Dual function of thalamic low-vigilance state oscillations: rhythm-regulation and plasticity.

During inattentive wakefulness and non-rapid eye movement (NREM) sleep, the neocortex and thalamus cooperatively engage in rhythmic activities that are exquisitely reflected in the electroencephalogram as distinctive rhythms spanning a range of frequencies from <1 Hz slow waves to 13 Hz alpha waves. In the thalamus, these diverse activities emerge through the interaction of cell-intrinsic mechanisms and local and long-range synaptic inputs. One crucial feature, however, unifies thalamic oscillations of different frequencies: repetitive burst firing driven by voltage-dependent Ca2+ spikes. Recent evidence reveals that thalamic Ca2+ spikes are inextricably linked to global somatodendritic Ca2+ transients and are essential for several forms of thalamic plasticity. Thus, we propose herein that alongside their rhythm-regulation function, thalamic oscillations of low-vigilance states have a plasticity function that, through modifications of synaptic strength and cellular excitability in local neuronal assemblies, can shape ongoing oscillations during inattention and NREM sleep and may potentially reconfigure thalamic networks for faithful information processing during attentive wakefulness.

Comparison of aspartame- and sugar-sweetened soft drinks on postprandial metabolism.

Aim: We compared the impact of artificially- and sugar-sweetened beverages co-ingested with a mixed meal on postprandial fat and carbohydrate oxidation, blood glucose, and plasma insulin and triglyceride concentrations. Methods: Eight college-aged, healthy males completed three randomly assigned trials, which consisted of a mixed macronutrient meal test with 20oz of Diet-Coke (AS), Coca-Cola (NS), or water (CON). One week separated each trial and each participant served as his own control. Resting energy expenditure (REE) via indirect calorimetry, blood pressure, and blood samples were obtained immediately before, 5, 10, 30, 60, 120, and 180 min after meal and beverage ingestion. A two-way (treatment × time) repeated-measures ANOVA was conducted to assess REE, fat and carbohydrate oxidation rates, blood glucose, and plasma insulin and triglyceride concentrations. Results: There was a significant main effect of treatment on total fat oxidation (P = 0.006), fat oxidation was significantly higher after AS (P = 0.006) and CON (P = 0.001) compared to following NS. There was a significant main effect of treatment on total carbohydrate oxidation (P = 0.005), carbohydrate oxidation was significantly lower after AS (P = 0.014) and CON (P = 0.001) compared to following NS. Plasma insulin concentration AUC was significantly lower after AS (P = 0.019) and trended lower in CON (P = 0.054) compared to following NS. Conclusion: Ingestion of a mixed meal with an artificially-sweetened beverage does not impact postprandial metabolism, whereas a sugar-sweetened beverage suppresses fat oxidation and increases carbohydrate oxidation compared to artificially-sweetened beverage and water.

Effect of Prior Exercise on Postprandial Lipemia: An Updated Meta-Analysis and Systematic Review.

The purpose of this systematic review was to synthesize the results from current literature examining the effects of prior exercise on the postprandial triglyceride (TG) response to evaluate current literature and provide future direction. A quantitative review was performed using meta-analytic methods to quantify individual effect sizes. A moderator analysis was performed to investigate potential variables that could influence the effect of prior exercise on postprandial TG response. Two hundred and seventy-nine effects were retrieved from 165 studies for the total TG response and 142 effects from 87 studies for the incremental area under the curve TG response. There was a moderate effect of exercise on the total TG response (Cohen's d = -0.47; p < .0001). Moderator analysis revealed exercise energy expenditure significantly moderated the effect of prior exercise on the total TG response (p < .0001). Exercise modality (e.g., cardiovascular, resistance, combination of both cardiovascular and resistance, or standing), cardiovascular exercise type (e.g., continuous, interval, concurrent, or combined), and timing of exercise prior to meal administration significantly affected the total TG response (p < .001). Additionally, exercise had a moderate effect on the incremental area under the curve TG response (Cohen's d = -0.40; p < .0001). The current analysis reveals a more homogeneous data set than previously reported. The attenuation of postprandial TG appears largely dependent on exercise energy expenditure (∼2 MJ) and the timing of exercise. The effect of prior exercise on the postprandial TG response appears to be transient; therefore, exercise should be frequent to elicit an adaptation.

