Weight loss in Parkinson's disease: A retrospective comparison between oral medication and device-assisted therapies.

OBJECTIVE: Weight loss (WL) is the most common symptom among patients with Parkinson's disease (PD) and has been reported to start several years before the diagnosis of PD. The relationship between WL and PD treatment is complex. This study aimed to characterize the impact of PD treatment on WL and find clues to establish the administration of nutrition for patients with PD. MATERIALS AND METHODS: Eighty-two patients with PD (mean age, 58.4 ± 10.2 years; mean Hoehn and Yahr stage, 3.2 ± 0.7) were recruited. Their treatments included deep brain stimulation (DBS) therapy (n = 34), levodopa/carbidopa intestinal gel (LCIG) therapy (n = 13), and oral medication alone (n = 35). Based on the medical records, the age of onset, disease duration, treatment options, videofluoroscopic dysphagia scale, blood test results, and weight change were collected. RESULTS: The median WL per year and rate of WL were -1.0 ± 2.8 kg and -1.9 ± 4.7 %, respectively. Most patients (93 %) were classified into normal nutrition and mild malnutrition groups by their CONUT scores. The median WL of the DBS group was significantly lower than that of the oral medication alone group (p < 0.01). The rate of WL showed a significant negative correlation with the age of onset (rho = -0.328, p = 0.003), but showed a significant positive correlation with the disease duration (rho = 0.231, p = 0.04). CONCLUSION: These results highlighted WL in the early stages of PD and suggested the need for adequate monitoring for patients undergoing device-aided therapy as well as oral medicine-treated patients with greater WL.

Factors that impact dysphagia and discontinuance of oral intake in patients with progressive supranuclear palsy.

Objective: To evaluate the swallowing function in the advanced stages of progressive supranuclear palsy (PSP) and clarify the factors that lead to adjustment of food consistency and discontinuation of oral intake. Methods: A total of 56 patients with PSP were recruited. Based on medical records, information about the basic attributes, clinical features (including axial rigidity and dementia), food intake, the results of a videofluoroscopic swallowing study (VFSS), and the timing of nasogastric tube transition and gastrostomy were extracted. From the VFSS images, the presence or absence of aspiration and retrocollis were assessed. Results: The average age at the onset, diagnosis, and the final follow-up examination were 67.6 ± 6.4 years, 71.6 ± 5.8 years, and 75.4 ± 5.6 years, respectively. The average duration of illness was 64.6 ± 42.8 months. Twenty-four individuals (42.9%) were continuing oral intake, while 32 were tube-fed, among whom 16 (50.0%) underwent gastrostomy tube placement. There were significant differences in the duration from the disease onset to tube feeding between the patients with and without cognitive decline at the time of the diagnosis (p < 0.01) and in the duration from the initial VFSS to tube feeding between the patients with and without aspiration on the initial VFSS (p < 0.01). There were significant differences in the duration from the diagnosis to tube feeding and from the initial VFSS to tube feeding between patients with and without axial rigidity at the time of the diagnosis (p < 0.05 and p < 0.05, respectively). Additionally, there was a significant association between axial rigidity and retrocollis (p < 0.01). Conclusion: Cognitive decline, axial rigidity and retrocollis, which are associated with the deterioration of dysphagia in PSP, are the highest risk factors for the discontinuation of oral intake. The early identification of these factors associated with the progression of dysphagia can contribute to the improvement of patient care and management.

Examination of hip function and muscle activity during clam exercise.

[Purpose] Clam exercise is commonly used to strengthen hip abductor muscles. This study aimed to classify the directions of greater trochanter movement during clam exercise and examine whether this classification reveals any differences in the characteristics of muscle activities. [Participants and Methods] Twenty healthy male participants were included and were divided into three groups according to the direction of greater trochanter movements during clam exercise: diagonally upward, backward, and upward. Muscle activity of the gluteus medius, gluteus maximus, tensor fascia lata, and external oblique was measured during clam exercise, along with the direction of greater trochanter movement and maximum muscle strength in the clam exercise limb position. [Results] In the diagonally upward group, the gluteus medius muscles showed higher activity than the other three muscles, and their activity was higher in the diagonally upward and backward groups than in the upward group. [Conclusion] The tension and action vector of the muscles changed due to differences in the direction of the greater trochanter movement caused by the movement pattern of each participant. The muscle activity around the hip joint changes with the direction of greater trochanter movement during clam exercise.

Relationship between motor dysfunction and chewing movement in patients with Parkinson's disease: A transversal study.

