Exposure to Non-Steady-State Oxygen Is Reflected in Changes to Arterial Blood Gas Values, Prefrontal Cortical Activity, and Systemic Cytokine Levels.

Onboard oxygen-generating systems (OBOGSs) provide increased inspired oxygen (FiO2) to mitigate the risk of neurologic injury in high altitude aviators. OBOGSs can deliver highly variable oxygen concentrations oscillating around a predetermined FiO2 set point, even when the aircraft cabin altitude is relatively stable. Steady-state exposure to 100% FiO2 evokes neurovascular vasoconstriction, diminished cerebral perfusion, and altered electroencephalographic activity. Whether non-steady-state FiO2 exposure leads to similar outcomes is unknown. This study characterized the physiologic responses to steady-state and non-steady-state FiO2 during normobaric and hypobaric environmental pressures emulating cockpit pressures within tactical aircraft. The participants received an indwelling radial arterial catheter while exposed to steady-state or non-steady-state FiO2 levels oscillating ± 15% of prescribed set points in a hypobaric chamber. Steady-state exposure to 21% FiO2 during normobaria produced arterial blood gas values within the anticipated ranges. Exposure to non-steady-state FiO2 led to PaO2 levels higher upon cessation of non-steady-state FiO2 than when measured during steady-state exposure. This pattern was consistent across all FiO2 ranges, at each barometric condition. Prefrontal cortical activation during cognitive testing was lower following exposure to non-steady-state FiO2 >50% and <100% during both normobaria and hypobaria of 494 mmHg. The serum analyte levels (IL-6, IP-10, MCP-1, MDC, IL-15, and VEGF-D) increased 48 h following the exposures. We found non-steady-state FiO2 levels >50% reduced prefrontal cortical brain activation during the cognitive challenge, consistent with an evoked pattern of neurovascular constriction and dilation.

Characterizing the Dose Response of Hyperoxia with Brain Perfusion.

BACKGROUND: Tactical aviators require administration of enhanced inspired oxygen concentrations (hyperoxia) to reduce risk of hypobaric hypoxia and decompression injuries. Hyperoxia is not without consequence; it reduces cerebral perfusion (CBF). Characterizing the relationship between FIO2 and CBF is necessary to establish FIO2 levels that do not reduce CBF yet are sufficient to mitigate risk of in-flight physiological stressors. To achieve that goal, this study's objective was to determine whether a dose-response relationship exists between FIO2 and CBF and, if so, the FIO2 at which CBF significantly declines.METHODS: Healthy male and female subjects (N = 26) were randomized to receive either low dose FIO2 of 30%, 40%, 50%, and 100% (Arm 1) or high dose FIO2 of 60%, 70%, 80%, and 100% (Arm 2), followed by a return to 21% for both groups. Subjects were placed within a 3-Tesla MRI scanner equipped with pseudocontinuous arterial spin labeling software (pCASL) to measure CBF. Baseline CBF measurements were obtained during exposure to 21% FIO2, with subsequent CBF measurements obtained at each predetermined FIO2 level.RESULTS: Baseline CBF did not differ between subjects in Arm 1 and Arm 2. Low dose FIO2 ≤ 50% did not affect CBF. In contrast, high dose FIO2 ≥ 60% significantly reduced CBF. Exposure to 100% FIO2 led to similar reductions of CBF for subjects in both Arm 1 and Arm 2.DISCUSSION: The neurovascular system appears to respond to increasing FIO2 levels in a dose dependent manner, with significant reductions in CBF with FIO2 exposures ≥ 60%.Damato EG, Fillioe SJ, Vannix IS, Norton LK, Margevicius SP, Beebe JL, Decker MJ. Characterizing the dose response of hyperoxia with brain perfusion. Aerosp Med Hum Perform. 2022; 93(6):493-498.

Increased Serum Levels of Proinflammatory Cytokines Are Accompanied by Fatigue in Military T-6A Texan II Instructor Pilots.

Tactical aviation imposes unprecedented physical challenges including repetitive exposure to hypergravity, hyperoxia, increased work of breathing, and profound cognitive workloads. Each stressor evokes outcomes ranging from musculoskeletal duress and atelectasis to physical and cognitive fatigue, the latter among the foremost threats to aviators. Whereas sleep loss is traditionally considered the primary cause of fatigue in aviators, converging experimental, observational, and medical studies have identified biochemical mechanisms promoting onset of fatigue. Those mechanisms, which fundamentally differ from sleep loss, revolve around increased proinflammatory cytokines, produced and released in response to tissue injury, chronic inflammatory disorders, allergens, or physical duress. This study's objective was to inform our understanding of potential relationships between serum levels of proinflammatory cytokines and onset of fatigue within a cohort of aviators who experience multiple high-performance sorties on a daily basis. Methods: Active duty and reservist T-6A Texan II instructor pilots were studied on three separate days across their week-long flying schedule. Data collected included a physical assessment, subjective fatigue levels, venous blood samples for measures of chemistry and serum analytes, and urine samples for specific gravity. Results: Twenty-three persons were studied, of which 22 fulfilled minimum study requirements of completing two sorties. The study cohort was comprised of primarily males, age 37.95 ± 4.73 years with a BMI of 26.63 ± 3.15 kg/m2. Of 37 measurable serum analytes, 20 differed significantly (p < 0.05) between baseline values with those measured at the study endpoint. Thirteen of the aviators reported increased fatigue scores across their flying schedule whereas nine did not. Eleven blood serum analytes were associated with increasing levels of fatigue. Discussion: Fatigue in aviators has been attributed almost solely to sleep loss, nocturnal sorties, or disrupted circadian rhythmicity. In contrast, our study findings suggest an alternative mechanism that can promote onset of fatigue: increased blood levels of proinflammatory cytokines. Specific mechanisms triggering synthesis and release of those cytokines and other analytes are yet to be determined. However, their expression patterns suggest responses to both chronic and acute inflammation, hyperoxia, or bronchopulmonary responses to inspiration of dry gas, positive airway pressure, or perhaps atelectasis.

Sleep pattern gender differences and fragmentation in postpartum parents of twins.

OBJECTIVE: Parents of newborn twins are at risk for both shortened sleep duration and sleep discontinuity. The purpose of this study was to characterize weekday and weekend sleep duration, sleep continuity, and awakenings in both mothers and fathers of newborn twins during the first 3 months at home. MATERIAL AND METHODS: Sleep-wake parameters were assessed at two time points using self-report diaries and actigraphy in 75 families with newborn twins. To assess sleep on weekdays and weekends with minimal subject burden, actigraphy recordings of both parents commenced at 9:00 p.m. Saturday and terminated at 9:00 p.m. Tuesday. RESULTS: Mean sleep duration over 24 hours for parents of twins ranged between 6.7 and 7.5 hours during the first 3 months postpartum and did not significantly differ on weekdays or weekends for mothers. Weekend sleep was more fragmented for fathers at both one month and three months with more awakenings, compared to weekday sleep. Mothers had more fragmented night sleep compared to fathers at one month. In contrast, at three months postpartum fathers had shorter total sleep time and night sleep time, but fewer night awakenings on weekdays than mothers. No differences were observed in weekend sleep duration or sleep patterns between mothers and fathers at three months. DISCUSSION: Consolidated sleep periods for both parents averages three hours or less during the first three months postpartum and sleep for both parents is fragmented. In families with newborn twins, the extent of sleep disruption for mothers and fathers is similar.

Neurovascular and cortical responses to hyperoxia: enhanced cognition and electroencephalographic activity despite reduced perfusion.

KEY POINTS: Extreme aviation is accompanied by ever-present risks of hypobaric hypoxia and decompression sickness. Neuroprotection against those hazards is conferred through fractional inspired oxygen ( FI,O2 ) concentrations of 60-100% (hyperoxia). Hyperoxia reduces global cerebral perfusion (gCBF), increases reactive oxygen species within the brain and leads to cell death within the hippocampus. However, an understanding of hyperoxia's effect on cortical activity and concomitant levels of cognitive performance is lacking. This limits our understanding of whether hyperoxia could lower the brain's threshold of tolerance to physiological stressors inherent to extreme aviation, such as high gravitational forces. This study aimed to quantify the impact of hyperoxia upon global cerebral perfusion (gCBF), cognitive performance and cortical electroencephalography (EEG). Hyperoxia evoked a rapid reduction in gCBF, yet cognitive performance and vigilance were enhanced. EEG measurements revealed enhanced alpha power, suggesting less desynchrony, within the cortical temporal regions. Collectively, this work suggests hyperoxia-induced brain hypoperfusion is accompanied by enhanced cognitive processing and cortical arousal. ABSTRACT: Extreme aviators continually inspire hyperoxic gas to mitigate risk of hypoxia and decompression injury. This neuroprotection carries a physiological cost: reduced cerebral perfusion (CBF). As reduced CBF may increase vulnerability to ever-present physiological challenges during extreme aviation, we defined the magnitude and duration of hyperoxia-induced changes in CBF, cortical electrical activity and cognition in 30 healthy males and females. Magnetic resonance imaging with pulsed arterial spin labelling provided serial measurements of global CBF (gCBF), first during exposure to 21% inspired oxygen ( FI,O2 ) followed by a 30-min exposure to 100% FI,O2 . High-density EEG facilitated characterization of cortical activity during assessment of cognitive performance, also measured during exposure to 21% and 100% FI,O2 . Acid-base physiology was measured with arterial blood gases. We found that exposure to 100% FI,O2 reduced gCBF to 63% of baseline values across all participants. Cognitive performance testing at 21% FI,O2 was accompanied by increased theta and beta power with decreased alpha power across multiple cortical areas. During cognitive testing at 100% FI,O2 , alpha activity was less desynchronized within the temporal regions than at 21% FI,O2 . The collective hyperoxia-induced changes in gCBF, cognitive performance and EEG were similar across observed partial pressures of arterial oxygen ( PaO2 ), which ranged between 276-548 mmHg, and partial pressures of arterial carbon dioxide ( PaCO2 ), which ranged between 34-50 mmHg. Sex did not influence gCBF response to 100% FI,O2 . Our findings suggest hyperoxia-induced reductions in gCBF evoke enhanced levels of cortical arousal and cognitive processing, similar to those occurring during a perceived threat.

Postnatal hypoxia evokes persistent changes within the male rat's dopaminergic system.

PURPOSE: Hypoxic insults occurring during the perinatal period remain the leading cause of permanent brain impairment. Severe cognitive and motor dysfunction, as seen in cerebral palsy, will occur in 4-10% of post-hypoxic newborns. Subtle cognitive impairment, apparent in disorders of minimal brain dysfunction will occur in > 3 million post-hypoxic newborns. Analyses of post-hypoxic rodent brains reveal reduced extracellular levels of dopamine, a key neurotransmitter of vigilance, execute function, and behavior. The purpose of this study was to assess whether synaptic levels of dopamine could be enhanced in post-hypoxic, hypodopaminergic rats. METHODS: Newborn male rats were exposed to subtle, repetitive hypoxic insults for 4-6 h per day, during postnatal days 7-11. During adolescence, we quantified dopamine content within the caudate nuclei. We then determined whether extracellular dopamine levels could be increased by injecting the psychostimulant d-amphetamine. We next assessed whether the post-hypoxic rat's response to d-amphetamine would differentially impact place preference behavior when compared with littermate controls. RESULTS: Total tissue content of dopamine was significantly higher in post-hypoxic rats. Injection of d-amphetamine liberated that dopamine which subsequently enhanced extracellular levels. Post-hypoxic rats acquired conditioned place preference for d-amphetamine during the training days. During the testing day, total time spent in the amphetamine-pairing box did not differ between post-hypoxic and control littermates. CONCLUSION: Postnatally occurring hypoxic insults promote remodeling of the dopaminergic system resulting in increased intracellular sequestering of this monoamine. That sequestered dopamine can be released using the psychostimulant d-amphetamine, which did not promote a conditioned place preference any greater than was observed in non-hypoxic littermate controls.

The Effects of an Afternoon Nap on Episodic Memory in Young and Older Adults.