Prophylactic nipple-sparing mastectomy with immediate breast reconstruction: results of a French prospective trial.

BACKGROUND: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is used increasingly when performing a prophylactic mastectomy. Few prospective studies have reported on complication rates. This complementary trial to the French prospective multicentre MAPAM trial aimed to evaluate the nipple-areola complex (NAC) necrosis rate in prophylactic NSM with IBR. METHODS: Patient characteristics and surgical data were recorded. Morbidity after prophylactic NSM with a focus on NAC necrosis was analysed. RESULTS: Among 59 women undergoing prophylactic NSM, 19 (32 per cent) of the incisions were partly on the NAC. Reconstructions were performed with 46 definitive implants and 13 expanders. The crude rate of postoperative complications was 25 per cent (15 patients). Complete NAC necrosis was reported in two women (3 per cent) and partial or total necrosis in nine (15 per cent). No NAC resection was necessary. Median BMI was lower in women with total or partial NAC necrosis compared with the others (20.0 versus 21.3 kg/m2 respectively; P = 0.034). CONCLUSION: Results of this prospective study confirm that prophylactic NSM with IBR is associated with a low risk of total NAC necrosis.

Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures.

Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in early adulthood. Recent studies, however, show that 30% of children with absence seizures are pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions, including impairments in attention, cognition, memory and mood. In particular, attention deficits can be detected before the epilepsy diagnosis, may persist even when seizures are pharmacologically controlled and are aggravated by valproic acid monotherapy. New functional MRI-magnetoencephalography and functional MRI-EEG studies provide conclusive evidence that changes in blood oxygenation level-dependent signal amplitude and frequency in children with absence seizures can be detected in specific cortical networks at least 1 min before the start of a seizure, spike-wave discharges are not generalized at seizure onset and abnormal cortical network states remain during interictal periods. From a neurobiological perspective, recent electrical recordings and imaging of large neuronal ensembles with single-cell resolution in non-anaesthetized models show that, in contrast to the predominant opinion, cortical mechanisms, rather than an exclusively thalamic rhythmogenesis, are key in driving seizure ictogenesis and determining spike-wave frequency. Though synchronous ictal firing characterizes cortical and thalamic activity at the population level, individual cortico-thalamic and thalamocortical neurons are sparsely recruited to successive seizures and consecutive paroxysmal cycles within a seizure. New evidence strengthens previous findings on the essential role for basal ganglia networks in absence seizures, in particular the ictal increase in firing of substantia nigra GABAergic neurons. Thus, a key feature of thalamic ictogenesis is the powerful increase in the inhibition of thalamocortical neurons that originates at least from two sources, substantia nigra and thalamic reticular nucleus. This undoubtedly provides a major contribution to the ictal decrease in total firing and the ictal increase of T-type calcium channel-mediated burst firing of thalamocortical neurons, though the latter is not essential for seizure expression. Moreover, in some children and animal models with absence seizures, the ictal increase in thalamic inhibition is enhanced by the loss-of-function of the astrocytic GABA transporter GAT-1 that does not necessarily derive from a mutation in its gene. Together, these novel clinical and experimental findings bring about paradigm-shifting views of our understanding of absence seizures and demand careful choice of initial monotherapy and continuous neuropsychiatric evaluation of affected children. These issues are discussed here to focus future clinical and experimental research and help to identify novel therapeutic targets for treating both absence seizures and their comorbidities.

The patient advisor, an organizational resource as a lever for an enhanced oncology patient experience (PAROLE-onco): a longitudinal multiple case study protocol.

