Development of a prediction model for target positioning by using diaphragm waveforms extracted from CBCT projection images.

PURPOSE: To develop a prediction model (PM) for target positioning using diaphragm waveforms extracted from CBCT projection images. METHODS: Nineteen patients with lung cancer underwent orthogonal rotational kV x-ray imaging lasting 70 s. IR markers placed on their abdominal surfaces and an implanted gold marker located nearest to the tumor were considered as external surrogates and the target, respectively. Four different types of regression-based PM were trained using surrogate motions and target positions for the first 60 s, as follows: Scenario A: Based on the clinical scenario, 3D target positions extracted from projection images were used as they were (PMCL ). Scenario B: The short-arc 4D-CBCT waveform exhibiting eight target positions was obtained by averaging the target positions in Scenario A. The waveform was repeated for 60 s (W4D-CBCT ) by adapting to the respiratory phase of the external surrogate. W4D-CBCT was used as the target positions (PM4D-CBCT ). Scenario C: The Amsterdam Shroud (AS) signal, which depicted the diaphragm motion in the superior-inferior direction was extracted from the orthogonal projection images. The amplitude and phase of W4D-CBCT were corrected based on the AS signal. The AS-corrected W4D-CBCT was used as the target positions (PMAS-4D-CBCT ). Scenario D: The AS signal was extracted from single projection images. Other processes were the same as in Scenario C. The prediction errors were calculated for the remaining 10 s. RESULTS: The 3D prediction error within 3 mm was 77.3% for PM4D-CBCT , which was 12.8% lower than that for PMCL . Using the diaphragm waveforms, the percentage of errors within 3 mm improved by approximately 7% to 84.0%-85.3% for PMAS-4D-CBCT in Scenarios C and D, respectively. Statistically significant differences were observed between the prediction errors of PM4D-CBCT and PMAS-4D-CBCT . CONCLUSION: PMAS-4D-CBCT outperformed PM4D-CBCT , proving the efficacy of the AS signal-based correction. PMAS-4D-CBCT would make it possible to predict target positions from 4D-CBCT images without gold markers.

Renal and Endocrine Responses to Arm Exercise in Persons with Cervical Spinal Cord Injury.

The aim of this study was to assess renal functions and endocrine responses to arm exercise in persons with cervical spinal cord injury (CSCI) under euhydrated conditions (free drinking of water), and to determine the physiological effects of exercise on renal function in these subjects. Eleven CSCI individuals (spinal lesions between C6 and C8, American Spinal Injury Association impairment scale A) and nine able-bodied (AB) persons rested for 30 min before performing 30 min arm-crank ergometer exercises at 50% of their maximum oxygen consumption, followed by 60-min of rest/recovery. Urine and blood samples were collected before and immediately after the exercise and recovery period. The CSCI patients showed no increase in plasma adrenaline and plasma renin activity compared with the AB controls, but showed similar changes in plasma aldosterone and the plasma antidiuretic hormone in response to the exercise. Creatinine clearance, osmolal clearance, free water clearance, and the fractional excretion of Na+ did not change during exercise in both groups of subjects, however free water clearance in the CSCI group was higher than in the AB group throughout the study. These findings suggested that activated plasma aldosterone without an increase in adrenaline or renin activity during exercise in CSCI individuals may reflect an adaptation to the disturbance of the sympathetic nervous system to compensate for renal function. As a result, no adverse effects of exercise on renal function in CSCI patients were observed.

Nanospiked paper: Microfibrous cellulose materials nanostructured via partial hydrolysis and self-assembly.

Nanocelluloses, such as cellulose nanofibers and nanocrystals, are sustainable nanomaterials that are generally extracted from natural raw materials in a top-down manner. These nanomaterials and their assemblies are facilitating new applications of biopolymers. However, creating nanostructures from conventional cellulosic materials including paper and cloth remains challenging. Herein, we report an approach for bottom-up nanostructuring of conventional microfibrous cellulose materials via a molecular self-assembly strategy. As a precursor cellulose material, paper was allowed to swell with aqueous phosphoric acid for the partial dissolution and hydrolysis of cellulose while maintaining its microfibrous structure. The generated cello-oligosaccharides in a dissolved state started to self-assemble upon adding water as a coagulant, resulting in nanospike-like assemblies on the microfiber surfaces. The resultant nanospiked papers were found to serve as a precursor for synthesizing silver nanoparticle-cellulose composites with bactericidal activities. Our findings promote the development of cellulose-based functional materials with nanostructures designed via molecular self-assembly.

