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The exercise pressor reflex (EPR), a neurocirculatory control mechanism, is exaggerated in hypertensive humans and rats. Disease-related abnormalities within the afferent arm of the reflex loop, including mechano- and metabosensitive receptors located at the terminal end of group III/IV muscle afferents, may contribute to the dysfunctional EPR in hypertension. Using control (WKY) and spontaneous hypertensive (SHR) rats, we examined dorsal root ganglion (DRG) gene and protein expression of molecular receptors recognized as significant determinants of the EPR. Twelve lumbar DRGs (6 left, 6 right) were harvested from each of 10 WKY [arterial blood pressure (MAP): 96 ± 9 mmHg] and 10 SHR (MAP: 144 ± 9 mmHg). DRGs from the left side were used for protein expression (Western blotting; normalized to GAPDH), whereas right-side DRGs (i.e., parallel structure) were used to determine mRNA levels (RNA-sequencing, normalized to TPM). Analyses focused on metabosensitive (ASIC3, Bradykinin receptor B2, EP4, P2X3, TRPv1) and mechanosensitive (Piezo1/2) receptors. Although Piezo1 was similar in both groups ( P = 0.75), protein expression for all other receptors was significantly higher in SHR compared with WKY. With the exception of a greater Bradykinin-receptor B2 in SHR ( P < 0.05), mRNA expression of all other receptors was not different between groups ( P > 0.18). The higher protein content of these sensory receptors in SHR indirectly supports the previously proposed hypothesis that the exaggerated EPR in hypertension is, in part, due to disease-related abnormalities within the afferent arm of the reflex loop. The upregulated receptor content, combined with normal mRNA levels, insinuates that posttranscriptional regulation of sensory receptor protein expression might be impaired in hypertension.

Introduction: By projecting to medullary respiratory center, group III/IV muscle afferents determine the ventilatory response during short (~3 min) bouts of locomotor exercise. However, their significance for the hyperpneic response, gas exchange efficiency, and arterial oxygenation during exercise of longer durations (>15min) remains unknown. Methods: On 2 separate days, 8 healthy subjects (22±3yrs, 4 f) performed two 20-min bicycling bouts at 30% (~50% V̇O2max) and 50% (~75% V̇O2max) of peak power (Wpeak) under a) control condition (intact leg muscle afferent feedback; CTRL), and b) lumbar intrathecal fentanyl (attenuated group III/IV leg muscle afferent feedback; FENT). Ventilation (V̇E) and gas exchange were continuously recorded, data averaged over the last min of each bout. Arterial blood samples (radial catheter) were used to determine O2 and CO2 partial pressures (PaO2 and PaCO2) and O2 saturation (HbO2). Alveolar O2 pressure (PAO2) was calculated, pulmonary gas exchange efficiency was evaluated using the alveolar-to-arterial O2 difference (A-aDO2) and the arterial-to-end-tidal PCO2 difference (PaCO2-PETCO2). Results: Fentanyl had no effect at rest. There was no difference in V̇O2, V̇CO2, and VT between CTRL and FENT. However, during FENT vs CTRL, V̇E (30 % Wpeak: 42±9 vs 46±8 L/min; 50 %Wpeak: 75±12 vs 71±12), f R (30 %: 25±3 vs 28±4b/min; 50%: 33±5 vs 35±5), V̇E/V̇O2 (30%: 25±3 vs 28±3; 50 %: 29±5 vs 32±4), V̇E/V̇CO2 (30 %: 31±4 vs 34±4; 50 %: 34±5 vs 37±5), PAO2 (30 %: 94±3 vs 97±5 mmHg; 50 %: 98±3 vs 100±4), PaO2 (30%: 84±5 vs 90±3 mmHg; 50%: 84±7 vs 88±4), HbO2 (30 %: 95±1 vs 96±1 %; 50 %: 95±2 vs 96±1 %), VD/VT (30 %: 0.18±0.04 vs 0.22±0.08; 50 %: 0.16±0.05 vs 0.21±0.07), and the PaCO2-PETCO2 difference (30 %: -2.6±1.6 vs -1.4±2.1 mmHg; 50 %: -2.8±2.4 vs -1.0±2.1) were lower ( PaCO2 (30 %: 33±3 vs 31±3 mmHg; 50 %: 30±3 vs 29±3) and A-aDO2 (30 %: 9±3 vs 5±5 mmHg; 50 %: 14±5 vs 10±5) were greater ( PaCO2, ↓PaO2). We conclude that group III/IV muscle afferent feedback is critical for matching the pulmonary response to the metabolic cost of locomotion and for perpetually optimizing gas exchange efficiency and arterial oxygenation during longer exercise. National Heart, Lung, and Blood Institute (HL-116579), U.S. Veterans Affairs Rehabilitation Research and Development (E3343-R) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background: The interaction of the exercise pressor reflex (EPR) and the carotid chemoreflex (CR) affects circulatory control during physical activity in health. It has been shown that patients with heart failure with reduced ejection fraction (HFrEF) have an abnormal cardiovascular response to EPR or CR activation, which contributes to impaired limb blood flow during exercise. However, the impact of the reflex interaction in HFrEF is unclear. Purpose: To evaluate the interaction between EPR and CR in HFrEF. Method: Five patients with HFrEF and 6 control subjects (Ctrl) completed two experimental sessions. In session 1, participants performed dynamic single-leg knee-extension at 60% of peak power output for 4 min while breathing room air (normoxia; NormC: SaO2~96%, PaO2~81 mmHg, PaCO2~33 mmHg, arterial pH~7.43) and pure O2 (hyperoxia; HyperC: SaO2~100%, PaO2~408 mmHg, PaCO2~35 mmHg, arterial pH~7.40). In session 2, following lumbar intrathecal fentanyl administration to attenuate group III/IV leg muscle afferent feedback, participants repeated the same exercise under normoxic and hyperoxic conditions (NormF and HyperF). Mean arterial pressure (MAP, radial artery catheter), heart rate (HR, 12-lead ECG), stroke volume (SV, finger photoplethysmography), cardiac output (CO), systemic vascular conductance (SVC), femoral blood flow of the working leg (LBF, Doppler ultrasound), and leg vascular conductance (LVC) were continuously quantified during exercise. Results: EPR activation (i.e., ΔHyperC-HyperF) in HFrEF resulted in no changes in MAP and HR, but significantly decreased SV (~10 mL), CO (~1 L min−1), SVC (~9 mL min−1 mmHg−1), LBF (~0.4 L min−1) and LVC (~4 mL min−1 mmHg−1). In contrast, EPR activation in Ctrl significantly increased MAP (~10 mmHg) and decreased LVC (~3 mL min−1 mmHg−1), but did not affect HR, SV, CO, SVC and LBF ( p≥0.20). CR activation in HFrEF (i.e., ΔNormF-HyperF) had no effects on any of the cardiovascular variables ( p≥0.12). CR activation in Ctrl significantly increased HR (~3 beats min−1) and SVC (~3 mL min−1 mmHg−1), but had no effects on MAP, SV, CO, LBF and LVC ( p≥0.10). During EPR:CR co-activation (i.e., ΔNormC-HyperF) in HFrEF, the observed responses were not significantly different from the sum of the responses evoked by each reflex individually. In Ctrl, MAP during EPR:CR co-activation was greater than the summated response (16±7 vs. 10±9 mmHg; p National Heart, Lung, and Blood Institute (HL-116579), U.S. Veterans Affairs Rehabilitation Research and Development (E3343-R) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

