 0.05). Knee flexion 1-RM strength increased similarly between all groups, as did muscle CSA (50% femur length; HL = 2.2%, LL + BFR = 3.0%, CON = 2.1%; TIME main effects). 4E-BP1 (Thr37/46) phosphorylation was lower in HL and LL + BFR immediately post-exercise compared with CON in both sessions (p < 0.05). Expression of other growth markers was similar between groups (p > 0.05). Overall, BFRT and HLRT improved muscle strength and size similarly, with comparable changes in intramuscular protein growth marker expression, both acutely and chronically, suggesting the activation of similar anabolic pathways. However, the low magnitude of muscle hypertrophy was not significantly different to the non-training control suggesting that strength adaptation following 7 weeks of BFRT is not driven by hypertrophy, but rather neurological adaptation.

Urban policy interventions to reduce traffic emissions and traffic-related air pollution: Protocol for a systematic evidence map.

INTRODUCTION: Cities are the world's engines of economic growth, innovation, and social change, but they are also hot spots for human exposure to air pollution, mainly originating from road traffic. As the urban population continues to grow, a greater quantity of people risk exposure to traffic-related air pollution (TRAP), and therefore also risk adverse health effects. In many cities, there is scope for further improvement in air quality through targeted urban policy interventions. The objective of this protocol is to detail the methods that will be used for a systematic evidence map (SEM) which will identify and characterize the evidence on policy interventions that can be implemented at the urban-level to reduce traffic emissions and/or TRAP from on-road mobile sources, thus reducing human exposures and adverse health impacts. METHODS: Articles will be searched for and selected based on a predetermined search strategy and eligibility criteria. A variety of databases will be searched for relevant articles published in English between January 1, 2000 and June 1, 2020 to encompass the interdisciplinary nature of this SEM, and articles will be stored and screened using Rayyan QCRI. Predetermined study characteristics will be extracted and coded from included studies in a Microsoft Excel sheet, which will serve as an open access, interactive database, and two authors will review the coded data for consistency. The database will be queryable, and various interactive charts, graphs, and maps will be created using Tableau Public for data visualization. The results of the evidence mapping will be detailed via narrative summary. CONCLUSION: This protocol serves to increase transparency of the SEM methods and provides an example for researchers pursuing future SEMs.