BACKGROUND: Quebec is one of the Canadian provinces with the highest rates of cancer incidence and prevalence. A study by the Rossy Cancer Network (RCN) of McGill university assessed six aspects of the patient experience among cancer patients and found that emotional support is the aspect most lacking. To improve this support, trained patient advisors (PAs) can be included as full-fledged members of the healthcare team, given that PA can rely on their knowledge with experiencing the disease and from using health and social care services to accompany cancer patients, they could help to round out the health and social care services offer in oncology. However, the feasibility of integrating PAs in clinical oncology teams has not been studied. In this multisite study, we will explore how to integrate PAs in clinical oncology teams and, under what conditions this can be successfully done. We aim to better understand effects of this PA intervention on patients, on the PAs themselves, the health and social care team, the administrators, and on the organization of services and to identify associated ethical and legal issues. METHODS/DESIGN: We will conduct six mixed methods longitudinal case studies. Qualitative data will be used to study the integration of the PAs into clinical oncology teams and to identify the factors that are facilitators and inhibitors of the process, the associated ethical and legal issues, and the challenges that the PAs experience. Quantitative data will be used to assess effects on patients, PAs and team members, if any, of the PA intervention. The results will be used to support oncology programs in the integration of PAs into their healthcare teams and to design a future randomized pragmatic trial to evaluate the impact of PAs as full-fledged members of clinical oncology teams on cancer patients' experience of emotional support throughout their care trajectory. DISCUSSION: This study will be the first to integrate PAs as full-fledged members of the clinical oncology team and to assess possible clinical and organizational level effects. Given the unique role of PAs, this study will complement the body of research on peer support and patient navigation. An additional innovative aspect of this study will be consideration of the ethical and legal issues at stake and how to address them in the health care organizations.

Tabata-style functional exercise increases resting and postprandial fat oxidation but does not reduce triglyceride concentrations.

NEW FINDINGS: What is the central question of this study? What are the metabolic impacts of high intensity functional Tabata exercise? What is the main finding and its importance? Tabata exercise with high intensity functional movements causes increases in fasted and postprandial fat oxidation the day after exercise without altering postprandial triglyceride concentrations. These results support the usage of a Tabata-style high intensity functional exercise to improve postprandial fat oxidation. ABSTRACT: We evaluated the effect of a high fat meal with and without prior high intensity functional exercise executed in a Tabata-style interval pattern on resting and postprandial substrate oxidation, as well as postprandial blood glucose and triglyceride concentrations. Eleven healthy males completed two trials (Tabata exercise (TE) and non-exercise control (CON)) in random order separated by 7 days. A two-day protocol was used in which TE or CON was performed on the first day and a high fat meal was administered ∼13 h later the following morning. Power output from the TE session was quantified using a kinematic approach by calculating external work performed per unit time for each of the four exercises (rowing, dumbbell thrusters, kettlebell swings and burpees). For the meal challenge, respiratory gases and blood samples were taken fasted and at 1, 2 and 3 h postprandial. Fat oxidation was significantly higher after TE compared to CON at all time points (P < 0.05). Carbohydrate oxidation was significantly lower after TE compared to CON at 1 h postprandial (P < 0.05). There were no significant effects of TE on fasting or postprandial glucose or triglyceride concentrations. Functional exercises performed in a high intensity TE pattern enhance fasting and postprandial fat oxidation on the following day with minimal influence on blood triglycerides or glucose levels.

Pharmacological and non-pharmacological treatments for neuropathic pain: Systematic review and French recommendations.

Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques and interventional management, but no comprehensive guideline encompassing all these treatments has yet been issued. We performed a systematic review of pharmacotherapy, neurostimulation, surgery, psychotherapies and other types of therapy for peripheral or central neuropathic pain, based on studies published in peer-reviewed journals before January 2018. The main inclusion criteria were chronic neuropathic pain for at least three months, a randomized controlled methodology, at least three weeks of follow-up, at least 10 patients per group, and a double-blind design for drug therapy. Based on the GRADE system, we provide weak-to-strong recommendations for use and proposal as a first-line treatment for SNRIs (duloxetine and venlafaxine), gabapentin and tricyclic antidepressants and, for topical lidocaine and transcutaneous electrical nerve stimulation specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a second-line treatment for pregabalin, tramadol, combination therapy (antidepressant combined with gabapentinoids), and for high-concentration capsaicin patches and botulinum toxin A specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a third-line treatment for high-frequency rTMS of the motor cortex, spinal cord stimulation (failed back surgery syndrome and painful diabetic polyneuropathy) and strong opioids (in the absence of an alternative). Psychotherapy (cognitive behavioral therapy and mindfulness) is recommended as a second-line therapy, as an add-on to other therapies. An algorithm encompassing all the recommended treatments is proposed.