This study examined the impact of aging on the elastic and resistive components of the work of breathing (W(b)) during locomotor exercise at a given 1) ventilatory rate, 2) metabolic rate, and 3) operating lung volume. Eight healthy younger (25 ± 4 yr) and 8 older (72 ± 6 yr) participants performed incremental bicycle exercise, from which retrospective analyses identified similar ventilatory rates (approximately 40, 70, and 100 L·min(−1)), similar metabolic rates (V̇o(2): approximately 1.2, 1.6, and 1.9 L·min(−1)), and similar lung volumes [inspiratory and expiratory reserve volumes (IRV/ERV: approximately 25/34%, 16/33%, and 13-34% of vital capacity]. W(b) at each level was quantified by integrating the averaged esophageal pressure-volume loop, which was then partitioned into elastic and resistive components of inspiratory and expiratory work using the modified Campbell diagram. IRV was smaller in the older participants during exercise at ventilations of 70 and 100 L·min(−1) and during exercise at the three metabolic rates (P < 0.05). Mainly because of a greater inspiratory elastic and resistive W(b) in the older group (P < 0.05), total W(b) was augmented by 40%–50% during exercise at matched ventilatory and matched metabolic rates. When examined during exercise evoking similar lung volumes, total W(b) was not different between the groups (P = 0.86). Taken together, although aging exaggerates total W(b) during locomotor exercise at a given ventilatory or a given metabolic rate, this difference is abolished during exercise at a given operating lung volume. These findings highlight the significance of operating lung volume in determining the age-related difference in W(b) during locomotor exercise. NEW & NOTEWORTHY This study evaluated the impact of aging on the work of breathing (W(b)) during locomotor exercise evoking similar ventilatory rates, metabolic rates, and operating lung volumes in young and older individuals. Mainly because of a greater inspiratory elastic and resistive W(b) in older participants, total W(b) was higher during exercise at any given ventilatory and metabolic rate with aging. However, this age-related difference was abolished during exercise evoking similar operating lung volumes in both age groups. These findings highlight the significance of lung volumes in determining the age-related difference in total W(b).

