Relationships between nitric oxide biomarkers and physiological outcomes following dietary nitrate supplementation.

Dietary nitrate (NO3-) supplementation can increase nitric oxide (NO) bioavailability, reduce blood pressure (BP) and improve muscle contractile function in humans. Plasma nitrite concentration (plasma [NO2-]) is the most oft-used biomarker of NO bioavailability. However, it is unclear which of several NO biomarkers (NO3-, NO2-, S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle correlate with the physiological effects of acute and chronic dietary NO3- supplementation. Using a randomized, double-blind, crossover design, 12 participants (9 males) consumed NO3--rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3--depleted placebo beetroot juice (PL) acutely and then chronically (for two weeks). Biological samples were collected, resting BP was assessed, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5-3.5 h following supplement ingestion on day 1 and day 14. Diastolic BP was significantly lower in BR (-2 ± 3 mmHg, P = 0.03) compared to PL following acute supplementation, while the absolute rate of torque development (RTD) was significantly greater in BR at 0-30 ms (39 ± 57 N m s-1, P = 0.03) and 0-50 ms (79 ± 99 N m s-1, P = 0.02) compared to PL following two weeks supplementation. Greater WB [RSNOs] rather than plasma [NO2-] was correlated with lower diastolic BP (r = -0.68, P = 0.02) in BR compared to PL following acute supplementation, while greater skeletal muscle [NO3-] was correlated with greater RTD at 0-30 ms (r = 0.64, P=0.03) in BR compared to PL following chronic supplementation. We conclude that [RSNOs] in blood, and [NO3-] in skeletal muscle, are relevant biomarkers of NO bioavailability which are related to the reduction of BP and the enhanced muscle contractile function following dietary NO3- ingestion in humans.

Inequality of opportunity in the double burden of malnutrition in Mexico.

This paper proposes a pseudo-birth-cohort approach to deal with a lack of longitudinal data to measure health inequities over time. Using Roemer's framework for inequality of opportunity, this study measures ex-ante and ex-post inequalities in malnutrition, a concept that spans both sides of the nutrition continuum. The total contribution of observed circumstances and the direct contribution of observed efforts to the variation of malnutrition are disentangled for people born between 1983 and 1988 in Mexico. Results indicate that inequality of opportunity has been persistent across this 30-year lifespan for that cohort. Some evidence suggests that a lack of opportunities has been transmitted from parents to children and that people's circumstances account for most of the explained variation in the double burden of malnutrition. However, stratifying the analysis by sex shows that efforts account for more of the explained variation of inequality of opportunity for women in their middle adulthood than for men in most of the outcomes analyzed.

Different categories of VO2 kinetics in the 'extreme' exercise intensity domain.

The aim of this study was to classify potential sub-zones within the extreme exercise domain. Eight well-trained male cyclists participated in this study. The upper boundary of the severe exercise domain (Pupper-bound) was estimated by constant-work-rate tests. Then three further extreme-work-rate tests were performed in discrete regions within the extreme domain: extreme-1) at a work-rate greater than the Pupper-bound providing an 80-110-s time to task failure; extreme-2) a 30-s maximal sprint; and extreme-3) a 4-s maximal sprint. Different functions were used to describe the behaviour of the V˙O2 kinetics over time. V˙O2 on-kinetics during extreme-1 exercise was best described by a single-exponential model (R2 ≥ 0.97; SEE ≤ 0.10; p < 0.001), and recovery V˙O2 decreased immediately after the termination of exercise. In contrast, V˙O2 on-kinetics during extreme-2 exercise was best fitted by a linear function (R2 ≥ 0.96; SEE ≤ 0.16; p < 0.001), and V˙O2 responses continued to increase during the first 10-20 s of recovery. During the extreme-3 exercise, V˙O2 could not be modelled due to inadequate data, and there was an M-shape recovery V˙O2 response with an exponential decay at the end. The V˙O2 response to exercise across the extreme exercise domain has distinct features and must therefore be characterised with different fitting strategies in order to describe the responses accurately.