Infrastructure for Integration of Legacy Electrical Equipment into a Smart-Grid Using Wireless Sensor Networks.

At present, the standardisation of electrical equipment communications is on the rise. In particular, manufacturers are releasing equipment for the smart grid endowed with communication protocols such as DNP3, IEC 61850, and MODBUS. However, there are legacy equipment operating in the electricity distribution network that cannot communicate using any of these protocols. Thus, we propose an infrastructure to allow the integration of legacy electrical equipment to smart grids by using wireless sensor networks (WSNs). In this infrastructure, each legacy electrical device is connected to a sensor node, and the sink node runs a middleware that enables the integration of this device into a smart grid based on suitable communication protocols. This middleware performs tasks such as the translation of messages between the power substation control centre (PSCC) and electrical equipment in the smart grid. Moreover, the infrastructure satisfies certain requirements for communication between the electrical equipment and the PSCC, such as enhanced security, short response time, and automatic configuration. The paper’s contributions include a solution that enables electrical companies to integrate their legacy equipment into smart-grid networks relying on any of the above mentioned communication protocols. This integration will reduce the costs related to the modernisation of power substations.

Direct Modification of Microcrystalline Cellulose with Ethylenediamine for use as Adsorbent for Removal Amitriptyline Drug from Environment.

Cellulose derivatives have been widely used as adsorbents for the removal of micropollutants such as drugs, dyes, and metals, due to their abundance, low cost and non-contaminating nature. In this context, several studies have been performed searching for new adsorbents (cellulose derivatives) efficient at contaminant removal from aqueous solutions. Thus, a new adsorbent was synthesized by chemical modification of cellulose with ethylenediamine in the absence of solvent and applied to the adsorption of amitriptyline (AMI) in aqueous solution. The modification reaction was confirmed by X-ray Diffraction (XRD), elemental analysis, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetry/Differential Scanning Calorimeter (TG/DSC), solid state Nuclear Magnetic Resonance of ¹H and 13C (¹H-NMR and 13C-NMR). Moreover, the effectiveness of reaction was confirmed by computational calculations using Density Functional Theory (DFT) at level B3LYP/6-31G(d). This adsorption process was influenced by pH, time, concentration, temperature and did not show significant changes due to the ionic strength variation. Through these experiments, it was observed that the maximum adsorption capacity of AMI by CN polymer at 298 K, 300 min, and pH 7 was 87.66 ± 0.60 mg·g-1.

Sleep slow wave-related homo and heterosynaptic LTD of intrathalamic GABAAergic synapses: involvement of T-type Ca2+ channels and metabotropic glutamate receptors.

Slow waves of non-REM sleep are suggested to play a role in shaping synaptic connectivity to consolidate recently acquired memories and/or restore synaptic homeostasis. During sleep slow waves, both GABAergic neurons of the nucleus reticularis thalami (NRT) and thalamocortical (TC) neurons discharge high-frequency bursts of action potentials mediated by low-threshold calcium spikes due to T-type Ca(2+) channel activation. Although such activity of the intrathalamic network characterized by high-frequency firing and calcium influx is highly suited to modify synaptic efficacy, very little is still known about its consequences on intrathalamic synapse strength. Combining in vitro electrophysiological recordings and calcium imaging, here we show that the inhibitory GABAergic synapses between NRT and TC neurons of the rat somatosensory nucleus develop a long-term depression (I-LTD) when challenged by a stimulation paradigm that mimics the thalamic network activity occurring during sleep slow waves. The mechanism underlying this plasticity presents unique features as it is both heterosynaptic and homosynaptic in nature and requires Ca(2+) entry selectively through T-type Ca(2+) channels and activation of the Ca(2+)-activated phosphatase, calcineurin. We propose that during slow-wave sleep the tight functional coupling between GABAA receptors, calcineurin, and T-type Ca(2+) channels will elicit LTD of the activated GABAergic synapses when coupled with concomitant activation of metabotropic glutamate receptors postsynaptic to cortical afferences. This I-LTD may be a key element involved in the reshaping of the somatosensory information pathway during sleep.

Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop.

Voltage-dependent calcium channels (Cav) of the T-type family (Cav3.1, Cav3.2, and Cav3.3) are activated by low threshold membrane depolarization and contribute greatly to neuronal network excitability. Enhanced T-type channel activity, especially Cav3.2, contributes to disease states, including absence epilepsy. Interestingly, the intracellular loop connecting domains I and II (I-II loop) of Cav3.2 channels is implicated in the control of both surface expression and channel gating, indicating that this I-II loop plays an important regulatory role in T-type current. Here we describe that co-expression of this I-II loop or its proximal region (Δ1-Cav3.2; Ser(423)-Pro(542)) together with recombinant full-length Cav3.2 channel inhibited T-type current without affecting channel expression and membrane incorporation. Similar T-type current inhibition was obtained in NG 108-15 neuroblastoma cells that constitutively express Cav3.2 channels. Of interest, Δ1-Cav3.2 inhibited both Cav3.2 and Cav3.1 but not Cav3.3 currents. Efficacy of Δ1-Cav3.2 to inhibit native T-type channels was assessed in thalamic neurons using viral transduction. We describe that T-type current was significantly inhibited in the ventrobasal neurons that express Cav3.1, whereas in nucleus reticularis thalami neurons that express Cav3.2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels.

Founder niche constrains evolutionary adaptive radiation.

Adaptive radiation of a lineage into a range of organisms with different niches underpins the evolution of life's diversity. Although the role of the environment in shaping adaptive radiation is well established, theory predicts that the evolvability and niche of the founding ancestor are also of importance. Direct demonstration of a causal link requires resolving the independent effects of these additional factors. Here, we accomplish this using experimental bacterial populations and demonstrate how the dynamics of adaptive radiation are constrained by the niche of the founder. We manipulated the propensity of the founder to undergo adaptive radiation and resolved the underlying causal changes in both its evolvability and niche. Evolvability did not change, but the propensity for adaptive radiation was altered by changes in the position and breadth of the niche of the founder. These observations provide direct empirical evidence for a link between the niche of organisms and their propensity for adaptive radiation. This general mechanism may have rendered the evolutionary dynamics of extant adaptive radiations dependent on chance events that determined their founding ancestors.

Essential thalamic contribution to slow waves of natural sleep.

Slow waves represent one of the prominent EEG signatures of non-rapid eye movement (non-REM) sleep and are thought to play an important role in the cellular and network plasticity that occurs during this behavioral state. These slow waves of natural sleep are currently considered to be exclusively generated by intrinsic and synaptic mechanisms within neocortical territories, although a role for the thalamus in this key physiological rhythm has been suggested but never demonstrated. Combining neuronal ensemble recordings, microdialysis, and optogenetics, here we show that the block of the thalamic output to the neocortex markedly (up to 50%) decreases the frequency of slow waves recorded during non-REM sleep in freely moving, naturally sleeping-waking rats. A smaller volume of thalamic inactivation than during sleep is required for observing similar effects on EEG slow waves recorded during anesthesia, a condition in which both bursts and single action potentials of thalamocortical neurons are almost exclusively dependent on T-type calcium channels. Thalamic inactivation more strongly reduces spindles than slow waves during both anesthesia and natural sleep. Moreover, selective excitation of thalamocortical neurons strongly entrains EEG slow waves in a narrow frequency band (0.75-1.5 Hz) only when thalamic T-type calcium channels are functionally active. These results demonstrate that the thalamus finely tunes the frequency of slow waves during non-REM sleep and anesthesia, and thus provide the first conclusive evidence that a dynamic interplay of the neocortical and thalamic oscillators of slow waves is required for the full expression of this key physiological EEG rhythm.

Role for T-type Ca2+ channels in sleep waves.