Study Objectives: In young adults, napping is hypothesized to benefit episodic memory retention (eg, via consolidation). Whether this relationship is present in older adults has not been adequately tested but is an important question because older adults display marked changes in sleep and memory. Design: Between-subjects design. Setting: Sleep laboratory at Emory University School of Medicine. Participants: Fifty healthy young adults (18-29) and 45 community-dwelling older adults (58-83). Intervention: Participants were randomly assigned to a 90-minute nap opportunity or an equal interval of quiet wakefulness. Measurements and Results: Participants underwent an item-wise directed forgetting learning procedure in which they studied words that were individually followed by the instruction to "remember" or "forget." Following a 90-minute retention interval filled with quiet wakefulness or a nap opportunity, they were asked to free recall and recognize those words. Young adults retained significantly more words following a nap interval than a quiet wakefulness interval on both free recall and recognition tests. There was modest evidence for greater nap-related retention of "remember" items relative to "forget" items for free recall but not recognition. Older adults' memory retention did not differ across nap and quiet wakefulness conditions, although they demonstrated greater fragmentation, lower N3, and lower rapid eye movement duration than the young adults. Conclusions: In young adults, an afternoon nap benefits episodic memory retention, but such benefits decrease with advancing age.

C57BL/6J mouse apolipoprotein A2 gene is deterministic for apnea.

RATIONALE: Brainstem apolipoprotein AII (apoa2) mRNA expression correlates with apnea in breathing present in the adult C57Bl/6J (B6) sleep apnea model. OBJECTIVES: To test the hypothesis that the B6 apoa2 gene contributes to the trait, we performed plethysmographic testing in apoa2 knock out (KO: -/-) mice, an in situ brainstem-spinal cord preparation comparing KO to WT (+/+) mice, and B6xDBA recombinant inbred strains (RISs). MEASUREMENTS AND MAIN RESULTS: Apoa2 WT do, but KO and heterozygote (+/-) mice do not exhibit apnea during post-hypoxic breathing, measured in vivo. In the in situ model, pauses and instability in fictive phrenic bursting are substantially reduced in KO vs. WT preparations. In 24 RISs, apnea number in vivo was higher in strains with B6 apoa2 than with DBA apoa2 alleles. CONCLUSIONS: The B6 apoa2 polymorphism is directly involved in breath production, and its identification suggests a novel pathway influencing risk for adult sleep apnea.

Maternal dietary supplementation with omega-3 polyunsaturated fatty acids confers neuroprotection to the newborn against hypoxia-induced dopamine dysfunction.

INTRODUCTION: Up to 84% of prematurely born infants suffer hypoxic, anoxic, and ischemic insults. Those infants with subsequent behavioral, motor or cognitive dysfunction represent 8-11% of all live births. Yet, no interventions employed during pregnancy attenuate risk of morbidity in those at-risk infants. Dietary supplementation with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) has been shown to reduce stroke-induced neuropathology in rat models emulating this adverse clinical event. To extend those studies we sought to determine whether maternal dietary supplementation with ω-3 PUFAs would confer neuroprotection against hypoxia-induced neurochemical dysfunction in newborn rat pups exposed to repetitive hypoxic insults. METHODS: We provided pregnant rats with either a ω-3 PUFA enriched diet or else a standard rat chow diet. At postnatal day 7, pups were assigned randomly to either repetitive hypoxic insults or repetitive bursts of room air. On postnatal day 12, pups were sacrificed and brain dopamine levels characterized. RESULTS: Baseline brain dopamine levels did not differ between rat pups born to dams who received ω-3 PUFA enriched versus standard rat chow diets. Rat pups born to dams maintained on normal diets, who were exposed to five days of repetitive hypoxic insults, experienced a 57% reduction in striatal dopamine levels accompanied by significant apoptosis. In contrast, ω-3 PUFA-enriched newborn pups experienced no loss in striatal dopamine levels, and only minimal apoptosis. CONCLUSIONS: Our findings suggest that it may be feasible to confer neuroprotection against hypoxia-induced dopamine dysfunction to newborns likely to experience hypoxic insults. This could significantly improve the outcomes of those 8-11% of newborns who would otherwise experience hypoxia-induced behavioral, motor and cognitive dysfunction.

