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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) (â¼12.8 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.
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Biomarcadores , Presión Sanguínea , Estudios Cruzados , Suplementos Dietéticos , Nitratos , Óxido Nítrico , Humanos , Nitratos/administración & dosificación , Nitratos/farmacología , Nitratos/sangre , Masculino , Biomarcadores/sangre , Femenino , Óxido Nítrico/metabolismo , Óxido Nítrico/sangre , Adulto , Método Doble Ciego , Presión Sanguínea/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Adulto Joven , Beta vulgaris/química , Nitritos/sangreRESUMEN
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.
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Endurance exercise performance is known to be closely associated with the three physiological pillars of maximal O2 uptake ( V Ì O 2 max $\dot{V}_{{\rm O}_{2}{\rm max}}$ ), economy or efficiency during submaximal exercise, and the fractional utilisation of V Ì O 2 max $\dot{V}_{{\rm O}_{2}{\rm max}}$ (linked to metabolic/lactate threshold phenomena). However, while 'start line' values of these variables are collectively useful in predicting performance in endurance events such as the marathon, it is not widely appreciated that these variables are not static but are prone to significant deterioration as fatiguing endurance exercise proceeds. For example, the 'critical power' (CP), which is a composite of the highest achievable steady-state oxidative metabolic rate and efficiency (O2 cost per watt), may fall by an average of 10% following 2 h of heavy intensity cycle exercise. Even more striking is that the extent of this deterioration displays appreciable inter-individual variability, with changes in CP ranging from <1% to â¼32%. The mechanistic basis for such differences in fatigue resistance or 'physiological resilience' are not resolved. However, resilience may be important in explaining superlative endurance performance and it has implications for the physiological evaluation of athletes and the design of interventions to enhance performance. This article presents new information concerning the dynamic plasticity of the three 'traditional' physiological variables and argues that physiological resilience should be considered as an additional component, or fourth dimension, in models of endurance exercise performance.
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Dietary nitrate (NO3-) supplementation can enhance nitric oxide (NO) bioavailability and lower blood pressure (BP) in humans. The nitrite concentration ([NO2-]) in the plasma is the most commonly used biomarker of increased NO availability. However, it is unknown to what extent changes in other NO congeners, such as S-nitrosothiols (RSNOs), and in other blood components, such as red blood cells (RBC), also contribute to the BP lowering effects of dietary NO3-. We investigated the correlations between changes in NO biomarkers in different blood compartments and changes in BP variables following acute NO3- ingestion. Resting BP was measured and blood samples were collected at baseline, and at 1, 2, 3, 4 and 24 h following acute beetroot juice (â¼12.8 mmol NO3-, â¼11 mg NO3-/kg) ingestion in 20 healthy volunteers. Spearman rank correlation coefficients were determined between the peak individual increases in NO biomarkers (NO3-, NO2-, RSNOs) in plasma, RBC and whole blood, and corresponding decreases in resting BP variables. No significant correlation was observed between increased plasma [NO2-] and reduced BP, but increased RBC [NO2-] was correlated with decreased systolic BP (rs = -0.50, P = 0.03). Notably, increased RBC [RSNOs] was significantly correlated with decreases in systolic (rs = -0.68, P = 0.001), diastolic (rs = -0.59, P = 0.008) and mean arterial pressure (rs = -0.64, P = 0.003). Fisher's z transformation indicated no difference in the strength of the correlations between increases in RBC [NO2-] or [RSNOs] and decreased systolic blood pressure. In conclusion, increased RBC [RSNOs] may be an important mediator of the reduction in resting BP observed following dietary NO3- supplementation.
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Beta vulgaris , Hipotensión , S-Nitrosotioles , Humanos , Presión Sanguínea , Nitratos , Nitritos , Dióxido de Nitrógeno , Óxido Nítrico/farmacología , Suplementos Dietéticos , Eritrocitos , S-Nitrosotioles/farmacología , Ingestión de Alimentos , Método Doble CiegoRESUMEN
Cystic fibrosis (CF) is a multisystem disease. This article provides an up-to-date review of many of the nonrespiratory complications of CF, including mental health issues, nutritional and gastrointestinal problems, fertility issues, diabetes mellitus, bone health and musculoskeletal problems, liver disease, renal problems, and risk of malignancy. It highlights the recent impact of new therapies, including CF transmembrane conductance regulator modulators, on the nonrespiratory complications of CF and provides insights into the potential challenges faced by an aging population of adults with CF and their caregivers, including the potential future risk for cardiovascular disease.
