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Chronic wounds are becoming an increasing burden on healthcare services, as they have extended healing times and are susceptible to infection, with many failing to heal, which can lead ultimately to amputation. Due to the additional rise in antimicrobial resistance and emergence of difficult-to-treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE pathogens), novel treatments will soon be required asides from traditional antibiotics. Many natural substances have been identified as having the potential to aid in both preventing infection and increasing the speed of wound closure processes. Manuka honey is already in some cases used as a topical treatment in the form of ointments, which in conjunction with dressings and fish skin grafts are an existing US Food and Drug Administration-approved treatment option. These existing treatment options indicate that fatty acids from fish oil and manuka honey are well tolerated by the body, and if the active components of the treatments were better understood, they could make valuable additions to topical treatment options. This review considers two prominent natural substances with established manufacturing and global distribution-marine based fatty acids (including their metabolites) and manuka honey-their function as antimicrobials and how they can aid in wound repair, two important aspects leading to resolution of chronic wounds.

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Both honey and fish oil have been historically used in medicine and identified as having antimicrobial properties. Although analyses of the substances have identified different components within them, it is not fully understood how these components interact and contribute to the observed effect. With the increase in multi-drug resistant strains of bacteria found in infections, new treatment options are needed. This study aimed to assess the antimicrobial abilities of fish oil components, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and derived resolvins (RvE1, RvD2, and RvD3), as well as two varieties of manuka honey, against a panel of medically relevant microorganisms and antimicrobial resistant organisms, such as Methicillin Resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were identified; further minimum biofilm eradication concentrations (MBEC) were investigated for responsive organisms, including S. aureus, E. coli, Staphylococcus epidermidis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Concurrent with the existing literature, manuka honey was found to be a broad-spectrum antimicrobial with varied potency according to methylglyoxal content. DHA and EPA were both effective against Gram-positive and negative bacteria, but some drug-resistant strains or pathogens were not protected by a capsule. Only E. coli was inhibited by the resolvins.

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Pulmonary rehabilitation programmes including aerobic training improve cardiorespiratory fitness in patients with COPD, but the optimal programme design is unclear. We used random effects additive component network meta-analysis to investigate the relative effectiveness of different programme components on fitness measured by V̇O2peak in COPD. The included 59 studies involving 2191 participants demonstrated that V̇O2peak increased after aerobic training of at least moderate intensity with the greatest improvement seen following high intensity training. Lower limb aerobic training (SMD 0.56 95% CI 0.32;0.81, intervention arms=86) and the addition of non-invasive ventilation (SMD 0.55 95% CI 0.04;1.06, intervention arms=4) appeared to offer additional benefit but there was limited evidence for effectiveness of other exercise and non-exercise components.

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Physical inactivity and a poor diet increase systemic inflammation, while chronic inflammation can be reduced through exercise and nutritional interventions. The mechanisms underlying the impacts of lifestyle interventions on inflammation remain to be fully explained; however, epigenetic modifications may be critical. The purpose of our study was to investigate the impacts of eccentric resistance exercise and fatty acid supplementation on DNA methylation and mRNA expression of TNF and IL6 in skeletal muscle and leukocytes. Eight non-resistance exercise-trained males completed three bouts of isokinetic eccentric contractions of the knee extensors. The first bout occurred at baseline, the second occurred following a three-week supplementation of either omega-3 polyunsaturated fatty acid or extra virgin olive oil and the final bout occurred after eight-weeks of eccentric resistance training and supplementation. Acute exercise decreased skeletal muscle TNF DNA methylation by 5% (p = 0.031), whereas IL6 DNA methylation increased by 3% (p = 0.01). Leukocyte DNA methylation was unchanged following exercise (p > 0.05); however, three hours post-exercise the TNF DNA methylation decreased by 2% (p = 0.004). In skeletal muscle, increased TNF and IL6 mRNA expression levels were identified immediately post-exercise (p < 0.027); however, the leukocyte mRNA expression was unchanged. Associations between DNA methylation and markers of exercise performance, inflammation and muscle damage were identified (p < 0.05). Acute eccentric resistance exercise is sufficient to induce tissue-specific DNA methylation modifications to TNF and IL6; however, neither eccentric training nor supplementation was sufficient to further modify the DNA methylation.

