Spinal protein phosphatase 1 constrains respiratory plasticity after sustained hypoxia.

Plasticity is an important aspect of the neural control of breathing. One well-studied form of respiratory plasticity is phrenic long-term facilitation (pLTF) induced by acute intermittent but not sustained hypoxia. Okadaic acid-sensitive protein phosphatases (PPs) differentially regulate phrenic nerve activity with intermittent vs. sustained hypoxia, at least partially accounting for pLTF pattern sensitivity. However, okadaic acid inhibits multiple serine/threonine phosphatases, and the relevant phosphatase (PP1, PP2A, PP5) for pLTF pattern sensitivity has not been identified. Here, we demonstrate that sustained hypoxia (25 min, 9-10.5% O2) elicits phrenic motor facilitation in rats pretreated with bilateral intrapleural injections of small interfering RNAs (siRNAs; Accell-modified to preferentially transfect neurons, 3.33 µM, 3 days) targeting PP1 mRNA (48 ± 14% change from baseline, n = 6) but not PP2A (14 ± 9% baseline, n = 6) or nontargeting siRNAs (4 ± 10% baseline, n = 7). In time control rats (no hypoxia) treated with siRNAs ( n = 6), no facilitation was evident (-9 ± 9% baseline). siRNAs had no effect on the hypoxic phrenic response. Immunohistochemistry revealed PP1 and PP2A protein in identified phrenic motoneurons. Although PP1 and PP2A siRNAs significantly decreased PP1 and PP2A mRNA in PC12 cell cultures, we were not able to verify "knockdown" in vivo after siRNA treatment. On the other hand, PP1 and PP2A siRNAs significantly decreased PP1 and PP2A mRNA in PC12 cell cultures, verifying the intended siRNA effects. In conclusion, PP1 (not PP2A) is the relevant okadaic acid-sensitive phosphatase constraining phrenic motor facilitation after sustained hypoxia and likely contributing to pLTF pattern sensitivity. NEW & NOTEWORTHY This study demonstrates that the relevant okadaic acid-sensitive Ser/Thr protein phosphatase (PP) constraining facilitation after sustained hypoxia is PP1 and not PP2A. It suggests that PP1 may be critical in the pattern sensitivity of hypoxia-induced phrenic motor plasticity.

Effects of Carbohydrate Ingestion and Carbohydrate Mouth Rinse on Repeat Sprint Performance.

The purpose of this investigation was to examine to the influence of carbohydrate ingestion (CHOI) and carbohydrate mouth rinse (CHOR) on acute repeat maximal sprint performance. Fourteen healthy males (age: 21.7 ± 1.8 years, mass: 82.3 ± 12.3 kg) completed a total of five 15-s maximal repeat sprints on a cycle ergometer against 0.075 kg ・ kg-1 body mass each separated by 4 min of active recovery. Subjects completed four experimental trials and were randomly assigned one of four treatments: (1) CHOI, (2) CHOR, (3) placebo mouth rinse (PLAR), (4) placebo ingestion (PLAI). Subjects rinsed or ingested six 50 mL 10% CHO solutions throughout each trial. Performance variables measured included rating of perceived exertion, peak heart rate, peak and mean power output, fatigue index, and total work. Significant treatment main effects were observed for mean power output (p = 0.026), total work (p = 0.020), fatigue index (p = 0.004), and heart rate (p = 0.013). Overall mean power output and total work were significantly greater with CHOI (659.3 ± 103.0 watts, 9849.8 ± 1598.8 joules) compared with CHOR (645.8 ± 99.7 watts, 9447.5 ± 1684.9 joules, p < .05). CHOI (15.3 ± 8.6 watts/s) significantly attenuated fatigue index compared with CHOR (17.7 ± 10.4 watts/s, p < .05). Based on our findings, CHOI was more likely to provide a beneficial performance effect compared with CHOR, PLAI, and PLAR. Athletes required to complete repeat bouts of high intensity exercise may benefit from CHOI.

Ingestion of an Amino Acid Electrolyte Beverage during Resistance Exercise Does Not Impact Fluid Shifts into Muscle or Performance.

