Menstrual cycle does not impact the hypoxic ventilatory response and acute mountain sickness prediction.

The relationship between the variations in ovarian hormones (i.e., estrogens and progesterone) and the hypoxic ventilatory response (HVR) remains unclear. HVR is a key adaptive mechanism to high altitude and has been proposed as a predictor for acute mountain sickness (AMS). This study aimed to explore the effects of hormonal changes across the menstrual cycle on HVR. Additionally, it assessed the predictive capacity of HVR for AMS and examined whether a particular menstrual phase could enhance its predictive accuracy. Thirteen eumenorrheic women performed a pure nitrogen breathing test near sea level, measuring HVR and cerebral oxygenation in early follicular, late follicular, and mid-luteal phases. Oxidative stress and ovarian hormone levels were also measured. AMS symptoms were evaluated after spending 14 h, including one overnight, at an altitude of 3,375 m. No differences in HVR, ventilation, peripheral oxygen saturation, or cerebral oxygenation were observed between the three menstrual cycle phases. Moreover, these parameters and the oxidative stress markers did not differ between the women with or without AMS (31% vs 69%), regardless of the menstrual cycle phase. In conclusion, ventilatory responses and cerebral oxygenation in normobaric hypoxia were consistent across the menstrual cycle. Furthermore, these parameters did not differentiate women with or without AMS.

Impact of Isolated Type 2 Endoleak on Subsequent Cardiovascular Events and Mortality.

BACKGROUND: Assess subsequent cardiovascular events and all-cause mortality in patients with intact abdominal aortic aneurysm (AAA) treated by endovascular aneurysm repair (EVAR) according to the existence of isolated endoleak type 2 (EL2) at 1 year after EVAR implantation. METHODS: This retrospective, single-center study included patients treated with EVAR between 2010 and 2017 in the vascular surgery department of the University Hospital of Lyon with an infrarenal AAA > 50 mm. The baseline clinical characteristics collected just before EVAR were retrieved from electronic patient records of our institution. AAA characteristics, procedure, and the 1-year postoperative computed tomography angiography (CTA) were reported. Study end points, major adverse cardiovascular events (MACE), major adverse lower-extremity events (MALE), and all-cause mortality were recorded during follow-up. Patients were divided into 2 groups according to the presence of isolated EL2 (EL2 +) or absence (EL2 -) of any endoleak on CTA at 1 year. MACE, MALE, and all-cause mortality were compared between both groups. RESULTS: During the study period, 589 patients were treated by endovascular surgery and 207 were included. According to the CTA results at 1 year, 60 patients (29%) were included in the EL2 + group and 147 patients (71%) in the EL2 - group. A total of 109 patients (53%) experienced a MACE or MALE; significantly fewer patients in the EL2 + than in the EL2 - group did so (P = 0.009). There were 47 patients (23%) who experienced at least 1 MALE, and the frequency was significantly lower in the EL2 + group (P = 0.017). CONCLUSIONS: Patients with AAA treated by EVAR who did not develop EL2 at 1 year were at higher risk of MALE during follow-up. This might be explained by more frequent symptomatic lower extremity peripheral arterial disease at baseline in this group. These patients therefore require a closer follow-up and strict control of cardiovascular risk factors to prevent cardiovascular morbi-mortality.

Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling.

Athletes increasingly engage in repeated sprint training consisting in repeated short all-out efforts interspersed by short recoveries. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN); however, the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle metabolic adaptations as compared to RSN. Sixteen healthy young men performed nine repeated sprint training sessions in either normoxia (FIO2 = 0.209, RSN, n = 7) or normobaric hypoxia (FIO2 = 0.136, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomics combined with western blot analysis. Similar improvements were observed in RSA and Wingate tests in both RSN and RSH groups. At the muscle level, RSN and RSH reduced oxidative phosphorylation protein content but triggered an increase in mitochondrial biogenesis proteins. Proteomics showed an increase in several S100A family proteins in the RSH group, among which S100A13 most strongly. We confirmed a significant increase in S100A13 protein by western blot in RSH, which was associated with increased Akt phosphorylation and its downstream targets regulating protein synthesis. Altogether our data indicate that RSH may activate an S100A/Akt pathway to trigger specific adaptations as compared to RSN.

