Sex-based differences in hematological values after normalization to body mass or fat-free mass in adults matched for aerobic fitness.

Blood properties influence aerobic exercise performance. While vascular volumes and hemoglobin mass (Hbmass) are elevated in trained individuals, evidence of sex differences in vascular volumes is equivocal due to inadequate matching of aerobic fitness between males and females. This cross-sectional study aimed to compare hematological values normalized to body mass (BM) and fat-free mass (FFM) between males (n=45) and females (n=34) matched for aerobic fitness (V̇O2max) normalized to FFM (mL∙kg FFM-1∙min-1). Data included body composition measured by dual-energy x-ray absorptiometry (DXA), V̇O2max from an incremental test, and hematological values derived from a CO rebreathe test. Fat mass was unrelated to blood volume (BV; R2 = 0.02, p=0.26) and Hbmass (R2=0.03, p=0.16), while FFM was the strongest predictor of both (R2=0.75 and R2=0.83, respectively, P<0.001). Females exhibited higher FFM-normalized BV (+4%, P<0.05) and plasma volume (PV) (+14%, P<0.001) and lower red blood cell volume (RBCV) (-8%, P<0.001) and Hbmass (-8%, P<0.001) compared to males. Positive correlations between aerobic fitness and relative Hbmass and BV were observed in both sexes when normalized to BM and FFM (0.48

The Effect of Duration on Performance and Perceived Fatigability During Acute High-Intensity Interval Exercise in Young, Healthy Males and Females.

Few studies have explored the kinetics of performance and perceived fatigability during high-intensity interval training, despite its popularity. We aimed to characterize the kinetics of fatigability and recovery during an 8 × 4-min HIIT protocol, hypothesizing that most muscle function impairment would occur during the initial four intervals. Fifteen healthy males and females (mean ± standard deviation; age = 26 ± 5 years, V̇O2max = 46.8 ± 6.1 mL·kg-1·min-1) completed eight, 4-min intervals at 105% of critical power with 3 min of rest. Maximal voluntary knee extension contractions (MVCs) coupled with electrical nerve stimulation were performed at baseline and after the first, fourth, and eighth intervals. MVC, potentiated twitch force (Pt), and Db10:100 ratio all declined throughout HIIT (p < 0.05). MVC sharply declined after interval 1 (-15 ± 9% relative to baseline; p < 0.05) and had only further declined after interval 8 (-26 ± 11%; p < 0.05), but not interval 4 (-19 ± 13%; p > 0.05). Pt and Db10:100 also sharply declined after interval 1 (Pt: -18 ± 13%, Db10:100: -14 ± 20%; p < 0.05) and further declined after interval 4 (Pt: -35 ± 19%, Db10:100: -30 ± 20%; p < 0.05) but not interval 8 (Pt: -41 ± 19%; Db10:100: -32 ± 18%; p > 0.05). Voluntary activation did not significantly change across the HIIT protocol (p > 0.05). Evoked force recovery was significantly blunted as more intervals were completed: after interval 1, Pt recovered by 7 ± 11% compared to -6 ± 7% recovery after interval 8 (p < 0.05). Ratings of perceived effort, fatigue, and leg pain rose throughout the session (p < 0.05 for each) and were greater (effort and fatigue) for females (p < 0.05). Otherwise, males and females exhibited similar performance fatigability kinetics, with contractile function declines blunted in response to additional intervals.

The influence of sex, hemoglobin mass, and skeletal muscle characteristics on cycling critical power.