The purpose of this study was to investigate the impact of ingesting an amino acid-electrolyte (AAE) beverage during upper body resistance exercise on transient muscle hypertrophy, exercise performance, markers of muscle damage, and recovery. Participants (n = 15) performed three sets of six repetitions-bench press, lat pull down, incline press, and seated row-followed by three sets of eight repetitions at 75% of the estimated 1 repetition maximum-triceps kickback, hammer curl, triceps push down, and preacher curl-with 90 s of rest between sets. The final set of the push down/preacher curl was performed to failure. Prior to and immediately post-exercise, as well as 24, 48, and 72 h post exercise, cross-sectional muscle thickness was measured. Blood samples were collected prior to exercise, as well as 24, 48, and 72 h post-exercise for serum creatine kinase (CK) analysis. No treatment effect was found for muscle cross-sectional area, repetitions to failure, or serum CK. A main effect (p < 0.001) was observed in the change in serum CK levels in the days following the resistance exercise session. The findings of this study suggest that the acute ingestion of a AAE beverage does not alter acute muscle thickness, performance, perceived soreness and weakness, or markers of muscle damage.

Efficacy of Carbohydrate Ingestion on CrossFit Exercise Performance.

The efficacy of carbohydrate (CHO) ingestion during high-intensity strength and conditioning type exercise has yield mixed results. However, little is known about shorter duration high-intensity exercise such as CrossFit. The purpose of this study was to investigate the performance impact of CHO ingestion during high-intensity exercise sessions lasting approximately 30 min. Eight healthy males participated in a total of four trials; two familiarizations, a CHO trial, and a similarly flavored, non-caloric placebo (PLA) trial. CrossFit's "Fight Gone Bad Five" (FGBF) workout of the day was the exercise model which incorporated five rounds of maximal repetition exercises, wall throw, box jump, sumo deadlift high pull, push press, and rowing, followed by one minute of rest. Total repetitions and calories expended were summated from each round to quantify total work (FGBF score). No difference was found for the total work between CHO (321 ± 51) or PLA (314 ± 52) trials (p = 0.38). There were also no main effects (p > 0.05) for treatment comparing exercise performance across rounds. Based on the findings of this study, it does not appear that ingestion of CHO during short duration, high-intensity CrossFit exercise will provide a beneficial performance effect.

Effects of acute carbohydrate ingestion on anaerobic exercise performance.

BACKGROUND: Carbohydrate (CHO) supplementation during endurance exercises has been shown to increase performance, but there is limited research with CHO supplementation during strength and conditioning exercises. Therefore, the purpose of this study was to examine the effects of various levels of CHO ingestion during acute testing sessions requiring participants to complete a strength and conditioning program designed for collegiate athletes. METHODS: Participants (n = 7) performed a series of exercises while ingesting an amino-acid electrolyte control (CON) or CON plus varying levels of CHO. The CHO beverages delivered a 2:1 (glucose: fructose) ratio at rates of 15 g/h, 30 g/h, and 60 g/h. The exercise protocol consisted of a series of short sprints, full body resistance training exercises, jumping, and shuttle running. Performance measurements were taken for sprint times, repetitions until failure [bench press, bent over row, biceps curl, overhead triceps extension], summation of total repetitions for all repetitions until failure, repetitions in a set time for two-foot line jumps, and 137-m shuttle times. RESULTS: A significant main effect (p < 0.05) was found in relation to CHO dose during the bench press final set repetitions to failure. Pairwise comparison with Bonferroni's correction identified that there was significant difference (p = 0.0024) between the dosage of 15 g/h and CON during bench press. Inferential statistics identified overall RT performance with a dosage of 15 g/h compared to 60 g/h and CON was 99.2 % (very likely) and 96.7 % (very likely) to have a beneficial effect. CONCLUSIONS: The results from this study suggest acute ingestion of CHO does not result in decrements in performance and may provide a beneficial effect to strength and conditioning performance. Strength and conditioning coaches may recommend their athletes ingest CHO during training sessions in order to maximize muscular adaptations.

Intermittent Hypoxia-Induced Spinal Inflammation Impairs Respiratory Motor Plasticity by a Spinal p38 MAP Kinase-Dependent Mechanism.

