Cardiorespiratory coordination in repeated maximal exercise

Increases in cardiorespiratory coordination (CRC) after training with no differences in performance and physiological variables have recently been reported using a principal component analysis approach. However, no research has yet evaluated the short-term effects of exercise on CRC. The aim of this study was to delineate the behavior of CRC under different physiological initial conditions produced by repeated maximal exercises. Fifteen participants performed 2 consecutive graded and maximal cycling tests. Test 1 was performed without any previous exercise, and Test 2 6 min after Test 1. Both tests started at 0 W and the workload was increased by 25 W/min in males and 20 W/min in females, until they were not able to maintain the prescribed cycling frequency of 70 rpm for more than 5 consecutive seconds. A principal component (PC) analysis of selected cardiovascular and cardiorespiratory variables (expired fraction of O2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate) was performed to evaluate the CRC defined by the number of PCs in both tests. In order to quantify the degree of coordination, the information entropy was calculated and the eigenvalues of the first PC (PC1) were compared between tests. Although no significant differences were found between the tests with respect to the performed maximal workload (Wmax), maximal oxygen consumption (VO2 max), or ventilatory threshold (VT), an increase in the number of PCs and/or a decrease of eigenvalues of PC1 (t = 2.95; p = 0.01; d = 1.08) was found in Test 2 compared to Test 1. Moreover, entropy was significantly higher (Z = 2.33; p = 0.02; d = 1.43) in the last test. In conclusion, despite the fact that no significant differences were observed in the conventionally explored maximal performance and physiological variables (Wmax, VO2 max, and VT) between tests, a reduction of CRC was observed in Test 2. These results emphasize the interest of CRC evaluation in the assessment and interpretation of cardiorespiratory exercise testing

Inter-individual different responses to continuous and interval training in recreational middle-aged women runners

A crucial subject in sports is identifying the inter-individual variation in response to training, which would allow creating individualised pre-training schedules, improving runner's performance. We aimed to analyse heterogeneity in individual responses to two half-marathon training programmes differing in running volume and intensity in middle-aged recreational women. Twenty women (40±7 years, 61±7kg, 167±6cm, VO2max=48±6 mL·kg-1·min-1) underwent either moderate-intensity continuous (MICT) or high-intensity interval (HIIT) 12-week training. They were evaluated before and after training with maximal incremental tests in the laboratory (VO2max) and in the field (time to exhaustion, TTE; short interval series and long run). All the women participated in the same half-marathon and their finishing times were compared with their previous times. Although the improvements in the mean finishing times were not significant, MICT elicited a greater reduction (3min 50s, P=0.298), with more women (70%) improving on their previous times, than HIIT (reduction of 2min 34s, P=0.197, 50% responders). Laboratory tests showed more differences in the HIIT group (P=0.008), while both groups presented homogeneous significant (P<0.05) increases in TTE. Both in the short interval series and in the long run, HIIT induced better individual improvements, with a greater percentage of responders compared to MICT (100% versus 50% in the short series and 78% versus 38% in the long run). In conclusion, variability in interindividual responses was observed after both MICT and HIIT, with some participants showing improvements (responders) while others did not (non-responders) in different performance parameters, reinforcing the idea that individualised training prescription is needed to optimise performance

Potential of atmospheric pressure chemical ionization source in gas chromatography tandem mass spectrometry for the screening of urinary exogenous androgenic anabolic steroids

The atmospheric pressure chemical ionization (APCI) source for gas chromatography-mass spectrometry analysis has been evaluated for the screening of 16 exogenous androgenic anabolic steroids (AAS) in urine. The sample treatment is based on the strategy currently applied in doping control laboratories i.e. enzymatic hydrolysis, liquid–liquid extraction (LLE) and derivatization to form the trimethylsilyl ether-trimethylsilyl enol ether (TMS) derivatives. These TMS derivatives are then analyzed by gas chromatography tandem mass spectrometry using a triple quadrupole instrument (GC-QqQ MS/MS) under selected reaction monitoring (SRM) mode. The APCI promotes soft ionization with very little fragmentation resulting, in most cases, in abundant [M + H]+ or [M + H-2TMSOH]+ ions, which can be chosen as precursor ions for the SRM transitions, improving in this way the selectivity and sensitivity of the method. Specificity of the transitions is also of great relevance, as the presence of endogenous compounds can affect the measurements when using the most abundant ions. The method has been qualitatively validated by spiking six different urine samples at two concentration levels each. Precision was generally satisfactory with RSD values below 25 and 15% at the low and high concentration level, respectively. Most the limits of detection (LOD) were below 0.5 ng mL−1. Validation results were compared with the commonly used method based on the electron ionization (EI) source. EI analysis was found to be slightly more repeatable whereas lower LODs were found for APCI. In addition, the applicability of the developed method has been tested in samples collected after the administration of 4-chloromethandienone. The highest sensitivity of the APCI method for this compound, allowed to increase the period in which its administration can be detected.Ministry of Education and Science, Spain, in the project DEP2011-28573-C02-01/02 Generalitat Valenciana (Research Group of Excellence Prometeo II/2014/023; ISIC EnviFood 2012/016

A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells

Altres ajuts: European Research Council (ERC); EIT Health under grant ID 20366 (R2U-Tox-Assay); IBEC Faster Future program (A por la COVID-19); European Regional Development Fund (FEDER); Gobierno de Navarra, Departamento de Desarrollo Económico y Empresarial (AGATA 0011-1411-2020-000011, DIANA 0011-1411-2017-000029); Ministerio de Economía y Competitividad (MINECO); IBEC International PhD Programme "La Caixa" Severo Ochoa fellowships (LCF/BQ/SO16/52270019); start-up funds from the College of Medicine at the University of Florida, Gainesville; T. von Zastrow Foundation; the FWF Wittgenstein award (Z 271-B19); the Austrian Academy of Sciences and the Canada 150 Research Chairs Program (F18-01336); the Canadian Institutes of Health Research COVID-19 (F20-02343, F20-02015); Swiss National Science Foundation fellowship (P400PM_194473/1); Swedish Research Council (2018-05766); the Innovative Medicines Initiative 2 Joint Undertaking (JU 101005026); Ayudas Fundación BBVA a Equipos de Investigación Científica SARS-CoV-2 y COVID-19 through the project "Identifying SARS-CoV-2-host cell interactions exploiting CRISPR-Cas9-engineered human organoids: through the development of specific therapies against COVID19"; Fundació la Marató de TV3 (201910-31 and 202125-3).It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism

CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction

Background: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. Methods: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. Results: The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). Conclusion: A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction

The Bifidobacterium dentium Bd1 Genome Sequence Reflects Its Genetic Adaptation to the Human Oral Cavity

Bifidobacteria, one of the relatively dominant components of the human intestinal microbiota, are considered one of the key groups of beneficial intestinal bacteria (probiotic bacteria). However, in addition to health-promoting taxa, the genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic cariogenic pathogen. The genetic basis for the ability of B. dentium to survive in the oral cavity and contribute to caries development is not understood. The genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to completion to uncover a single circular 2,636,368 base pair chromosome with 2,143 predicted open reading frames. Annotation of the genome sequence revealed multiple ways in which B. dentium has adapted to the oral environment through specialized nutrient acquisition, defences against antimicrobials, and gene products that increase fitness and competitiveness within the oral niche. B. dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent with genome-based predictions, while colonization and persistence factors implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva-derived compounds were also identified. Global transcriptome analysis demonstrated that many of the genes encoding these predicted traits are highly expressed under relevant physiological conditions. This is the first report to identify, through various genomic approaches, specific genetic adaptations of a Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a cariogenic microorganism in the oral cavity. In silico analysis and comparative genomic hybridization experiments clearly reveal a high level of genome conservation among various B. dentium strains. The data indicate that the genome of this opportunistic cariogen has evolved through a very limited number of horizontal gene acquisition events, highlighting the narrow boundaries that separate commensals from opportunistic pathogens

Mobile Technology in Allergic Rhinitis : Evolution in Management or Revolution in Health and Care?

Smart devices and Internet-based applications (apps) are largely used in allergic rhinitis and may help to address some unmet needs. However, these new tools need to first of all be tested for privacy rules, acceptability, usability, and cost-effectiveness. Second, they should be evaluated in the frame of the digital transformation of health, their impact on health care delivery, and health outcomes. This review (1) summarizes some existing mobile health apps for allergic rhinitis and reviews those in which testing has been published, (2) discusses apps that include risk factors of allergic rhinitis, (3) examines the impact of mobile health apps in phenotype discovery, (4) provides real-world evidence for care pathways, and finally (5) discusses mobile health tools enabling the digital transformation of health and care, empowering citizens, and building a healthier society. (C) 2019 American Academy of Allergy, Asthma & ImmunologyPeer reviewe

Next-generation care pathways for allergic rhinitis and asthma multimorbidity:a model for multimorbid non-communicable diseases-Meeting Report (Part 1)

International audienceIn all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system for integrated care with organizational health literacy. MASK (Mobile Airways Sentinel NetworK) (1), a new development of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health) (2), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life integrated care pathways (ICPs) (3)-centred around the patient with rhinitis and using mHealth monitoring of environmental exposure (4).An expert meeting took place at the Pasteur Institute in Paris, December 3, 2018. The aim was to discuss next-generation care pathways: (I) Patient participation, health literacy and self-care through technology-assisted “patient activation”; (II) Implementation of care pathways by pharmacists and (III) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) assessed by mobile technology.The EU (5) and global political agendas are of great importance in supporting health care transformation. MASK has been recognized by DG Santé as a Good Practice (6) in the field of digitally-enabled, integrated, person-centred care.The one-day meeting objectives were clear (Figure 1). The meeting was followed by a workshop. The present paper reports the background of the two-day meeting

2019 ARIA Care pathways for allergen immunotherapy

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.Peer reviewe