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BACKGROUND: Beneficial effects of breathing at FIO2 < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with FIO2 as low as 0.11 in 5 healthy volunteers. METHODS: All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from FIO2 of 0.16 on the first day to FIO2 of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' SpO2, heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments. RESULTS: Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased SpO2 and increased heart rate. At FIO2 of 0.14, the mean SpO2 was 92%; at FIO2 of 0.13, the mean SpO2 was 93%; at FIO2 of 0.12, the mean SpO2 was 88%; at FIO2 of 0.11, the mean SpO2 was 85%; and, finally, at an FIO2 of 0.21, the mean SpO2 was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension. CONCLUSIONS: Results of the current physiologic study suggests that, within a hospital setting, delivering FIO2 as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested. [ABSTRACT FROM AUTHOR]

The article discusses research which evaluated the effect of helmet continuous positive airway pressure (CPAP) on tidal volume assessed by bioelectrical impedance. The study analyzed the variation in respiratory parameters including tidal volumes, breathing frequency and minute ventilation before helmet application and after helmet CPAP application. Results of arterial blood gas analysis, respiratory and hemodynamics parameters are presented.

The study of transcription factors that determine specialized neuronal functions has provided invaluable insights into the physiology of the nervous system. Peripheral chemoreceptors are neurone-like electrophysiologically excitable cells that link the oxygen concentration of arterial blood to the neuronal control of breathing. In the adult, this oxygen chemosensitivity is exemplified by type I cells of the carotid body, and recent work has revealed one isoform of the hypoxia- inducible transcription factor (HIF), HIF-2[alpha], as having a nonredundant role in the development and function of that organ. Here, we show that activation of HIF-2[alpha], including isolated overexpression of HIF-2[alpha] but not HIF-1[alpha], is sufficient to induce oxygen chemosensitivity in adult adrenal medulla. This phenotypic change in the adrenal medulla was associated with retention of extra-adrenal paraganglioma-like tissues resembling the fetal organ of Zuckerkandl, which also manifests oxygen chemosensitivity. Acquisition of chemosensitivity was associated with changes in the adrenal medullary expression of gene classes that are ordinarily characteristic of the carotid body, including G protein regulators and atypical subunits of mitochondrial cytochrome oxidase. Overall, the findings suggest that, at least in certain tissues, HIF-2[alpha] acts as a phenotypic driver for cells that display oxygen chemosensitivity, thus linking 2 major oxygen-sensing systems., Introduction One of the most vital, but still incompletely understood, functions in homeostatic physiology is that of the arterial chemoreceptors that control breathing in response to changes in blood oxygen, [...]

The article discusses the limitations of linear regression in modeling complex biological relationships.

Introduction: The most widespread treatment for obstructive sleep apnoea and obesity hypoventilation syndrome is continuous positive airway pressure (CPAP). The addition of inspiratory support is a potential alternative. This is a physiological study to determine the effect of CPAP and inspiratory support pressure on respiratory effort measured by diaphragm thickening fraction (DTF) in healthy volunteers. Methods: DTF was measured in spontaneously breathing, healthy volunteers during 4 phases: (I) without connection to a ventilator, (II) on a ventilator without any applied pressures, (III) with a CPAP of 5 cmH2O, and (IV) with an additional inspiratory support pressure of 5 cmH2O. Results: Twenty-nine individuals agreed to participate. DTF was similar during the first two phases (32 ± 13% and 35 ± 22%). A considerable increase in DTF to 51 ± 21% was noted in phase III. The introduction of inspiratory support pressure during phase IV led to a reduction in DTF back to 36 ± 23% (p < 0.001). Tidal volume and minute ventilation were both slightly higher in phase IV compared to phase III. Conclusion: CPAP without inspiratory support pressure increases respiratory effort measured by DTF in healthy subjects. Further research is required to investigate this phenomenon in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Various Positive End-Expiratory Pressure (PEEP) titration strategies have been proposed to optimize ventilation in patients with acute respiratory distress syndrome (ARDS). We aimed to compare PEEP titration strategies based on electrical impedance tomography (EIT) to methods derived from respiratory system mechanics with or without esophageal pressure measurements, in terms of PEEP levels and association with recruitability. Methods: Nineteen patients with ARDS were enrolled. Recruitability was assessed by the estimated Recruitment-to-Inflation ratio (R/Iest) between PEEP 15 and 5 cmH2O. Then, a decremental PEEP trial from PEEP 20 to 5 cmH2O was performed. PEEP levels determined by the following strategies were studied: (1) plateau pressure 28–30 cmH2O (Express), (2) minimal positive expiratory transpulmonary pressure (Positive PLe), (3) center of ventilation closest to 0.5 (CoV) and (4) intersection of the EIT-based overdistension and lung collapse curves (Crossing Point). In addition, the PEEP levels determined by the Crossing Point strategy were assessed using different PEEP ranges during the decremental PEEP trial. Results: Express and CoV strategies led to higher PEEP levels than the Positive PLe and Crossing Point ones (17 [14–17], 20 [17–20], 8 [5–11], 10 [8–11] respectively, p < 0.001). For each strategy, there was no significant association between the optimal PEEP level and R/Iest (Crossing Point: r2 = 0.073, p = 0.263; CoV: r2 < 0.001, p = 0.941; Express: r2 < 0.001, p = 0.920; Positive PLe: r2 = 0.037, p = 0.461). The PEEP level obtained with the Crossing Point strategy was impacted by the PEEP range used during the decremental PEEP trial. Conclusions: CoV and Express strategies led to higher PEEP levels than the Crossing Point and Positive PLe strategies. Optimal PEEP levels proposed by these four methods were not associated with recruitability. Recruitability should be specifically assessed in ARDS patients to optimize PEEP titration. [ABSTRACT FROM AUTHOR]

Background: In the last decades, the use of the helmet interface to deliver noninvasive respiratory support has steadily increased. When delivering oxygen therapy, conditioning of inspired gas is mandatory, as the water content of medical gas is neglectable. To minimize the risk of airway damage, it is recommended to achieve an absolute humidity greater than 10 mg H2O/L. The primary aim of the study was to assess the performance of 3 different heated humidifiers to condition gas during helmet continuous positive airway pressure and to compare them with a setting without active humidification. Methods: We performed a crossover randomized physiological study in healthy volunteers. Absolute humidity, relative humidity, and temperature were measured during 4 steps (no humidification and the 3 heated humidifiers, performed in a randomized order) and at 3 time points (after 1, 5, and 10 minutes). Results: Eight subjects participated to the study. Without active humidification, absolute humidity was constantly below the recommended level. All humidifiers conditioned the inspired gases to an average absolute humidity greater than 10 mg H2O/L. Overall, the best performance, in terms of absolute humidity, was obtained with H900 (19.74 ± 0.50 mg H2O/L), followed by TurbH2O (−6.82 mg H2O/L vs H900; 95% confidence interval, −8.49 to −5.14; P <.05) and F&P 810 (−9.03 mg H2O/L vs H900; 95% confidence interval, −10.70 to −7.35; P <.05). Conclusions: Active humidification is required to achieve adequate conditioning of inspired gas during helmet continuous positive airway pressure. The choice between different humidifiers available on the market should be made according to the local needs and expertise. [ABSTRACT FROM AUTHOR]