Neurovascular complications post bronchial artery embolisation in patients with cystic fibrosis. A 7-year single centre retrospective review.

Bronchial artery embolisation (BAE) is a treatment used to manage haemoptysis. We performed a 7-year review of BAE procedures for haemoptysis at our CF centre aiming to evaluate the incidence and outcomes of patients with neurovascular complications post-BAE. Our review suggests that whilst BAE is an effective method for controlling life-threatening haemoptysis, patients are at risk of developing neurovascular complications with long term residual symptoms, and therefore careful consideration should be given in offering BAE, especially to otherwise well patients with chronic small volume haemoptysis and managing teams should have a low threshold to image symptomatic patients.

Effect of Supplemental Oxygen on Physiological Responses to Exercise in Fibrotic Interstitial Lung Disease.

PURPOSE: We studied the effect of O2 supplementation on physiological response to exercise in patients with moderate to severe interstitial lung disease (ILD). METHODS: 13 patients (age 66 ± 10 yrs., 7 males) with ILD (TLC 71 ± 22% predicted, carbon monoxide diffusion capacity (DLCO) 44 ± 16% predicted) and 13 healthy individuals (age 50 ± 17 yrs., 7 males) were tested. ILD patients performed symptom-limited cardiopulmonary exercise tests and constant work-rate tests (CWRTs) at 80% of the work-rate (WR) at the gas exchange threshold (GET). Tests breathing room air (RA, 21% O2) were compared to tests performed breathing 30% O2. Oxygen-uptake (V̇O2) kinetics were calculated from the CWRT results. RESULTS: In the ILD group, peak WR, peak V̇O2 and V̇O2 at the GET improved significantly when breathing 30% O2 compared to RA (mean ± SD 66 ± 23 vs 75 ± 26 watts, 15 ± 2 vs 17 ± 4 ml/kg/min and 854 ± 232 vs 932 ± 245 ml/min; p = 0.004, p = 0.001 and p = 0.01, respectively). O2 saturation (SPO2%) at peak exercise was higher with 30% O2 (97 ± 4% vs 88 ± 9%, p = 0.002). The time constant (tau) of V̇O2 kinetics was faster in ILD patients while breathing 30% O2 (41 ± 10 sec) compared to RA (52 ± 14 sec, p = 0.003). There was a negative linear relation between tau and SPO2% with RA (r = -0.76, p = 0.006) and while breathing 30% O2 (r = -0.68, p = 0.02). CONCLUSIONS: Using a clinically applicable level of O2 supplementation (30%) improved maximal, aerobic exercise capacity and V̇O2 kinetics in ILD patients, likely due to increased blood O2 content subsequently increasing the O2 delivery to the working muscles.

Localisation of nitrate-reducing and highly abundant microbial communities in the oral cavity.

The nitrate (NO3-) reducing bacteria resident in the oral cavity have been implicated as key mediators of nitric oxide (NO) homeostasis and human health. NO3--reducing oral bacteria reduce inorganic dietary NO3- to nitrite (NO2-) via the NO3--NO2--NO pathway. Studies of oral NO3--reducing bacteria have typically sampled from either the tongue surface or saliva. The aim of this study was to assess whether other areas in the mouth could contain a physiologically relevant abundance of NO3- reducing bacteria, which may be important for sampling in clinical studies. The bacterial composition of seven oral sample types from 300 individuals were compared using a meta-analysis of the Human Microbiome Project data. This analysis revealed significant differences in the proportions of 20 well-established oral bacteria and highly abundant NO3--reducing bacteria across each oral site. The genera included Actinomyces, Brevibacillus, Campylobacter, Capnocytophaga, Corynebacterium, Eikenella, Fusobacterium, Granulicatella, Haemophilus, Leptotrichia, Microbacterium, Neisseria, Porphyromonas, Prevotella, Propionibacterium, Rothia, Selenomonas, Staphylococcus, Streptococcus and Veillonella. The highest proportion of NO3--reducing bacteria was observed in saliva, where eight of the bacterial genera were found in higher proportion than on the tongue dorsum, whilst the lowest proportions were found in the hard oral surfaces. Saliva also demonstrated higher intra-individual variability and bacterial diversity. This study provides new information on where samples should be taken in the oral cavity to assess the abundance of NO3--reducing bacteria. Taking saliva samples may benefit physiological studies, as saliva contained the highest abundance of NO3- reducing bacteria and is less invasive than other sampling methods. These results inform future studies coupling oral NO3--reducing bacteria research with physiological outcomes affecting human health.