Combined effects of exercise and immuno-chemotherapy treatments on tumor growth in MC38 colorectal cancer-bearing mice.

Acute exercise induces transient modifications in the tumor microenvironment and has been linked to reduced tumor growth along with increased infiltration of immune cells within the tumor in mouse models. In this study, we aimed to evaluate the impact of acute exercise before treatment administration on tumor growth in a mice model of MC38 colorectal cancer receiving an immune checkpoint inhibitor (ICI) and chemotherapy. Six-week-old mice injected with colorectal cancer cells (MC38) were randomized in 4 groups: control (CTRL), immuno-chemotherapy (TRT), exercise (EXE) and combined intervention (TRT/EXE). Both TRT and TRT-EXE received ICI: anti-PD1-1 (1 injection/week) and capecitabine + oxaliplatin (5 times a week) for 1 week (experimentation 1), 3 weeks (experimentation 2). TRT-EXE and EXE groups were submitted to 50 minutes of treadmill exercise before each treatment administration. Over the protocol duration, tumor size has been monitored daily. Tumor growth and microenvironment parameters were measured after the intervention on Day 7 (D7) and Day 16 (D16). From day 4 to day 7, tumor volumes decreased in the EXE/TRT group while remaining stable in the TRT group (p=0.0213). From day 7 until day 16 tumor volume decreased with no significant difference between TRT and TRT/EXE. At D7 the TRT/EXE group exhibited a higher total infiltrate T cell (p=0.0118) and CD8+ cytotoxic T cell (p=0.0031). At D16, tumor marker of apoptosis, vascular integrity and inflammation were not significantly different between TRT and TRT/EXE. Our main result was that acute exercise before immuno-chemotherapy administration significantly decreased early-phase tumor growth (D0 to D4). Additionally, exercise led to immune cell infiltration changes during the first week after exercise, while no significant molecular alterations in the tumor were observed 3 weeks after exercise.

Differential effects of high-altitude exposure on markers of oxidative stress, antioxidant capacity, and iron profiles.

High-altitude (HA) exposure may stimulate significant physiological and molecular changes, resulting in HA-related illnesses. HA may impact oxidative stress, antioxidant capacity, and iron homeostasis, yet it is unclear how both repeated exposure and HA acclimatization may modulate such effects. Therefore, we assessed the effects of weeklong repeated daily HA exposure (2,900-5,050 m) in altitude-naïve individuals (n = 21 individuals, 13 females, mean ± SD, 25.3 ± 3.7 yr) to mirror the working schedule of HA workers (n = 19 individuals, all males, 41.1 ± 9.4 yr) at the Atacama Large Millimeter Array (ALMA) Observatory (San Pedro de Atacama, Chile). Markers of oxidative stress, antioxidant capacity, and iron homeostasis were measured in blood plasma. Levels of protein oxidation (P < 0.001) and catalase activity (P = 0.023) increased and serum iron (P < 0.001), serum ferritin (P < 0.001), and transferrin saturation (P < 0.001) levels decreased with HA exposure in both groups. HA workers had lower levels of oxidative stress, and higher levels of antioxidant capacity, iron supply, and hemoglobin concentration as compared with altitude-naïve individuals. On a second week of daily HA exposure, changes in levels of protein oxidation, glutathione peroxidase, and nitric oxide metabolites were lower as compared with the first week in altitude-naïve individuals. These results indicate that repeated exposure to HA may significantly alter oxidative stress and iron homeostasis, and the degree of such changes may be dependent on if HA is visited naïvely or routinely. Further studies are required to fully elucidate differences in HA-induced changes in oxidative stress and iron homeostasis profiles among visitors of HA.