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Fibrosis Quística , Enfermedades Gastrointestinales , Infertilidad , Hepatopatías , Adulto , Humanos , Anciano , Fibrosis Quística/complicaciones , Fibrosis Quística/terapia , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Pulmón , Hepatopatías/complicaciones , MutaciónRESUMEN
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 VËO2 kinetics over time. VËO2 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 VËO2 decreased immediately after the termination of exercise. In contrast, VËO2 on-kinetics during extreme-2 exercise was best fitted by a linear function (R2 ≥ 0.96; SEE ≤ 0.16; p < 0.001), and VËO2 responses continued to increase during the first 10-20 s of recovery. During the extreme-3 exercise, VËO2 could not be modelled due to inadequate data, and there was an M-shape recovery VËO2 response with an exponential decay at the end. The VËO2 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.
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Prueba de Esfuerzo , Consumo de Oxígeno , Humanos , Masculino , Consumo de Oxígeno/fisiología , Ejercicio Físico/fisiología , CinéticaRESUMEN
Dietary nitrate (NO3-) ingestion can be beneficial for health and exercise performance. Recently, based on animal and limited human studies, a skeletal muscle NO3- reservoir has been suggested to be important in whole body nitric oxide (NO) homeostasis. The purpose of this study was to determine the time course of changes in human skeletal muscle NO3- concentration ([NO3-]) following the ingestion of dietary NO3-. Sixteen participants were allocated to either an experimental group (NIT: n = 11) which consumed a bolus of â¼1300 mg (12.8 mmol) potassium nitrate (KNO3), or a placebo group (PLA: n = 5) which consumed a bolus of potassium chloride (KCl). Biological samples (muscle (vastus lateralis), blood, saliva and urine) were collected shortly before NIT or PLA ingestion and at intervals over the course of the subsequent 24 h. At baseline, no differences were observed for muscle [NO3-] and [NO2-] between NIT and PLA (P > 0.05). In PLA, there were no changes in muscle [NO3-] or [NO2-] over time. In NIT, muscle [NO3-] was significantly elevated above baseline (54 ± 29 nmol/g) at 0.5 h, reached a peak at 3 h (181 ± 128 nmol/g), and was not different to baseline from 9 h onwards (P > 0.05). Muscle [NO2-] did not change significantly over time. Following ingestion of a bolus of dietary NO3-, skeletal muscle [NO3-] increases rapidly, reaches a peak at â¼3 h and subsequently declines towards baseline values. Following dietary NO3- ingestion, human m. vastus lateralis [NO3-] expressed a slightly delayed pharmacokinetic profile compared to plasma [NO3-].
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Músculo Esquelético/química , Nitratos/análisis , Nitritos/análisis , Adulto , Suplementos Dietéticos , Femenino , Humanos , Masculino , Nitratos/administración & dosificación , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE OF REVIEW: This article reviews the impact of some of the most recent changes in clinical care management in cystic fibrosis on infection prevention practice and advice for people with cystic fibrosis. RECENT FINDINGS: People with cystic fibrosis (CF) consistently highlight infection control as one of their major concerns. Infection prevention guidance and practice has facilitated successful decreases in rates of many transmissible CF pathogens. The coronavirus disease 2019 pandemic highlighted the clinical significance of respiratory viral infections and has accelerated the implementation of remote monitoring and telemedicine consultations as standard practice in CF. The continued improvement in health of the CF population is being further augmented by the introduction of new therapies, in particular cystic fibrosis transmembrane conductance regulator modulators. Infection prevention will remain pertinent to CF care, but these recent changes in clinical practice will have ongoing implications for infection prevention guidance in CF. SUMMARY: Recent changes in CF clinical care have implications that will lead to further evolution of infection control practice and advice.
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COVID-19 , Fibrosis Quística , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/terapia , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Humanos , Control de Infecciones , Mutación , Pandemias/prevención & controlRESUMEN
Nonenzymatic nitric oxide (NO) generation via the reduction of nitrate and nitrite ions, along with remarkably high levels of nitrate ions in skeletal muscle, have been described recently. Skeletal muscle nitrate storage may be critical for maintenance of NO homeostasis in healthy aging, and nitrate supplementation may be useful for the treatment of specific pathophysiologies and for enhancing normal functions.