Total Hemoglobin Mass Correlates with Peak Oxygen Consumption in Patients with Chronic Stroke.

BACKGROUND: The peak oxygen consumption (V.O2peak) and blood hemoglobin concentration [Hb] are lower in stroke patients than in age-matched healthy subjects. The ability of skeletal muscles to extract oxygen is diminished after stroke. We hypothesized that the oxygen extraction capacity of skeletal muscles in stroke patients depends on [Hb]. To test the hypothesis, we determined the relationship between V.O2peak and total hemoglobin mass (tHb-mass) in stroke patients. METHODS: The subjects were 19 stroke patients (age: 74 ± 2, mean ± SD, 10 males) and 11 age-matched normal subjects (age 76 ± 3, 6 males). Plasma volume (PV) and V.O2peak were measured on the same day. PV was measured using Evans Blue dye dilution method. Blood volume (BV) was calculated from PV and hematocrit, while tHb-mass was estimated from BV and [Hb]. Each subject underwent cardiopulmonary exercise test on a bicycle ergometer using a V.O2peak respiratory gas analyzer. RESULTS: There were no differences in age, height, and weight between the two groups. V.O2peak was lower in stroke patients than in the control. BV and tHb mass were not significantly different between the two groups, but [Hb] was significantly lower in stroke patients. In stroke patients, V.O2peak correlated significantly with tHb-mass (r = 0.497, p < 0.05), but not with BV. CONCLUSION: Our results suggested that low [Hb] seems to contribute to V.O2peak in stroke patients. The significant correlation between tHb-mass and V.O2peak suggested that treatment to improve [Hb] can potentially improve V.O2peak in stroke patients.

Effects of Combination of Functional Electric Stimulation and Robotic Leg Movement Using Dynamic Tilt Table on Walking Characteristics in Post-Stroke Patients with Spastic Hemiplegia: A Randomized Crossover-Controlled Trial.

BACKGROUND: Spastic hemiplegia causes slow and unstable walking in post-stroke patients. Dynamic tilt table with robotic leg movement (DTTRLM) is safe and effective in improving walking. Functional electric stimulation (FES) improves walking speed in post-stroke patients with spastic hemiplegia. The aim of this study was to determine the effects of combined DTTRLM + FES on walking speed compared with DTTRLM alone. METHODS: Twenty post-stroke patients were randomly assigned to receive either a single session of stepping + FES treatment or a single session of stepping alone treatment. After a one-week washout period, the same two groups underwent a single session of the other treatment, and the same measurements were taken. We measured walking speed, cadence, and the number of steps in a 10 m walking test (10MWT) and assessed Modified Ashworth Scale (MAS), Fugl-Meyer Assessment (FMA), and range of motion (ROM) before and after the intervention. RESULTS: Stepping + FES significantly improved walking speed, number of steps, and ankle inversion ROM, compared with stepping alone. Adverse events were not observed in any subject. CONCLUSIONS: Robotic stepping therapy combined with FES significantly improved 10 m walking speed (10MWS) compared with stepping only in patients with post-stroke and spastic hemiplegia. Further studies are needed to determine the long-term effects of the combination treatment.

Three-week exercise and protein intake immediately after exercise increases the 6-min walking distance with simultaneously improved plasma volume in patients with chronic cerebrovascular disease: a preliminary prospective study.

