京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19176号 / 医博第4018号 / 新制||医||1010(附属図書館) / 32168 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小川 修, 教授 柳田 素子, 教授 三森 経世 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Both resistance and endurance exercise elicit an increase in muscle protein synthesis during recovery from exercise. Ingestion of amino acids augments the exercise-induced stimulation of muscle protein synthesis following resistance exercise. Our work showed that 8 wk of unilateral resistance training induced muscle hypertrophy only in the exercised limb. Importantly, using this unilateral model we showed that muscle hypertrophy was confined to the exercised leg and occurred without measurable changes in circulating anabolic hormones. We then went on to use the unilateral leg resistance exercise model to study how animal-derived (milk) and plant-derived (soy) proteins impacted acute post-exercise protein turnover. We observed that ingestion of soy or milk protein resulted in a positive net protein balance following resistance exercise. Moreover, milk promoted a greater net protein balance and muscle protein synthesis than soy protein. In the final study, a key finding was that acute endurance and resistance exercise differentially stimulated myofibrillar and mitochondrial protein synthesis and also differentially affected cellular signaling proteins involved in the regulation of the protein synthetic response. Specifically, the acute, untrained state response showed that resistance exercise stimulated myofibrillar and mitochondrial protein synthesis while endurance exercise stimulated mitochondrial protein synthesis. Following resistance training only myofibrillar protein synthesis increased after exercise, while mitochondrial protein synthesis was unchanged. Endurance exercise training did not affect the acute protein synthetic response and so following training mitochondrial protein synthesis was stimulated as it was acutely, prior to training. In conclusion, the studies within this thesis provided novel insights on the impact of intact dietary proteins and differing modes of exercise on the control skeletal muscle protein metabolism. / Thesis / Doctor of Philosophy (PhD)

Cross education is the phenomenon by which the untrained limb will experience a gain in strength following a unilateral resistance training program. However, little is known as to the underlying adaptation occurring in the untrained limb. Purpose: To examine the effect of dynamic unilateral resistance training on the strength and neuromuscular adaptations of both the trained and untrained legs. Methods: Eight previously untrained males (22.38±2.92 y, 1.73±0.08 m, 75.26±14.53 kg) completed a four-week unilateral resistance training program, while another eight untrained males (24.00±4.57 y, 1.84±0.05 m, 94.21±16.14 kg) served as controls. Isometric leg extension strength, leg press 1 repetition maximum (1RM), leg extension 1RM, root mean square of the maximal electromyographic amplitude (EMG), submaximal EMG, dynamic neuromuscular economy (NME) and the slope of NME-power output relationship were determined before and after training to assess the changes in strength and neuromuscular adaptations of the vastus lateralis (VL) and rectus femoris (RF) in both the trained and untrained legs. The unilateral resistance training program was conducted on the dominant leg (DOM) in the unilateral resistance training group (URT) and was compared to the dominant leg of the control group (CON). Cross education was measured in the nondominant leg (NON) for both groups. The unilateral resistance training program was completed three days per week for a total of twelve training sessions. Exercises included in the training program were unilateral leg press, unilateral leg extension, bilateral chest press and bilateral low row. All data was analyzed using one-way analysis of covariance of the post-testing values using the pre-testing values as the covariate. Further analysis of the EMG and NME data was performed using magnitude-based inferences. Results: The URT group improved their isometric (DOM:11.03%, NON:4.98%), leg press (DOM:77.63%, NON:64.88%) and leg extension (DOM:46.76%, NON:16.43%) strength after the four weeks of resistance training. There was no difference between the groups in isometric strength in the dominant (p=0.188) or nondominant (p=0.948) leg. For leg extension 1RM, there was a significant difference between groups in the dominant leg (p=0.018), but not the nondominant leg (p=0.482). However, there were significant group differences in both the dominant (p=0.003) and nondominant (p=0.034) leg for leg press 1RM. In terms of maximal EMG, the training groups improved in the vastus lateralis (DOM:29.81%, NON:31.44%) and rectus femoris (DOM:20.71%, NON:6.26%) individually, as well as in total EMG (DOM:24.78%, NON:17.57%). There was a Likely Positive or Very Likely Positive effect of unilateral resistance training on the changes in maximal EMG of the vastus lateralis and rectus femoris in both the dominant and nondominant legs. There was a Likely Positive effect of unilateral resistance training on the submaximal EMG of the dominant