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The start in swimming is a crucial phase of a race, where improvements in performance can be made. Twenty-four elite swimmers race pace starts were recorded from five above and below water 50 Hz video cameras. Body position at toe off was calculated from the recordings and consisted of the two-dimensional mass centre position at toe off, and the arm, trunk, front leg and rear leg angles.Horizontal, vertical and resultant velocity of the mass centre at toe off, time to 5 m, 10 m and 15 m were also determined. Whilst time to 5 m (starting performance) differed by 0.17 s between genders, body position at toe off showed no significant differences. The difference in start performance was mainly due to a difference in horizontal velocity at toe off. The relationship between arm angle and start performance warrants further investigation as there was a range of techniques adopted but no clear link to performance. The trunk angle at toe off was correlated to starting performance for both males and females. This study demonstrates that the body position at toe off is no different between genders but is a critical determinant of starting performance for both males and females.

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Exhaled volatile organic compounds (VOCs) are of interest due to their minimally invasive sampling procedure. Previous studies have investigated the impact of exercise, with evidence suggesting that breath VOCs reflect exercise-induced metabolic activity. However, these studies have yet to investigate the impact of maximal exercise to exhaustion on breath VOCs, which was the main aim of this study. Two-litre breath samples were collected onto thermal desorption tubes using a portable breath collection unit. Samples were collected pre-exercise, and at 10 and 60 min following a maximal exercise test (VO2MAX). Breath VOCs were analysed by thermal desorption-gas chromatography-mass spectrometry using a non-targeted approach. Data showed a tendency for reduced isoprene in samples at 10 min post-exercise, with a return to baseline by 60 min. However, inter-individual variation meant differences between baseline and 10 min could not be confirmed, although the 10 and 60 min timepoints were different (p = 0.041). In addition, baseline samples showed a tendency for both acetone and isoprene to be reduced in those with higher absolute VO2MAX scores (mL(O2)/min), although with restricted statistical power. Baseline samples could not differentiate between relative VO2MAX scores (mL(O2)/kg/min). In conclusion, these data support that isoprene levels are dynamic in response to exercise.

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Identifying the characteristics of bacterial species can improve treatment outcomes and mass spectrometry methods have been shown to be capable of identifying biomarkers of bacterial species. This study is the first to use volatile atmospheric pressure chemical ionisation mass spectrometry to directly and non-invasively analyse the headspace of E. coli and S. aureus bacterial cultures, enabling major biological classification at species level (Gram negative/positive respectively). Four different protocols were used to collect data, three utilising discrete 5 min samples taken between 2 and 96 h after inoculation and one method employing 24 h continuous sampling. Characteristic marker ions were found for both E. coli and S. aureus. A model to distinguish between sample types was able to correctly identify the bacteria samples after sufficient growth (24-48 h), with similar results obtained across different sampling methods. This demonstrates that this is a robust method to analyse and classify bacterial cultures accurately and within a relevant time frame, offering a promising technique for both clinical and research applications.

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BACKGROUND: Fatty acids, specifically polyunsaturated fatty acids (PUFAs) play an important role in inflammation and its resolution, however, their interaction with the epigenome is relatively unexplored. Here we investigate the relationship between circulating blood fatty acids and the DNA methylation of the cytokine encoding gene tumour necrosis factor (TNF, OMIM 191160). METHODS: Using a cross-sectional study approach, we collected blood samples from adults (N=88 (30 males, 58 females); 18-74 years old) for DNA methylation pyrosequencing analysis at four sites in TNF exon 1 and gas-chromatography mass-spectrometry analysis of the fatty acid profile of dried blood spots (DBS). RESULTS: Methylation levels of TNF exon 1 are significantly correlated with specific fatty acids in a gender-specific manner. In the males the PUFAs Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) were positively associated with TNF methylation, as was the saturated fatty acid (SFA) Stearic Acid; in contrast, mono-unsaturated fatty acids (MUFAs) had a negative association. In the females, omega-6 PUFA γ-Linolenic acid (GLA) was negatively correlated with TNF methylation; Adrenic acid and Eicosadienoic Acid were positively correlated with TNF methylation. CONCLUSION: These results suggest that one way that fatty acids interact with the inflammation is through altered methylation profiles of cytokine genes; thus, providing potential therapeutic targets for nutritional and health interventions.