Effect of acute aerobic exercise before immunotherapy and chemotherapy infusion in patients with metastatic non-small-cell lung cancer: protocol for the ERICA feasibility trial.

INTRODUCTION: Patients with metastatic non-small cell lung cancer (mNSCLC) suffer from numerous symptoms linked to disease and treatment which may further impair the patient's overall condition. In addition to its benefits on quality of life and fatigue, physical exercise may improve treatment response, notably due to its known effects on the immune system. The ERICA study is designed to assess the feasibility of a supervised acute physical exercise therapy realised immediately prior immune-chemotherapy infusion in patients with mNSCLC. Secondary objectives will examine the effects of acute exercise combined with an unsupervised home-walking programme on clinical, physical, psychosocial and biological parameters. METHODS AND ANALYSIS: ERICA is a prospective, monocentric, randomised controlled, open-label feasibility study conducted at the Centre Léon Bérard Comprehensive Cancer Center (France). Thirty patients newly diagnosed with mNSCLC will be randomised (2:1 ratio) to the 'exercise' or the 'control' group. At baseline and during the last treatment cycle, participants in both groups will receive Physical Activity recommendations, and two nutritional assessments. In the exercise group, participants will receive a 3-month programme consisting of a supervised acute physical exercise session prior to immune-chemotherapy infusion, and an unsupervised home-based walking programme with an activity tracker. The acute exercise consists of 35 min interval training at submaximal intensity scheduled to terminate 15 min prior to infusion. Clinical, physical, biological and psychosocial parameters will be assessed at baseline, 3 and 6 months after inclusion. Biological measures will include immune, inflammatory, metabolic, oxidative stress biomarkers and molecular profiling. ETHICS AND DISSEMINATION: The study protocol was approved by the French ethics committee (Comité de protection des personnes Ile de France II, N°ID-RCB 20.09.04.65226, 8 December 2020). The study is registered on ClinicalTrials.gov (NCT number:NCT04676009) and is at the pre-results stage. All participants will sign an informed consent form. The findings will be disseminated in peer-reviewed journals and academic conferences.

Effectiveness of an individualized home-based physical activity program in surgery-free non-endarterectomized asymptomatic stroke patients: a study protocol for the PACAPh interventional randomized trial.

BACKGROUND: Carotid atherosclerotic plaques remain silent until their rupture, which may lead to detrimental ischemic events such as strokes. This is due, in part, to intraplaque hemorrhages (IPH) and the resulting inflammatory processes, which may promote carotid plaque vulnerability. Currently, the benefits of carotid endarterectomy remain unclear for asymptomatic patients. Interestingly, the completion of physical activity (PA) may have beneficial effects; however, the paucity of current data warrants robust longitudinal interventions. We therefore aim to study the effects of a 6-month longitudinal personalized home-based PA program on IPH, biological, and inflammatory markers in asymptomatic stroke patients. METHODS: Eighty patients (≥ 18 years old) will be recruited for the Physical Activity and Carotid Atherosclerotic Plaque Hemorrhage (PACAPh) clinical trial from the Hospices Civils de Lyon. Patients will be eligible if they present with carotid stenosis ≥ 50% and are asymptomatic from any ischemic events for at least 6 months. Recruited patients will be randomized into either a PA or a control group, and assessed at baseline and after 6 months. At both time points, all patients will be assessed using magnetic resonance imaging to assess IPH, blood sampling to measure inflammatory markers and monocytic phenotyping, PA and sedentary behavior questionnaires, 6-min walking test, and maximal isometric quadricep contraction test. The randomized PA intervention will consist of reaching a daily walking step goal individually tailored to each patient. Steps will be collected using a wirelessly connected wristband. The number of steps completed by individuals in the PA group will be re-evaluated bimonthly to encourage walking habits. DISCUSSION: The PACAPh study is the first of its kind representing a feasible, easily accessible therapeutic strategy for asymptomatic stroke patients. We hypothesize that the personalized home-based PA program will reduce IPH and modulate inflammatory and biological parameters in patients presenting with carotid plaques. If the results of the PACAPh study prove to be beneficial on such health parameters, the implementation of such kind of intervention in the daily treatment of these patients would be an advantageous and cost-effective practice to adopt globally. TRIAL REGISTRATION: This study has been approved by the National Ethics Committee (IDRCB:2019-A01543-54/SI:19.06.21.40640). ClinicalTrials.gov NCT04053166.