Critical power (CP) represents an important threshold for exercise performance and fatiguability. We sought to determine the extent to which sex, hemoglobin mass (Hbmass), and skeletal muscle characteristics influence CP. Before CP determination (i.e., 3-5 constant work rate trials to task failure), Hbmass and skeletal muscle oxidative capacity (τ) were measured and vastus lateralis (VL) muscle biopsy samples were collected from 12 females and 12 males matched for aerobic fitness relative to fat-free mass (FFM) [means (SD); V̇o2max: 59.2 (7.7) vs. 59.5 (7.1) mL·kg·FFM-1·min-1, respectively]. Males had a significantly greater CP than females in absolute units [225 (28) vs. 170 (43) W; P = 0.001] but not relative to body mass [3.0 (0.6) vs. 2.7 (0.6) W·kg·BM-1; P = 0.267] or FFM [3.6 (0.7) vs. 3.7 (0.8) W·kg·FFM-1; P = 0.622]. Males had significantly greater W' (P ≤ 0.030) and greater Hbmass (P ≤ 0.016) than females, regardless of the normalization approach; however, there were no differences in mitochondrial protein content (P = 0.375), τ (P = 0.603), or MHC I proportionality (P = 0.574) between males and females. Whether it was expressed in absolute or relative units, CP was positively correlated with Hbmass (0.444 ≤ r ≤ 0.695; P < 0.05), mitochondrial protein content (0.413 ≤ r ≤ 0.708; P < 0.05), and MHC I proportionality (0.506 ≤ r ≤ 0.585; P < 0.05), and negatively correlated with τ when expressed in relative units only (-0.588 ≤ r ≤ -0.527; P < 0.05). Overall, CP was independent of sex, but variability in CP was related to Hbmass and skeletal muscle characteristics. The extent to which manipulations in these physiological parameters influence CP warrants further investigation to better understand the factors underpinning CP.NEW & NOTEWORTHY In males and females matched for aerobic fitness [maximal oxygen uptake normalized to fat-free mass (FFM)], absolute critical power (CP) was greater in males, but relative CP (per kilogram body mass or FFM) was similar between sexes. CP correlated with hemoglobin mass, mitochondrial protein content, myosin heavy chain type I proportion, and skeletal muscle oxidative capacity. These findings demonstrate the importance of matching sexes for aerobic fitness, but further experiments are needed to determine causality.

Contraction intensity affects NIRS-derived skeletal muscle oxidative capacity but not its relationships to mitochondrial protein content or aerobic fitness.

To further refine the near-infrared spectroscopy (NIRS)-derived measure of skeletal muscle oxidative capacity in humans, we sought to determine whether the exercise stimulus intensity affected the τ value and/or influenced the magnitude of correlations with in vitro measures of mitochondrial content and in vivo indices of exercise performance. Males (n = 12) and females (n = 12), matched for maximal aerobic fitness per fat-free mass, completed NIRS-derived skeletal muscle oxidative capacity tests for the vastus lateralis following repeated contractions at 40% (τ40) and 100% (τ100) of maximum voluntary contraction, underwent a skeletal muscle biopsy of the same muscle, and performed multiple intermittent isometric knee extension tests to task failure to establish critical torque (CT). The value of τ100 (34.4 ± 7.0 s) was greater than τ40 (24.2 ± 6.9 s, P < 0.001), but the values were correlated (r = 0.688; P < 0.001). The values of τ40 (r = -0.692, P < 0.001) and τ100 (r = -0.488, P = 0.016) correlated with myosin heavy chain I percentage and several markers of mitochondrial content, including COX II protein content in whole muscle (τ40: r = -0.547, P = 0.006; τ100: r = -0.466, P = 0.022), type I pooled fibers (τ40: r = -0.547, P = 0.006; τ100: r = -0.547, P = 0.006), and type II pooled fibers (τ40: r = -0.516, P = 0.009; τ100: r = -0.635, P = 0.001). The value of τ40 (r = -0.702, P < 0.001), but not τ100 (r = -0.378, P = 0.083) correlated with critical torque (CT); however, neither value correlated with W' (τ40: r = 0.071, P = 0.753; τ100: r = 0.054, P = 0.812). Overall, the NIRS method of assessing skeletal muscle oxidative capacity is sensitive to the intensity of skeletal muscle contraction but maintains relationships to whole body fitness, isolated limb critical intensity, and mitochondrial content regardless of intensity.NEW & NOTEWORTHY Skeletal muscle oxidative capacity measured using near-infrared spectroscopy (NIRS) was lower following high-intensity compared with low-intensity isometric knee extension contractions. At both intensities, skeletal muscle oxidative capacity was correlated with protein markers of mitochondrial content (in whole muscle and pooled type I and type II muscle fibers) and critical torque. These findings highlight the importance of standardizing contraction intensity while using the NIRS method with isometric contractions and further demonstrate its validity.

The influence of skeletal muscle mitochondria and sex on critical torque and performance fatiguability in humans.