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BACKGROUND: Eccentric cycling (ECC) may be an attractive exercise method in COPD because of both low cardiorespiratory demand and perception of effort compared with conventional concentric cycling (CON) at matched mechanical loads. However, it is unknown whether ECC can be performed by individuals with COPD at an intensity able to cause sufficient metabolic stress to improve aerobic capacity. RESEARCH QUESTION: What are the cardiopulmonary and metabolic responses to ECC in people with COPD and healthy volunteers when compared with CON at matched mechanical loads? STUDY DESIGN AND METHODS: Thirteen people with COPD (mean ± SD age, 64 ± 9 years; FEV1, 45 ± 19% predicted; BMI, 24 ± 4 kg/m2; oxygen uptake at peak exercise [V̇O2peak], 15 ± 3 mL/kg/min) and 9 age-matched control participants (FEV1, 102 ± 13% predicted; BMI, 28 ± 5 kg/m2; V̇O2peak, 23 ± 5 mL/kg/min), performed up to six 4-min bouts of ECC and CON at matched mechanical loads of increasing intensity. In addition, 12 individuals with COPD underwent quadriceps muscle biopsies before and after 20 min of ECC and CON at 65% peak power. RESULTS: At matched mechanical loads, oxygen uptake, minute ventilation, heart rate, systolic BP, respiratory exchange ratio (all P < .001), capillary lactate, perceived breathlessness, and leg fatigue (P < .05) were lower in both groups during ECC than CON. Muscle lactate content increased (P = .008) and muscle phosphocreatine decreased (P = .012) during CON in COPD, which was not evident during ECC. INTERPRETATION: Cardiopulmonary and blood lactate responses during submaximal ECC were less compared with during CON at equivalent mechanical workloads in healthy participants and COPD patients, and this was confirmed at a muscle level in COPD patients. Submaximal ECC was well tolerated and allowed greater mechanical work at lower ventilatory cost. However, in people with COPD, a training intervention based on ECC is unlikely to stimulate cardiovascular and metabolic adaptation to the same extent as CON.

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BACKGROUND: Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (V˙O2peak) with aerobic training. RESEARCH QUESTION: The goal of this study was to investigate the effect of aerobic training and exercise prescription on V˙O2peak in COPD. STUDY DESIGN AND METHODS: A systematic review was performed by using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases for all studies measuring V˙O2peak prior to and following supervised lower-limb aerobic training in COPD. A random effects meta-analysis limited to randomized controlled trials comparing aerobic training vs usual care was conducted. Other study designs were included in a secondary meta-analysis and meta-regression to investigate the influence of program and patient factors on outcome. RESULTS: A total of 112 studies were included (participants, N = 3,484): 21 controlled trials (n = 489), of which 13 were randomized (n = 288) and 91 were uncontrolled (n = 2,995) studies. Meta-analysis found a moderate positive change in V˙O2peak (standardized mean difference, 0.52; 95% CI, 0.34-0.69) with the intervention. The change in V˙O2peak was positively associated with target duration of exercise session (P = .01) and, when studies > 1 year duration were excluded, greater total volume of exercise training (P = .01). Similarly, the change in V˙O2peak was greater for programs > 12 weeks compared with those 6 to 12 weeks when adjusted for age and sex. However, reported prescribed exercise intensity (P = .77), training modality (P > .35), and mode (P = .29) did not affect V˙O2peak. Cohorts with more severe airflow obstruction exhibited smaller improvements in V˙O2peak (P < .001). INTERPRETATION: Overall, people with COPD achieved moderate improvements in V˙O2peak through supervised aerobic training. There is sufficient evidence to show that programs with greater total exercise volume, including duration of exercise session and program duration, are more effective. Reduced effects in severe disease suggest alternative aerobic training methods may be needed in this population. CLINICAL TRIAL REGISTRATION: PROSPERO; No.: CRD42018099300; URL: https://www.crd.york.ac.uk/prospero/.

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OBJECTIVE: Epigenetics has been described as one of the most exciting areas of contemporary biology, and research has begun to explore whether epigenetic modifications are influenced by psychological processes. The present research explored the associations of health-related motivation and behavior with the DNA methylation of tumor necrosis factor (TNF) gene. METHOD: Participants (N = 88) completed questionnaires examining engagement with health-related behavior (i.e., physical activity, diet, and smoking) and health-related motivation from the perspective of self-determination theory. They also provided a capillary blood sample for DNA extraction and analysis of four CpG sites via bisulfite conversion within Exon 1 of TNF. RESULTS: Health-related autonomous motivation was weakly but positively associated with TNF methylation (ß = .18, p = .08). Indirect effects were identified in a subsequent step; autonomous motivation was positively associated with fruit consumption (ß = .29, p = .004), negatively associated with smoking (ß = -.22, p = .03), but not associated with physical activity (ß = .10, p = .34). Moreover, TNF methylation was positively associated with lifetime physical activity (ß = .18, p = .08) and negatively associated with smoking (ß = -.23, p = .03). Direct effects of autonomous motivation on DNA methylation did not persist when these indirect effects were included (ß = .09, p = .43). CONCLUSIONS: Results support the idea that autonomous motivation is associated with DNA methylation, albeit indirectly through tobacco consumption. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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Chlorine-based disinfectants protect pool water from pathogen contamination but produce potentially harmful halogenated disinfection by-products (DBPs). This study characterized the bioaccumulation and elimination of exhaled DBPs post-swimming and investigated changes in exhaled breath profiles associated with chlorinated pool exposure. Nineteen participants provided alveolar-enriched breath samples prior to and 5, 90, 300, 510, and 600 minutes post-swimming. Known DBPs associated with chlorinated water were quantitated by thermal desorption-gas chromatography-mass spectrometry. Two distinct exhaled DBP elimination profiles were observed. Most participants (84%) reported peak concentrations immediately post-swimming that reduced exponentially. A sub-group exhibited a previously unobserved and delayed washout profile with peak levels at 90 minutes post-exposure. Metabolomic investigations tentatively identified two candidate biomarkers associated with swimming pool exposure, demonstrating an upregulation in the hours after exposure. These data demonstrated a hitherto undescribed exhaled DBP elimination profile in a small number of participants which contrasts previous findings of uniform accumulation and exponential elimination. This sub-group which exhibited delayed peak-exhaled concentrations suggests the uptake, processing, and immediate elimination of DBPs are not ubiquitous across individuals as previously understood. Additionally, non-targeted metabolomics highlighted extended buildup of compounds tentatively associated with swimming in a chlorinated pool environment that may indicate airway responses to DBP exposure.

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An indium-mediated isomerization of 1,4-dienols to 1,3-dienols is described. This procedure consists of the addition of pentadienylindium, in a protic solvent, to aldehydes giving the kinetic γ-allylation product in high yields. The subsequent conversion of this γ-allylation product to its thermodynamic 1,3-dienol α-isomer can be achieved by its exposure to indium triflate in the presence of a substoichiometric amount of aldehyde at room temperature. This transformation exhibited moderate to good substrate scope and has been shown to proceed by a 2-oxonia Cope rearrangement.

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Compact mass spectrometry (CMS) is a versatile and transportable analytical instrument that has the potential to be used in clinical settings to quickly and non-invasively detect a wide range of relevant conditions from breath samples. The purpose of this study is to optimise data preprocessing protocols by three proposed methods of breath sampling, using the CMS. It also lays out a general framework for which data processing methods can be evaluated. METHODS: This paper considers data from three previous studies, each using a different breath sampling method. These include a peppermint washout study using continuous breath sampling with a purified air source, an exercise study using continuous breath sampling with an ambient air source, and a single breath sampling study with an ambient air source. For each dataset, different breath selection (data preprocessing) methods were compared and benchmarked according to predictive performance on a validation set and quantitative reliability of m/z bin intensity measurements. RESULTS: For both continuous methods, the best breath selection method improved the predictive model compared to no preselection, as measured by the 95% CI range for Youden's index, from 0.68-0.86 to 0.86-0.97 for the exercise study and 0.69-0.82 to 1.00-1.00 for the peppermint study. The reliability of intensity measurements for both datasets (as measured by median relative standard deviation (RSD)), was improved slightly by the best selection method compared to no preselection, from 18% to 14% for the exercise study and 7%-5% for the peppermint study. For the single breath samples, all the models resulted in perfect prediction, with a 95% CI range for Youden's index of 1.00-1.00. The reliability of the proposed method was 38%. CONCLUSION: The method of selecting exhaled breath from CMS data can affect the reliability of the measurement and the ability to distinguish between breath samples taken under different conditions. The application of appropriate data processing methods can improve the quality of the data and results obtained from CMS. The methods presented will enable untargeted analysis of breath VOCs using CMS to be performed.

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Redox enzymes modulate intracellular redox balance and are secreted in response to cellular oxidative stress, potentially modulating systemic inflammation. Both aerobic and resistance exercise are known to cause acute systemic oxidative stress and inflammation; however, how redox enzyme concentrations alter in extracellular fluids following bouts of either type of exercise is unknown. Recreationally active men (n = 26, mean ± SD: age 28 ± 8 yr) took part in either: 1) two separate energy-matched cycling bouts: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE) or 2) an eccentric-based resistance exercise protocol (RES). Alterations in plasma (study 1) and serum (study 2) peroxiredoxin (PRDX)-2, PRDX-4, superoxide dismutase-3 (SOD3), thioredoxin (TRX-1), TRX-reductase and interleukin (IL)-6 were assessed before and at various timepoints after exercise. There was a significant increase in SOD3 (+1.5 ng/mL) and PRDX-4 (+5.9 ng/mL) concentration following HIIE only, peaking at 30- and 60-min post-exercise respectively. TRX-R decreased immediately and 60 min following HIIE (-7.3 ng/mL) and MOD (-8.6 ng/mL), respectively. In non-resistance trained men, no significant changes in redox enzyme concentrations were observed up to 48 h following RES, despite significant muscle damage. IL-6 concentration increased in response to all trials, however there was no significant relationship between absolute or exercise-induced changes in redox enzyme concentrations. These results collectively suggest that HIIE, but not MOD or RES increase the extracellular concentration of PRDX-4 and SOD3. Exercise-induced changes in redox enzyme concentrations do not appear to directly relate to systemic changes in IL-6 concentration.NEW & NOTEWORTHY Two studies were conducted to characterize changes in redox enzyme concentrations after single bouts of exercise to investigate the emerging association between extracellular redox enzymes and inflammation. We provide evidence that SOD3 and PRDX-4 concentration increased following high-intensity aerobic but not eccentric-based resistance exercise. Changes were not associated with IL-6. The results provide a platform to investigate the utility of SOD3 and PRDX-4 as biomarkers of oxidative stress following exercise.