This study investigated the impact of dietary nitrate supplementation on peripheral hemodynamics, the development of neuromuscular fatigue, and time to task failure during cycling exercise. Eleven recreationally active male participants (27 ± 5 yr, V̇o(2max): 42 ± 2 mL/kg/min) performed two experimental trials following 3 days of either dietary nitrate-rich beetroot juice (4.1 mmol NO(3)(−)/day; DNS) or placebo (PLA) supplementation in a blinded, counterbalanced order. Exercise consisted of constant-load cycling at 50, 75, and 100 W (4 min each) and, at ∼80% of peak power output (218 ± 12 W), to task-failure. All participants returned to repeat the shorter of the two trials performed to task failure, but with the opposite supplementation regime (iso-time comparison; ISO). Mean arterial pressure (MAP), leg blood flow (Q(L); Doppler ultrasound), leg vascular conductance (LVC), and pulmonary gas exchange were continuously assessed during exercise. Locomotor muscle fatigue was determined by the change in pre to postexercise quadriceps twitch-torque (ΔQ(tw)) and voluntary activation (ΔVA; electrical femoral nerve stimulation). Following DNS, plasma [nitrite] (∼670 vs. ∼180 nmol) and [nitrate] (∼775 vs. ∼11 μmol) were significantly elevated compared with PLA. Unlike PLA, DNS lowered both Q(L) and MAP by ∼8% (P < 0.05), but did not alter LVC (P = 0.31). V̇O(2) across work rates, as well as cycling time to task-failure (∼7 min) and locomotor muscle fatigue following the ISO-time comparison were not different between the two conditions (ΔQ(tw) ∼42%, ΔVA ∼4%). Thus, despite significant hemodynamic changes, DNS did not alter the development of locomotor muscle fatigue and, ultimately, cycling time to task failure. NEW & NOTEWORTHY This study sought to characterize the impact of dietary nitrate supplementation on the hemodynamic response, locomotor muscle fatigue, and time to task failure during cycling exercise. Although nitrate supplementation lowered mean arterial pressure and exercising leg blood flow, leg vascular conductance and oxygen utilization were unaffected. Despite significant hemodynamic changes, there was no effect of dietary nitrate on neuromuscular fatigue development and, ultimately, cycling time to task failure.

Recently it was documented that fatiguing, high-intensity exercise resulted in a significant attenuation in maximal skeletal muscle mitochondrial respiratory capacity, potentially due to the intramuscular metabolic perturbation elicited by such intense exercise. With the utilization of intrathecal fentanyl to attenuate afferent feedback from group III/IV muscle afferents, permitting increased muscle activation and greater intramuscular metabolic disturbance, this study aimed to better elucidate the role of metabolic perturbation on mitochondrial respiratory function. Eight young, healthy males performed high-intensity cycle exercise in control (CTRL) and fentanyl-treated (FENT) conditions. Liquid chromatography-mass spectrometry and high-resolution respirometry were used to assess metabolites and mitochondrial respiratory function, respectively, pre- and postexercise in muscle biopsies from the vastus lateralis. Compared with CTRL, FENT yielded a significantly greater exercise-induced metabolic perturbation (PCr: −67% vs. −82%, Pi: 353% vs. 534%, pH: −0.22 vs. −0.31, lactate: 820% vs. 1,160%). Somewhat surprisingly, despite this greater metabolic perturbation in FENT compared with CTRL, with the only exception of respiratory control ratio (RCR) (−3% and −36%) for which the impact of FENT was significantly greater, the degree of attenuated mitochondrial respiratory capacity postexercise was not different between CTRL and FENT, respectively, as assessed by maximal respiratory flux through complex I (−15% and −33%), complex II (−36% and −23%), complex I + II (−31% and −20%), and state 3CI+CII control ratio (−24% and −39%). Although a basement effect cannot be ruled out, this failure of an augmented metabolic perturbation to extensively further attenuate mitochondrial function questions the direct role of high-intensity exercise-induced metabolite accumulation in this postexercise response.

Neural drive originating in higher brain areas reaches exercising limb muscles through the corticospinal-motoneuronal pathway, which links the motor cortex and spinal motoneurones. The properties of this pathway have frequently been observed to change during fatiguing exercise in ways that could influence the development of central fatigue (i.e. the progressive reduction in voluntary muscle activation). However, based on differences in motor cortical and motoneuronal excitability between exercise modalities (e.g. single-joint vs. locomotor exercise), there is no characteristic response that allows for a categorical conclusion about the effect of these changes on functional impairments and performance limitations. Despite the lack of uniformity in findings during fatigue, there is strong evidence for marked 'inhibition' of motoneurones as a direct result of voluntary drive. Endogenous forms of neuromodulation, such as via serotonin released from neurones, can directly affect motoneuronal output and central fatigue. Exogenous forms of neuromodulation, such as brain stimulation, may achieve a similar effect, although the evidence is weak. Non-invasive transcranial direct current stimulation can cause transient or long-lasting changes in cortical excitability; however, variable results across studies cast doubt on its claimed capacity to enhance performance. Furthermore, with these studies, it is difficult to establish a cause-and-effect relationship between brain responsiveness and exercise performance. This review briefly summarizes changes in the corticomotoneuronal pathway during various types of exercise, and considers the relevance of these changes for the development of central fatigue, as well as the potential of non-invasive brain stimulation to enhance motor cortical excitability, motoneuronal output and, ultimately, exercise performance.