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Nitratos , Óxido Nítrico , Homeostasis , Humanos , Músculo Esquelético , NitritosRESUMEN
This paper extends earlier on socioeconomic inequality in mental health, measured by the General Health Questionnaire, to include the second national lockdown up to March 2021.
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COVID-19 , Distrés Psicológico , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Humanos , Pandemias , SARS-CoV-2 , Factores Socioeconómicos , Reino Unido/epidemiologíaRESUMEN
Shocks to health have been shown to reduce labor supply for the individual affected. Less is known about household self-insurance through a partner's response. Previous studies have presented inconclusive empirical evidence on the existence of a health-related Added Worker Effect, and results limited to labor and income responses. We use UK longitudinal data to investigate within households both the labor supply and informal care responses of an individual to the event of an acute health shock to their partner. Relying on the unanticipated timing of shocks, we combine Coarsened Exact Matching and Entropy Balancing algorithms with parametric analysis and exploit lagged outcomes to remove bias from observed confounders and time-invariant unobservables. We find no evidence of a health-related Added Worker Effect but a significant and sizable Informal Carer Effect. This holds irrespective of spousal labor market position or household financial status and ability to purchase formal care provision, suggesting that partners' substitute informal care provision for time devoted to leisure activities.
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Composición Familiar , Renta , Humanos , Recursos Humanos , Atención al Paciente , Reino UnidoRESUMEN
PURPOSE: Peak power output ([Formula: see text]peak) in an incremental exercise test (EXT) is considered an important predictor of performance for cyclists. However, [Formula: see text]peak is protocol dependent. The purpose of this study was to model the effect of EXT design on [Formula: see text]peak. METHODS: An adapted version of a previously developed mathematical model was used. For the purpose of validity testing, we compared predicted [Formula: see text]peak differences (predicted Δ[Formula: see text]peak) with actual Δ[Formula: see text]peak found in sports science literature. RESULTS: The model quantified Δ[Formula: see text]peak between 36 EXT designs with stage durations in the range 1-5 min and increments in the range 10-50 W. Predicted Δ[Formula: see text]peak and actual Δ[Formula: see text]peak across a wide range of performance levels of cyclists were in good agreement. Depending on the specific combination of increment and stage duration, [Formula: see text]peak may be widely different or equivalent. A minimum difference in increment (5 W) or in stage duration (1 min) already results in significantly different [Formula: see text]peak. In EXTs having the same ratio between increment and stage duration, [Formula: see text]peak in the EXT with the shortest stage duration or the greatest increment is significantly higher. Tests combining 15 W, 25 W or 40 W increments with 2, 3 and 4 min stage durations, respectively, are 'special' in that their [Formula: see text]peak approximates the power output associated with maximal oxygen uptake ([Formula: see text]). CONCLUSIONS: The modeling results allow comparison of [Formula: see text]peak between widely different EXT designs. Absolute performance level does not affect Δ[Formula: see text]peak. [Formula: see text]peak15/2, [Formula: see text]peak25/3 and [Formula: see text]peak40/4 constitute a practical physiologic reference for performance diagnostics and exercise intensity prescription.
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Ciclismo/fisiología , Prueba de Esfuerzo/métodos , Adaptación Fisiológica , Adulto , Rendimiento Atlético/fisiología , Fatiga , Humanos , Masculino , Modelos Estadísticos , Consumo de Oxígeno/fisiologíaRESUMEN
Dietary nitrate (NO3-) supplementation can reduce the oxygen cost of submaximal exercise, but this has not been reported consistently. We hypothesised that the number of step transitions to moderate-intensity exercise, and corresponding effects on the signal-to-noise ratio for pulmonary VË O2, may be important in this regard. Twelve recreationally active participants were assigned in a randomised, double-blind, crossover design to supplement for 4 days in three conditions: 1) control (CON; water); 2); PL (NO3--depleted beetroot juice); and 3) BR (NO3--rich beetroot juice). On days 3 and 4, participants completed two 6-min step transitions to moderate-intensity cycle exercise. Breath-by-breath VË O2 data were collected and VË O2 kinetic responses were determined for a single transition and when the responses to 2, 3 and 4 transitions were ensemble-averaged. Steady-state VË O2 was not different between PL and BR when the VË O2 response to one-, two- or three-step transition was compared but was significantly lower in BR compared to PL when four-step transitions was considered (PL: 1.33 ± 0.34 vs. BR: 1.31 ± 0.34 L·min-1, P < 0.05). There were no differences in pulmonary VË O2 responses between CON and PL (P > 0.05). Multiple step transitions may be required to detect the influence of NO3- supplementation on steady-state VË O2.