Objective: To assess the impact of chewing movement in patients with Parkinson's disease (PD), we examined the relation between chewing movement and motor dysfunction in association with PD progression. Methods: Thirty patients with PD (mean age, 68.9 ± 9.0 years; mean Hoehn and Yahr stage, 3.0 ± 0.7) were recruited. The PD condition was assessed in each patient by using the score of Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) part III score, body mass index (BMI), serum albumin (Alb), and tongue pressure, number of chews, mealtime, and chewing speed were collected. The patients were divided into two groups (mild and moderate PD groups) based on an MDS-UPDRS part III cut-off value of 32. Results: The chewing speed positively correlated with tongue pressure (rho = 0.69, p < 0.01) in the mild group, and with BMI (rho = 0.54, p = 0.03), serum Alb (rho = 0.63, p = 0.02), and number of chews (rho = 0.69, p < 0.01) in the moderate group. The MDS-UPDRS part III scores for all participants correlated negatively with chewing speed (rho = -0.48, p < 0.01), serum Alb (rho = -0.49, p < 0.01), and positively with mealtime (rho = 0.43, p = 0.01). Tongue pressure and serum Alb were identified to be as factors affecting the chewing speed (ß= 0.560, p < 0.01; ß= 0.457, p < 0.01, respectively). Conclusions: These results indicated that the progression of motor dysfunction in patients with PD is likely to affect chewing speed and the nutritional status decline may be linked to the impairment of chewing movement in these patients.

Strategies for selection and identification of rabbit single-chain Fv antibodies as ligand in affinity chromatography.

We developed affinity chromatographic resins that immobilized rabbit single-chain Fv antibodies (scFvs). By biopanning using antigen-coupled multilamellar vesicles (Ag-MLVs), 152 types of original scFv clones that specifically bind to human IgG were isolated and identified. Apparent dissociation rate constants, appkoff, of six different candidates were less than 10-3 s-1 and their dissociation constants, KDs, were ranged from 5.56 × 10-10 to 4.04 × 10-8 M. Consequently, the clones, R1-27, R2-18, and R3-26 were further investigated for use in affinity purification of human IgG. Both the clones, R1-27 and R3-26 maintained more than 40% of antigen-binding activities on the surface of affinity resins. Especially, R3-26 had a relatively high alkaline resistance. The direct separation of human IgG from 10% FBS-D-MEM by use of the column with R1-27 achieved 97.2% purity, while the column with R3-26 showed almost 100% recovery. The affinity resins at the densities between 4.32 and 15.19 mg-scFv/cm3 exhibited maximum binding amount of human IgG, while the highest ligand utilization was achieved by use of the resin at approximately 9 mg-scFv/cm3. The resin exhibited 7.69 mg/cm3 of equilibrium binding capacity (EBC) in affinity chromatography. It was expected that the EBC of affinity resins was strongly dependent on the specific surface area as well as the pore volume of the base resin. Therefore, the strategies to develop affinity ligands will be beneficial for development of on-demand affinity columns with higher affinity/selectivity, chemical resistance, while optimization of pore size and pore volume for scFv-coupled resins will further improve the EBC.

An attempt to construct the individual model of daily facial skin temperature using variational autoencoder.

Facial skin temperature (FST) has also gained prominence as an indicator for detecting anomalies such as fever due to the COVID-19. When FST is used for engineering applications, it is enough to be able to recognize normal. We are also focusing on research to detect some anomaly in FST. In a previous study, it was confirmed that abnormal and normal conditions could be separated based on FST by using a variational autoencoder (VAE), a deep generative model. However, the simulations so far have been a far cry from reality. In this study, normal FST with a diurnal variation component was defined as a normal state, and a model of normal FST in daily life was individually reconstructed using VAE. Using the constructed model, the anomaly detection performance was evaluated by applying the Hotelling theory. As a result, the area under the curve (AUC) value in ROC analysis was confirmed to be 0.89 to 1.00 in two subjects.

Factors Enhancing Serum Syndecan-1 Concentrations: A Large-Scale Comprehensive Medical Examination.

Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018 to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by the collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.

Accuracy of positioning and irradiation targeting for multiple targets in intracranial image-guided radiation therapy: a phantom study.

This study investigated the accuracy of positioning and irradiation targeting for multiple off-isocenter targets in intracranial image-guided radiation therapy (IGRT). A phantom with nine circular targets was created to evaluate both accuracies. First, the central point of the isocenter target was positioned with a combination of an ExacTrac x-ray (ETX) and a 6D couch. The positioning accuracy was determined from the deviations of coordinates of the central point in each target obtained from the kV-cone beam computed tomography (kV-CBCT) for IGRT and the planning CT. Similarly, the irradiation targeting accuracy was evaluated from the deviations of the coordinates between the central point of each target and the central point of each multi-leaf collimator (MLC) field for multiple targets. Secondly, the 6D couch was intentionally rotated together with both roll and pitch angles of 0.5° and 1° at the isocenter and similarly the deviations were evaluated. The positioning accuracy for all targets was less than 1 mm after 6D positioning corrections. The irradiation targeting accuracy was up to 1.3 mm in the anteroposterior (AP) direction for a target 87 mm away from isocenter. For the 6D couch rotations with both roll and pitch angles of 0.5° and 1°, the positioning accuracy was up to 1.0 mm and 2.3 mm in the AP direction for the target 87 mm away from the isocenter, respectively. The irradiation targeting accuracy was up to 2.1 mm and 2.6 mm in the AP direction for the target 87 mm away from the isocenter, respectively. The off-isocenter irradiation targeting accuracy became worse than the positioning accuracy. Both off-isocenter accuracies worsened in proportion to rotation angles and the distance from the isocenter to the targets. It is necessary to examine the set-up margin for off-isocenter multiple targets at each institution because irradiation targeting accuracy is peculiar to the linac machine.

[Dose impact of a carbon fiber couch for stereotactic body radiation therapy of lung tumors].

The aim of this study was to measure the dose attenuation caused by a carbon fiber radiation therapy table (Imaging Couch Top; ICT, BrainLab) and to evaluate the dosimetric impact of ICT during stereotactic body radiation therapy (SBRT) in lung tumors. The dose attenuation of ICT was measured using an ionization chamber and modeled by means of a treatment planning system (TPS). SBRT was planned with and without ICT in a lung tumor phantom and ten cases of clinical lung tumors. The results were analyzed from isocenter doses and a dose-volume histogram (DVH): D95, Dmean, V20, V5, homogeneity index (HI), and conformity index (CI). The dose attenuation of the ICT modeled with TPS agreed to within ±1% of the actually measured values. The isocenter doses, D95 and Dmean with and without ICT showed differences of 4.1-5% for posterior single field and three fields in the phantom study, and differences of 0.6-2.4% for five fields and rotation in the phantom study and six fields in ten clinical cases. The dose impact of ICT was not significant for five or more fields in SBRT. It is thus possible to reduce the dose effect of ICT by modifying the beam angle and beam weight in the treatment plan.

Angular dependence correction of MatriXX and its application to composite dose verification.

We measured the angular dependence of central and off-axis detectors in a 2D ionization chamber array, MatriXX, and applied correction factors (CFs) to improve the accuracy of composite dose verification of IMRT and VMAT. The MatriXX doses were measured with a 10° step for gantry angles (θ) of 0°-180°, and a 1° step for lateral angles of 90°-110° in a phantom, with a 30 × 10 cm2 field for 6 MV and 10 MV photons. The MatriXX doses were also calculated under the same conditions by the Monte Carlo (MC) algorithm. The CFs for the angular dependence of MatriXX were obtained as a function of θ from the ratios of MatriXX-measured doses to MC-calculated doses, and normalized at θ = 0°. The corrected MatriXX were validated with different fields, various simple plans, and clinical treatment plans. The dose distributions were compared with those of MC calculations and film. The absolute doses were also compared with ionization chamber and MC-calculated doses. The angular dependence of MatriXX showed over-responses of up to 6% and 4% at θ = 90° and under-responses of up to 15% and 11% at 92°, and 8% and 5% at 180° for 6 MV and 10 MV photons, respectively. At 92°, the CFs for the off-axis detectors were larger by up to 7% and 6% than those for the central detectors for 6 MV and 10 MV photons, respectively, and were within 2.5% at other gantry angles. For simple plans, MatriXX doses with angular correction were within 2% of those measured with the ionization chamber at the central axis and off-axis. For clinical treatment plans, MatriXX with angular correction agreed well with dose distributions calculated by the treatment planning system (TPS) for gamma evaluation at 3% and 3 mm. The angular dependence corrections of MatriXX were useful in improving the measurement accuracy of composite dose verification of IMRT and VMAT.

Optimal isotope labelling for NMR protein structure determinations.

Nuclear-magnetic-resonance spectroscopy can determine the three-dimensional structure of proteins in solution. However, its potential has been limited by the difficulty of interpreting NMR spectra in the presence of broadened and overlapping resonance lines and low signal-to-noise ratios. Here we present stereo-array isotope labelling (SAIL), a technique that can overcome many of these problems by applying a complete stereospecific and regiospecific pattern of stable isotopes that is optimal with regard to the quality and information content of the resulting NMR spectra. SAIL uses exclusively chemically and enzymatically synthesized amino acids for cell-free protein expression. We demonstrate for the 17-kDa protein calmodulin and the 41-kDa maltodextrin-binding protein that SAIL offers sharpened lines, spectral simplification without loss of information, and the ability to rapidly collect the structural restraints required to solve a high-quality solution structure for proteins twice as large as commonly solved by NMR. It thus makes a large class of proteins newly accessible to detailed solution structure determination.