Determinants of Fatigue in the Biceps Brachii During Blood Flow Restriction Training

poster abstractTraining loads of 60% - 80% of maximum are traditionally recommended for increasing muscular strength. Lifting lighter loads (~20% of 1RM) with concomitant blood flow restriction (BFR) can also increase muscle strength. It is unknown if adaptation with BFR is limited to the muscle or also due to changes in the nervous system. We examined changes in the output of the motor cortex and the muscle with stimulation, when subjects perform 1.) Training with light loads, 2.) Training with light loads with BFR, and 3.) Training with moderate loads. 5 subjects completed three training sessions with the elbow flexor muscles. Maximal strength was measured before and after each training session. Voluntary activation was tested with cortical stimulation (TMS) and with electrical stimulation of the biceps during additional MVCs. Subjects trained with a block of 4 isometric contractions at 20% MVC (120s, 60s, 60s, 60s durations) or at 60% MVC (40s, 20s, 20s, 20s durations). Fatigue (% decrease in MVC after training) was similar between 20% with BFR and 60% conditions (18.6% and 16%) and less in the 20% without BFR condition (9.7%). Cortical voluntary activation decreased similarly between the 20% BFR and 60% conditions (-3.6% and -3.3%) and showed less change with 20% without BFR (-1.8%). Alternatively, with electrical stimulation of the muscle, both 20% training conditions showed a decline in voluntary activation (-3.1% and -5.15), while voluntary activation increased by 8% after the 60% condition. Similar levels of fatigue occur at different contraction intensities when BFR is applied during the lighter contraction. Both 20% with BFR and 60% loading causes deficits in cortical activation, though the limiting factor in the 20% BFR condition is a decrease in activation of the muscle directly, while in the 60% contraction it is due to an inability to drive the motorneuron pool sufficiently

KAATSU Cuff Tightness and Limb Anthropometry: Effect on Blood Flow Restriction

abstractKAATSU resistance training involves low loads (20%1RM) and partial blood flow restriction (BFR). When applying a BFR cuff, the initial cuff tightness (ICT) is important. ICTs can potentially impact the degree of BFR (%BFR) caused by the subsequent inflation to the target training pressures. It’s known that limb anthropometrics can affect the amount of BFR that is produced at specific pressures. Understanding the interaction between limb anthropometrics and ICT is an important first step in standardizing BFR dose between individuals for KAATSU training prescription. Purpose: To determine what limb anthropometrics (circumference, muscle or fat composition) have the greatest effect on %BFR with various ICTs. Methods: Forty-two volunteers (26 men, 16 women) provided informed consent. Caliper skin folds (anterior and posterior), Gulick tape circumferences, and peripheral quantitative computed tomography (pQCT) scans were performed on the randomly assigned ipsilateral arm and leg at the level of the KAATSU cuff. %BFR was measured via pulse-wave Doppler ultrasound at baseline (no cuff) and at 5 ICT pressures (20, 30, 40, 50 and 60mmHg). Variable relationships were assessed using Pearson correlations and stepwise linear regression. Results: The dependent variable for regression analysis was %BFR at each ICT. pQCT-determined muscle (R2= .147, .614, .445, .360, & .232, respectively) and fat composition (R2= .138, .587, .429, .338, & .220, respectively) were significant (p<.05) determinants of BFR at all ICT pressures in the arm. At 30mmHg, circumference was also a determinant (R2=.163). There were no significant correlations between %BFR and any of the ICT pressures for the leg. pQCT fat composition and sum of skin folds correlated significantly (r=.915, p<.05). pQCT circumference and Gulick circumference measures correlated significantly (r=.991, p<.05). Conclusion: Arm anthropometrics impact the %BFR created by 5 ICTs in the arm. Skin fold measures and circumference measures were highly correlated with pQCT data. As a result, skin fold and Gulick circumference measures can be used to predict arm composition at the level of the cuff and may inform prescription of appropriate ICTs that result in more consistent initial %BFR across individuals