BACKGROUND: Blood volume (BV) is a critical factor for physical endurance in chronic stroke patients, while hypervolemia can worsen hypertension in these patients. This prospective study assessed whether rehabilitation combined with protein supplementation immediately after each exercise for 3 weeks would improve plasma volume (PV) and BV as well as physical endurance without worsening hypertension. METHODS: Ambulatory patients with chronic cerebrovascular disease who received a 3-week rehabilitation program with high protein jelly (intervention group [PG]; n = 8; 10-g protein) or protein-free jelly (control group [CG]; n = 8) consumed within 30 min after each exercise. PV and BV were assessed while measuring the 6-min walking distance (6MWD), peak oxygen consumption (VO2peak), strength of knee extension, and resting blood pressure before and after the intervention. Two-way ANOVA was used to determine whether there was an interaction of time × group. The difference between before and after intervention or between the groups by post-hoc test (Tukey's test) at the level of P < 0.05. RESULTS: The 6MWD increased only in the PG (P = 0.001; an interaction of Group and Time, P = 0.037). PV and BV increased only in the PG (P < 0.05). VO2peak and strength of knee extension in the paralysed limb increased in both groups (P < 0.05). The resting blood pressure did not worsen after the intervention. CONCLUSIONS: In chronic post-stroke patients, 3-week rehabilitation combined with protein intake immediately after exercise increased 6MWD simultaneously with increased PV and BV, but it did not increase resting blood pressure. The present regimen is acceptable and effective for ambulatory patients with chronic cerebrovascular disease. Name of the registry Examining effects of protein supplementation on functional improvement during rehabilitation intervention in chronic stroke patients Trial registration number UMIN000028009; date of registration: 30/06/2017. This study was registered prospectively.

Spinal Cord Injury in Middle-aged and Older Adults Who Had Undergone Active Rehabilitation Treatment at a Remote Hospital: A Case Series.

Background: Middle-aged and older individuals with spinal cord injury (SCI) often require long-term care even after receiving rehabilitation treatment, making it difficult for them to return home. We retrospectively investigated our active rehabilitation treatment for patients with SCI. Case: Included in this case series were ten patients with SCI who were admitted to our general hospital (located in the southern part of Wakayama Prefecture) and who underwent active rehabilitation treatment. The participants were investigated retrospectively by access to electronic medical records. The Barthel index scores for discharged patients were determined at an outpatient clinic, and the community phase of rehabilitation management was recorded. The average age of the 10 patients was 67.4 ± 13.4 years, and the average period from onset to transfer to our hospital was 102.6 ± 69.9 days. The Barthel index scores significantly improved from 39.0 ± 30.9 at admission to 65.0 ± 28.2 at discharge (P<0.05). Among the seven patients who were discharged to their homes, six had cervical SCI. Some patients with American Spinal Injury Association impairment scale grades A and B at admission could be discharged home, and their Barthel index scores were maintained after discharge. Discussion: : Even in a remote rural hospital, the activities of daily living of patients with SCI improved, and seven of the ten patients were discharged home. The activities of daily living of the discharged patients were maintained. To achieve these results, active rehabilitation treatment conducted by rehabilitation specialists is important.

Increased serum levels of brain-derived neurotrophic factor following wheelchair half marathon race in individuals with spinal cord injury.

Objective: Brain-derived neurotrophic factor (BDNF) has beneficial effects on metabolism as well as the peripheral and central nervous systems. The aim of this study was to assess the response of serum BDNF concentration ([BDNF]s) to wheelchair half marathon race in individuals with spinal cord injury (SCI).Design: Prospective observational study.Setting: The 34th Oita International Wheelchair Marathon Race in Japan.Participants: Nine cervical SCIs (CSCI) and 8 thoracic and lumber SCIs (LSCI) male athletes. Interventions: Wheelchair half-Marathon Race.Outcome measures: [BDNF]s, plasma concentrations of adrenaline ([Ad]p), noradrenaline ([Nor]p), and cortisol ([Cor]p), hematocrit, and platelet count were measured the day before, immediately after, and an hour after the race.Results: [BDNF]s increased significantly immediately after the race in both groups (CSCI; P = 0.0055, LSCI; P = 0.0312) but returned to the baseline levels at one hour after the race. However, [BDNF]s immediately and one hour after the race were significantly higher in LSCI than in CSCI (immediately after the race; P = 0.0037, 1 h after the race; P = 0.0206). Hematocrit and platelet count remained unchanged throughout the study. In LSCI, [Ad]p, [Nor]p and [Cor]p increased significantly immediately after and one hour after the race, compared with the baseline values (P < 0.05). On the other hand, these variables remained unchanged throughout the study in the CSCI.Conclusions: [BDNF]s increased significantly from the baseline in both LCSI and CSCI but was higher in LSCI than in CSCI immediately after and one hour after the race.

The effects of endurance exercise combined with high-temperature head-out water immersion on serum concentration of brain-derived neurotrophic factor in healthy young men.