Since their discovery more than 30 years ago, low-threshold T-type Ca(2+) channels (T channels) have been suggested to play a key role in many EEG waves of non-REM sleep, which has remained exclusively linked to the ability of these channels to generate low-threshold Ca(2+) potentials and associated high-frequency bursts of action potentials. Our present understanding of the biophysics and physiology of T channels, however, highlights a much more diverse and complex picture of the pivotal contributions that they make to different sleep rhythms. In particular, recent experimental evidence has conclusively demonstrated the essential contribution of thalamic T channels to the expression of slow waves of natural sleep and the key role played by Ca(2+) entry through these channels in the activation or modulation of other voltage-dependent channels that are important for the generation of both slow waves and sleep spindles. However, the precise contribution to sleep rhythms of T channels in cortical neurons and other sleep-controlling neuronal networks remains unknown, and a full understanding of the cellular and network mechanisms of sleep delta waves is still lacking.

The many faces of T-type calcium channels.

Since the discovery of low-voltage-activated T-type calcium channels in sensory neurons and the initial characterization of their physiological function mainly in inferior olive and thalamic neurons, studies on neuronal T-type currents have predominantly focused on the generation of low-threshold spike (and associated action potential burst firing) which is strictly conditioned by a preceding hyperpolarization. This T-type current mediated activity has become an archetype of the function of these channels, constraining our view of the potential physiological and pathological roles that they may play in controlling the excitability of single cells and neural networks. However, greatly helped by the recent availability of the first potent and selective antagonists for this class of calcium channels, novel T-type current functions are rapidly being uncovered, including their surprising involvement in neuronal excitability at depolarized membrane potentials and their complex control of dendritic integration and neurotransmitter release. These and other data summarized in this short review clearly indicate a much wider physiological involvement of T-type channels in neuronal activity than previously expected.

Search for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ in Super-Kamiokande.

We present the results of searches for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ using data from a combined 172.8 kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τn→ν[over ¯]π0>1.1×10(33) years and τp→ν[over ¯]π+>3.9×10(32) years at a 90% confidence level.

Search for dinucleon decay into kaons in Super-Kamiokande.

A search for the dinucleon decay pp → K+ K+ has been performed using 91.6 kton·yr data from Super-Kamiokande-I. This decay provides a sensitive probe of the R-parity-violating parameter λ112''. A boosted decision tree analysis found no signal candidates in the data. The expected background was 0.28±0.19 atmospheric neutrino induced events and the estimated signal detection efficiency was 12.6%±3.2%. A lower limit of 1.7×10(32) years has been placed on the partial lifetime of the decay O16 → C14K+ K+ at 90% C.L. A corresponding upper limit of 7.8×10(-9) has been placed on the parameter λ112''.

Impact of aerobic fitness status, menstrual cycle phase, and oral contraceptive use on exercise substrate oxidation and metabolic flexibility in females.

The influence of menstrual cycle phase and fitness status on metabolism during high-intensity interval exercise (HIIE) was assessed. Twenty-five females (24.4 (3.6) years) were categorized by normal menstrual cycle (n = 14) vs. oral contraceptive (OC) use (n = 11) and by aerobic fitness, high-fitness females (HFF; n = 13) vs. low-fitness females (LFF; n = 12). HIIE was four sets of four repetitions with a 3 min rest between intervals on a cycle ergometer at a power output halfway between the ventilatory threshold and V̇O2peak and performed during follicular (FOL: days 2-7 or inactive pills) and luteal phases (LUT: day ∼21 or 3rd week of active pills). Substrate oxidation was assessed via indirect calorimetry, blood lactate via finger stick, and recovery of skeletal muscle oxidative metabolism (mV̇O2) via continuous-wave near-infrared spectroscopy. HFF oxidized more fat (g·kg-1) during the full session (FOL: p = 0.050, LUT: p = 0.001), high intervals (FOL: p = 0.048, LUT: p = 0.001), low intervals (FOL: p = 0.032, LUT: p = 0.024), and LUT recovery (p = 0.033). Carbohydrate oxidation area under the curve was greater in HFF during FOL (FOL: p = 0.049, LUT: p = 0.124). Blood lactate was lower in LFF in FOL (p ≤ 0.05) but not in LUT. Metabolic flexibility (Δ fat oxidation g·kg-1·min-1) was greater in HFF than LFF during intervals 2-3 in FOL and 1-4 in LUT (p ≤ 0.05). Fitness status more positively influences exercise metabolic flexibility during HIIE than cycle phase or OC use.