Initial KAATSU Cuff Tightness: Effect of Limb Anthropometrics on Blood Flow Restriction

abstractINTRODUCTION KAATSU training involves low load (20%1RM) resistance exercise combined with partial blood flow restriction (BFR). BFR is achieved by positioning a specially designed pneumatic cuff around the proximal aspect of the limb, cinching it to an initial cuff tightness (ICT), then inflating the cuff to a higher restrictive training pressure. ICTs can potentially impact the degree of BFR (%BFR) caused at the higher training pressures, yet many studies use the same ICTs for all subjects (1). Identifying that discrepancies in %BFR exist between subjects with different limb anthropometrics is an important step in moving toward standardization of BFR dose for KAATSU training prescription. The purpose of this study was to identify variation in %BFR between subjects experiencing the same ICT and what limb anthropometrics (circumference, muscle, and fat composition) may be determinants. METHODS Forty-two volunteers (26 men, 16 women) provided informed consent. Caliper skin folds, Gulick tape circumferences, and peripheral quantitative computed tomography (pQCT) scans were performed on the randomly assigned ipsilateral arm and leg at the level of the KAATSU cuff application. %BFR was measured via pulse-wave Doppler ultrasound at baseline (no cuff) and at an ICT of 30 mmHg. Variable relationships were assessed using Pearson correlations and stepwise linear regression. RESULTS The average %BFR (avg±st. dev.) for the arm and leg was 16.01±11.42% and 16.75±9.27% with a range of 46.66% and 36.41%, respectively. The dependent variable for regression analysis was %BFR. In the arm, pQCT-determined muscle (R2=0.614) and fat composition (R2=0.587) were significant (p<0.05) determinants of %BFR. Circumference was also a determinant (R2=0.163). There were no significant correlations between %BFR and the anthropometrics for the leg. pQCT fat composition and sum of skin folds correlated significantly (r=0.915, p<0.05). pQCT circumference and Gulick circumference measures correlated significantly (r=0.991, p<0.05). DISCUSSION Conflicting BFR training results have been reported in the literature. A potential cause could be universal ICT usage causing some individuals to receive an inadequate training stimulus. Individuals using a 30 mmHg ICT will experience different %BFR when limb anthropometrics vary. Thus a method of assigning ICTs specific to individuals’ anthropometric characteristics is needed to ensure equally potent stimuli. Skin fold measures and circumference measures were highly correlated with pQCT data. As a result, skin fold and Gulick circumference measures can be used to predict arm composition at the level of the cuff and may inform prescription of appropriate ICTs that result in more consistent initial %BFR across individuals

Cutaneous Silent Period Characteristics are Dependent on the Organization of Upper Limb Muscles

abstractCutaneous silent periods (CSPs) are inhibitory spinal reflexes mediated by small diameter A-δ fibers, serving to protect the body from harmful stimuli (Leis et al., 1992; Kofler, 2003). Currently, CSPs are believed to only inhibit the extensor muscles of the upper limb halting motions such as reaching, while exciting flexor muscles to withdraw the limb. The present study sought to determine if CSPs could be evoked in both extensor and flexor muscles of the upper limb, thereby providing further insight into the organization of the spinal circuitry associated with this reflex. 22 subjects performed contractions with seven muscles from the hand, forearm, upper arm, and shoulder while muscle activity was recorded with electromyography. Subjects were electrically stimulated (10x perceptual threshold) with 20 individual pulses delivered to each digit II (radial nerve) and digit V (ulnar nerve) of the right hand during each contraction. Results demonstrated significant main effects (p<0.001) across muscles for the key dependent variables of the CSP: onsets (F[6,21] = 15.42, p <0.001), durations (F[6,21] = 65.39, p <0.001), and % of suppression (F[6,21] = 91, p <0.001), similarly for both nerves stimulated. Distal muscles presented with the earliest onset times, longest duration of inhibition, and largest amount of inhibition. Moving proximally, the onset times became later with duration and the amount of inhibition decreasing. Linear regressions showed that the distance of the muscle from the spinal cord (cm) was a significant predictor of the duration (digit II r2 = 0.43; digit V r2 = 0.46) and amount of inhibition (digit II r2 = 0.51; digit V r2 = 0.48). The results demonstrate the occurrence of CSPs throughout the upper limb, with the greatest inhibition of distal muscles, leading us to hypothesize that the corticospinal tract, specifically direct cortico-motorneuronal connections, are directly influenced by the inhibitory input

Cortical Representation and Excitability Increases for a Thenar Muscle Mediate Improvement in Short-Term Cellular Phone Text Messaging Ability