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Beta vulgaris , Nitratos , Estudios Cruzados , Suplementos Dietéticos , Método Doble Ciego , Tolerancia al Ejercicio/fisiología , Humanos , Nitritos , Oxígeno , Consumo de Oxígeno/fisiología , Intercambio Gaseoso PulmonarRESUMEN
The purpose of this study was to investigate effects of concurrent and independent administration of dietary nitrate (NO3-), administered as NO3--rich beetroot juice (BR; ~12.4 mmol of NO3-), and N-acetylcysteine (NAC; 70 mg·kg-1) on physiological responses during prolonged exercise and subsequent high-intensity exercise tolerance. Sixteen recreationally active males supplemented with NO3--depleted beetroot juice (PL) or BR for 6 days and ingested an acute dose of NAC or maltodextrin (MAL) 1 h prior to performing 1 h of heavy-intensity cycling exercise immediately followed by a severe-intensity time-to-exhaustion (TTE) test in four conditions: 1) PL+MAL, 2) PL+NAC, 3) BR+MAL and 4) BR+NAC. Pre-exercise plasma [NO3-] and nitrite ([NO2-]) were elevated following BR+NAC and BR+MAL (both P < 0.01) compared with PL+NAC and PL+MAL; plasma [cysteine] was increased in PL+NAC and BR+NAC (both P < 0.01) compared to PL+MAL. Muscle excitability declined over time during the prolonged cycling bout in all conditions but was better preserved in PL+NAC compared to BR+NAC (P < 0.01) and PL+MAL (P < 0.05). There was no effect of supplementation on subsequent TTE . These findings indicate that co-ingestion of BR and NAC does not appreciably alter physiological responses during prolonged heavy-intensity cycling or enhance subsequent exercise tolerance.
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Acetilcisteína , Suplementos Dietéticos , Ejercicio Físico , Jugos de Frutas y Vegetales , Nitratos , Extractos Vegetales , Humanos , Masculino , Ejercicio Físico/fisiología , Nitratos/sangre , Acetilcisteína/administración & dosificación , Antioxidantes/administración & dosificación , Estudios Cruzados , Especies Reactivas de Oxígeno , Entrenamiento Aeróbico , Consumo de Oxígeno/fisiología , Nitritos/sangre , Adulto , Extractos Vegetales/farmacología , Raíces de PlantasRESUMEN
Dietary nitrate supplementation has been shown to reduce pulmonary O2 uptake during submaximal exercise and enhance exercise performance. However, the effects of nitrate supplementation on local metabolic and haemodynamic regulation in contracting human skeletal muscle remain unclear. To address this, eight healthy young male sedentary subjects were assigned in a randomized, double-blind, crossover design to receive nitrate-rich beetroot juice (NO3, 9 mmol) and placebo (PLA) 2.5 h prior to the completion of a double-step knee-extensor exercise protocol that included a transition from unloaded to moderate-intensity exercise (MOD) followed immediately by a transition to intense exercise (HIGH). Compared with PLA, NO3 increased plasma levels of nitrate and nitrite. During MOD, leg VÌO2 and leg blood flow (LBF) were reduced to a similar extent (â¼9%-15%) in NO3. During HIGH, leg VÌO2 was reduced by â¼6%-10% and LBF by â¼5%-9% (did not reach significance) in NO3. Leg VÌO2 kinetics was markedly faster in the transition from passive to MOD compared with the transition from MOD to HIGH both in NO3 and PLA with no difference between PLA and NO3. In NO3, a reduction in nitrate and nitrite concentration was detected between arterial and venous samples. No difference in the time to exhaustion was observed between conditions. In conclusion, elevation of plasma nitrate and nitrate reduces leg skeletal muscle VÌO2 and blood flow during exercise. However, nitrate supplementation does not enhance muscle VÌO2 kinetics during exercise, nor does it improve time to exhaustion when exercising with a small muscle mass. KEY POINTS: Dietary nitrate supplementation has been shown to reduce systemic O2 uptake during exercise and improve exercise performance. The effects of nitrate supplementation on local metabolism and blood flow regulation in contracting human skeletal muscle remain unclear. By using leg exercise engaging a small muscle mass, we show that O2 uptake and blood flow are similarly reduced in contracting skeletal muscle of humans during exercise. Despite slower VÌO2 kinetics in the transition from moderate to intense exercise, no effects of nitrate supplementation were observed for VÌO2 kinetics and time to exhaustion. Nitrate and nitrite concentrations are reduced across the exercising leg, suggesting that these ions are extracted from the arterial blood by contracting skeletal muscle.