Critical torque (CT) represents the highest oxidative steady state for intermittent knee extensor exercise, but the extent to which it is influenced by skeletal muscle mitochondria and sex is unclear. Vastus lateralis muscle biopsy samples were collected from 12 females and 12 males -matched for relative maximal oxygen uptake normalized to fat-free mass (FFM) (F: 57.3 (7.5) ml (kg FFM)-1  min-1 ; M: 56.8 (7.6) ml (kg FFM)-1  min-1 ; P = 0.856) - prior to CT determination and performance fatiguability trials. Males had a lower proportion of myosin heavy chain (MHC) I isoform (40.6 (18.4)%) compared to females (59.5 (18.9)%; P = 0.021), but MHC IIa and IIx isoform distributions and protein markers of mitochondrial content were not different between sexes (P > 0.05). When normalized to maximum voluntary contraction (MVC), the relative CT (F: 42.9 (8.3)%; M: 37.9 (9.0)%; P = 0.172) and curvature constant, W' (F: 26.6 (11.0) N m s (N m)-1 ; M: 26.4 (6.5) N m s (N m)-1 ; P = 0.962) were not significantly different between sexes. All protein biomarkers of skeletal muscle mitochondrial content, as well as the proportion of MHC I isoform, positively correlated with relative CT (0.48 < r < 0.70; P < 0.05), and the proportion of MHC IIx isoform correlated positively with relative W' (r = 0.57; P = 0.007). Indices of performance fatiguability were not different between males and females for MVC- and CT-controlled trials (P > 0.05). Greater mitochondrial protein abundance was associated with attenuated declines in potentiated twitch torque for exercise at 60% MVC (P < 0.05); however, the influence of mitochondrial protein abundance on performance fatiguability was reduced when exercise was prescribed relative to CT. Whether these findings translate to whole-body exercise requires additional research. KEY POINTS: The quadriceps critical torque represents the highest intensity of intermittent knee extensor exercise for which an oxidative steady state is attainable, but its relationship with skeletal muscle mitochondrial protein abundance is unknown. Matching males and females for maximal oxygen uptake relative to fat-free mass facilitates investigations of sex differences in exercise physiology, but studies that have compared critical torque and performance fatiguability during intermittent knee extensor exercise have not ensured equal aerobic fitness between sexes. Skeletal muscle mitochondrial protein abundance was correlated with critical torque and fatigue resistance for exercise prescribed relative to maximum voluntary contraction but not for exercise performed relative to the critical torque. Differences between sexes in critical torque, skeletal muscle mitochondrial protein abundance and performance fatiguability were not statistically significant. Our results suggest that skeletal muscle mitochondrial protein abundance may contribute to fatigue resistance by influencing the critical intensity of exercise.

Time course and fibre type-dependent nature of calcium-handling protein responses to sprint interval exercise in human skeletal muscle.

Sprint interval training (SIT) causes fragmentation of the skeletal muscle sarcoplasmic reticulum Ca2+ release channel, ryanodine receptor 1 (RyR1), 24 h post-exercise, potentially signalling mitochondrial biogenesis by increasing cytosolic [Ca2+ ]. Yet, the time course and skeletal muscle fibre type-specific patterns of RyR1 fragmentation following a session of SIT remain unknown. Ten participants (n = 4 females; n = 6 males) performed a session of SIT (6 × 30 s 'all-out' with 4.5 min rest after each sprint) with vastus lateralis muscle biopsy samples collected before and 3, 6 and 24 h after exercise. In whole muscle, full-length RyR1 protein content was significantly reduced 6 h (mean (SD); -38 (38)%; P < 0.05) and 24 h post-SIT (-30 (48)%; P < 0.05) compared to pre-exercise. Examining each participant's largest response in pooled samples, full-length RyR1 protein content was reduced in type II (-26 (30)%; P < 0.05) but not type I fibres (-11 (40)%; P > 0.05). Three hours post-SIT, there was also a decrease in sarco(endo)plasmic reticulum Ca2+ ATPase 1 in type II fibres (-23 (17)%; P < 0.05) and sarco(endo)plasmic reticulum Ca2+ ATPase 2a in type I fibres (-19 (21)%; P < 0.05), despite no time effect for either protein in whole muscle samples (P > 0.05). PGC1A mRNA content was elevated 3 and 6 h post-SIT (5.3- and 3.7-fold change from pre, respectively; P < 0.05 for both), but peak PGC1A mRNA expression was not significantly correlated with peak RyR1 fragmentation (r2  = 0.10; P > 0.05). In summary, altered Ca2+ -handling protein expression, which occurs primarily in type II muscle fibres, may influence signals for mitochondrial biogenesis as early as 3-6 h post-SIT in humans. KEY POINTS: Sprint interval training (SIT) has been shown to cause fragmentation of the sarcoplasmic reticulum calcium-release channel, ryanodine receptor 1 (RyR1), 24 h post-exercise, which may act as a signal for mitochondrial biogenesis. In this study, the time course was examined of RyR1 fragmentation in human whole muscle and pooled type I and type II skeletal muscle fibres following a single session of SIT. Full-length RyR1 protein content was significantly lower than pre-exercise by 6 h post-SIT in whole muscle, and fragmentation was detectable in type II but not type I fibres, though to a lesser extent than in whole muscle. The peak in PGC1A mRNA expression occurred earlier than RyR1 fragmentation. The increased temporal resolution and fibre type-specific responses for RyR1 fragmentation provide insights into its importance to mitochondrial biogenesis in humans.