Beneficial Effects of High Intensity Interval Training and/or Linseed Oil Supplementation to Limit Obesity-Induced Oxidative Stress in High Fat Diet-Fed Rats.

High-intensity interval training (HIIT) and linseed oil (LO) supplementation are effective strategies to reduce obesity-induced oxidative stress. Our aim was to determine whether the HIIT + LO combination prevents obesity-induced oxidative stress in high fat diet (HFD)-fed rats. HFD-fed 8-week-old, male, Wistar rats were subdivided in four groups: HFD, LO (2% of sunflower oil replaced with 2% of LO in the HFD), HIIT (4 days/week for 12 weeks), and HIIT + LO. Wistar rats fed a low-fat diet (LFD) were used as controls. Epididymal and subcutaneous adipose tissue, gastrocnemius muscle, liver, and plasma samples were collected to measure oxidative stress markers (AOPP, oxLDL), antioxidant (SOD, CAT, and GPx activities) and pro-oxidant (NOx and XO) enzyme activities. Compared with the LFD, the HFD altered the pro/antioxidant status in different tissues (increase of AOPP, oxLDL, SOD and catalase activities in plasma, and SOD activity increase in liver and decrease in adipose tissues) but not in gastrocnemius. LO upregulated CAT activity and decreased NOx in liver. HIIT alleviated HFD negative effects in liver by reducing SOD and NOx activities. Moreover, the HIIT + LO combination potentiated SOD activity upregulation in subcutaneous tissue. HIIT and LO supplementation have independent beneficial effects on the pro/antioxidant balance. Their association promotes SOD activity in subcutaneous adipose tissue.

Impact of Physical Activity on Oxidative Stress Markers in Patients with Metastatic Breast Cancer.

PURPOSE: Regular physical activity (PA) can affect oxidative stress, known to be involved in carcinogenesis. The objective of this study was to evaluate the associations between a six-month PA intervention and oxidative stress biomarkers, PA, and clinical outcomes in patients with metastatic breast cancer. METHODS: Forty-nine newly diagnosed patients with metastatic breast cancer were recruited for a single-arm, unsupervised, and personalized six-month walking intervention with activity tracker. PA level and PA fitness, plasma concentrations of DNA oxidation (8OhdG), lipid peroxidation (MDA), and protein oxidation (AOPP), plasma activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase, plasma and leucocyte activities of myeloperoxidase (MPO) and NADPH oxidase (NOX), and clinical markers of tumor progression (RECIST criteria) were measured at baseline and after the six-month intervention. RESULTS: GPX activity (+17%) and MDA (+9%) significantly increased between baseline and the end of the intervention. Changes in PA level and fitness were significantly positively correlated with changes in plasma GPX and significantly negatively with changes in NOX in the leucocytes. Plasma MDA was significantly higher (+20%) whereas plasma AOPP was lower (-46%) for patients with tumor progression or that died during the six months as compared to patients without progression. CONCLUSION: A six-month PA intervention may be potentially beneficial in metastatic breast cancer patients for enhancing antioxidant enzyme activity and decreasing prooxidant enzyme activity. Moreover, AOPP and MDA could also be favorable and unfavorable biomarkers, respectively, since they are associated with disease progression and fitness level in this population. This trial is registered with NCT number: NCT03148886.

The TOTUM-63 Supplement and High-Intensity Interval Training Combination Limits Weight Gain, Improves Glycemic Control, and Influences the Composition of Gut Mucosa-Associated Bacteria in Rats on a High Fat Diet.

Obesity and prediabetes are the two strongest risk factors of type 2 diabetes. It has been reported that TOTUM-63, a polyphenol-rich plant extract, has beneficial effects on body weight (BW) and insulin resistance in mice fed a high fat diet (HFD). The study aim was to determine whether high-intensity interval training (HIIT) and/or TOTUM-63 supplementation improved body composition and glycemic control and gut microbiota composition in a Western diet-induced obesity rat model. Wistar rats received a standard diet (CTRL; control; n = 12) or HFD (HFD; n = 48) for 16 weeks. Then, HFD rats were divided in four groups: HFD, HFD + TOTUM-63 (T63), HFD + HIIT (HIIT), and HFD + HIIT +T63 (HIIT + T63). Training was performed 4 days/week for 12 weeks. TOTUM-63 was included in diet composition (2%). The HIIT + T63 combination significantly limited BW gain, without any energy intake modulation, and improved glycemic control. BW variation was correlated with increased α-diversity of the colon mucosa microbiota in the HIIT + T63 group. Moreover, the relative abundance of Anaeroplasma, Christensenellaceae and Oscillospira was higher in the HIIT + T63 group. Altogether, these results suggest that the HIIT and TOTUM-63 combination could be proposed for the management of obesity and prediabetes.

Sarcopenia and serum biomarkers of oxidative stress after a 6-month physical activity intervention in women with metastatic breast cancer: results from the ABLE feasibility trial.

PURPOSE: Sarcopenia has been identified as an important prognostic factor for patients with cancer. This study aimed at exploring the potential associations between a 6-month physical activity intervention and muscle characteristics, sarcopenia, oxidative stress and toxicities in patients with metastatic breast cancer. METHODS: Women newly diagnosed with metastatic breast cancer (N = 49) participated in an unsupervised, personalized, 6-month physical activity intervention with activity tracker. Computerized tomography images at the third lumbar vertebra were analysed at baseline, three months and six months to assess sarcopenia (muscle mass index < 40 cm2/m2) and muscle quality (poor if muscle attenuation < 37.8 Hounsfield Units). Oxidative markers included plasma antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase activities), prooxidant enzymes (NADPH oxidase and myeloperoxidase activities) and oxidative stress damage markers (advanced oxidation protein products, malondialdehyde (MDA) and DNA oxidation. RESULTS: At baseline 53% (mean age 55 years (SD 10.41)) were sarcopenic and 75% had poor muscle quality. Muscle cross sectional area, skeletal muscle radiodensity, lean body mass remained constant over the six months (p = 0.75, p = 0.07 and p = 0.75 respectively), but differed significantly between sarcopenic and non-sarcopenic patients at baseline and 6-months. Sarcopenic patients at baseline were more likely to have an increase of MDA (p = 0.02) at 6 months. Being sarcopenic during at least one moment during the 6-month study was associated with a higher risk of developing severe toxicities (grade > 2) (p = 0.02). CONCLUSIONS: This study suggests potential benefits of physical activity for maintenance of muscle mass. Sarcopenia can alter many parameters and disturb the pro and antioxidant balance.

Effects of an Exercise and Nutritional Intervention on Circulating Biomarkers and Metabolomic Profiling During Adjuvant Treatment for Localized Breast Cancer: Results From the PASAPAS Feasibility Randomized Controlled Trial.