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Beta vulgaris , Nitratos , Estudios Cruzados , Suplementos Dietéticos , Método Doble Ciego , Ingestión de Alimentos , Hemodinámica , Humanos , Masculino , Músculo Esquelético/metabolismo , Nitratos/metabolismo , Nitritos/metabolismo , Consumo de OxígenoRESUMEN
INTRODUCTION: Ivacaftor was the first therapy licensed to address the underlying defect in cystic fibrosis (CF). The improvements in lung function, nutritional status and pulmonary exacerbations in patients carrying a Gly551Asp mutation were greater than previously seen in clinical trials for other therapies. Limited data are available regarding long-term outcomes and adherence to ivacaftor outside clinical trials. METHODS: We conducted a 5-year single-centre retrospective study of people with CF carrying the Gly551Asp mutation who received ivacaftor. Clinical outcome data were extracted from medical notes and databases. Drug delivery data were used to assess medicine possession ratio (MPR). RESULTS: 35 people were included. After commencing ivacaftor, FEV1 improved by 9.6% (SE±1.59%) predicted by 6 months. Thereafter, FEV1 declined, and at 5 years had returned to pre-ivacaftor baseline. Ivacaftor did not alter annual rate of FEV1 decline (1.57% pre vs 1.82% post, p=0.74). Body mass index (BMI) increased for 4 years. There was a significant reduction in inpatient and total intravenous antibiotic days sustained over 5 years. MPR remained high but declined over time (-2.5±0.9% per year, p=0.007). FEV1 was better maintained in patients with higher MPRs. CONCLUSION: The addition of ivacaftor provides acute benefits for people with the Gly551Asp mutation and established lung disease. We report a sustained reduction in intravenous antibiotic use but following acute improvement in lung function, decline continues, and patients will continue to require medical observation and optimisation. Strategies to maintain high adherence should be a priority to prolong the benefits of ivacaftor.
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Aminofenoles/uso terapéutico , Agonistas de los Canales de Cloruro/uso terapéutico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Quinolonas/uso terapéutico , Adolescente , Adulto , Femenino , Humanos , Masculino , Mutación , Estudios RetrospectivosRESUMEN
We use data from the UK Household Longitudinal Study (UKHLS) to compare measures of socioeconomic inequality in psychological distress, measured by the General Health Questionnaire (GHQ), before (Waves 9 and the Interim 2019 Wave) and during the first wave of the COVID-19 pandemic (April to July 2020). Based on a caseness measure, the prevalence of psychological distress increased from 18.5% to 27.7% between the 2019 Wave and April 2020 with some reversion to earlier levels in subsequent months. Also, there was a systematic increase in total inequality in the Likert GHQ-12 score. However, measures of relative socioeconomic inequality have not increased. A Shapley-Shorrocks decomposition analysis shows that during the peak of the first wave of the pandemic (April 2020) other socioeconomic factors declined in their share of socioeconomic inequality, while age and gender account for a larger share. The most notable increase is evident for younger women. The contribution of working in an industry related to the COVID-19 response played a small role at Wave 9 and the Interim 2019 Wave, but more than tripled its share in April 2020. As the first wave of COVID-19 progressed, the contribution of demographics declined from their peak level in April and chronic health conditions, housing conditions, and neighbourhood characteristics increased their contributions to socioeconomic inequality.