Background: Sleep on the first night in a sleep laboratory is characterized by a lower sleep quality and frequency of rhythmic masticatory muscle activity (RMMA) than that on the second night in moderate to severe sleep bruxism (SB) patients. Objective: The aims of this study was to clarify the physiological factors contributing to the first night effect on oromotor activity during sleep and investigate whether physiological factors involved in the first night effect differed between rhythmic and non‐rhythmic oromotor activities. Methods: Polysomnographic data collected on two consecutive nights from 15 moderate to severe SB subjects (F 7: M 8; age: 23.2 ± 1.3 [mean ± SD] years) were retrospectively analysed. Sleep variables, RMMA and non‐specific masticatory muscle activity (NSMA) were scored in relation to episode types (i.e. phasic or tonic and cluster or isolated), sleep architecture and transient arousals. The relationships between nightly differences in oromotor and sleep variables were assessed. The distribution of oromotor events, arousals, cortical electroencephalographic power, RR intervals and heart rate variability were examined in relation to sleep cycle changes. These variables were compared between the first and second nights and between RMMA and NSMA. Results: Sleep variables showed a lower sleep quality on Night 1 than on Night 2. In comparisons with Night 1, the RMMA index increased by 18.8% (p <.001, the Wilcoxon signed‐rank test) on Night 2, while the NSMA index decreased by 17.9% (p =.041). Changes in the RMMA index did not correlate with those in sleep variables, while changes in the NSMA index correlated with those in arousal‐related variables (p <.001, Spearman's rank correlation). An increase in the RMMA index on Night 2 was found for the cluster type and stage N1 related to sleep cyclic fluctuations in cortical and cardiac activities. In contrast, the decrease in the NSMA index was associated with increases in the isolated type and the occurrence of stage N2 and wakefulness regardless of the sleep cycle. Conclusion: Discrepancies in first night effect on the occurrence of RMMA and NSMA represent unique sleep‐related processes in the genesis of oromotor phenotypes in SB subjects. [ABSTRACT FROM AUTHOR]

Background: There has been an increased interest in understanding social anxiety (SA) and SA disorder (SAD) antecedents and consequences as they occur in real time, resulting in a proliferation of studies using ambulatory assessment (AA). Despite the exponential growth of research in this area, these studies have not been synthesized yet. Objective: This review aimed to identify and describe the latest advances in the understanding of SA and SAD through the use of AA. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic literature search was conducted in Scopus, PubMed, and Web of Science. Results: A total of 70 articles met the inclusion criteria. The qualitative synthesis of these studies showed that AA permitted the exploration of the emotional, cognitive, and behavioral dynamics associated with the experience of SA and SAD. In line with the available models of SA and SAD, emotion regulation, perseverative cognition, cognitive factors, substance use, and interactional patterns were the principal topics of the included studies. In addition, the incorporation of AA to study psychological interventions, multimodal assessment using sensors and biosensors, and transcultural differences were some of the identified emerging topics. Conclusions: AA constitutes a very powerful methodology to grasp SA from a complementary perspective to laboratory experiments and usual self-report measures, shedding light on the cognitive, emotional, and behavioral antecedents and consequences of SA and the development and maintenance of SAD as a mental disorder. [ABSTRACT FROM AUTHOR]

On the surface, baseball does not appear overly complex. Not only is the sport easy enough for millions of children to understand and play in their Little League games, its [...]

Low energy availability (LEA) is a complex health condition that most commonly affects female athletes. Research on LEA is weighted to quantitative approaches, and few studies have employed qualitative methods to understand the development of LEA. Current research fails to understand the complexity of LEA by largely operating within isolated research paradigms. This paper aims to demonstrate the value of integrating a mixed-methods research approach to understand the influence of sporting cultures on the physiological experiences of female athletes with LEA. The mixed-methods approach implemented the use of physiological (quantitative) and socio-psychological (qualitative) data obtained from elite female athletes in three sports: triathlons and running, (n = 11), rugby sevens (n = 9), and track cycling (n = 10). The physiological data consisted of energy availability, haematological analysis, bone health, and body composition. The socio-psychological data consisted of individual semi-structured interviews with topics covering nutrition, body image, the impact of the sporting environment, and experience with LEA. The interview data were thematically analysed. By bringing qualitative and quantitative data together, this paper illustrates the complex relationship between sporting culture and the physiology of LEA. First, endurance athletes categorised as having an LEA showed a positive correlation between the relative energy intake (EI) and serum ferritin, with the interviews revealing a focus on a low body weight and reducing the EI. Second, the interviews with the rugby players showed a strong but hierarchical team culture, with the experienced players monitoring and controlling the EI of novice players. Third, among the cyclists, the EI was reduced in those categorised as having an LEA, with the interviews revealing a coach–athlete power relationship impacting dietary behaviours. To conclude, this paper demonstrates how mixed methods are important for capturing how different sporting cultures impact athletes' socio-psychological and physiological experiences of LEA. [ABSTRACT FROM AUTHOR]

Forest therapy has been proven to have a quantifiable positive impact on human physiological and psychological health. Given that graduating students at university are easy to stress due to changes in life, pressure from their studies, and independence in finance. The main purpose of this research was to explore the effects of guided forest therapy on graduating college students through a field experiment in Pacific Spirit Regional Park which held significant geographical value. This paper investigated the pressure of graduating college students and their needs for forest therapy, and explored the psychological and physiological changes after guided forest therapy. This study also analyzed gender-related psychological and physiological differences. Thirty-six healthy graduating college students were invited to participate in a 2-hour forest therapy program. Likert scales were used to assess students' pressure and the demand for forest therapy. Most of the students were facing the pressure of graduation and were willing to participate in forest therapy. Systolic and diastolic blood pressure, pulse rate, and heart rate variability (HRV) were used as physiological measurement indices. Our physiological results indicated that blood pressure significantly decreased, the high-frequency component of HRV (HF) was significantly larger, and the low-to-high-frequency component ratio (LF/HF) was smaller after the forest therapy program, and some beneficial changes in females were more significant than that in males. The participants' mean HR decreased throughout the forest therapy, but there were no significant differences. Mental status was assessed before and after forest therapy using the Profile of Mood States (POMS), employment stress scale and State-Trait Anxiety Inventory (STAI) for participants. Overall, the guided forest therapy program effectively reduced participants' employment stress and state anxiety. Our research showed that guided forest therapy had positive physiological and psychological benefits for graduating college students. In addition, females obtained more positive physiological benefits than males, and males obtained more positive psychological benefits than females throughout forest therapy. [ABSTRACT FROM AUTHOR]