OBJECTIVES: To evaluate acute changes in serum brain-derived neurotrophic factor (BDNF) concentration following combined endurance exercise and heat stress through head-out water immersion (HOI). SETTING: Observational study with crossover design. METHODS: Ten healthy young male participants performed HOI at 40 °C (40 °C HOI) or continuous cycling at 60% of maximal oxygen uptake while immersed in 40 °C (40 °C HOI-ex) or 23 °C water (23 °C HOI-ex) for 15 min. Serum BDNF, cortisol and lactate concentrations, and core temperature (Tcore) were measured pre, immediately post, and 15 and 30 min post-immersion. RESULTS: BDNF concentration increased immediately and 15 min after 40 °C HOI-ex, but not after 40 °C or 23 °C HOI-ex. No changes in Tcore concentration were observed during 23 °C HOI-ex (Pre; 37.3 °C ± 0.3 °C, Post; 37.8 °C ± 0.2 °C, Post 15; 37.4 °C ± 0.3 °C, Post 30; 37.2 °C ± 0.2 °C). Tcore increased significantly post, post 15, and post 30 min of 40 °C HOI (Pre; 37.1 °C ± 0.4 °C, Post; 38.8 °C ± 0.5 °C, Post 15; 37.9 °C ± 0.4 °C, Post 30; 37.9 °C ± 0.2 °C) and 40 °C HOI-ex (Pre; 37.2 °C ± 0.2 °C, Post; 40.2 °C ± 0.7 °C, Post 15; 38.9 °C ± 0.5 °C, Post 30; 38.3 °C ± 0.5 °C). Tcore was higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex immediately post and post 15 min. Plasma lactate and cortisol were significantly higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex after immersion (p = 0.001). CONCLUSION: While 15 min HOI alone or thermoneutral exercise do not increase BDNF concentration, both combined may form a time-efficient strategy to acutely elevate BDNF.

Attenuation of core temperature elevation and interleukin-6 excretion during head-out hot water immersion in elderly people.

[Purpose] Previous studies have demonstrated a link between core body temperature and interleukin-6 production. Recent studies have reported that 20 minutes of head-out immersion in hot water (42°C) increased serum interleukin-6 levels in young males. This study aimed to compare the efficacy of head-out immersion in hot water (42°C) on serum interleukin-6 levels in seven elderly (66-75 years old) and eight young males (21-32 years old). [Participants and Methods] Venous blood samples were drawn at rest, immediately after head-out immersion in hot water (42°C), after 1 hour, and after 2 hours. Levels of serum interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein; blood cell counts; and core temperature were measured. [Results] It was found that 20 minutes of head-out immersion in hot water (42°C) increased the core temperature in both the elderly and young participants; however, the rise in core temperature was more attenuated in elderly participants. Serum interleukin-6 levels were significantly higher in young participants 1 hour after the head-out immersion in hot water (42°C); however, serum interleukin-6 levels did not change in elderly participants. Serum tumor necrosis factor-α and high-sensitivity C-reactive protein levels remained constant throughout the study the elderly and young participants. [Conclusion] The current study demonstrated that head-out immersion in hot water (42°C) more attenuated core temperature and interleukin-6 levels in elderly participants than in young participants. We assert that these differences are likely to be related to age-related changes in core temperature regulation and muscle fibers.

Optimization-based synthesis of stochastic biocircuits with statistical specifications.

Model-guided design has become a standard approach to engineering biomolecular circuits in synthetic biology. However, the stochastic nature of biomolecular reactions is often overlooked in the design process. As a result, cell-cell heterogeneity causes unexpected deviation of biocircuit behaviours from model predictions and requires additional iterations of design-build-test cycles. To enhance the design process of stochastic biocircuits, this paper presents a computational framework to systematically specify the level of intrinsic noise using well-defined metrics of statistics and design highly heterogeneous biocircuits based on the specifications. Specifically, we use descriptive statistics of population distributions as an intuitive specification language of stochastic biocircuits and develop an optimization-based computational tool that explores parameter configurations satisfying design requirements. Sensitivity analysis methods are also performed to ensure the robustness of a biocircuit design against extrinsic perturbations. These design tools are formulated with convex optimization programs to enable rigorous and efficient quantification of the statistics. We demonstrate these features by designing a stochastic negative feedback biocircuit that satisfies multiple statistical constraints and perform an in-depth study of noise propagation and regulation in negative feedback pathways.