PURPOSE: Exercise has been shown to improve physical and psychological conditions during cancer therapy, but mechanisms remain poorly understood. The purpose of the present study was to report the results of cancer-related biomarkers and metabolomics outcomes from the PASAPAS feasibility study. METHODS: In the PASAPAS randomized controlled trial, 61 women beginning adjuvant chemotherapy for localized breast cancer were randomized in a 6-month program of weekly aerobic exercises associated with nutritional counseling versus usual care with nutritional counseling. In the present analysis of 58 women for whom blood samples were available, first, circulating levels of biomarkers (ie, insulin, insulin-like growth factor 1, estradiol, adiponectin, leptin, interleukin-6, and tumor necrosis factor α) were measured at baseline and 6-month follow-up. Changes in biomarkers were compared between exercisers (n = 40) and controls (n = 18) using mixed-effect models. Second, serum metabolites were studied using an untargeted 1H nuclear magnetic resonance spectroscopy, and orthogonal partial least squares analyses were performed to discriminate exercisers and controls at baseline and at 6 months. RESULTS: Over the 6-month intervention, no statistically significant differences were observed between exercisers and controls regarding changes in biomarkers and metabolomic profiles. CONCLUSION: The present analysis of the PASAPAS feasibility trial did not reveal any improvement in circulating biomarkers nor identified metabolic signatures in exercisers versus controls during adjuvant breast cancer treatment. Larger studies preferably in women with poor physical activity level to avoid ceiling effect, testing different doses and types of exercise on additional biological pathways, could allow to clarify the mechanisms mediating beneficial effects of physical exercise during cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01331772. Registered 8 April 2011, https://clinicaltrials.gov/ct2/show/NCT01331772?term=pasapas&rank=1.

Lung oxidative stress and transcriptional regulations induced by estradiol and intermittent hypoxia.

We determined the effects of chronic intermittent hypoxia (CIH) and estradiol (E2) on oxidative stress and gene expression in the lungs. Female Sprague-Dawley rats were left intact (sham) or ovariectomized (OVX) and implanted with pumps delivering vehicle or E2 (0.5 mg/kg/day). Two weeks following surgery, the rats were exposed to room air (RA) or CIH for 7 days (10% O2, 10 cycles/hour, 8 h/day). Lung samples were used to measure the activities of pro- (NADPH and xanthine oxidases) and antioxidant (superoxide dismutase, catalase and glutathione peroxidase) enzymes, and concentrations of advanced oxidation of protein products (AOPP). We determined gene expression with an RNA microarray and enrichment analysis of differentially expressed genes. In rats exposed to RA, OVX and E2 supplementation increased pro- and antioxidant activities and AOPP concentration. In rats exposed to CIH, AOPP concentration, pro- and antioxidant enzymes activities increased in sham, did not changed in OVX-Veh rats, and were reduced in OVX-E2 rats. In rats exposed to RA, genes involved in extracellular matrix were up-regulated by OVX and down-regulated by E2, while E2 up-regulated genes involved in cell mobility/adherence and leukocytes migration. OVX downregulated expression of roughly 200 olfactory receptor genes without effect of E2. CIH altered gene expression in sham and OVX-E2, but not in OVX-Veh rats. Enrichment analysis confirmed the antioxidant effects of E2 under CIH. There are important interactions between ovarian hormones and CIH that can be relevant to better understand the consequences of sleep apnea (i.e. CIH) on the occurrence of lung pathologies in women.

Carotid intraplaque haemorrhage: pathogenesis, histological classification, imaging methods and clinical value.

Vulnerable carotid atherosclerotic plaques are characterised by several risk factors, such as inflammation, neovascularization and intraplaque haemorrhage (IPH). Vulnerable plaques can lead to ischemic events such as stroke. Many studies reported a relationship between IPH, plaque rupture, and ischemic stroke. Histology is the gold standard to evaluate IPH, but it required carotid endarterectomy (CEA) surgery to collect the tissue sample. In this context, several imaging methods can be used as a non-invasive way to evaluate plaque vulnerability and detect IPH. Most imaging studies showed that IPH is associated with plaque vulnerability and stroke, with magnetic resonance imaging (MRI) being the most sensitive and specific to detect IPH as a predictor of ischemic events. These conclusions are however still debated because of the limited number of patients included in these studies; further studies are required to better assess risks associated with different IPH stages. Moreover, IPH is implicated in plaque vulnerability with other risk factors which need to be considered to predict ischemic risk. In addition, MRI sequences standardization is required to compare results from different studies and agree on biomarkers that need to be considered to predict plaque rupture. In these circumstances, IPH detection by MRI could be an efficient clinical method to predict stroke. The goal of this review article is to first describe the pathophysiological process responsible for IPH, its histological detection in carotid plaques and its correlation with plaque rupture. The second part will discuss the benefits and limitations of imaging the carotid plaque, and finally the clinical interest of imaging IPH to predict plaque rupture, focusing on MRI-IPH.