vastus lateralis at 75 and 125 watts. Conversely, in the rectus femoris, there was Unclear effects of unilateral resistance training on the submaximal EMG of the dominant leg. There was no consistent effect of unilateral resistance training on submaximal EMG values of the vastus lateralis in the nondominant leg. However, the rectus femoris in the nondominant leg experienced a Likely Positive effect of unilateral resistance training on submaximal EMG. NME improved in the URT group in the VL at 75 (DOM:9.73%, NON:13.42%), 100 (DOM:8.76%, NON:8.21%), and 125(DOM:24.26%, NON:12.8%) watts and in the RF at 75 (DOM:22.25%, NON:15.73%), 100(DOM:24.85%, NON:17.05%) and 125 (DOM:30.99%) watts. In terms of neuromuscular economy, there was a Likely Positive or Very Likely Positive effect of unilateral resistance training on most measures of NME on both the vastus lateralis and rectus femoris in both the dominant and nondominant legs. In terms of NME slope, there was only a Likely Positive effect of unilateral resistance training on the dominant vastus lateralis. Conclusion: Based on these results, it appears that the cross education of strength from unilateral resistance training is modality-specific. Furthermore, the NME of both the vastus lateralis and rectus femoris in both legs appear to improve following unilateral resistance training. However, in the nondominant leg, the improvement in NME appears to be due solely to the increase in maximal EMG, whereas the improved NME in the dominant leg is due to both an increase in maximal EMG and a decrease in submaximal EMG.

yes / Background Unilateral trans-tibial amputees have bilaterally reduced toe clearance, and an increased risk of foot contact, while crossing obstacles compared to the able-bodied. While the able-bodied tend to lead with a ‘preferred’ limb it is equivocal whether amputees prefer to lead with the intact or prosthetic limb. This study determined the effects of laterality, compared to side of amputation, on amputees' obstacle crossing performance. To help understand why laterality could affect performance we also assessed knee proprioception for both limbs. Methods Foot placement and toe clearance parameters were recorded while nine amputees crossed obstacles of varying heights leading with both their intact and prosthetic limbs. Joint-position sense was also assessed. Participants self-reported which limb was their preferred (dominant) limb. Findings There were no significant differences in foot placements or toe clearance variability across lead-limb conditions. There were no significant differences in toe clearance between intact and prosthetic lead-limbs (p = 0.28) but toe clearance was significantly higher when amputees led with their preferred compared to non-preferred limb (p = 0.025). There was no difference in joint-position sense between the intact and residual knees (p = 0.34) but joint-position sense tended to be more accurate for the preferred, compared to non-preferred limb (p = 0.08). Interpretation Findings suggest that, despite the mechanical constraints imposed by use of a prosthesis, laterality may be as important in lower-limb amputees as it is in the able bodied. This suggests that amputees should be encouraged to cross obstacles leading with their preferred limb. / Engineering and Physical Sciences Research Council

Yes / Background: Individuals with lower-limb amputation can use running specific prostheses (RSP) that store and then return elastic energy during stance. However, it is unclear whether varying the stiffness category of the same RSP affects spring-mass behaviour during self-selected, submaximal speed running in individuals with unilateral transtibial amputation. Research question: The current study investigates how varying RSP stiffness affects limb stiffness, running performance, and associated joint kinetics in individuals with a unilateral transtibial amputation. Methods: Kinematic and ground reaction force data were collected from eight males with unilateral transtibial amputation who ran at self-selected submaximal speeds along a 15 m runway in three RSP stiffness conditions; recommended habitual stiffness (HAB) and, following 10-minutes of familiarisation, stiffness categories above (+1) and below (-1) the HAB. Stance-phase centre of mass velocity, contact time, limb stiffness’ and joint/RSP work were computed for each limb across RSP stiffness conditions. Results: With increased RSP stiffness, prosthetic limb stiffness increased, whilst intact limb stiffness decreased slightly (p

<p> The present study was undertaken to investigate the mechanism underlying the observation that the maximal voluntary strength of the two legs acting together or bilaterally in isometric leg extension was less than the summed unilateral (sum of the left and right legs tested separately) strength. Observations were made on this phenomenon under both isometric and concentric contraction conditions by testing young adult males performing unilateral and bilateral leg press contractions on a modified isokinetic dynamometer. </p> <p> Electromyographical evidence indicated that there was a lesser activation of motor units in bilateral contraction as compared to unilateral, under isometric conditions and at a low and high concentric velocity. To determine whether a particular type of motor unit was being activated to a lesser extent in bilateral contractions, two physiological parameters of unilateral and bilateral contractions were compared: the strength-velocity relation and fatigability. This investigative method was based on the known physiological differences between the motor unit types; namely fast-twitch (FT), type two motor units have a faster twitch contraction time, greater force output at high velocities of shortening and lesser resistance to fatigue than the slow-twitch (ST), type one units. </p> <p> Results showed a greater relative decline in the strength of bilateral contractions as the velocity of contraction was increased through a range from 0°/s to 424°/s (0 to 7.40 radians/s). The bilateral to summed unilateral strength ratio (B/U-ratio) decreased from 0.91 under isometric conditions to 0.51 at the highest test velocity. Lesser fatigability was found in the bilateral condition in a 100 consecutive concentric contraction fatigue test. These results provided complementary evidence for the conclusion that FT motor units were active to a lesser degree in bilateral contractions. </p> / Thesis / Master of Science (MSc)

The continual increase in anterior cruciate ligament (ACL) injuries in sports makes it the most common ligament injury and leads the athlete down a difficult road with reconstruction surgery (ACLR) and months of rehabilitation. Specifically, females are at a greater risk of both primary and secondary ACL injuries compared to males. The purpose of this research was to understand the differences in movement and loading variability between ACLR and healthy athletes during unilateral and bilateral landings while utilizing limb symmetry to understand between group differences. It was hypothesized that females with an ACLR would have greater variability compared to males with an ACLR and healthy female athletes. 40 ACLR and 67 healthy athletes were asked to complete seven stop jumps and 25 ACLR and 30 healthy athletes completed seven single hop trials to assess intra-subject variability. The stop jump task utilized embedded force plates and motion capture technology while the single hop task used loadsol® in-shoe force sensors. The measures studied with the stop jump included posterior and vertical ground reaction force (GRF), knee/hip abduction/adduction angles, and loading rate. The single hop measures included peak force, loading rate, and impulse. To assess variability and limb symmetry, coefficient of variation (CV) and the limb symmetry index (LSI) were calculated for each of outcome measure. A linear mixed effects model was completed in JMP (SAS Institute Inc., Cary, NC) with p<0.05 to see the effects of group, sex, and limb. During the stop jump task, the ACLR athletes showed higher variability for both posterior GRF (p<0.001), posterior GRF LSI (p<0.001), and loading rate (p=0.027) compared to controls. Females with an ACLR had higher variability in vertical GRF (p<0.001) and vertical GRF symmetry (p=0.029) compared to HC females. Additionally, females with an ACLR had higher variability in the vertical GRF (p=0.033) when compared to males with an ACLR. Knee abduction angle (p=0.024) showed males with an ACLR to have higher variability compared to females with an ACLR. For the single hop task, there was a significant difference between sex for loading rate (p<0.001), loading rate LSI (p=0.004), impulse (p=0.006), and impulse LSI (p=0.001) with males producing a higher mean CV compared to females in all measures regardless of group. Overall, these results support the hypothesis that group and sex differences exist and that females with an ACLR will have higher variability and asymmetrical movements than male ACLR patients and healthy females during bilateral landings, which could lead to increased injury risk. In unilateral landings, the results suggest that females are landing with less variability compared to males. With increased variability on the surgical limb of an athlete with an ACLR, it is likely that the athlete will have a more successful return to sport as they can react and adapt to changes in landing during sports. Future work should report reinjury rates to investigate the potential role of movement variability in injury risk and potentially determine variability thresholds for injury risk. The evaluation of bilateral and unilateral landings revealed the need to include both landing tasks in return to sport testing as well as a limb symmetry metric to understand an athlete's functional readiness to react to changing conditions during sports related movement. / Master of Science / Anterior cruciate ligament (ACL) injuries continue to rise in all sports and result in athletes having to undergo reconstruction surgery (ACLR) and months of rehabilitation if they want to compete at a high level again. Specifically, females have a greater risk of suffering both a primary and secondary ACL injury compared to males. Movement differences have been previously researched in hopes of decreasing injury risk. Variability, or the differences between one trial to the next, is a way to visualize the athlete's ability to adapt following injury. The ideal level of adaptability is still unclear as too much variability can be seen as unstable while too little can be seen as unforgiving. The purpose of this project was to better understand movement and loading variability between ACLR and healthy athletes during one legged (unilateral) and two legged (bilateral) landings. Differences between limbs were analyzed to understand whether one leg was favored over the other. Every participant completed seven stop jump trials which required them to run forward, jump off one leg and landing with two legs followed by a maximum vertical jump; another different group completed a series of seven single leg hop tasks during which they started on one-leg and jumped forward as far as they could while maintaining their balance. The measures studied with the stop jump included peak vertical and posterior force, frontal plane knee and hip angles, and loading rate. The single hop measures included peak force, loading rate, and impulse. The loading rate is defined as the ratio of peak force divided by the time it takes the athlete to reach peak force following initial contact. Impulse is the area under the force time curve and provides insight into the athlete's ability to dissipate load. The force data from each trial performed were collected using force plate technology and loadsol® shoe inserts. Variability was calculated using the coefficient of variation (CV) which is the ratio between the standard deviation and the mean value across the trails. The limb symmetry index (LSI) was calculated as the ratio between the surgical/non-dominant and the non-surgical/dominant limbs. During a stop jump, female patients with an ACLR showed greater variability in peak force and force LSI revealing asymmetric landing compared to healthy females. Additionally, females with an ACLR had greater variability compared to males with an ACLR in peak force. The ACLR group had greater variability in posterior force, posterior force symmetry, and loading rate compared to the athletes in the healthy group. During a single hop, males had higher greater variability in loading rate, loading rate limb difference, impulse, and impulse limb difference compared to females. These results suggest that all females have a more unstable and asymmetrical landing compared to all males during bilateral landing. However, during a unilateral landing, females had a less forgiving landing compared to males, which could also indicate an increased injury risk. Future work should investigate reinjury rates to determine whether variability impacts injury risk and if differences in injury risk between males and females are associated with differences in variability.

The Russian Federation has claimed that its unilateral intervention in Crimea represents a case for Responsibility to Protect. This study investigates how the international community reacts to and determines a case of Responsibility to Protect. Three criteria to justify use of Responsibility to Protect are created from an analysis of international deliberations in previous interventions in Côte d'Ivoire (2010), Libya (2011), and Syria (2011). The Russian Federation involvement in Kosovo is analyzed in order to better understand its stance regarding intervention in Crimea. Classification as Responsibility to Protect requires (1) the case must have confirmed human rights violations; (2) the state must demonstrate that the human rights violations are more important than the state's sovereignty; and, (3) the state must use the multilateral system in the United Nations Security Council. The Russian Federation's intervention in Crimea constitutes a case for Responsibility to Protect to a minimal extent as their case did not have confirmed human rights violations and did not intervene multilaterally through the United Nations Security Council. / Master of Arts / The Russian Federation has claimed that its unilateral intervention in Crimea represents a case for Responsibility to Protect. The study investigates how the international community reacts to and determines a case of Responsibility to protect. By analyzing the humanitarian intervention of Kosovo and the prior Responsibility to Protect cases of Côte d'Ivoire (2010), Libya (2011), and Syria (2011), three criteria are established to determine if use of Responsibility to Protect is appropriate. The case of Kosovo is analyzed since the Russian Federation used this to further justify its intervention in Crimea. Classification as Responsibility to Protect requires the following: (1) the case must have confirmed human rights violations; (2) the state must demonstrate that the human rights violations are more important than the state's right to rule over its own population; and, (3) the state must use the multilateral system in the United Nations Security Council. The Russian Federation's intervention in Crimea constitutes a case for Responsibility to Protect to a minimal extent only since its case did not have confirmed human rights violations and did not intervene multilaterally through the United Nations Security Council.