The activation of the [[alpha].sub.1]-adrenoceptor-([[alpha].sub.1]-AR) by norepinephrine results in the G-protein (Gq[alpha]) mediated increase in the phosphoinositide-specific phospholipase C (PLC) activity. The byproducts of PLC hydrolytic activity, namely, 1,2-diacylglycerol and inositol-1,4,5-trisphosphate, are important downstream signal transducers for increased protein synthesis in the cardiomyocyte and the subsequent hypertrophic response. In this article, evidence was outlined to demonstrate the role of cardiomyocyte PLC isozymes in the catecholamine-induced increase in protein synthesis by using a blocker of [[alpha].sub.1]-AR and an inhibitor of PLC. The discussion was focused on the [[alpha].sub.1]-AR-Gq[alpha]-PLC-mediated hypertrophic signalling pathway from the viewpoint that it may compliment the other [[beta].sub.1]-AR-Gs protein-adenylyl cyclase signal transduction mechanisms in the early stages of cardiac hypertrophy development, but may become more relevant at the late stage of cardiac hypertrophy. From the information provided here, it is suggested that some specific PLC isozymes may potentially serve as important targets for the attenuation of cardiac hypertrophy in the vulnerable patient population at-risk for heart failure. Key words: phospholipase C isozymes, norepinephrine, [[alpha].sub.1]-adrenoceptor, cardiomyocytes, protein synthesis, signal transduction, hypertrophic response L'activation des recepteurs [[alpha].sub.1] adrenergiques (R[[alpha].sub.1]-A) par la norepinephrine entraine une augmentation de l'activite de la phospholipase C (PLC) specifique a la phosphoinositide, mediee par la proteine G (Gq[alpha]). Les sous-produits de l'activite hydrolytique de la PLC, soit le 1,2-diacylglycerol et l'inositol-1,4,5-trisphosphate, sont d'importants transducteurs du signal en aval pour l'augmentation de la synthese proteique dans le cardiomyocyte, avec la reaction d'hypertrophie qui s'en suit. Dans cet article, nous circonscrivons les donnees pour montrer le role des isoenzymes de la PLC des cardiomyocytes dans l'augmentation de la synthese proteique engendree par les catecholamines a l'aide d'un agent bloquant les R[[alpha].sub.1]-A et d'un inhibiteur de la PLC. La discussion sera centree sur la voie de signalisation de l'hypertrophie mediee par l'axe R[[alpha].sub.1]-A-Gq[alpha]-PLC a partir de la notion qu'elle pourrait completer les autres modes d'action de transduction du signal par l'axe R[[beta].sub.1]-A-proteine Gs-adenylyl cyclase aux stades precoces de l'evolution de l'hypertrophie, mais qu'elle pourrait jouer un role encore plus important aux stades tardifs de l'hypertrophie cardiaque. A partir des renseignements apportes ici, nous laissons entendre que certaines isoenzymes specifiques de la PLC pourraient eventuellement servir de cibles de choix pour l'attenuation de l'hypertrophie cardiaque dans une population de patients vulnerables exposes a un risque accru d'insuffisance cardiaque. [Traduit par la Redaction] Mots-cles : isoenzymes de la phospholipase C, norepinephrine; recepteur [[alpha].sub.1]-adrenergique, cardiomyocytes, synthese proteique, transduction du signal, reaction d'hypertrophie, Introduction Although the sympathetic nervous system regulates cardiac function, overactivity of the sympathetic nervous system under stressful conditions is known to result in the excessive production of circulating catecholamines as [...]

Diet influences athletes performance while the foods chosen in training and competition determines how well competitors prepare and compete. Competitors should know about their nourishing objectives and how they can choose an eating technique to meet those objectives. However, there exists paucity of literature expounding on that. Many athletes have limited knowledge on matters of nutrition, and their nutrition practices do not conform to athletes' requirements. The sources of nutrition information among this group are also conflicting. The purpose of this study was to assess the nutrition knowledge and sources of nutrition knowledge among middle (800m-2500km) and long-distance ( Key words: Knowledge, Performance, Sports, Nutrition, Elite, Middle and Long Distance Athlete, INTRODUCTION Athletics involve a variety of events of different categories which include running, walking, jumping or throwing. All athletic events are governed by the International Association of Athletics Federations (IAAF) [...]

Early mobilization is regarded as important in patients with severe acquired brain injury. To explore the feasibility, physical and physiological responses of using a new assistive, electric standing device, Innowalk Pro (IP), that passively moves the legs in an upright position. A single-subject experimental design. A three-phase model (A1-B-A2) was chosen; A1: baseline using a standing frame, B: an intervention using IP and A2: withdrawal using a standing frame. Outcome measures: Patient's and assistive personnel's experiences with Likert scales, Modified Trunk Impairment Scale, Modified Ashworth Scale (MAS), Lidcombe Template (passive ankle dorsiflexion), duration of the training, blood pressure and heart rate. A 40-year-old female, with subarachnoid haemorrhage, perceived training in the IP as more physically exhausting than training in a standing frame, influencing the training time. However, she preferred the IP over the standing frame. Trunk control did not improve, until the withdrawal phase. A small MAS reduction in ankle plantar flexors was maintained in the A2-phase. The heart rate showed an ascending trend in A1, and a non-significant descending trend in B- and A2-phases. Blood pressure showed a flat trend line in A1 and B-phases, and a descending trend in A2. The new IP was considered a feasible and motivating intervention. Heart rate tended to decrease during IP training, while the blood pressure remained stable. Further research is needed to evaluate whether the IP should be a preferable or a supplementary assistive device for early mobilization. A new electrical standing device, Innowalk Pro, which moves the legs in upright position, was found to be feasible in early mobilisation of a patient with severe brain injury. Trained physiotherapist and assistive personnel are recommended for safe training. Physiological responses like heart rate and blood pressure remained relatively stable when training in Innowalk Pro. We question whether the leg movements when standing in Innowalk Pro, may contribute to improvement in trunk control. [ABSTRACT FROM AUTHOR]