Association Between Elevated Blood Eosinophils and Chronic Kidney Disease Progression: Analyses of a Large United States Electronic Health Records Database.

Background: Blood eosinophils can increase in response to infection, inflammation, and hypersensitivity reactions, yet their involvement in the progression of chronic kidney disease (CKD) is poorly understood. This study explores the relationship between blood eosinophils and CKD progression among patients in a real-world setting. Methods: This retrospective study analyzed data obtained from the Optum® de-identified electronic health records dataset in the United States. Patients diagnosed with CKD stage 3 or 4 (International Classification of Diseases diagnosis code or estimated glomerular filtration rate [eGFR] <60 mL/min) between January 2011 and March 2018 were included and followed until progression to the next CKD stage, death, or dropout. The primary objective of this study was to assess the relationship between blood eosinophil counts (bEOS) and CKD progression, adjusting for clinical and demographic features as well as known risk factors for CKD stages 3-4. The primary outcomes were CKD progression and all-cause mortality. Results: We found that high eosinophilic levels (bEOS ≥300 cells/µL) were associated with CKD progression from stage 3 to stages 4 or 5 (hazard ratio [HR] ranging from 1.30 to 1.50) and from stages 4 to 5 (HR ranging from 1.28 to 1.50). Among patients with CKD progression, those with blood eosinophils ≥300 cells/µL appeared to have a relatively lower eGFR, higher all-cause mortality, and reduced time to CKD progression and death than those with <300 cells/µL. Factors including sex, race, hypertension, anemia, and treatments for cardiovascular and hematopoietic drugs were associated with CKD progression. Conclusion: Elevated eosinophils may increase the risk for CKD progression. Larger studies are needed to assess whether the risk of mortality is increased among patients with elevated eosinophils.

Low Carbohydrate, High Fat Diet Alters the Oral Microbiome without Negating the Nitrite Response to Beetroot Juice Supplementation.

A low carbohydrate, high fat (LCHF) diet in athletes increases fat oxidation but impairs sports performance, potentially due to impaired exercise economy. Dietary nitrate supplementation can improve exercise economy via an increase in nitric oxide production, which is initiated by the reduction of nitrate to nitrite within the oral cavity. This reaction is dependent on the presence of nitrate-reducing oral bacteria, which can potentially be altered by dietary changes, including a LCHF diet. This study explored the effect of a LCHF diet on the oral microbiome and subsequent changes to plasma nitrite concentration following nitrate supplementation. Following five days of LCHF or high carbohydrate (HCHO) control dietary intervention, highly trained male race walkers consumed 140 mL beetroot juice containing 8.4 mmol nitrate; they then provided (a) blood samples for plasma nitrate and nitrite analysis and (b) saliva samples for 16S rRNA sequencing of the oral microbiome. The LCHF diet (n = 13) reduced oral bacterial diversity and changed the relative abundance of the genera Neisseria (+10%), Fusobacteria (+3%), Prevotella (-9%), and Veillonella (-4%), with no significant changes observed following the HCHO diet (n = 11). Following beetroot juice ingestion, plasma nitrite concentrations were higher for the LCHF diet compared to the HCHO diet (p = 0.04). However, the absence of an interaction with the trial (pre-post) (p = 0.71) suggests that this difference was not due to the dietary intervention. In summary, we found an increase in plasma nitrate and nitrite concentrations in response to nitrate supplementation independent of diet. This suggests the oral microbiome is adaptive to dietary changes and can maintain a nitrate reduction capacity despite a decrease in bacterial diversity following the LCHF diet.