Inflammation is characteristic of most clinical disorders that challenge the neural control of breathing. Since inflammation modulates neuroplasticity, we studied the impact of inflammation caused by prolonged intermittent hypoxia on an important form of respiratory plasticity, acute intermittent hypoxia (three, 5 min hypoxic episodes, 5 min normoxic intervals) induced phrenic long-term facilitation (pLTF). Because chronic intermittent hypoxia elicits neuroinflammation and pLTF is undermined by lipopolysaccharide-induced systemic inflammation, we hypothesized that one night of intermittent hypoxia (IH-1) elicits spinal inflammation, thereby impairing pLTF by a p38 MAP kinase-dependent mechanism. pLTF and spinal inflammation were assessed in anesthetized rats pretreated with IH-1 (2 min hypoxia, 2 min normoxia; 8 h) or sham normoxia and allowed 16 h for recovery. IH-1 (1) transiently increased IL-6 (1.5 ± 0.2-fold; p = 0.02) and inducible nitric oxide synthase (iNOS) (2.4 ± 0.4-fold; p = 0.01) mRNA in cervical spinal homogenates, (2) elicited a sustained increase in IL-1ß mRNA (2.4 ± 0.2-fold; p < 0.001) in isolated cervical spinal microglia, and (3) abolished pLTF (-1 ± 5% vs 56 ± 10% in controls; p < 0.001). pLTF was restored after IH-1 by systemic NSAID administration (ketoprofen; 55 ± 9%; p < 0.001) or spinal p38 MAP kinase inhibition (58 ± 2%; p < 0.001). IH-1 increased phosphorylated (activated) p38 MAP kinase immunofluorescence in identified phrenic motoneurons and adjacent microglia. In conclusion, IH-1 elicits spinal inflammation and impairs pLTF by a spinal p38 MAP kinase-dependent mechanism. By targeting inflammation, we may develop strategies to manipulate respiratory motor plasticity for therapeutic advantage when the respiratory control system is compromised (e.g., sleep apnea, apnea of prematurity, spinal injury, or motor neuron disease).

Phrenic long-term facilitation requires PKCθ activity within phrenic motor neurons.

Acute intermittent hypoxia (AIH) induces a form of spinal motor plasticity known as phrenic long-term facilitation (pLTF); pLTF is a prolonged increase in phrenic motor output after AIH has ended. In anesthetized rats, we demonstrate that pLTF requires activity of the novel PKC isoform, PKCθ, and that the relevant PKCθ is within phrenic motor neurons. Whereas spinal PKCθ inhibitors block pLTF, inhibitors targeting other PKC isoforms do not. PKCθ is highly expressed in phrenic motor neurons, and PKCθ knockdown with intrapleural siRNAs abolishes pLTF. Intrapleural siRNAs targeting PKCζ, an atypical PKC isoform expressed in phrenic motor neurons that underlies a distinct form of phrenic motor plasticity, does not affect pLTF. Thus, PKCθ plays a critical role in spinal AIH-induced respiratory motor plasticity, and the relevant PKCθ is localized within phrenic motor neurons. Intrapleural siRNA delivery has considerable potential as a therapeutic tool to selectively manipulate plasticity in vital respiratory motor neurons.

Refractive optical wing oscillators with one reflective surface.

An optical wing is a cambered rod that experiences a force and torque owing to the reflection and transmission of light from the surface. Here we address how such a wing may be designed to maintain an efficient thrust from radiation pressure (RP) while also providing a torque that returns the wing to a source facing orientation. The torsional stiffness of two different wing cross-sections is determined from numerical ray-tracing analyses. These results demonstrate the potential to construct a passive sun-tracking, space flight system or a microscopic surface measurement device based on RP force and torque.

Optical lift from dielectric semicylinders.

A wave optics numerical analysis of the force and torque on a semicylindrical optical wing is presented. Comparisons with a recently reported ray optics analysis indicate good agreement when the radius is large compared with the wavelength of light, as expected. Surprisingly, we find that the dominant rotationally stable angle of attack at α≈-15° is relatively invariant to changes in radius and refractive index. However, the torsional stiffness at the equilibrium point is found to increase, approximately, as the cubic power of the radius. Quasi-resonant internal modes of light produce complex size-dependent variations of the angle and magnitude of the optical lift force.

Extreme response style in recurrent and chronically depressed patients: change with antidepressant administration and stability during continuation treatment.

The authors examined extreme response style in recurrently and chronically depressed patients, assessing its role in therapeutic outcome. During the acute phase, outpatients with major depressive disorder (N = 384) were treated with fluoxetine for 8 weeks. Remitted patients (n = 132) entered a continuation phase during which their fluoxetine dose increased and they were randomly assigned to treatment with or without cognitive-behavioral therapy (CBT). Results showed a predictive relationship between extreme response style and clinical outcome. Patients in the medication-only group showed a significant increase in the frequency of extreme responses, whereas patients receiving CBT showed no significant change. These results are consistent with recent findings suggesting that metacognitive factors may be as important as changes in thought content when treating depression.