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This study investigated the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that mitogen-activated protein kinase kinase (MEK1/2) signaling pathway, voltage-gated potassium ([K.sub.V]) channels, small-conductance calcium-activated potassium ([SK.sub.Ca]) channels, and large-conductance calcium-activated potassium ([BK.sub.Ca]) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with [10.sup.-5] M phenylephrine (PHE), and then the concentration-dependent responses of irisin ([10.sup.-9] - [10.sup.-6] M) were examined in endothelium-intact and - denuded rat thoracic aortas. Also, the effects of irisin incubations on PHE-mediated contraction and acetylcholine (ACh)--mediated relaxation were studied. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of [10.sup.-8], [10.sup.-7], and [10.sup.-6] M compared with the control groups (p < 0.001). Besides, pre-incubation of aortic rings with irisin (10 nM, 100 nM, or 1 [micro]M for 30 min) augmented ACh-mediated ([10.sup.9] - [10.sup.5]) vasodilation in PHE-precontracted thoracic aorta segments but did not modulate PHE-mediated ([10.sup.9] - [10.sup.5]) contraction. In addition, MEK1/2 inhibitor U0126, [K.sub.V] channel blocker XE-991, [SK.sub.Ca] channel blocker apamin, and [BK.sub.Ca] channel blocker tetraethylammonium (TEA) incubations significantly inhibited the irisin-induced relaxation responses. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact and (or) endothelium-denuded aortic rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are related to the activity of the MEK1/2 pathway, [K.sub.V] channels, and calcium-activated [K.sup.+] ([SK.sub.Ca] and [BK.sub.Ca]) channels. Key words: irisin, rat thoracic aorta, vasodilation, mitogen-activated protein kinase kinase, potassium channels. Cette etude portait sur les effets de l'irisine sur la contractilite du muscle lisse vasculaire dans l'aorte thoracique de rat, avec pour hypothese que la voie de signalisation de la MEK1/2 (pour << mitogen-activated protein kinase kinase >>), les canaux potassiques dependants du voltage ([K.sub.V]), les canaux potassiques a faible conductance actives par le calcium ([SK.sub.Ca]) et les canaux potassiques a conductance elevee actives par le calcium ([BK.sub.Ca]) peuvent jouer un role dans ces effets. Nous avons mesure la contraction et la relaxation isometriques dans des anneaux isoles d'aorte thoracique en bain d'organe. Nous avons obtenu la contraction stable a l'aide de phenylephrine (PHE) a [10.sup.-5] M, puis examine les reactions dependantes des concentrations d'irisine ([10.sup.-9] - [10.sup.-6] M) dans des aortes thoraciques de rats denudees et dont l'endothelium etait intact. Nous avons aussi etudie les effets de l'incubation en presence d'irisine sur la contraction mediee par la PHE et la relaxation mediee par l'acetylcholine (ACh). Dans les anneaux dont l'endothelium etait intact comme denudes, l'irisine entrainait des effets vasorelaxants plus marques que chez les temoins a des concentrations de [10.sup.-8], de [10.sup.-7] et de [10.sup.-6] M (p < 0,001). Par ailleurs, l'incubation prealable des anneaux aortiques en presence d'irisine (10 nM, 100 nM ou 1 [micro]M pendant 30 minutes) entrainait une augmentation de la vasodilatation mediee par l'ACh ([10.sup.9] - [10.sup.5]) dans les segments d'aorte thoracique precontractes a l'aide de PHE, mais sans modulation de la contraction mediee par la PHE ([10.sup.9] - [10.sup.5]). De plus, l'incubation en presence de U0126 (un inhibiteur de la MEK1/2), de XE-991 (un bloqueur des canaux [K.sub.V]), d'apamine (un bloqueur des canaux [SK.sub.Ca]) et de tetraethylammonium (ou TEA, un bloqueur des canaux [BK.sub.Ca]) entrainait une inhibition marquee de la relaxation entrainee par l'irisine. En conclusion, nous avons obtenu les premiers resultats physiologiques quant a la relaxation fonctionnelle entrainee par l'irisine dans l'aorte thoracique chez le rat. Les resultats ont montre avec des anneaux aortiques denudes et/ou dont l'endothelium etait intact que l'irisine entraine des relaxations proportionnelles a la concentration. En outre, il s'agit de la premiere etude qui rapporte que les relaxations entrainees par l'irisine sont liees a l'activite de la voie de signalisation de la MEK1/2, des canaux [K.sub.V] et des canaux [K.sub.+] actives par le calcium ([SK.sub.Ca] et [BK.sub.Ca]). [Traduit par la Redaction] Mots-cles : irisine, aorte thoracique de rat, vasodilatation, MEK1/2, canaux potassiques., 1. Introduction Irisin, a newly identified hormone containing 112 amino acids that is secreted mainly by skeletal muscle cells during exercise, is a cleavage product of fibronectin type III domain-containing [...]

Background: Current inactivity rates are alarming, and often due to simple barriers: lack of time and enjoyment. Recent literature has focused on high-intensity interval training to reduce exercise time, less emphasis has been given to enjoyment. Purpose: Examine the acute effects of playing volleyball (Active) on affective valence and enjoyment relative to a no exercise control. Methods: Participants [N = 24, 6 females; age (M [+ or -] SD); 29.0 [+ or -] 6.8 yrs; BMI (M [+ or -] SD); 24.0 [+ or -] 4.1] played volleyball and a no exercise control for 60 min. Affective valence (FS) and perceived exertion (RPE) were assessed before, immediately and 10-min after, while enjoyment (PACES) was assessed after both conditions. Results: FS was increased following the active condition [[M.sub.diff] [+ or -] SE ; 1.29 [+ or -] 0.43; Cohen's d = .93]. Enjoyment was greater following the active relative to control [[M.sub.diff] [+ or -] SE; 30.13 [+ or -] 2.35; Cohen's d = 3.22]. Conclusion: Playing volleyball was sufficient to increase RPE while also increasing FS values. Additionally, enjoyment was significantly greater following the active condition. This study provides evidence to support the use of sport/alternative modes of exercise to increase exercise enjoyment and affect. Keywords: Enjoyment; Volleyball; Exercise; Physical Activity; Affect; Adherence, Despite a significant increase in literature highlighting the physiological and psychological benefits of exercise, American adults remain largely inactive. According to Centers for Disease Control and Prevention (CDC), over 25 [...]

Objective The objectives of this study were to evaluate neuromuscular recruitment and efficiency in participants who recovered from COVID-19 and assess the association between neuromuscular efficiency and symptom-limited aerobic exercise capacity. Methods Participants who recovered from mild (n = 31) and severe (n = 17) COVID-19 were evaluated and compared with a reference group (n = 15). Participants underwent symptom-limited ergometer exercise testing with simultaneous electromyography evaluation after a 4-week recovery period. Activation of muscle fiber types IIa and IIb and neuromuscular efficiency (watts/percentage of root-mean-square obtained at the maximum effort) were determined from electromyography of the right vastus lateralis. Results Participants who had recovered from severe COVID-19 had lower power output and higher neuromuscular activity than the reference group and those who had recovered from mild COVID-19. Type IIa and IIb fibers were activated at a lower power output in participants who had recovered from severe COVID-19 than in the reference group and those who had recovered from mild COVID-19, with large effect sizes (0.40 for type IIa and 0.48 for type IIb). Neuromuscular efficiency was lower in participants who had recovered from severe COVID-19 than in the reference group and those who had recovered from mild COVID-19, with a large effect size (0.45). Neuromuscular efficiency showed a correlation with symptom-limited aerobic exercise capacity (r  = 0.83). No differences were observed between participants who had recovered from mild COVID-19 and the reference group for any variables. Conclusion This physiological observational study supports the notion that more severe COVID-19 symptoms at disease onset appear to correspondingly impair neuromuscular efficiency in survivors over a short time frame of 4 weeks after recovery, potentially contributing to reduced cardiorespiratory capacity. Further studies are needed to replicate and extend these findings with respect to their clinical implications for assessment/evaluation and interventions. Impact After 4 weeks of recovery, neuromuscular impairment is particularly evident in severe cases; this problem may contribute to reduced cardiopulmonary exercise capacity. [ABSTRACT FROM AUTHOR]

The article demonstrates that monitoring airway driving pressure during positive end-expiratory pressure (PEEP) titration provides a better method for choosing PEEP than oxygenation in obese subjects. Topics discussed include respiratory and lung mechanics and gas exchange, mechanical consequences of obesity, and changes in transpulmonary airway driving pressure.

Contemporary evolutionary medicine has unified the idea of 'evolutionary mismatch', derived from the older idea of 'adaptive lag' in evolution, with ideas about the mismatch in development and physiology derived from the Developmental Origins of Health and Disease (DOHaD) paradigm. A number of publications in evolutionary medicine have tried to make this theoretical framework explicit. The integrative theory of mismatch captures how organisms track environments across space and time on multiple scales in order to maintain an adaptive match to the environment, and how failures of adaptive tracking lead to disease. In this review, we try to present this complex body of theory as clearly and simply as possible with the aim of facilitating its application in new domains. We introduce terminology, which is as far as possible consistent with earlier usage, to distinguish the different forms of mismatch. Mismatch in its modern form is a productive organizing concept that can help researchers articulate how physiology, development and evolution interact with one another and with environmental change to explain health outcomes. [ABSTRACT FROM AUTHOR]

This review contains 208 citation items from 31 countries in total. The highest number of citations come from Spain (34) then from the USA (23), Italy (18) and China (16). Only one citation comes from Denmark, Georgia, Macedonia, and New Zealand. They are all included into 16 topics arranged in alphabetical order. The results or conclusions of each study are briefly described and arranged according to the year of the publication and alphabetical order of the authors. The most important topic was the physiological research containing 40 citations and then the evaluation of cultivars containing 33 citations. From the years of the review, the most important was 2017 with 122 items, whereas the least prolific year was 2015 containing only 35 items.