We examined the effect of intravenous ascorbate (VitC) administration on exercise-induced redox balance, inflammation, exertional dyspnea, neuromuscular fatigue, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Eight COPD patients completed constant-load cycling (∼80% of peak power output, 83 ± 10 W) to task failure after intravenous VitC (2 g) or saline (placebo, PL) infusion. All participants repeated the shorter of the two exercise trials (isotime) with the other infusate. Quadriceps fatigue was determined by pre- to postexercise changes in quadriceps twitch torque (ΔQ(tw), electrical femoral nerve stimulation). Corticospinal excitability before, during, and after exercise was assessed by changes in motor evoked potentials triggered by transcranial magnetic stimulation. VitC increased superoxide dismutase (marker for endogenous antioxidant capacity) by 129% and mitigated C-reactive protein (marker for inflammation) in the plasma during exercise but failed to alter the exercise-induced increase in lipid peroxidation (malondialdehyde) and free radicals [electron paramagnetic resonance (EPR)-spectroscopy]. Although VitC did, indeed, decrease neuromuscular fatigue (ΔQ(tw): PL −29 ± 5%, VitC −23 ± 6%, P < 0.05), there was no impact on corticospinal excitability and time to task failure (∼8 min, P = 0.8). Interestingly, in terms of pulmonary limitations to exercise, VitC had no effect on perceived exertional dyspnea (∼8.5/10) and its determinants, including oxygen saturation ([Formula: see text]) (∼92%) and respiratory muscle work (∼650 cmH(2)O·s·min(−1)) (P > 0.3). Thus, although VitC facilitated indicators for antioxidant capacity, diminished inflammatory markers, and improved neuromuscular fatigue resistance, it failed to improve exertional dyspnea and cycling exercise tolerance in patients with COPD. As dyspnea is recognized to limit exercise tolerance in COPD, the otherwise beneficial effects of VitC may have been impacted by this unaltered sensation. NEW & NOTEWORTHY We investigated the effect of intravenous vitamin C on redox balance, exertional dyspnea, neuromuscular fatigue, and exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. Acute vitamin C administration increased superoxide dismutase (marker of antioxidant capacity) and attenuated fatigue development but failed to improve exertional dyspnea and exercise tolerance. These findings suggest that a compromised redox balance plays a critical role in the development of fatigue in COPD but also highlight the significance of exertional dyspnea as an important symptom limiting the patients’ exercise tolerance.

The Lancet Countdown is an international collaboration, established to provide an independent, global monitoring system dedicated to tracking the emerging health profile of the changing climate. The 2020 report presents 43 indicators across five sections: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. This report represents the findings and consensus of the 35 leading academic institutions and UN agencies that make up the Lancet Countdown, and draws on the expertise of climate scientists, geographers, and engineers; of energy, food, and transport experts; and of economists, social and political scientists, data scientists, public health professionals, and doctors.

This study investigated the impact of HFpEF on neuromuscular fatigue and peripheral hemodynamics during small muscle mass exercise not limited by cardiac output. Eight HFpEF patients (NYHA II-III, ejection-fraction: 61 ± 2%) and eight healthy controls performed dynamic knee extension exercise (80% peak workload) to task failure and maximal intermittent quadriceps contractions (8 × 15 s). Controls repeated knee extension at the same absolute intensity as HFpEF. Leg blood flow (Q(L)) was quantified using Doppler ultrasound. Pre/postexercise changes in quadriceps twitch torque (ΔQ(tw); peripheral fatigue), voluntary activation (ΔVA; central fatigue), and corticospinal excitability were quantified. At the same relative intensity, HFpEF (24 ± 5 W) and controls (42 ± 6 W) had a similar time-to-task failure (∼10 min), ΔQ(tw) (∼50%), and ΔVA (∼6%). This resulted in a greater exercise-induced change in neuromuscular function per unit work in HFpEF, which was significantly correlated with a slower Q(L) response time. Knee extension exercise at the same absolute intensity resulted in an ∼40% lower Q(L) and greater ΔQ(tw) and ΔVA in HFpEF than in controls. Corticospinal excitability remained unaltered during exercise in both groups. Finally, despite a similar ΔVA, ΔQ(tw) was larger in HFpEF versus controls during isometric exercise. In conclusion, HFpEF patients are characterized by a similar development of central and peripheral fatigue as healthy controls when tested at the same relative intensity during exercise not limited by cardiac output. However, HFpEF patients have a greater susceptibility to neuromuscular fatigue during exercise at a given absolute intensity, and this impairs functional capacity. The patients’ compromised Q(L) response to exercise likely accounts, at least partly, for the patients’ attenuated fatigue resistance. NEW & NOTEWORTHY The susceptibility to neuromuscular fatigue during exercise is substantially exaggerated in individuals with heart failure with a preserved ejection fraction. The faster rate of fatigue development is associated with the compromised peripheral hemodynamic response characterizing these patients during exercise. Given the role of neuromuscular fatigue as a factor limiting exercise, this impairment likely accounts for a significant portion of the exercise intolerance typical for this population.

The cardiovascular response resulting from the individual activation of the muscle mechanoreflex (MMR) or the chemoreflex (CR) is different between men and women. Whether the haemodynamic consequence resulting from the interaction of these sympathoexcitatory reflexes is also sex-dependent remains unknown. MMR and CR were activated by passive leg movement (LM) and exposure to hypoxia (O

Author(s): Agrawala, Shardul; Amann, Markus; Binimelis de Raga, Graciela; Borgford-Parnell, Nathan; Brauer, Michael; Clark, Harry; Emberson, Lisa; Haines, Andy; Kejun, Jiang; Kunzli, Nino; Kuylenstierna, Johan; Lacy, Rodolfo; Liu, Jian; Mulugetta, Yacob; Pachauri, Shonali; Ramanathan, V; Ravishankara, AR; Shindell, Drew; Wongwangwatana, Supat; Scientific Advisory Panel of the Climate and Clean Air Coalition and Invited Experts

Achieving carbon neutral development will take a roughly 40-year-long structural transformation, especially in developing and emerging economies, where most people exposed to poor air quality live. In the meantime, 6-7 million people die each year by breathing polluted air. But does climate action always lead to better air quality? Likewise, do air pollution policies always lead to cooler climate? The answers are not as obvious as one might expect. For example, while short-lived climate pollutants contribute to air pollution, some important air pollutants cool the climate with an equal countervailing force. Retrofitting coal-fired power plants with modern air pollution filters can quickly reduce most air pollution but slightly increases carbon emissions. In the absence of effective carbon pricing, this can lock in carbon-intensive installations for decades. On the other hand, putting a price on carbon in the absence of effective air-quality policies can encourage firms to switch off air pollution filters. Carbon pricing can also push lower-income households to use biomass and waste instead of gas, electricity, or district heating for cooking and heating and increase population exposure to air pollution. These tensions do not justify inaction on any of these major market failures. But neither of these environmental problems can be solved effectively by pursuing one-sided environmental policies. This report brings much-needed realism to the climate and air pollution debate. It analyzes international experience to identify effective pathways to coherent policy packages that harness synergies and manage inevitable tensions between climate mitigation and air-quality management. It helps decision makers to prioritize pollutants and emission sources and implement regulations that will encourage economic actors to implement technical and behavioral measures in a way that quickly saves people's lives while navigating the longer journey to a low-carbon future.

City clusters play an important role in air pollutant and greenhouse gas (GHG) emissions reduction in China, primarily due to their high fossil energy consumption levels. The “2 + 26” Cities, i.e., Beijing, Tianjin and 26 other perfectures in northern China, has experienced serious air pollution in recent years. We employ the Greenhouse Gas and Air Pollution Interactions and Synergies model adapted to the “2 + 26” Cities (GAINS-JJJ) to evaluate the impacts of structural adjustments in four major sectors, industry, energy, transport and land use, under the Three-Year Action Plan for Blue Skies (Three-Year Action Plan) on the emissions of both the major air pollutants and CO2 in the “2 + 26” Cities. The results indicate that the Three-Year Action Plan applied in the “2 + 26” Cities reduces the total emissions of primary fine particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM2.5), SO2, NOx, NH3 and CO2 by 17%, 25%, 21%, 3% and 1%, respectively, from 2017 to 2020. The emission reduction potentials vary widely across the 28 prefectures, which may be attributed to the differences in energy structure, industrial composition, and policy enforcement rate. Among the four sectors, adjustment of industrial structure attains the highest co-benefits of CO2 reduction and air pollution control due to its high CO2 reduction potential, while structural adjustments in energy and transport attain much lower co-benefits, despite their relatively high air pollutant emissions reductions, primarily resulting from an increase in the coal-electric load and associated carbon emissions caused by electric reform policies.

PURPOSE: The impact of an acute bout of exercise, especially high-intensity exercise, on the function of mitochondrial respiratory complexes is not well understood, with potential implications for both the healthy population and patients undergoing exercise based rehabilitation. Therefore, this study sought to comprehensively examine respiratory flux through the different complexes of the electron transport chain (ETC) in skeletal muscle mitochondria before and immediately after high-intensity aerobic exercise. METHOD: Muscle biopsies of the vastus lateralis were obtained at baseline and immediately following a 5 km time-trial performed on a cycle ergometer. Mitochondrial respiratory flux through the complexes of the ETC was measured in permeabilized skeletal muscle fibers by high-resolution respirometry. RESULTS: Complex I+II state 3 respiration (state 3(CI+CII)), a measure of oxidative phosphorylation capacity, was diminished immediately after the exercise (PRE: 27±3 ρm.mg(−1).s(−1); POST: 17±2 ρm.mg(−1).s(−1), P

The Lancet Countdown: tracking progress on health and climate change was established to provide an independent, global monitoring system dedicated to tracking the health dimensions of the impacts of, and the response to, climate change. The Lancet Countdown tracks 41 indicators across five domains: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; finance and economics; and public and political engagement. This report is the product of a collaboration of 27 leading academic institutions, the UN, and intergovernmental agencies from every continent. The report draws on world-class expertise from climate scientists, ecologists, mathematicians, geographers, engineers, energy, food, livestock, and transport experts, economists, social and political scientists, public health professionals, and. doctors. The Lancet Countdown’s work builds on decades of research in this field, and was first proposed in the 2015 Lancet Commission on health and climate change,1 which documented the human impacts of climate change and provided ten global recommendations to respond to this public health emergency and secure the public health benefits available (panel 1).

Muscle fatigue induced by voluntary exercise, which requires central motor drive, causes central fatigue that impairs endurance performance of a different, nonfatigued muscle. This study investigated the impact of quadriceps fatigue induced by electrically induced (no central motor drive) contractions on single-leg knee-extension (KE) performance of the subsequently exercising ipsilateral quadriceps. On two separate occasions, eight males completed constant-load (85% of maximal power-output) KE exercise to exhaustion. In a counterbalanced manner, subjects performed the KE exercise with no pre-existing quadriceps fatigue in the contralateral leg on one day (No-PreF), whereas on the other day, the same KE exercise was repeated following electrically induced quadriceps fatigue in the contralateral leg (PreF). Quadriceps fatigue was assessed by evaluating pre- to postexercise changes in potentiated twitch force (ΔQtw,pot; peripheral fatigue), and voluntary muscle activation (ΔVA; central fatigue). As reflected by the 57 ± 11% reduction in electrically evoked pulse force, the electrically induced fatigue protocol caused significant knee-extensors fatigue. KE endurance time to exhaustion was shorter during PreF compared with No-PreF (4.6 ± 1.2 vs 7.7 ± 2.4 min; P < 0.01). Although ΔQtw,pot was significantly larger in No-PreF compared with PreF (−60% vs −52%, P < 0.05), ΔVA was greater in PreF (−14% vs −10%, P < 0.05). Taken together, electrically induced quadriceps fatigue in the contralateral leg limits KE endurance performance and the development of peripheral fatigue in the ipsilateral leg. These findings support the hypothesis that the crossover effect of central fatigue is mainly mediated by group III/IV muscle afferent feedback and suggest that impairments associated with central motor drive may only play a minor role in this phenomenon.

The effect of a spinal cord injury (SCI) on vascular function has been clouded by both the physiological and mathematical bias of assessing vasodilation in arteries with differing diameters both above and below the lesion and when comparing with healthy, nondisabled controls (CTRL). Thus, we measured vascular function, with flow-mediated vasodilation (FMD), in 10 SCI and 10 CTRL with all arteries matched for diameter (≈0.5 cm): brachial artery (BA, arm, functional limb in both groups) and popliteal artery (PA, leg, disused limb in SCI, functional limb in CTRL). PA %FMD was significantly attenuated in SCI (5.6 ± 0.6%) compared with CTRL (8.4 ± 1.3%), with no difference in the BA (SCI: 8.6 ± 0.9%; CTRL: 8.7 ± 0.7%). However, unlike the arm, where muscle mass was preserved, the legs of the SCI were significantly smaller than CTRL (∼70%). Thus, reactive hyperemia (RH), which is heavily dependent on the volume of muscle occluded, in the PA was attenuated in the SCI (144 ± 22 mL) compared with CTRL (258 ± 16 mL) but not different in the BA. Consequently, shear rate was significantly diminished in the PA of the SCI, such that %FMD/shear rate (vascular responsiveness) was actually greater in the SCI (1.5 ± 0.1% · s(−1)) than CTRL (1.2 ± 0.1% · s(−1)). Of note, this was significantly greater than both their own BA (0.9 ± 0.1% · s(−1)) and that of the CTRL (0.9 ± 0.1% · s(−1)). Therefore, examining vessels of similar size, this study reveals normal vascular function above the lesion and vascular dysfunction below the lesion. However, below the lesion there was, actually, evidence of increased vascular responsiveness in this population. NEW & NOTEWORTHY This study examined the effect of a spinal cord injury (SCI) and subsequent limb disuse on vascular function, assessed by %FMD, in diameter-matched vessels above and below the lesion in subjects with SCI and controls. The results reveal normal vascular function above the lesion and vascular dysfunction below the lesion (%FMD). However, below the lesion there was, actually, evidence of increased vascular responsiveness (%FMD/shear rate) in this population.

The role of nitric oxide (NO) as a modulator of functional sympatholysis has been debated in the literature, but the preponderance of evidence suggests that the magnitude of NO-mediated dilation is restrained by sympathetic vasoconstriction. Therefore, we hypothesized that passive leg movement (PLM)-induced vasodilation, which is predominantly NO-mediated, would be attenuated by an exercise-induced increase in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA, leg blood flow (LBF), and mean arterial blood pressure (MAP) were measured and leg vascular conductance (LVC) calculated in 9 healthy subjects (30 ± 3 yr), during PLM with and without sympathoexcitation evoked by arm-cranking exercise (ACE), at 25, 50, and 75% of maximal capacity. During this incremental intensity ACE, MSNA increased significantly (26 ± 2, 34 ± 3, and 41 ± 5 bursts/100 HB, respectively). LVC during PLM fell markedly (~1.2 ml/min/mmHg) with each increase in ACE intensity, and there was a strong relationship (r = 0.92; p < 0.05) between ΔMSNA and ΔPeak LVC induced by the three intensities of ACE. Thus, as anticipated, this study reveals that the, NO-mediated, PLM-induced vasodilation, is significantly and proportionally attenuated by exercise-induced MSNA. This finding highlights the dominant role of MSNA in regulating skeletal muscle vascular conductance.

We examined the interactive influence of the muscle reflex (MR) and the chemoreflex (CR) on the ventilatory response to exercise. Eleven healthy subjects (5 women/6 men) completed three bouts of constant-load single-leg knee-extension exercise in a control trial and an identical trial conducted with lumbar intrathecal fentanyl to attenuate neural feedback from lower-limb group III/IV muscle afferents. The exercise during the two trials was performed while breathing ambient air ([Formula: see text] ~97%, [Formula: see text] ~84 mmHg, [Formula: see text] ~32 mmHg, pH ~7.39), or under normocapnic hypoxia ([Formula: see text] ~79%, [Formula: see text] ~43 mmHg, [Formula: see text] ~33 mmHg, pH ~7.39) or normoxic hypercapnia ([Formula: see text] ~98%, [Formula: see text] ~105 mmHg, [Formula: see text] ~50 mmHg, pH ~7.26). During coactivation of the MR and the hypoxia-induced CR (O(2)-CR), minute ventilation (V̇e) and tidal volume (V(T)) were significantly greater compared with the sum of the responses to the activation of each reflex alone; there was no difference between the observed and summated responses in terms of breathing frequency (f(B); P = 0.4). During coactivation of the MR and the hypercapnia-induced CR (CO(2)-CR), the observed ventilatory responses were similar to the summated responses of the reflexes (P ≥ 0.1). Therefore, the interaction between the MR and the O(2)-CR exerts a hyperadditive effect on V̇e and V(T) and an additive effect on f(B), whereas the interaction between the MR and the CO(2)-CR is simply additive for all ventilatory parameters. These findings reveal that the MR:CR interaction further augments the ventilatory response to exercise in hypoxia. NEW & NOTEWORTHY Although the muscle reflex and the chemoreflex are recognized as independent feedback mechanisms regulating breathing during exercise, the ventilatory implications resulting from their interaction remain unclear. We quantified the individual and interactive effects of these reflexes during exercise and revealed differential modes of interaction. Importantly, the reflex interaction further amplifies the ventilatory response to exercise under hypoxemic conditions, highlighting a potential mechanism for optimizing arterial oxygenation in physically active humans at high altitude.

This short review offers a general summary of the consequences of whole body exercise on neuromuscular fatigue pertaining to the locomotor musculature. Research from the past two decades have shown that whole body exercise causes considerable peripheral and central fatigue. Three determinants characteristic for locomotor exercise are discussed, namely, pulmonary system limitations, neural feedback mechanisms, and mental/psychological influences. We also discuss existing data suggesting that the impact of whole body exercise is not limited to locomotor muscles, but can also impair non-locomotor muscles, such as respiratory and cardiac muscles, and other limb muscles not directly contributing to the task.

This review discusses evidence suggesting that group III/IV muscle afferents affect locomotor performance by influencing neuromuscular fatigue. These neurons regulate the hemodynamic and ventilatory response to exercise and, thus, assure appropriate locomotor muscle O2 delivery, which optimizes peripheral fatigue development and facilitates endurance performance. In terms of central fatigue, group III/IV muscle afferents inhibit motoneuronal output and thereby limit exercise performance.

Concentration of air pollutants such as tropospheric ozone and aerosols are mainly affected by meteorological variables and emissions. East Asia has large amount of anthropogenic and natural air pollutant emissions and has been putting lots of efforts to improve air quality. In order to seek effective ways to mitigate future air pollution, it is essential to understand the current emissions and their impacts on air quality. Emission inventory is one of the key datasets required to understand air quality and find ways to improve it. Amounts and spatial-temporal distributions of emissions are, however, not easy to estimate due to their complicate nature, therefore introduce significant uncertainties.In this study, we had developed an updated version of our Asian emissions inventory, named NIER/KU-CREATE (Comprehensive Regional Emissions inventory for Atmospheric Transport Experiment) in support of climate-air quality study. We first inter-compare multiple bottom-up inventories to understand discrepancies among the dataset(sectoral, spatial). We then inter-compare those bottom-up emissions to the satellite-based top-down emission estimates to understand uncertainties of the databases. The bottom-up emission inventories used for this study are: CREATE, MEIC(Multiresolution Emission Inventory for China), REAS (Regional Emission inventory in ASia), and ECLIPSE(Evaluating the Climate and Air Quality Impacts of Short-Lived Pollutants). The satellite-derived top-down emission inventory had been acquired from the DECSO (Daily Emission derived Constrained by Satellite Observations) algorithm data from the GlobEmissions website.The analysis showed that some discrepancies, in terms of emission amounts, sectoral shares and spatial distribution patterns, exist among the datasets. We analyzed further to find out which parameters could affect more on those discrepancies. Co-analysis of top-down and bottom-up emissions inventory help us to evaluate emissions amount and spatial distribution. These analysis are helpful for the development of more consistent and reliable inventories with the aim of reducing the uncertainties in air quality study. More results of evaluation of emissions will be presented on site. Acknowledgements : This work was supported by National Institute of Environment Research (NIER-2019-03-02-005), Korea Environment Industry & Technology Institute(KEITI) through Public Technology Program based on Environmental Policy Program, funded by Korea Ministry of Environment(MOE)(2019000160007). This research was supported by the National Strategic Project-Fine particle of the National Research Foundation of Korea(NRF) funded by the Ministry of Science and ICT(MSIT), the Ministry of Environment(ME), and the Ministry of Health and Welfare(MOHW) (NRF-2017M3D8A1092022).