Design and methods of a national, multicenter, randomized and controlled trial to assess the efficacy of a physical activity program to improve health-related quality of life and reduce fatigue in women with metastatic breast cancer: ABLE02 trial.

BACKGROUND: Patients with a metastatic breast cancer suffer from a deteriorated health-related quality of life and numerous symptoms such as pain, severe fatigue and a decrease of their physical fitness. As the feasibility of a physical activity program has been demonstrated in this population, ABLE02 aims to assess the efficacy of a 6 month-physical activity program using connected devices to improve health-related quality of life and to reduce fatigue in women with metastatic breast cancer. METHODS: ABLE02 is a prospective, national, multicenter, randomized, controlled and open-label study. A total of 244 patients with a metastatic breast cancer, with at least one positive hormone receptor and a first-line chemotherapy planned, will be randomly assigned (1:1 ratio) to: (i) the intervention arm to receive physical activity recommendations, an activity tracker to wear 24 h a day during the whole intervention (6 months) with at least three weekly walking sessions and quizzes each week on physical activity and nutrition (ii) the control arm to receive physical activity recommendations only. Health-related quality of life will be assessed every 6 weeks and main assessments will be conducted at baseline, M3, M6, M12 and M18 to evaluate the clinical, physical, biological and psychological parameters and survival of participants. All questionnaires will be completed on a dedicated application. DISCUSSION: An activity program based on a smartphone application linked to an activity tracker may help to improve quality of life and reduce fatigue of patients with a metastatic breast cancer. The growth of e-health offers the opportunity to get real-time data as well as improving patient empowerment in order to change long-term behaviors. TRIAL REGISTRATION: NCT number: NCT04354233 .

Progesterone decreases apnoea and reduces oxidative stress induced by chronic intermittent hypoxia in ovariectomized female rats.

NEW FINDINGS: What is the central question of this study? Does progesterone reduce the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory control and oxidative stress in the central nervous system in ovariectomized rats? What is the main finding and its importance? Progesterone does not prevent the elevation of arterial blood pressure in rats exposed to CIH, but normalizes respiratory control, and reduces cerebral oxidative stress. This study draws focus to a potential role of progesterone and the consequences of sleep apnoea in menopausal women. ABSTRACT: We tested the hypothesis that progesterone (Prog) reduces the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory chemoreflexes and oxidative stress in the central nervous system. Ovariectomized female rats were implanted with osmotic pumps delivering vehicle (Veh) or Prog (4 mg kg-1  day-1 ). Two weeks following the surgery, rats were exposed to room air (Air) or CIH (7 days, 10% O2 , 10 cycles h-1 , 8 h day-1 ). We studied three groups: Veh-Air, Veh-CIH and Prog-CIH. After the CIH exposures, we measured the mean arterial pressure (MAP; tail cuff) and assessed the frequency of apnoeas at rest and ventilatory responses to hypoxia and hypercapnia (whole body plethysmography). The activities of the pro-oxidant enzyme NADPH oxidase (NOX) and antioxidant enzymes superoxide dismutase (SOD; in mitochondrial and cytosolic fractions) and glutathione peroxidase (GPx), as well as the concentration of malondialdehyde (MDA), a marker of lipid peroxidation, were measured in brain cortex and brainstem samples. CIH exposure increased the MAP, the frequency of apnoeas, and the respiratory frequency response to hypoxia and hypercapnia. Prog did not prevent the CIH-induced elevation in MAP, but it reduced the CIH-induced frequency of apnoeas and increased hypoxic and hypercapnic ventilatory responses. In the brain cortex, CIH increased NOX activity, and decreased the cytosolic and mitochondrial SOD activities. These effects were prevented by Prog. NOX activity was increased by CIH in the brainstem, and this was also blocked by Prog. The study draws focus to the links between ovarian hormones and the consequences of sleep apnoea in women.