Elevated serotonergic signaling amplifies synaptic noise and facilitates the emergence of epileptiform network oscillations.

Serotonin fibers densely innervate the cortical sheath to regulate neuronal excitability, but its role in shaping network dynamics remains undetermined. We show that serotonin provides an excitatory tone to cortical neurons in the form of spontaneous synaptic noise through 5-HT3 receptors, which is persistent and can be augmented using fluoxetine, a selective serotonin re-uptake inhibitor. Augmented serotonin signaling also increases cortical network activity by enhancing synaptic excitation through activation of 5-HT2 receptors. This in turn facilitates the emergence of epileptiform network oscillations (10-16 Hz) known as fast runs. A computational model of cortical dynamics demonstrates that these two combined mechanisms, increased background synaptic noise and enhanced synaptic excitation, are sufficient to replicate the emergence fast runs and their statistics. Consistent with these findings, we show that blocking 5-HT2 receptors in vivo significantly raises the threshold for convulsant-induced seizures.

Altered sleep regulation in a mouse model of SCN1A-derived genetic epilepsy with febrile seizures plus (GEFS+).

PURPOSE: Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A are responsible for a number of epilepsy disorders, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. In addition to seizures, patients with SCN1A mutations often experience sleep abnormalities, suggesting that SCN1A may also play a role in the neuronal pathways involved in the regulation of sleep. However, to date, a role for SCN1A in the regulation of sleep architecture has not been directly examined. To fill this gap, we tested the hypothesis that SCN1A contributes to the regulation of sleep architecture, and by extension, that SCN1A dysfunction contributes to the sleep abnormalities observed in patients with SCN1A mutations. METHODS: Using immunohistochemistry we first examined the expression of mouse Scn1a in regions of the mouse brain that are known to be involved in seizure generation and sleep regulation. Next, we performed detailed analysis of sleep and wake electroencephalography (EEG) patterns during 48 continuous hours of baseline recordings in a knock-in mouse line that expresses the human SCN1A GEFS+ mutation R1648H (RH mutants). We also characterized the sleep-wake pattern following 6 h of sleep deprivation. KEY FINDINGS: Immunohistochemistry revealed broad expression of Scn1a in the neocortex, hippocampus, hypothalamus, thalamic reticular nuclei, dorsal raphe nuclei, pedunculopontine, and laterodorsal tegmental nuclei. Co-localization between Scn1a immunoreactivity and critical cell types within these regions was also observed. EEG analysis under baseline conditions revealed increased wakefulness and reduced non-rapid eye movement (NREM) and rapid eye movement (REM) sleep amounts during the dark phase in the RH mutants, suggesting a sleep deficit. Nevertheless, the mutants exhibited levels of NREM and REM sleep that were generally similar to wild-type littermates during the recovery period following 6 h of sleep deprivation. SIGNIFICANCE: These results establish a direct role for SCN1A in the regulation of sleep and suggest that patients with SCN1A mutations may experience chronic alterations in sleep, potentially leading to negative outcomes over time. In addition, the expression of Scn1a in specific cell types/brain regions that are known to play critical roles in seizure generation and sleep now provides a mechanistic basis for the clinical features (seizures and sleep abnormalities) associated with human SCN1A mutations.

Rehabilitation exercise progression for the gluteus medius muscle with consideration for iliopsoas tendinitis: an in vivo electromyography study.

BACKGROUND: It is common for hip arthroscopy patients to demonstrate significant gluteus medius muscle weakness and concurrent iliopsoas tendinitis. Restoration of gluteus medius muscle function is essential for normal hip function. HYPOTHESIS: A progression of hip rehabilitation exercises to strengthen the gluteus medius muscle could be identified that minimize concurrent iliopsoas muscle activation to reduce the risk of developing or aggravating hip flexor tendinitis STUDY DESIGN: Descriptive laboratory study. METHODS: Electromyography (EMG) signals of the gluteus medius and iliopsoas muscles were recorded from 10 healthy participants during 13 hip rehabilitation exercises. The indwelling fine-wire EMG electrodes were inserted under ultrasound guidance. The average and peak EMG amplitudes, normalized by the peak EMG amplitude elicited during maximum voluntary contractions, were determined and rank-ordered from low to high. The ratio of iliopsoas to gluteus medius muscle activity was calculated for each exercise. Exercises were placed into respective time phases based on average gluteus medius EMG amplitude, except that exercises involving hip rotation were avoided in phase I (phase I, initial 4 or 8 weeks; phase II, subsequent 4 weeks; phase III, final 4 weeks). RESULTS: A continuum of hip rehabilitation exercises was identified. Resisted terminal knee extension, resisted knee flexion, and double-leg bridges were identified as appropriate for phase I and resisted hip extension, stool hip rotations, and side-lying hip abduction with wall-sliding for phase II. Hip clam exercises with neutral hips may be used with caution in patients with hip flexor tendinitis. Prone heel squeezes, side-lying hip abduction with internal hip rotation, and single-leg bridges were identified for phase III. CONCLUSION/CLINICAL RELEVANCE: This study identified the most appropriate hip rehabilitation exercises for each phase to strengthen the gluteus medius muscle after hip arthroscopy and those to avoid when iliopsoas pain or tendinitis is a concern.

The influence of arm and shoulder position on the bear-hug, belly-press, and lift-off tests: an electromyographic study.

BACKGROUND: Clinical testing for the integrity of the subscapularis muscle includes the belly-press, lift-off, and bear-hug examinations. While these tests have been widely applied in clinical practice, there is considerable variation in arm positioning within each clinical examination. HYPOTHESIS: To determine the ideal arm and shoulder positions for isolating the subscapularis muscle while performing the bear-hug, belly-press, and lift-off tests. STUDY DESIGN: Controlled laboratory study. METHODS: The activity of 7 muscles was monitored in 20 healthy participants: upper and lower divisions of the subscapularis, supraspinatus, infraspinatus, latissimus dorsi, teres major, triceps, pectoralis major. Electromyogram data were collected and compared across each clinical test at varying arm positions: bear-hug (ideal position, 10° superior, 10° inferior to the shoulder line), belly-press (ideal position, maximum shoulder external rotation, and maximal shoulder internal rotation), and lift-off (ideal position, hand position 5 in. [12.7 cm] superior and 5 in. [12.7 cm] inferior to the midlumbar spine). RESULTS: Regardless of arm and shoulder position, the upper and lower subscapularis muscle activities were significantly greater than all other muscles while performing each test. No significant differences were observed between the upper and lower subscapularis divisions at any position within and across the 3 tests. There were no significant differences in subscapularis electromyogram activities across the 3 tests. CONCLUSION: The level of subscapularis muscle activation was similar among the bear-hug, belly-press, and lift-off tests. The 3 tests activated the subscapularis significantly more than all other muscles tested but were not different from one another when compared across tests and positions. Although the bear-hug and lift-off tests have been described to activate differential portions of the subscapularis, the findings of this study do not support the preferential testing of a specific subscapular division across the 3 tests. As such, all 3 tests are effective in testing the integrity of the entire subscapularis muscle, although there does not appear to be an ideal position for selectively testing its divisions. CLINICAL RELEVANCE: Clinicians may feel comfortable in using any of the 3 tests, depending on the patient, to isolate the function of the subscapularis as a single muscle. Furthermore, clinicians should not solely focus on a patient's arm position when administering an examination but also compare the affected arm to the contralateral shoulder when appropriate.

A comparison of forearm supination and elbow flexion strength in patients with long head of the biceps tenotomy or tenodesis.

PURPOSE: The purpose of this study was to compare the forearm supination and elbow flexion strength of the upper extremity in patients who have had an arthroscopic long head of the biceps tendon (LHBT) release with patients who have had an LHBT tenodesis. METHODS: Cybex isokinetic strength testing (Cybex Division of Lumex, Ronkonkoma, NY) was performed on 17 patients who underwent arthroscopic LHBT tenotomy, 19 patients who underwent arthroscopic LHBT tenodesis, and 31 age-, gender-, and body mass index-matched control subjects. Subjects were considered fully recovered from shoulder surgery, were released for unrestricted activities, and were at least 6 months after surgery before testing. Subjects were tested for forearm supination and elbow flexion strength of both arms by use of a Cybex II NORM isokinetic dynamometer at 60°/s and 120°/s. Testing was performed on injured and uninjured arms as well as dominant and nondominant arms in control subjects. Both forearm supination and elbow flexion strength values were recorded. RESULTS: Comparison between the involved and uninvolved upper extremities within each group by use of a paired t test showed a 7% increase in elbow flexion strength when the dominant and nondominant arms were compared at 60°/s. Neither the tenotomy nor tenodesis groups exhibited elbow flexion strength differences at 120°/s (all P ≥ .147). Comparison between groups by use of 2 × 3 analysis of variance (speed × group) showed no statistical difference in either forearm supination or elbow flexion strength when we compared the tenotomy, tenodesis, and control groups. CONCLUSIONS: In asymptomatic patients who have had biceps tenotomy or tenodesis, no statistically significant forearm supination or elbow flexion strength differences existed in the involved extremity between the 2 study groups. LEVEL OF EVIDENCE: Level III, case-control study.

Paradoxical sleep suppresses immediate early gene expression in the rodent suprachiasmatic nuclei.

Light stimulates neuronal activity with subsequent expression of the protein product of the immediate early gene, c-fos, in the Suprachiasmatic Nuclei (SCN). Non-photic stimuli is also thought to modulate activity within the SCN. Here, we sought to determine the effects intrinsic stimuli, specifically, the states of sleep upon c-fos protein expression in the SCN. In 16 rats, c-fos protein expression was evaluated at a fixed time of 1600 h (subjective night), following 1 h of electroencephalographically defined sleep. During sleep, as the state of paradoxical sleep (PS) increased, c-fos protein expression decreased (r = -0.41, p < 0.033). The PS-associated reduction of c-fos positive cells occurred equally between animals asleep in the light and those asleep in the dark. We propose a model whereby PS duration might function as a homeostatic-entraining mechanism to reduce neuronal activity within the SCN, and thereby modulate circadian rhythms during sleep.

Validation of ECG-derived sleep architecture and ventilation in sleep apnea and chronic fatigue syndrome.

PURPOSE: Newly developed algorithms putatively derive measures of sleep, wakefulness, and respiratory disturbance index (RDI) through detailed analysis of heart rate variability (HRV). Here, we establish levels of agreement for one such algorithm through comparative analysis of HRV-derived values of sleep-wake architecture and RDI with those calculated from manually scored polysomnographic (PSG) recordings. METHODS: Archived PSG data collected from 234 subjects who participated in a 3-day, 2-night study characterizing polysomnographic traits of chronic fatigue syndrome were scored manually. The electrocardiogram and pulse oximetry channels were scored separately with a novel scoring algorithm to derive values for wakefulness, sleep architecture, and RDI. RESULTS: Four hundred fifty-four whole-night PSG recordings were acquired, of which, 410 were technically acceptable. Comparative analyses demonstrated no difference for total minutes of sleep, wake, NREM, REM, nor sleep efficiency generated through manual scoring with those derived through HRV analyses. When NREM sleep was further partitioned into slow-wave sleep (stages 3-4) and light sleep (stages 1-2), values calculated through manual scoring differed significantly from those derived through HRV analyses. Levels of agreement between RDIs derived through the two methods revealed an R = 0.89. The Bland-Altman approach for determining levels of agreement between RDIs generated through manual scoring with those derived through HRV analysis revealed a mean difference of -0.7 +/- 8.8 (mean +/- two standard deviations). CONCLUSION: We found no difference between values of wakefulness, sleep, NREM, REM sleep, and RDI calculated from manually scored PSG recordings with those derived through analyses of HRV.

Anterior shoulder forces in professional and Little League pitchers.

BACKGROUND: The developing musculoskeletal system of a youth pitcher is substantially different from that of the adult professional pitcher, predisposing the younger players to a different set of injuries. METHODS: High-speed videography of 39 professional and 13 youth pitchers were obtained. High-speed motion analysis was performed to calculate average anterior forces and arm positions at maximal force generation. RESULTS: Professional players generated an average of 33.8+/-14.4 N/kg maximal anterior force, corresponding to 151.9+/-17.0 degrees of external rotation. Youth pitchers generated 16.2+/-3.8 N/kg of anterior forces, corresponding to 118.0+/-23.4 degrees of external rotation. The degree of coronal abduction and horizontal abduction between the 2 groups were not significantly different-92.4+/-9.0 degrees in professionals versus 91.7+/-7.9 degrees in the youth and 11.1+/-11.1 degrees of horizontal abduction in professionals versus 7.8+/-14.1 degrees in the younger throwers. Professional pitchers exerted higher internal rotation torque at 19.4+/-4.1 Nm/kg versus 5.6+/-1.0 Nm/kg in youth, and compressive forces were found to be 121.7+/-21.7 N/kg in professional pitchers compared with 47.5+/-7.6 N/kg in the youth pitchers. CONCLUSIONS: Youth pitchers experience significant anterior shoulder forces and internal rotation torques, although these are lower than professional pitchers. CLINICAL RELEVANCE: Overhead throwing as a youth can lead to shoulder injuries and can predispose the shoulder to more significant injuries as an adult pitcher.

Electroencephalographic correlates of Chronic Fatigue Syndrome.

BACKGROUND: Unremitting fatigue and unrefreshing sleep, hallmark traits of Chronic Fatigue Syndrome (CFS), are also pathognomonic of sleep disorders. Yet, no reproducible perturbations of sleep architecture, multiple sleep latency times or Epworth Sleepiness Scores are found to be associated consistently with CFS. This led us to hypothesize that sleep homeostasis, rather than sleep architecture, may be perturbed in CFS. To probe this hypothesis, we measured and compared EEG frequencies associated with restorative sleep between persons with CFS and matched controls, both derived from a population-based sample. METHODS: We evaluated overnight polysomnography (PSG) in 35 CFS and 40 control subjects. PSG records were manually scored and epochs containing artifact removed. Fast Fourier Transformation was utilized to deconstruct individual EEG signals into primary frequency bands of alpha, delta, theta, sigma, and beta frequency domains. The spectral power of each frequency domain for each sleep state was compared between persons with CFS and matched controls. RESULTS: In persons with CFS, delta power was diminished during slow wave sleep, but elevated during both stage 1 and REM. Alpha power was reduced during stage 2, slow wave, and REM sleep. Those with CFS also had significantly lower theta, sigma, and beta spectral power during stage 2, Slow Wave Sleep, and REM. DISCUSSION: Employing quantitative EEG analysis we demonstrate reduced spectral power of cortical delta activity during SWS. We also establish reduced spectral power of cortical alpha activity, with the greatest reduction occurring during REM sleep. Reductions in theta, beta, and sigma spectral power were also apparent. CONCLUSION: Unremitting fatigue and unrefreshing sleep, the waking manifestations of CFS, may be the consequence of impaired sleep homeostasis rather than a primary sleep disorder.

Breathing and sleep: measurement methods, genetic influences, and developmental impacts.

Sleep-disordered breathing comprises alterations in respiratory rate, rhythm, and depth that present during sleep and may or may not be recognizable in breathing during wakefulness. Primary disorders include repetitive apneas, near apneas (hypopneas), or reductions in overall ventilation during sleep (hypoventilation), all of which lead to reductions in pulmonary gas exchange resulting in arousals, arrhythmia, hypercapnia, acidosis, and/or hypoxic stress responses such as pulmonary hypertension or polycythemia. Because the underlying mechanisms resulting in sleep-disordered breathing and its resulting comorbidities remain unclear, researchers use a variety of animal models to better understand the disorder. These models allow for conditioning paradigms, more detailed measurements of respiratory control, and the use of fewer preparations to provide a detailed picture of the individual components that contribute to breathing patterns. Both noninvasive and reduced methods are applicable with conditioned, inbred, and/or genetically manipulated animals to determine effect size and imply mechanisms. Research in animals has established preclinical models showing that intermediate traits of breathing pattern (e.g., responses to hypoxia, hypercapnia, and reoxygenation) vary according to genetic background and conditioning. Such findings permit new ideas about pathogenesis and prevention and form the rationale for observational and interventional studies in the human population. In this article we focus on methods of investigating respiratory control and applicable rodent models.