America's founding fathers designed the Constitution as a malleable contract for governance, envisioning a republic with a struggle among co-equal actors that would serve to constrain and channel the struggle for power. The problem this study was designed to address is that presidents have used executive orders (EOs) when legislation is too difficult to pass due to divided party government, or when making sweeping changes to executive departments or agencies that historically required congressional approval. The purpose of this analysis was to explore whether a contemporary Democratic president are more likely than a Republican to use the EO as a unilateral strategy to pursue domestic/economic policy objectives during times of divided party government. This study compared the use of executive orders under divided government by Republican President Ronald Reagan and Democratic President Barack Obama, examining three EOs issued by each. Reagan and Obama viewed government differently. President Obama saw government as a solution to problems and President Reagan saw government as a source of problems. From this, I inferred that Democrats would be more likely than Republicans to favor federal government intervention in domestic/economic policy. Yet, though both presidents had different agendas and approaches, they both used the EO as a unilateral strategy under divided government. This may reflect that presidents understand that many in the public hold the president accountable for the economic performance of the United States, and economic wellbeing may lead to reelection of a president. / Master of Arts / America's founding fathers designed the Constitution as a flexible contract for control, imagining a republic with a struggle among co-equal actors that would serve to limit and guide the struggle for power. The problem this study was designed to address is that presidents have used executive orders (EOs) when laws were too difficult to pass due to divided party government, or when making far-reaching changes to departments or agencies that usually need congressional approval. The purpose of this study was to gain more insight as to whether a Democratic president was more likely than a Republican president to use executive orders to pursue domestic/economic policy goals when different parties controlled Congress and the presidency. The study examined the use of executive orders by Republican President Ronald Reagan and Democratic President Barack Obama under divided government, looking in depth at three executive orders each President issued. Reagan saw government as a source of problems and Obama saw government as a source of solutions. This led to the expectation that Democratic President Obama might use domestic/economic intervention by the federal government more often than Republican President Reagan would. Yet, although both presidents had different plans and methods, they used the executive order similarly during times of divided government. This likely reflects that presidents -- regardless of party -- understand that many in the public hold the president accountable for the economic performance of the United States, and economic wellbeing may lead to reelection of a president.

A perda auditiva unilateral (PAUn) é caracterizada pela diminuição da audição em apenas uma orelha. Indivíduos com este tipo de perda auditiva podem apresentar comprometimento nas habilidades auditivas de localização sonora, processamento temporal, ordenação e resolução temporal. O objetivo deste estudo foi verificar as habilidades auditivas de ordenação temporal, resolução temporal e localização sonora, antes e após a adaptação do aparelho de amplificação sonora individual (AASI). Foram avaliados 22 indivíduos, com idades entre 18 e 60 anos, com diagnóstico de PAUn sensorioneural ou mista, de graus leve a severo. O estudo foi dividido em duas etapas: a pré e a pós-adaptação de AASI. Em ambas as etapas, os indivíduos foram submetidos a uma anamnese, aplicação do Questionário de Habilidade Auditiva da Localização da fonte sonora, avaliação simplificada do processamento auditivo (ASPA) e Random Gap Detection Test (RGDT). O presente estudo encontrou diferença estatisticamente significante na avaliação da ASPA, exceto no teste de memória para sons não verbais em sequência (TMSnV), no RGDT e no Questionário de Habilidade Auditiva da Localização Sonora. A conclusão do estudo foi que com o uso efetivo do AASI, indivíduos com PAUn apresentaram melhora nas habilidades auditivas de localização sonora, ordenação e resolução temporal. / The Unilateral hearing loss (UHL) is characterized by decreased hearing in one ear. In individuals with this type of hearing loss the hearing abilities of sound localization, and temporal processing, ordering and temporal resolution, are affected. The objective of this study was to assess the hearing abilities of temporal ordering, temporal resolution and sound localization before and after the fitting of a hearing aid (HA). They evaluated 22 subjects, aged 18 to 60 years, diagnosed with sensorineural or mixed UHL, from mild to severe degrees. The study was divided into two stages: the pre and post-adaptation of HA. In both phases, subjects were submitted to an interview, application of Questionnarie for Desabilities Associated with Impaired Auditory Localization, auditory processing screening protocol (APSP) and Random Gap Detection Test (RGDT). This study found no statistically significant difference in the evaluation of APSP except in the memory test for non-verbal sounds in sequence, in RGDT and Questionnarie for Desabilities Associated with Impaired Auditory Localization. The conclusion was that with the effective use of hearing aids, individuals with UHL showed improvement in the auditory abilities of sound localization, ordering and temporal resolution.