Tidal Volume-Dependent Activation of the Renin-Angiotensin System in Experimental Ventilator-Induced Lung Injury.

OBJECTIVES: Ventilator-induced lung injury (VILI) is a major contributor to morbidity and mortality in critically ill patients. Mechanical damage to the lungs is potentially aggravated by the activation of the renin-angiotensin system (RAS). This article describes RAS activation profiles in VILI and discusses the effects of angiotensin (Ang) 1-7 supplementation or angiotensin-converting enzyme (ACE) inhibition with captopril as protective strategies. DESIGN: Animal study. SETTING: University research laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: Anesthetized mice ( n = 12-18 per group) were mechanically ventilated with low tidal volume (LV T , 6 mL/kg), high tidal volume (HV T , 15 mL/kg), or very high tidal volume (VHV T , 30 mL/kg) for 4 hours, or killed after 3 minutes (sham). Additional VHV T groups received infusions of 60 µg/kg/hr Ang 1-7 or a single dose of 100 mg/kg captopril. MEASUREMENTS AND MAIN RESULTS: VILI was characterized by increased bronchoalveolar lavage fluid levels of interleukin (IL)-6, keratinocyte-derived cytokine, and macrophage inflammatory protein-2 (MIP2). The Ang metabolites in plasma measured with liquid chromatography tandem mass spectrometry showed a strong activation of the classical (Ang I, Ang II) and alternative RAS (Ang 1-7, Ang 1-5), with highest concentrations found in the HV T group. Although the lung-tissue ACE messenger RNA expression was unchanged, its protein expression showed a dose-dependent increase under mechanical ventilation. The ACE2 messenger RNA expression decreased in all ventilated groups, whereas ACE2 protein levels remained unchanged. Both captopril and Ang 1-7 led to markedly increased Ang 1-7 plasma levels, decreased Ang II levels, and ACE activity (Ang II/Ang I ratio), and effectively prevented VILI. CONCLUSIONS: VILI is accompanied by a strong activation of the RAS. Based on circulating Ang metabolite levels and tissue expression of RAS enzymes, classical ACE-dependent and alternative RAS cascades were activated in the HV T group, whereas classical RAS activation prevailed with VHV T ventilation. Ang 1-7 or captopril protected from VILI primarily by modifying the systemic RAS profile.

Methodological considerations for and validation of the ultrasonographic determination of human skeletal muscle hypertrophy and atrophy.

Magnetic resonance imaging (MRI) is the current gold standard for measuring changes in muscle size (cross-sectional area [CSA] and volume) but can be cost-prohibitive and resource-intensive. We evaluated the validity of B-mode ultrasonography (US) as a low-cost alternative to MRI for measuring muscle hypertrophy and atrophy in response to resistance training and immobilization, respectively. Fourteen young men performed 10wk of unilateral resistance training (RT) to induce muscle hypertrophy. In the final two weeks of the 10wk, the subjects' contralateral leg was immobilized (IMB). The cross-sectional area of the vastus lateralis (VLCSA) was measured at the mid-thigh before and after each intervention using MRI (VLCSAMRI ) and US (VLCSAUS ). The relationship and agreement between methods were assessed. Reliability of US measurements ranged from good to excellent in all comparisons (ICC >0.67). VLCSA significantly increased after 10 weeks of RT (VLCSAUS : 7.9 ± 3.8%; VLCSAMRI : 7.8 ± 4.5%) and decreased after 2 weeks of IMB (VLCSAUS : -8.2%±5.8%; VLCSAMRI : -8.7 ± 6.1%). Significant correlations were identified between MRI and US at each time point measured (all r > 0.85) and, importantly, between MRI- and US-derived changes in VLCSA. Bland-Altman analysis revealed minimal bias in US measurements relative to the MRI (-0.5 ± 3.0%) and all measurements were within the upper and lower limits of agreement. Our data suggest that B-mode ultrasonography can be a suitable alternative to MRI for measuring changes in muscle size in response to increased and decreased muscle loading in young men.