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COVID-19/economía , Distrés Psicológico , Factores Socioeconómicos , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos Económicos , Prevalencia , Características de la Residencia , Reino UnidoRESUMEN
Using monthly data from the Understanding Society (UKHLS) COVID-19 Survey we analyse the evolution of unmet need and assess how the UK health care system performed against the principle of horizontal equity in health care use during the first wave of COVID-19 wave. Unmet need was most evident for hospital care, and less pronounced for primary health services (non-emergency medical helplines, GP consultations, community pharmacist advice, over the counter medications and prescriptions). Despite this, there is no evidence that horizontal equity, with respect to income, was violated for NHS hospital outpatient and inpatient care during the first wave of the pandemic. There is evidence of pro-rich inequities in use of GP consultations, prescriptions and medical helplines at the peak of the first wave, but these were eliminated as the pandemic progressed. There are persistent pro-rich inequities for services that may relate to individuals' ability to pay (over the counter medications and advice from community pharmacists).
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COVID-19 , Atención a la Salud , Equidad en Salud , Necesidades y Demandas de Servicios de Salud , Renta/estadística & datos numéricos , Encuestas de Atención de la Salud , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Factores Socioeconómicos , Reino UnidoRESUMEN
The metabolic boundary separating the heavy-intensity and severe-intensity exercise domains is of scientific and practical interest but there is controversy concerning whether the maximal lactate steady state (MLSS) or critical power (synonymous with critical speed, CS) better represents this boundary. We measured the running speeds at MLSS and CS and investigated their ability to discriminate speeds at which [Formula: see text] was stable over time from speeds at which a steady-state [Formula: see text] could not be established. Ten well-trained male distance runners completed 9-12 constant-speed treadmill tests, including 3-5 runs of up to 30-min duration for the assessment of MLSS and at least 4 runs performed to the limit of tolerance for assessment of CS. The running speeds at CS and MLSS were significantly different (16.4 ± 1.3 vs. 15.2 ± 0.9 km/h, respectively; P < 0.001). Blood lactate concentration was higher and increased with time at a speed 0.5 km/h higher than MLSS compared to MLSS (P < 0.01); however, pulmonary [Formula: see text] did not change significantly between 10 and 30 min at either MLSS or MLSS + 0.5 km/h. In contrast, [Formula: see text] increased significantly over time and reached [Formula: see text] at end-exercise at a speed ~ 0.4 km/h above CS (P < 0.05) but remained stable at a speed ~ 0.5 km/h below CS. The stability of [Formula: see text] at a speed exceeding MLSS suggests that MLSS underestimates the maximal metabolic steady state. These results indicate that CS more closely represents the maximal metabolic steady state when the latter is appropriately defined according to the ability to stabilise pulmonary [Formula: see text].
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Ácido Láctico/sangre , Consumo de Oxígeno/fisiología , Aptitud Física/fisiología , Carrera/fisiología , Aceleración , Prueba de Esfuerzo , Humanos , Masculino , Adulto JovenRESUMEN
The Burkholderia genus encompasses many Gram-negative bacteria living in the rhizosphere. Some Burkholderia species can cause life-threatening human infections, highlighting the need for clinical interventions targeting specific lipopolysaccharide proteins. Burkholderia cenocepacia O-linked protein glycosylation has been reported, but the chemical structure of the O-glycan and the machinery required for its biosynthesis are unknown and could reveal potential therapeutic targets. Here, using bioinformatics approaches, gene-knockout mutants, purified recombinant proteins, LC-MS-based analyses of O-glycans, and NMR-based structural analyses, we identified a B. cenocepacia O-glycosylation (ogc) gene cluster necessary for synthesis, assembly, and membrane translocation of a lipid-linked O-glycan, as well as its structure, which consists of a ß-Gal-(1,3)-α-GalNAc-(1,3)-ß-GalNAc trisaccharide. We demonstrate that the ogc cluster is conserved in the Burkholderia genus, and we confirm the production of glycoproteins with similar glycans in the Burkholderia species: B. thailandensis, B. gladioli, and B. pseudomallei Furthermore, we show that absence of protein O-glycosylation severely affects bacterial fitness and accelerates bacterial clearance in a Galleria mellonella larva infection model. Finally, our experiments revealed that patients infected with B. cenocepacia, Burkholderia multivorans, B. pseudomallei, or Burkholderia mallei develop O-glycan-specific antibodies. Together, these results highlight the importance of general protein O-glycosylation in the biology of the Burkholderia genus and its potential as a target for inhibition or immunotherapy approaches to control Burkholderia infections.