Air pollution in Indian cities is a serious problem and a threat to human health. Kolkata Metropolitan City (KMC) is one of the Indian metro cities urgently requiring policy interventions to ensure breathable air in the near future. We developed a detailed emissions inventory of key air pollutants for 2015 in KMC, considering both particulate matter (PM10, PM2.5, BC, OC) and gaseous pollutants (SO2, NOx, CO, VOC and NH3). We estimated the emissions in a business-as-usual (BAU) scenario for the year 2030, while accounting for the impacts of current and planned policies. Our results reveal that current policies/measures are not sufficient to reduce PM2.5 emissions substantially in KMC by 2030. We thus explored three alternative policy scenarios considering various emission control strategies and non-technical city-specific control measures, along with associated cost implications. Our results indicate that significant emission reductions can be achieved (35% for PM2.5 and 45% for NOx) by spending €1.15 billion for advanced control measures across various sectors, compared with the business-as-usual scenario, are expected to cost €0.78 billion by 2030. Advanced control measures, coupled with the control of non-technical emission sources, may prove to be the most effective solution, yielding a significant reduction of key air pollutants (51% for PM2.5 and 54% for NOx) with a cost implication of €1.18 billion by 2030. Low carbon policies may also be able to substantially reduce key air pollutants with the additional co-benefit of reduced emissions of greenhouse gas, CO2 by 24% in 2030, with a running cost of €0.70 billion.

Air pollution is linked with many of the United Nations Sustainable Development Goals. Strategies aiming at the improved air quality interact directly with climate mitigation targets, access to clean energy services, waste management, and other aspects of socio-economic development. Continuation of current policies in the key emitting sectors implies that a number of sustainability goals will likely not be met within the next two decades: emissions of air pollutants would cause 40% more premature deaths from outdoor air pollution than today, carbon emissions would rise globally by 0.4% per year, while nearly two billion people would not have access to clean cooking. This paper examines integrated policies to put the world on track towards three interlinked goals of achieving universal energy access, limiting climate change and reducing air pollution. Scenario analysis suggests that these goals can be attained simultaneously with substantial benefits. By 2040, emissions of main pollutants are projected to drop by 60–80% relative to today, and associated health impacts are quantified at two million avoided deaths from ambient and household air pollution combined. In comparison to costs needed for the decarbonization of global economy, additional investments in air pollution control and access to clean fuels are very modest against major societal gains. However, holistic and systemic policy assessment is required to avoid potential trade-offs.

Key points This study investigated the influence of group III/IV muscle afferents on corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. The study provides novel evidence to demonstrate that group III/IV muscle afferent feedback facilitates inhibitory intracortical neurons during whole body exercise. Firing of these interneurons probably contributes to the development of central fatigue during physical activity. Abstract We investigated the influence of group III/IV muscle afferents in determining corticospinal excitability during cycling exercise and focused on GABAB neuron-mediated inhibition as a potential underlying mechanism. Both under control conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from group III/IV leg muscle afferents, subjects (n = 11) cycled at a comparable vastus-lateralis EMG signal (∼0.26 mV) before (PRE; 100 W) and immediately after (POST; 90 ± 2 W) fatiguing constant-load cycling exercise (80% Wpeak; 221 ± 10 W; ∼8 min). During, PRE and POST cycling, single and paired-pulse (100 ms interstimulus interval) transcranial magnetic stimulations (TMS) were applied to elicit unconditioned and conditioned motor-evoked potentials (MEPs), respectively. To distinguish between cortical and spinal contributions to the MEPs, cervicomedullary stimulations (CMS) were used to elicit unconditioned (CMS only) and conditioned (TMS+CMS, 100 ms interval) cervicomedullary motor-evoked potentials (CMEPs). While unconditioned MEPs were unchanged from PRE to POST in CTRL, unconditioned CMEPs increased significantly, resulting in a decrease in unconditioned MEP/CMEP (P 0.2). These findings reveal that feedback from group III/IV muscle afferents innervating locomotor muscle decreases the excitability of the motor cortex during fatiguing cycling exercise. This impairment is, at least in part, determined by the facilitating effect of these sensory neurons on inhibitory GABAB intracortical interneurons.