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Lifestyle interventions, including exercise and dietary supplementation, can modify DNA methylation and exert health benefits; however, the underlying mechanisms are poorly understood. Here we investigated the impact of acute aerobic exercise and the supplementation of omega-3 polyunsaturated fatty acids (n-3 PUFA) and extra virgin olive oil (EVOO) on global and gene-specific (PPARGC1A, IL6 and TNF) DNA methylation, and DNMT mRNA expression in leukocytes of disease-free individuals. Eight trained male cyclists completed an exercise test before and after a four-week supplementation of n-3 PUFA and EVOO in a double-blind, randomised, repeated measures design. Exercise triggered global hypomethylation (Pre 79.2%; Post 78.7%; p = 0.008), alongside, hypomethylation (Pre 6.9%; Post 6.3%; p < 0.001) and increased mRNA expression of PPARGC1A (p < 0.001). Associations between PPARGC1A methylation and exercise performance were also detected. An interaction between supplement and trial was detected for a single CpG of IL6 indicating increased DNA methylation following n-3 PUFA and decreased methylation following EVOO (p = 0.038). Global and gene-specific DNA methylation associated with markers of inflammation and oxidative stress. The supplementation of EVOO reduced DNMT1 mRNA expression compared to n-3 PUFA supplementation (p = 0.048), whereas, DNMT3a (p = 0.018) and DNMT3b (p = 0.046) mRNA expression were decreased following exercise. In conclusion, we demonstrate that acute exercise and dietary supplementation of n-3 PUFAs and EVOO induce DNA methylation changes in leukocytes, potentially via the modulation of DNMT mRNA expression. Future studies are required to further elucidate the impact of lifestyle interventions on DNA methylation.

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Resolution of inflammation is now known to be an active process which in part is instigated and controlled by specialized pro-resolving lipid mediators (SPM's) derived from dietary omega-3 fatty acids. Resolvin E1 (Rv E1 ) is one of these SPM's derived from the omega-3 fatty acid eicosapentaenoic acid. Using both molecular and phenotypic functional measures we report that in a model of Lipopolysaccharide (LPS) induced inflammation, Rv E1 attenuated mRNA levels of both interlukin-6 and monocyte chemoattractant protein-1 whilst having no effect on tumor necrosis factor-α or interlukin-1ß in C2C12 skeletal muscle myotubes. Findings at the molecular level were transferred into similar changes in extracellular protein levels of the corresponding genes with the greatest attenuation being noted in IL-6 protein concentrations. Rv E1 instigated beneficial morphological changes through the prevention of LPS induced skeletal muscle atrophy, in tandem with attenuation of the LPS induced reduction in contractile force in tissue engineered skeletal muscle. These findings demonstrate, in our model of endotoxin induced inflammation in skeletal muscle, that Rv E1 has pro-resolving properties in this cell type. Our data provides rationale for further investigation into the mechanistic action of Rv E1 in skeletal muscle, with the vision of having potential benefits for the prevention/resolution of in-vivo skeletal muscle atrophy.

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BACKGROUND: Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α -308 (G/A), TNF-ß +252 (A/G), IL-6 -174 (G/C) and IL-6 -597 (G/A), and IFN-É£ +874 (T/A) with coronary artery disease (CAD) among north Indian patients. MATERIALS AND METHODS: 143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-α -308 (G/A) (rs1800797), TNF-ß +252 (A/G) (rs909253), IL-6 -174 (G/C) (rs1800795), IL6 -597 (G/A) (rs1800797), and IFN-É£ +874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p≤0.05 was considered significant. RESULTS: Significant risk association with CAD was found for TNF-α -308 (G/A) "A" allele (OR=5.6, CI 1.8-17.4, p=0.001) and TNF-ß +252 (A/G) "G" allele (OR=3.4, CI=1.9-6.0, p<0.001). However, no statistical significance was found for IL-6 -174 (G/C) or IL6 -597 (G/A), with CAD. TNF-α -308 (G/A), and TNF-ß +252 (A/G) haplotype "GG" "AG" increased CAD risk significantly (GG haplotype, adjusted OR=2.6, CI 1.4-5.0, p=0.003 and AG haplotype OR=8.5, CI 2.2-33.35, p=0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet. DISCUSSION: The present study found significant risk association for TNF-α -308 (G/A), and TNF-ß +252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population.

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