Molecular Transducers of Human Skeletal Muscle Remodeling under Different Loading States.

Loading of skeletal muscle changes the tissue phenotype reflecting altered metabolic and functional demands. In humans, heterogeneous adaptation to loading complicates the identification of the underpinning molecular regulators. A within-person differential loading and analysis strategy reduces heterogeneity for changes in muscle mass by ∼40% and uses a genome-wide transcriptome method that models each mRNA from coding exons and 3' and 5' untranslated regions (UTRs). Our strategy detects ∼3-4 times more regulated genes than similarly sized studies, including substantial UTR-selective regulation undetected by other methods. We discover a core of 141 genes correlated to muscle growth, which we validate from newly analyzed independent samples (n = 100). Further validating these identified genes via RNAi in primary muscle cells, we demonstrate that members of the core genes were regulators of protein synthesis. Using proteome-constrained networks and pathway analysis reveals notable relationships with the molecular characteristics of human muscle aging and insulin sensitivity, as well as potential drug therapies.

NIRS-derived skeletal muscle oxidative capacity is correlated with aerobic fitness and independent of sex.

Near-infrared spectroscopy (NIRS) provides a simple and reliable measure of skeletal muscle oxidative capacity; however, its relationship to aerobic fitness and sex are unclear. We hypothesized that NIRS-derived oxidative capacity in the vastus lateralis (VL) and medial gastrocnemius (MG) would be correlated with indices of aerobic fitness and independent of sex. Twenty-six participants (13 males, 13 females) performed ramp- and step-incremental tests to volitional exhaustion on separate days to establish maximal oxygen uptake (V̇o2max), peak power output (PPO), lactate threshold (LT), gas exchange threshold (GET), respiratory compensation point (RCP), and maximal fat oxidation (MFO). Data were normalized to lean body mass to account for sex-based differences in body composition. Exercise tests were preceded by duplicate measurements of NIRS-derived oxidative capacity on the VL and MG muscles (i.e., repeated arterial occlusions following a brief set of muscle contractions). Skeletal muscle oxidative capacity for the VL (means ± SD: 21.9 ± 4.6 s) and MG (22.5 ± 6.1 s) were similar but unrelated (r2 = 0.03, P = 0.39). Skeletal muscle oxidative capacity for the VL, but not the MG (P > 0.05 for all variables), was significantly correlated with V̇o2max (r2 = 0.24; P = 0.01), PPO (r2 = 0.23; P = 0.01), LT (r2 = 0.23; P = 0.01), GET (r2 = 0.23; P = 0.01), and RCP (r2 = 0.27; P = 0.006). MFO was not correlated with VL or MG skeletal muscle oxidative capacity (P > 0.05). Females (54.9 ± 4.5 mL·kg LBM-1·min-1) and males (56.0 ± 6.2 mL·kg LBM-1·min-1), matched for V̇o2max (P = 0.62), had similar NIRS-derived oxidative capacities for VL (20.7 ± 4.4 vs. 23.2 ± 4.6 s; P = 0.18) and MG (24.4 ± 6.8 vs. 20.5 ± 4.8 s; P = 0.10). Overall, NIRS-derived skeletal muscle oxidative capacity in VL is indicative of aerobic fitness and independent of sex in humans.NEW & NOTEWORTHY Near-infrared spectroscopy (NIRS) can be used to measure skeletal muscle oxidative capacity. Here, we demonstrated that NIRS-derived skeletal muscle oxidative capacity of the vastus lateralis was independent of sex, reliable across and within days, and correlated with maximal and submaximal indices of aerobic fitness, including maximal oxygen uptake, lactate threshold, and respiratory compensation point. These findings highlight the utility of NIRS for investigating skeletal muscle oxidative capacity in females and males.

From helping hands to harmful acts: When and how employee volunteering promotes workplace deviance.