Purpose: The goal of this study was to examine the effects of increases in vocal effort, without changing speech intensity, on respiratory and articulatory kinematics in young adults with typical voices. Method: A total of 10 participants completed a reading task under three speaking conditions: baseline, mild vocal effort, and maximum vocal effort. Respiratory inductance plethysmography bands around the chest and abdomen were used to estimate lung volumes during speech, and sensor coils for electromagnetic articulography were used to transduce articulatory movements, resulting in the following outcome measures: lung volume at speech initiation (LVSI) and at speech termination (LVST), articulatory kinematic vowel space (AKVS) of two points on the tongue dorsum (body and blade), and lip aperture. Results: With increases in vocal effort, and no statistical changes in speech intensity, speakers showed: (a) no statistically significant differences in LVST, (b) statistically significant increases in LVSI, (c) no statistically significant differences in AKVS measures, and (d) statistically significant reductions in lip aperture. Conclusions: Speakers with typical voices exhibited larger lung volumes at speech initiation during increases in vocal effort, paired with reduced lip displacements. To our knowledge, this is the first study to demonstrate evidence that articulatory kinematics are impacted by modulations in vocal effort. However, the mechanisms underlying vocal effort may differ between speakers with and without voice disorders. Thus, future work should examine the relationship between articulatory kinematics, respiratory kinematics, and laryngeal-level changes during vocal effort in speakers with and without voice disorders. Supplemental Material: https://doi.org/10.23641/asha.17065457, Vocal effort is the perceived exertion as experienced by the speaker and not the listener (Banister, 1979; Borg, 1982; Hunter et al., 2020), and previous work implicates both psychological and [...]

The liberation of energy stores from adipocytes is critical to support survival in times of energy deficit; however, uncontrolled or chronic lipolysis associated with insulin resistance and/or insulin insufficiency disrupts metabolic homeostasis.sup.1,2. Coupled to lipolysis is the release of a recently identified hormone, fatty-acid-binding protein 4 (FABP4).sup.3. Although circulating FABP4 levels have been strongly associated with cardiometabolic diseases in both preclinical models and humans.sup.4-7, no mechanism of action has yet been described.sup.8-10. Here we show that hormonal FABP4 forms a functional hormone complex with adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK) to regulate extracellular ATP and ADP levels. We identify a substantial effect of this hormone on beta cells and given the central role of beta-cell function in both the control of lipolysis and development of diabetes, postulate that hormonal FABP4 is a key regulator of an adipose-beta-cell endocrine axis. Antibody-mediated targeting of this hormone complex improves metabolic outcomes, enhances beta-cell function and preserves beta-cell integrity to prevent both type 1 and type 2 diabetes. Thus, the FABP4-ADK-NDPK complex, Fabkin, represents a previously unknown hormone and mechanism of action that integrates energy status with the function of metabolic organs, and represents a promising target against metabolic disease. Hormonal FABP4 is discovered to be a pivotal regulator of an adipose-beta-cell endocrine axis that coordinates energy status and metabolic organ function, and targeting this axis improved metabolic outcomes., Author(s): Kacey J. Prentice [sup.1] , Jani Saksi [sup.1] , Lauren T. Robertson [sup.1] , Grace Y. Lee [sup.1] , Karen E. Inouye [sup.1] , Kosei Eguchi [sup.1] , Alexandra [...]

Simple Summary: E2F1 and E2F2 are highly expressed in many cancer types, but their contribution to malignancy is not well understood. Here we aimed to define the impact of E2F1/E2F2 deregulation in prostate cancer. We show that inhibition of E2F sensitizes prostate cancer cells to drug-induced replication stress and cell death. We found that E2F target genes involved in nucleotide biosynthesis contribute to maintaining genome stability in prostate cancer cells, but their enzymatic activity is insufficient to prevent replication stress after E2F1/E2F2 depletion. Instead, E2F1/E2F2 hinder premature CDK1 activation during S phase, which is key to ensure genome stability and viability of prostate cancer cells. From a therapeutic perspective, inhibiting E2F activity provokes catastrophic levels of replication stress and blunts xenograft growth in combination with drugs targeting nucleotide biosynthesis or DNA repair. Our results highlight the suitability of targeting E2F for the treatment of prostate cancer. E2F1/E2F2 expression correlates with malignancy in prostate cancer (PCa), but its functional significance remains unresolved. To define the mechanisms governed by E2F in PCa, we analyzed the contribution of E2F target genes to the control of genome integrity, and the impact of modulating E2F activity on PCa progression. We show that silencing or inhibiting E2F1/E2F2 induces DNA damage during S phase and potentiates 5-FU-induced replication stress and cellular toxicity. Inhibition of E2F downregulates the expression of E2F targets involved in nucleotide biosynthesis (TK1, DCK, TYMS), whose expression is upregulated by 5-FU. However, their enzymatic products failed to rescue DNA damage of E2F1/E2F2 knockdown cells, suggesting additional mechanisms for E2F function. Interestingly, targeting E2F1/E2F2 in PCa cells reduced WEE1 expression and resulted in premature CDK1 activation during S phase. Inhibition of CDK1/CDK2 prevented DNA damage induced by E2F loss, suggesting that E2F1/E2F2 safeguard genome integrity by restraining CDK1/CDK2 activity. Importantly, combined inhibition of E2F and ATR boosted replication stress and dramatically reduced tumorigenic capacity of PCa cells in xenografts. Collectively, inhibition of E2F in combination with drugs targeting nucleotide biosynthesis or DNA repair is a promising strategy to provoke catastrophic levels of replication stress that could be applied to PCa treatment. [ABSTRACT FROM AUTHOR]

According to Dorothea Debus (2007), all emotional aspects related to an act of remembering are present and new emotional responses to the remembered past event. This is a common conception of the nature of the emotional aspect of personal memories, if not explicitly defended then at least implicitly accepted in the literature. In this article, I first criticize Debus’ arguments and demonstrate that she does not give us valid reasons to believe that all the emotional aspects related to a memory are present and new emotional responses to that past event. I then criticize Debus’ thesis tout court for being a direct consequence of assuming a particular conceptualization of the nature of emotions: emotions as physiological changes. Finally, based on a different conceptualization of emotions that focuses on their relational nature, I propose an alternative framework for analyzing the different possible emotional aspects of our personal memories. This leads me to conclude, contrary to Debus, that some emotional aspects of our memories are not occurrent emotions but are better conceived as a sort of quasi-emotions. [ABSTRACT FROM AUTHOR]