Feasibility and Health Benefits of an Individualized Physical Activity Intervention in Women With Metastatic Breast Cancer: Intervention Study.

BACKGROUND: There is limited knowledge regarding the potential benefits of physical activity in patients with metastatic breast cancer. OBJECTIVE: The Advanced stage Breast cancer and Lifestyle Exercise (ABLE) Trial aimed to assess the feasibility of a physical activity intervention in women with metastatic breast cancer and to explore the effects of physical activity on functional, psychological, and clinical parameters. METHODS: The ABLE Trial was a single-arm, 6-month intervention study with a home-based, unsupervised, and personalized walking program using an activity tracker. At baseline and 6 months, we assessed anthropometrics, functional fitness, physical activity level, sedentary behavior, quality of life, fatigue, and tumor progression. Paired proportions were compared using the McNemar test and changes of parameters during the intervention were analyzed using the Wilcoxon signed-rank test, the Mann-Whitney test, and Spearman rank correlations. RESULTS: Overall, 49 participants (mean age 55 years; recruitment rate 94%) were enrolled and 96% adhered to the exercise prescription (attrition rate 2%). Statistically significant improvements in the 6-minute walking distance test (+7%, P<.001) and isometric quadriceps strength (+22%, P<.001), as well as decreases in body mass index (-2.5%, P=.03) and hip circumference (-4.0%, P<.001) were observed at 6 months. Quality of life remained stable and a nonstatistically significant decrease (-16%, P=.07) in fatigue was observed. CONCLUSIONS: The high recruitment and adherence rates suggest the willingness of patients with metastatic breast cancer to participate in a physical activity program. The beneficial outcomes regarding physical fitness and anthropometry of this unsupervised physical activity program may encourage these patients to maintain a physically active lifestyle. Future randomized controlled trials with larger sample sizes are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT03148886; https://clinicaltrials.gov/ct2/show/NCT03148886.

Association between physical activity and sedentary behaviour on carotid atherosclerotic plaques: an epidemiological and histological study in 90 asymptomatic patients.

OBJECTIVE: Carotid atherosclerotic plaques are a source of emboli for stroke. 'Unstable' carotid atherosclerotic plaques may have intraplaque haemorrhages, neovessels, prevalent macrophages, excessive calcium deposits, a large lipid core and a thin fibrous cap. Regular physical activity (PA) may lower the risk of plaques becoming unstable. We evaluated the association of both PA and sedentary behaviour (SB) with carotid plaque histopathology. METHODS: 90 asymptomatic patients who were undergoing carotid endarterectomy for carotid artery narrowing identified on ultrasound reported their PA and SB by questionnaires. We calculated PA intensity in MET (metabolic equivalent of task)-min/week. For analysis, the population was divided into tertiles according to PA (T1PA: the less PA patients; T2PA: the intermediate PA patients; T3PA: the most physically active patients) (T1PA900 and <900 MET-min/week, respectively). All the other features that associate with plaque instability (eg, neovessels, macrophages, etc) did not differ by level of PA or SB. CONCLUSION: In this cross-sectional study of asymptomatic patients who underwent endarterectomy (i) higher reported PA, (ii) intensity of PA and (iii) lower reported SB were associated with lower prevalence of intraplaque haemorrhage. This could be a mechanism whereby PA protects against cerebrovascular disease (stroke) and death.