This study examines how the laudable behavior of employee volunteering can lead to deviant workplace behavior. We draw on the moral licensing and organizational justice literatures to propose that the relationship between employee volunteering and workplace deviance is serially mediated by moral license (moral credits and moral credentials) and psychological entitlement. Results from 2 multiwave survey studies of full-time employees from a variety of organizations and industries confirm that moral credits and psychological entitlement serially mediate this relationship, although the proposed mediating role of moral credentials was not supported. Organizational justice moderates the impact of psychological entitlement on workplace deviance; the indirect relationship between employee volunteering and workplace deviance weakens when perceptions of organizational justice are high. This study demonstrates a potential dark side to employee volunteering and also contributes to the moral licensing and behavioral ethics literatures. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Lactalbumin, Not Collagen, Augments Muscle Protein Synthesis with Aerobic Exercise.

INTRODUCTION: Protein ingestion and the ensuing hyperaminoacidemia stimulates skeletal muscle protein synthesis in the postexercise period. This response facilitates muscle remodeling, which is important during intensified training. The aim of this study was to determine whether supplementation with α-lactalbumin (LA), with high leucine and tryptophan contents, would improve responses to short periods of intensified aerobic training compared with supplementation with an isonitrogenous quantity of collagen peptides (CP). METHODS: Endurance-trained participants (5 male, 6 female, 24 ± 4 yr, V˙O2 = 53.2 ± 9.1 mL·kg·min, peak power output = 320 ± 48 W; means ± SD) consumed a controlled diet (1.0 g·kg·d protein) and refrained from habitual training for 11 d while taking part in this double-blind randomized, crossover trial. The two intervention phases, which consisted of brief intensified training (4 × 4-min cycling intervals at 70% of peak power output on 3 consecutive days) combined with the ingestion of LA or CP supplements after exercise (20 g) and before sleep (40 g), were separated by 4 d of washout without protein supplementation (i.e., the control phase). In response to each phase, myofibrillar (MyoPS), sarcoplasmic protein synthesis (SarcPS) rates (via H2O ingestion) and parameters of sleep quality were measured. RESULTS: LA ingestion increased plasma leucine (P < 0.001) and tryptophan concentrations (P < 0.001) relative to CP. Intensified training increased MyoPS and SarcPS above the washout phase in LA- and CP-supplemented phases (P < 0.01), with increases being 13% ± 5% and 5% ± 7% greater with LA than CP for MyoPS (P < 0.01) and SarcPS, respectively (P < 0.01). CONCLUSIONS: Despite an isonitrogenous diet, protein synthesis was enhanced to a greater extent when trained participants consumed LA compared with CP during intensified aerobic training, suggesting that protein quality is an important consideration for endurance-trained athletes aiming to augment adaption to exercise training.

Effect of short-term, high-intensity exercise training on human skeletal muscle citrate synthase maximal activity: single versus multiple bouts per session.

The legs of 9 men (age 21 ± 2 years, 45 ± 4 mL/(kg·min)) were randomly assigned to complete 6 sessions of high-intensity exercise training, involving either one or four 5-min bouts of counterweighted, single-leg cycling. Needle biopsies from vastus lateralis revealed that citrate synthase maximal activity increased after training in the 4-bout group (p = 0.035) but not the 1-bout group (p = 0.10), with a significant difference between groups post-training (13%, p = 0.021). Novelty Short-term training using brief intense exercise requires multiple bouts per session to increase mitochondrial content in human skeletal muscle.

PO2 oscillations induce lung injury and inflammation.

BACKGROUND: Mechanical ventilation can lead to ventilator-induced lung injury (VILI). In addition to the well-known mechanical forces of volutrauma, barotrauma, and atelectrauma, non-mechanical mechanisms have recently been discussed as contributing to the pathogenesis of VILI. One such mechanism is oscillations in partial pressure of oxygen (PO2) which originate in lung tissue in the presence of within-breath recruitment and derecruitment of alveoli. The purpose of this study was to investigate this mechanism's possible independent effects on lung tissue and inflammation in a porcine model. METHODS: To separately study the impact of PO2 oscillations on the lungs, an in vivo model was set up that allowed for generating mixed-venous PO2 oscillations by the use of veno-venous extracorporeal membrane oxygenation (vvECMO) in a state of minimal mechanical stress. While applying the identical minimal-invasive ventilator settings, 16 healthy female piglets (weight 50 ± 4 kg) were either exposed for 6 h to a constant mixed-venous hemoglobin saturation (SmvO2) of 65% (which equals a PmvO2 of 41 Torr) (control group), or an oscillating SmvO2 (intervention group) of 40-90% (which equals PmvO2 oscillations of 30-68 Torr)-while systemic normoxia in both groups was maintained. The primary endpoint of histologic lung damage was assessed by ex vivo histologic lung injury scoring (LIS), the secondary endpoint of pulmonary inflammation by qRT-PCR of lung tissue. Cytokine concentration of plasma was carried out by ELISA. A bioinformatic microarray analysis of lung samples was performed to generate hypotheses about underlying pathomechanisms. RESULTS: The LIS showed significantly more severe damage of lung tissue after exposure to PO2 oscillations compared to controls (0.53 [0.51; 0.58] vs. 0.27 [0.23; 0.28]; P = 0.0025). Likewise, a higher expression of TNF-α (P = 0.0127), IL-1ß (P = 0.0013), IL-6 (P = 0.0007), and iNOS (P = 0.0013) in lung tissue was determined after exposure to PO2 oscillations. Cytokines in plasma showed a similar trend between the groups, however, without significant differences. Results of the microarray analysis suggest that inflammatory (IL-6) and oxidative stress (NO/ROS) signaling pathways are involved in the pathology linked to PO2 oscillations. CONCLUSIONS: Artificial mixed-venous PO2 oscillations induced lung damage and pulmonary inflammation in healthy animals during lung protective ventilation. These findings suggest that PO2 oscillations represent an independent mechanism of VILI.

College instruction is not so stress free after all: A qualitative and quantitative study of academic entitlement, uncivil behaviors, and instructor strain and burnout.

The vast majority of today's college students are millennials, who have traits of confidence, tolerance, but also of entitlement and narcissism (Twenge, 2006). Therefore, college instructors face a unique challenge: dealing with the requests from academically entitled students, who have unreasonable expectations of receiving academic success, regardless of performance (Chowning & Campbell, 2009). We conducted two studies to examine whether student academic entitlement would increase instructors' strain and burnout via uncivil behaviors. A qualitative inquiry asked 136 instructors with college-teaching experience to describe types of behaviors entitled students display, their responses to entitled students, and the influence of these interactions on instructors' well-being. Next, a quantitative study with data from 857 college students nested in 34 instructors tested a multilevel mediation model where students' academic entitlement was related to instructor-reported uncivil behaviors, which in turn related to instructors' strain and burnout. Both studies largely support our hypothesis that uncivil behaviors fully mediate the relationship between students' academic entitlement and instructors' strain and burnout. We recommend employing behavioral modification strategies to decrease uncivil behaviors (e.g., class rules regarding uncivil behaviors might be specified in the course syllabus and consistently enforced) because academic entitlement attitudes are largely stable beliefs and thus may be less amenable to modification.

An empirical test of forgiveness motives' effects on employees' health and well-being.

Two critical-incident studies were conducted to determine what motivates employees to forgive (or reconcile) with coworkers who offend them. Data from the first study's exploratory factor analysis revealed five types of motives for forgiveness: apology, moral, religious, relationship, and lack of alternatives. Data from the second study on a different sample confirmed the five-factor structure, and structural equation modeling demonstrated differential relationships between the five motives and the outcome variables, stress and health. Individuals who claimed to have forgiven because they believed they had no other alternatives, or who forgave because they believed a higher power (religious) required it, were more likely to report greater stress and poorer health. Positive outcomes of forgiveness were discovered for those employees who forgave because they believed it was the right (moral) thing to do. Those who forgave for moral reasons reported less stress than those who forgave because they believed they had no other choice or because a higher power demanded it. Forgiving for relationship and apology reasons was not significantly related to either stress or general health. Future research directions are discussed.

Getting even or moving on? Power, procedural justice, and types of offense as predictors of revenge, forgiveness, reconciliation, and avoidance in organizations.

A field study and an experimental study examined relationships among organizational variables and various responses of victims to perceived wrongdoing. Both studies showed that procedural justice climate moderates the effect of organizational variables on the victim's revenge, forgiveness, reconciliation, or avoidance behaviors. In Study 1, a field study, absolute hierarchical status enhanced forgiveness and reconciliation, but only when perceptions of procedural justice climate were high; relative hierarchical status increased revenge, but only when perceptions of procedural justice climate were low. In Study 2, a laboratory experiment, victims were less likely to endorse vengeance or avoidance depending on the type of wrongdoing, but only when perceptions of procedural justice climate were high.