Background: The respiratory consequences of daily nursing care interventions in patients with acute respiratory distress syndrome (ARDS) are not clearly established. Aims and objectives: The main objective of this study was to assess the feasibility of alveolar collapse analysis by the measurement of lung impedance distribution technique during nursing care in patients with ARDS. Design: Prospective observational pilot physiologic study in a surgical intensive care unit of a tertiary care hospital including adult intubated patients with moderate‐to‐severe ARDS. Methods: Each patient was monitored for 12 hours using a chest impedance device. Daily care interventions studied were as follows: endotracheal suctioning, mouth care, bed‐bathing, and blood sampling. The primary endpoint was the variation in end‐expiratory lung impedance (reflecting functional residual capacity) before and 1, 5, 15, and 30 minutes after nursing care interventions. Data are presented as median (interquartile‐range). Results: One hundred and eight events were collected in 18 patients. Endotracheal suctioning (n = 42), mouth care (n = 26), and bed‐bathing (n = 23) induced a significant decrease in lung impedance after care: endotracheal suctioning (−40.0 [−53.8; −28.6]% at 1 minute [P <.001], −10.4 [−27.9; 1.8]% at 30 minutes [P =.03]; mouth care −17.9 [−45.4; −14.6]% at 1 minute [P <.001], −10.4 [−21.3; 3.4]% at 30 minutes [P =.01]; bed‐bathing −40.2 [−53.5; −14.3]% at 1 minute [P <.001], −10.6 [−36.4; 1.6]% at 30 minutes [P =.01]). Blood sampling (n = 17) did not induce significant changes in lung impedance. Conclusions: The lung impedance distribution technique during nursing care appears feasible in the majority of patients with ARDS. Some daily nursing care in ARDS patients (including bed‐bathing and mouth care) resulted in a prolonged decrease in lung functional residual capacity and therefore could be associated with pulmonary de‐recruitment. Relevance to clinical practice: A caregiver who has to assess the functional residual capacity of these patients should probably be informed of the schedules of the nursing care interventions. [ABSTRACT FROM AUTHOR]

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development.sup.1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure.sup.2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation. MC3R deficiency is associated with a delay in the onset of puberty, and a reduction in growth and lean mass., Author(s): B. Y. H. Lam [sup.1] [sup.2] , A. Williamson [sup.1] [sup.2] [sup.3] , S. Finer [sup.4] , F. R. Day [sup.3] , J. A. Tadross [sup.1] [sup.2] [sup.5] , [...]

Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases.sup.1-3. Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5[alpha]-reductase (5AR) and 3[beta]-hydroxysteroid dehydrogenase (3[beta]-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis. The microbiota of centenarians (aged 100 years and older) comprise gut microorganisms that are capable of generating unique secondary bile acids, including isoallolithocholic acid, a bile acid with potent antimicrobial effects against Gram-positive--but not Gram-negative--multidrug-resistant pathogens., Author(s): Yuko Sato [sup.1] [sup.2] [sup.3] , Koji Atarashi [sup.1] [sup.2] [sup.3] , Damian R. Plichta [sup.4] , Yasumichi Arai [sup.5] , Satoshi Sasajima [sup.1] [sup.3] , Sean M. Kearney [...]

Understanding human organ formation is a scientific challenge with far-reaching medical implications.sup.1,2. Three-dimensional stem-cell cultures have provided insights into human cell differentiation.sup.3,4. However, current approaches use scaffold-free stem-cell aggregates, which develop non-reproducible tissue shapes and variable cell-fate patterns. This limits their capacity to recapitulate organ formation. Here we present a chip-based culture system that enables self-organization of micropatterned stem cells into precise three-dimensional cell-fate patterns and organ shapes. We use this system to recreate neural tube folding from human stem cells in a dish. Upon neural induction.sup.5,6, neural ectoderm folds into a millimetre-long neural tube covered with non-neural ectoderm. Folding occurs at 90% fidelity, and anatomically resembles the developing human neural tube. We find that neural and non-neural ectoderm are necessary and sufficient for folding morphogenesis. We identify two mechanisms drive folding: (1) apical contraction of neural ectoderm, and (2) basal adhesion mediated via extracellular matrix synthesis by non-neural ectoderm. Targeting these two mechanisms using drugs leads to morphological defects similar to neural tube defects. Finally, we show that neural tissue width determines neural tube shape, suggesting that morphology along the anterior-posterior axis depends on neural ectoderm geometry in addition to molecular gradients.sup.7. Our approach provides a new route to the study of human organ morphogenesis in health and disease. Stem cells cultured in a micropattern-constrained platform form a quantitative and robust model of human neural tube morphogenesis., Author(s): Eyal Karzbrun [sup.1] [sup.2] , Aimal H. Khankhel [sup.3] , Heitor C. Megale [sup.1] , Stella M. K. Glasauer [sup.4] [sup.5] , Yofiel Wyle [sup.4] , George Britton [sup.6] [...]

Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1).sup.1,2. Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic [beta]-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1. Adipocyte-specific deletion of a scaffolding protein, protein targeting to glycogen (PTG), reduces glycogen levels in beige adipocytes, attenuating UCP1 expression and responsiveness to cold or [beta]-adrenergic receptor-stimulated weight loss in obese mice. Unexpectedly, we observed that glycogen synthesis and degradation are increased in response to catecholamines, and that glycogen turnover is required to produce reactive oxygen species leading to the activation of p38 MAPK, which drives UCP1 expression. Thus, glycogen has a key regulatory role in adipocytes, linking glucose metabolism to thermogenesis. Increased glycogen metabolism in adipocytes leads to expression of uncoupling protein 1, thereby linking glucose metabolism to thermogenesis., Author(s): Omer Keinan [sup.1] , Joseph M. Valentine [sup.1] , Haopeng Xiao [sup.2] [sup.3] , Sushil K. Mahata [sup.4] , Shannon M. Reilly [sup.1] , Mohammad Abu-Odeh [sup.1] , Julia [...]

Glutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse.sup.1-7. In the brain, the trafficking, gating kinetics and pharmacology of kainate receptors are tightly regulated by neuropilin and tolloid-like (NETO) proteins.sup.8-11. Here we report cryo-electron microscopy structures of homotetrameric GluK2 in complex with NETO2 at inhibited and desensitized states, illustrating variable stoichiometry of GluK2-NETO2 complexes, with one or two NETO2 subunits associating with GluK2. We find that NETO2 accesses only two broad faces of kainate receptors, intermolecularly crosslinking the lower lobe of ATD.sup.A/C, the upper lobe of LBD.sup.B/D and the lower lobe of LBD.sup.A/C, illustrating how NETO2 regulates receptor-gating kinetics. The transmembrane helix of NETO2 is positioned proximal to the selectivity filter and competes with the amphiphilic H1 helix after M4 for interaction with an intracellular cap domain formed by the M1-M2 linkers of the receptor, revealing how rectification is regulated by NETO2. The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2., Author(s): Lingli He [sup.1] [sup.2] [sup.3] , Jiahui Sun [sup.4] [sup.5] , Yiwei Gao [sup.1] [sup.3] , Bin Li [sup.1] [sup.3] , Yuhang Wang [sup.1] [sup.3] , Yanli Dong [sup.1] [...]

Genistein, an isoflavonoid that can inhibit protein tyrosine kinase (PTK) phosphorylation, has been shown to play pivotal roles in the signal transduction pathways of hypoxic disorders. In this study, we established a rat model of isolated beating atrium and investigated the regulator role of genistein and its downstream signaling pathways in acute hypoxia-induced atrial natriuretic peptide (ANP) secretion. Radioimmunoassay was used to detect the ANP content in the atrial perfusates. Western blot analysis was used to determine the protein level of hypoxia-inducible factor 1[alpha] (HIF-1[alpha]), and GATA4 in the atrial tissue. The results showed that acute hypoxia substantially promoted ANP secretion, whereas this effect was partly attenuated by the PTKs inhibitor genistein (3 [micro]M). By Western blotting analysis, we found that hypoxia-induced increase in phosphorylation of Akt and transcriptional factors, including HIF-1[alpha], were also reversed by genistein. The perfused HIF-1[alpha] inhibitors rotenone (0.5 [micro]M) or CAY10585 (10 [micro]M) plus genistein significantly abolished the enhanced ANP section induced by hypoxia. Additionally, the perfused PI3K/Akt agonist insulin-like growth factor 1 (30 [micro]M) also abolished ANP secretion induced by genistein and inhibited expression of HIF-1[alpha]. In summary, our data suggested that acute hypoxia markedly increased ANP secretion by PTKs through the phosphoinositide-3 kinase (PI3K)/HIF-1[alpha] dependent pathway. Key words: atrial natriuretic peptide, hypoxia, hypoxia inducible factor-1a, protein tyrosine kinases, genistein. On a montre que la genisteine, un isoflavonoide pouvant entrainer une inhibition de la phosphorylation des PTK (<< protein tyrosine kinases >>), joue un role central dans les voies de transduction des signaux dans les troubles hypoxiques. Dans cette etude, nous avons mis au point un modele d'atrium contractile isole chez le rat, et etudie le role regulateur de la genisteine et ses voies de signalisation en aval dans la secretion de peptide natriuretique atrial (ANP) engendree par l'hypoxie aigue. A l'aide d'un radioimmunoessai, nous avons evalue les taux d'ANP dans les perfusats atriaux. A l'aide de l'immunobuvardage de Western, nous avons etabli les taux en proteines d'HIF-1[alpha] (<< hypoxia-inducible factor-1a >>) et de GATA4 dans le tissu atrial. Les resultats ont montre que l'hypoxie aigue favorise substantiellement la secretion d'ANP, tandis que cet effet s'attenuait partiellement avec l'inhibiteur des PTK genisteine (a 3 [micro]M). A l'aide de l'immunobuvardage de Western, nous avons observe que l'augmentation de la phosphorylation d'Akt et de facteurs de la transcription, y compris HIF-1[alpha], engendree par l'hypoxie etait aussi inversee avec la genisteine. La perfusion des inhibiteurs de l'HIF-1[alpha] rotenone (a 0,5 [micro]M) ou CAY10585 (a 10 [micro]M) avec la genisteine permettait clairement d'inhiber completement l'augmentation de la secretion d'ANP engendree par l'hypoxie. De plus, la perfusion de l'agoniste de l'axe PI3K/Akt IGF-1 (a 30 [micro]M) a aussi permis d'inhiber completement la secretion d'ANP engendree par la genisteine, ainsi que d'inhiber l'expression de l'HIF-1[alpha]. En resume, nos donnees laissaient entendre que l'hypoxie aigue entrainerait une augmentation marquee de la secretion d'ANP engendree par les PTK par l'intermediate de la voie de signalisation dependante de PI3K/HIF-1[alpha]. [Traduit par la Redaction] Mots-cles: peptide natriuretique atrial, hypoxie, HIF-1[alpha], PTK, genisteine., Introduction Atrial natriuretic peptide (ANP) is one of the cardiac hormones synthesized and primarily stored in the cardiac atria with multiple functions on cardio-related disease (Cannone et al. 2019; Zhou [...]

[micro]-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose.sup.1-3. Despite its evident importance, the endogenous mechanisms for MOPR regulation of consummatory behaviour have remained unknown.sup.4. Here we report that endogenous MOPR regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection. MOPR-mediated inhibition of raphe terminals is necessary and sufficient to determine consummatory response, while select enkephalin-containing nucleus accumbens ensembles are engaged prior to reward consumption, suggesting that local enkephalin release is the source of the endogenous MOPR ligand. Selective modulation of nucleus accumbens enkephalin neurons and CRISPR-Cas9-mediated disruption of enkephalin substantiate this finding. These results isolate a fundamental endogenous opioid circuit for state-dependent consumptive behaviour and suggest alternative mechanisms for opiate modulation of reward. Studies in mice show that [micro]-opioid peptide receptor regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection and requires enkephalin-producing neurons., Author(s): Daniel C. Castro [sup.1] [sup.2] [sup.3] [sup.4] , Corinna S. Oswell [sup.1] [sup.4] , Eric T. Zhang [sup.4] [sup.5] , Christian E. Pedersen [sup.4] [sup.5] , Sean C. Piantadosi [...]

Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing.sup.1,2. Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals. Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote., Author(s): Tim H. H. Coorens [sup.1] , Luiza Moore [sup.1] [sup.2] , Philip S. Robinson [sup.1] [sup.3] , Rashesh Sanghvi [sup.1] , Joseph Christopher [sup.1] [sup.3] [sup.4] , James Hewinson [...]

Vascular endothelial cell senescence is a leading cause of age-associated diseases and cardiovascular diseases. Interventions and therapies targeting endothelial cell senescence and dysfunction would have important clinical implications. This study evaluated the effect of 10 resveratrol analogues, including pterostilbene (Pts) and its derivatives, against endothelial senescence and dysfunction. All the tested compounds at the concentrations from [10.sup.-9] M to [10.sup.-6] M did not show cytotoxicity in endothelial cells by MTT assay. Among the 10 resveratrol analogues, Pts and Pts nicotinate attenuated the expression of senescence-associated [beta]-galactosidase, downregulated p21 and p53, and increased the production of nitric oxide (NO) in both angiotensin II - and hydrogen peroxide - induced endothelial senescence models. In addition, Pts and Pts nicotinate elicited endothelium-dependent relaxations, which were attenuated in the presence of endothelial NO synthase (eNOS) inhibitor L-NAME or sirtuin 1 (SIRT1) inhibitor sirtinol. Pts and Pts nicotinate did not alter SIRT1 expression but enhanced its activity. Both Pts and Pts nicotinate have high binding activities with SIRT1, according to surface plasmon resonance results and the molecular docking analysis. Inhibition of SIRT1 by sirtinol reversed the anti-senescent effects of Pts and Pts nicotinate. Moreover, Pts and Pts nicotinate shared similar ADME (absorption, distribution, metabolism, excretion) profiles and physiochemical properties. This study suggests that the Pts and Pts nicotinate ameliorate vascular endothelial senescence and elicit endothelium-dependent relaxations via activation of SIRT1. These two compounds may be potential drugs for the treatment of cardiovascular diseases related to endothelial senescence and dysfunction. Key words: endothelial cells, senescence, pterostilbene, sirtuin 1. La senescence des cellules endotheliales vasculaires et l'une des principales causes de maladies associees au vieillissement et de maladies cardiovasculaires. Des interventions et des traitements ciblant la senescence et le dysfonctionnement des cellules endotheliales auraient d'importantes repercussions en clinique. Cette etude visait a evaluer l'effet de 10 analogues du resveratrol, y compris le pterostilbene (Pts) et ses derives, sur la senescence et le dysfonctionnement endotheliaux. Aucun des composes evalues a des concentrations de [10.sup.-9] M a [10.sup.-6] M n'ont montre de cytotoxicite dans les cellules endotheliales soumises au test du MTT. Parmi les 10 analogues du resveratrol, le Pts et le nicotinate de Pts ont permis d'attenuer l'expression de la [beta]-galactosidase associee a la senescence, de reguler a la baisse p21 et p53, ainsi que de faire augmenter la production d'oxyde nitrique (NO) dans des modeles de senescence endotheliale engendree par l'angiotensine II comme le [H.sub.2][O.sub.2]. De plus, le Pts et le nicotinate de Pts ont suscite des relaxations dependantes de l'endothelium, lesquelles s'attenuaient en presence de L-NAME, inhibiteur de la NO synthase endotheliale (eNOS), ou de sirtinol, inhibiteur de la sirtuine 1 (SIRT1). Ni le Pts ni le nicotinate de Pts n'ont altere l'expression de la SIRT1, mais ils ont entraine une augmentation de son activite. Tant le Pts que le nicotinate de Pts ont des activites de liaison elevees avec la SIRT1, selon les resultats de resonance plasmon de surface (SPR) et d'analyses d'arrimage moleculaire. L'inhibition de la SIRT1 par le sirtinol entrainait une inversion des effets anti-senescent du Pts et du nicotinate de Pts. En outre, le Pts et le nicotinate de Pts ont des profils d'ADME et des proprietes physiochimiques similaires. En conclusion, cette etude laisse entendre que le Pts et le nicotinate de Pts permettraient d'attenuer la senescence de l'endothelium vasculaire et de susciter des relaxations dependantes de l'endothelium par l'intermediaire de l'activation de la SIRT1. Ces deux composes pourraient constituer des medicaments eventuels pour le traitement de maladies cardiovasculaires liees a la senescence et au dysfonctionnement de l'endothelium. [Traduit par la Redaction] Mots-cles: cellules endotheliales, senescence, pterostilbene, sirtuine 1., Introduction Vascular endothelial cells play a pivotal role in regulating vascular hemostasis, vascular tone and permeability, angiogenesis, as well as vascular inflammation (Vanhoutte et al. 2017); however, the endothelial cells [...]

BACKGROUND: High-frequency oscillatory ventilation (HFOV) is widely used in neonatal critical care, and several modern ventilators using different technologies are available to provide HFOV. These devices have different technical characteristics that might interact with patient lung mechanics to influence the effectiveness of ventilation. To verify this, we studied the oscillation transmission of 5 neonatal oscillators in a lung model mimicking the mechanical patterns commonly observed in neonatal practice. METHODS: This was a benchtop, in vitro, physiological, pragmatic study using a model mimicking airways and lung of a 1-kg preterm neonate and the following patterns: normal (compliance: 1.0 mL/cm H2O, resistance: 50 cm H2O/L/s), restrictive (compliance: 0.3 mL/cm H2O, resistance: 50 cm H2O/L/s), and mixed mechanics (compliance: 0.3 mL/cm H2O, resistance: 250 cm H2O/L/s). Several permutations of HFOV parameters (variable mean airway pressure or amplitude or frequency protocols) were tested. Oscillations were measured with a dedicated pressure transducer validated for use during HFOV, and oscillatory pressure ratio (OPR) was calculated to estimate the oscillation transmission. RESULTS: Overall OPR (calculated on all experiments) was significantly different between ventilators and the mechanical patterns (both P < .001). Different ventilators and patterns accounted for 35.6% and 20.6% of the variation in oscillation transmission, respectively. Sub-analyses per changing amplitude or frequency protocols and multivariate regressions showed that VN500 (standardized β coefficient [St.β]: 0.548, P < .001) and Fabian HFO (St.β: 0.421, P < .001; adjusted R²: 0.615) provided the best oscillation transmission. Fabian HFO also delivered oscillations with the lowest variability when increasing amplitude. CONCLUSIONS: In an experimental setting mimicking typical neonatal lung disorders, the oscillation transmission was more dependent on the ventilator model than on the mechanical lung conditions at equal HFOV parameters. Fabian HFO and VN500 provided better oscillation transmission overall, and when increasing amplitude, Fabian HFO delivered oscillations with the lowest variability. [ABSTRACT FROM AUTHOR]

This review contains 208 citation items from 31 countries in total. The highest number of citations come from Spain (34) then from the USA (23), Italy (18) and China (16). Only one citation comes from Denmark, Georgia, Macedonia, and New Zealand. They are all included into 16 topics arranged in alphabetical order. The results or conclusions of each study are briefly described and arranged according to the year of the publication and alphabetical order of the authors. The most important topic was the physiological research containing 40 citations and then the evaluation of cultivars containing 33 citations. From the years of the review, the most important was 2017 with 122 items, whereas the least prolific year was 2015 containing only 35 items. [ABSTRACT FROM AUTHOR]

Electrical activity in the brain and heart depends on rhythmic generation of action potentials by pacemaker ion channels (HCN) whose activity is regulated by cAMP binding.sup.1. Previous work has uncovered evidence for both positive and negative cooperativity in cAMP binding.sup.2,3, but such bulk measurements suffer from limited parameter resolution. Efforts to eliminate this ambiguity using single-molecule techniques have been hampered by the inability to directly monitor binding of individual ligand molecules to membrane receptors at physiological concentrations. Here we overcome these challenges using nanophotonic zero-mode waveguides.sup.4 to directly resolve binding dynamics of individual ligands to multimeric HCN1 and HCN2 ion channels. We show that cAMP binds independently to all four subunits when the pore is closed, despite a subsequent conformational isomerization to a flip state at each site. The different dynamics in binding and isomerization are likely to underlie physiologically distinct responses of each isoform to cAMP.sup.5 and provide direct validation of the ligand-induced flip-state model.sup.6-9. This approach for observing stepwise binding in multimeric proteins at physiologically relevant concentrations can directly probe binding allostery at single-molecule resolution in other intact membrane proteins and receptors. Direct monitoring of individual cAMP molecules binding to HCN ion channels reveals the binding dynamics underlying the distinct physiological responses of ion channel isoforms., Author(s): David S. White [sup.1] [sup.2] [sup.4] , Sandipan Chowdhury [sup.1] [sup.5] , Vinay Idikuda [sup.1] [sup.6] , Ruohan Zhang [sup.1] [sup.2] , Scott T. Retterer [sup.3] , Randall H. [...]

Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules.sup.1-3, yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites in diverse sample types. We report the metabolic profiles of 178 gut microorganism strains using our library of 833 metabolites. Using this metabolomics resource, we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover a previously undescribed type of metabolism in Bacteroides, and reveal candidate biochemical pathways using comparative genomics. Microbiota-dependent metabolites can be detected in diverse biological fluids from gnotobiotic and conventionally colonized mice and traced back to the corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microorganisms and interactions between microorganisms and their host. A microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for the characterization of gut-resident microorganisms and the interactions between microorganisms and their host., Author(s): Shuo Han [sup.1] , Will Van Treuren [sup.1] [sup.2] , Curt R. Fischer [sup.3] [sup.4] , Bryan D. Merrill [sup.1] [sup.2] , Brian C. DeFelice [sup.4] , Juan M. [...]