Cortical representations expand during skilled motor learning. We studied a unique model of motor learning with cellular phone texting, where the thumbs are used exclusively to interact with the device and the prominence of use can be seen where 3200 text messages are exchanged a month in the 18-24 age demographic. The purpose of the present study was to examine the motor cortex representation and input-output (IO) recruitment curves of the abductor pollicis brevis (APB) muscle of the thumb and the ADM muscle with transcranial magnetic stimulation (TMS), relative to individuals' texting abilities and short-term texting practice. Eighteen individuals performed a functional texting task (FTT) where we scored their texting speed and accuracy. TMS was then used to examine the cortical volumes and areas of activity in the two muscles and IO curves were constructed to measure excitability. Subjects also performed a 10-min practice texting task, after which we repeated the cortical measures. There were no associations between the cortical measures and the FTT scores before practice. However, after practice the APB cortical map expanded and excitability increased, whereas the ADM map constricted. The increase in the active cortical areas in APB correlated with the improvement in the FTT score. Based on the homogenous group of subjects that were already good at texting, we conclude that the cortical representations and excitability for the thumb muscle were already enlarged and more receptive to changes with short-term practice, as noted by the increase in FTT performance after 10-min of practice

Cortical Representation and Excitability Increases for a Thenar Muscle Mediate Improvement in Short-Term Cellular Phone Text Messaging Ability

Cortical representations expand during skilled motor learning. We studied a unique model of motor learning with cellular phone texting, where the thumbs are used exclusively to interact with the device and the prominence of use can be seen where 3200 text messages are exchanged a month in the 18–24 age demographic. The purpose of the present study was to examine the motor cortex representation and input–output (IO) recruitment curves of the abductor pollicis brevis (APB) muscle of the thumb and the ADM muscle with transcranial magnetic stimulation (TMS), relative to individuals’ texting abilities and short-term texting practice. Eighteen individuals performed a functional texting task (FTT) where we scored their texting speed and accuracy. TMS was then used to examine the cortical volumes and areas of activity in the two muscles and IO curves were constructed to measure excitability. Subjects also performed a 10-min practice texting task, after which we repeated the cortical measures. There were no associations between the cortical measures and the FTT scores before practice. However, after practice the APB cortical map expanded and excitability increased, whereas the ADM map constricted. The increase in the active cortical areas in APB correlated with the improvement in the FTT score. Based on the homogenous group of subjects that were already good at texting, we conclude that the cortical representations and excitability for the thumb muscle were already enlarged and more receptive to changes with short-term practice, as noted by the increase in FTT performance after 10-min of practice

Cost-effectiveness of a structured progressive task-oriented circuit class training programme to enhance walking competency after stroke: The protocol of the FIT-Stroke trial

<p>Abstract</p> <p>Background</p> <p>Most patients who suffer a stroke experience reduced walking competency and health-related quality of life (HRQoL). A key factor in effective stroke rehabilitation is intensive, task-specific training. Recent studies suggest that intensive, patient-tailored training can be organized as a circuit with a series of task-oriented workstations.</p> <p>Primary aim of the FIT-Stroke trial is to evaluate the effects and cost-effectiveness of a structured, progressive task-oriented circuit class training (CCT) programme, compared to usual physiotherapeutic care during outpatient rehabilitation in a rehabilitation centre. The task-oriented CCT will be applied in groups of 4 to 6 patients. Outcome will be defined in terms of gait and gait-related ADLs after stroke. The trial will also investigate the generalizability of treatment effects of task-oriented CCT in terms of perceived fatigue, anxiety, depression and perceived HRQoL.</p> <p>Methods/design</p> <p>The multicentre single-blinded randomized trial will include 220 stroke patients discharged to the community from inpatient rehabilitation, who are able to communicate and walk at least 10 m without physical, hands-on assistance. After discharge from inpatient rehabilitation, patients in the experimental group will receive task-oriented CCT two times a week for 12 weeks at the physiotherapy department of the rehabilitation centre. Control group patients will receive usual individual, face-to-face, physiotherapy. Costs will be evaluated by having each patient keep a cost diary for the first 24 weeks after randomisation. Primary outcomes are the mobility part of the Stroke Impact Scale (SIS-3.0) and the EuroQol. Secondary outcomes are the other domains of SIS-3.0, lower limb muscle strength, walking endurance, gait speed, balance, confidence not to fall, instrumental ADL, fatigue, anxiety, depression and HRQoL.</p> <p>Discussion</p> <p>Based on assumptions about the effect of intensity of practice and specificity of treatment effects, FIT-Stroke will address two key aims. The first aim is to investigate the effects of task-oriented CCT on walking competency and HRQoL compared to usual face-to-face physiotherapy. The second aim is to reveal the cost-effectiveness of task-oriented CCT in the first 6 months post stroke. Both aims were recently recommended as priorities by the American Hearth Association and Stroke Council.</p> <p>Trial registration</p> <p>This study is registered in the Dutch Trial Register as NTR1534.</p

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival