Cerebral Oxygenation Dynamics During Incremental Exercise: Comparison of Arm Cranking and Leg Cycling.

This study aimed to compare cerebral oxyhemoglobin (O2Hb) levels during incremental exercise by cycling vs. arm cranking in 12 healthy adult men aged 20.8 ± 0.2 years old. O2Hb was measured by near-infrared spectroscopy. Regions of interest included the left and right prefrontal cortices (LtPFC and RtPFC, respectively), the left and right premotor cortices (LtPMC and RtPMC, respectively), and the supplementary motor area (SMA) bilaterally. After 4 min of rest, 4 min of warm-up was performed by using ergometer followed by incremental exercise (increasing work rate by 5 W/min for arm cranking and 20 W/min for cycling exercise). All values were averaged every tenth of the participant's exercise time period from beginning of incremental exercise to end point. At the middle exercise intensity (50% exercise time), the averaged O2Hb values obtained at all regions of interest seemed to be higher during arm cranking exercise as compared to cycling; however, there were no significant differences between two types of exercise. At the end point of incremental exercise (100% exercise time), the O2Hb obtained at all regions of interest was significantly higher during arm cranking exercise compared to cycling (LtPFC 0.081 ± 0.019 vs. -0.001 ± 0.013 mM·cm, RtPFC 0.076 ± 0.021 vs. 0.018 ± 0.015 mM·cm, SMA 0.012 ± 0.040 vs. 0.040 ± 0.016 mM·cm; arm cranking vs. cycling; p < 0.05, respectively). We conclude that exercise-induced cerebral oxygenation is greater with arm cranking than with leg cycling.

Effects of 20-Minute Intensive Exercise on Subjects with Different Working Memory Bases.

Continuous moderate-intensity aerobic exercise improves cognitive function including working memory (WM). We aimed to determine the differences in the effects of exercise on WM based on pre-exercise WM function and oxyhemoglobin (O2Hb) changes. We enrolled 12 healthy adult males who, after a 4-min rest and warm-up, performed a 20-min exercise regime at a workload corresponding to 50% of maximal oxygen consumption. They performed a pre- and postexercise two-back test, and the reaction times were recorded. Near-infrared spectroscopy was used to monitor the O2Hb concentration in the left prefrontal cortex during the exercise. Based on the pre-exercise reaction time, the subjects were allocated into either a fast group (FG) or a slow group (SG). The pre- and postexercise changes in the reaction time and time-to-peak O2Hb were compared. Further, we determined the relationship between the change in the reaction time and time-to-peak O2Hb. There was no significant change in the reaction time of the FG; however, that in the SG decreased significantly. The time-to-peak O2Hb in the FG was significantly less than that in the SG. These results showed differences in the changes of reaction time and O2Hb changes between the FG and SG.

Supine Cycling Exercise Enhances Cerebral Oxygenation of Motor-Related Areas in Healthy Male Volunteers.

It has been reported that the cardiovascular response in the supine position is different from that in the sitting position. However, there are few reports on the effects of posture on cerebral oxygenation during exercise. Cycling exercises change oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) levels in motor-related areas. Therefore, this study compared O2Hb levels at motor-related areas during recumbent versus supine cycling. Eleven healthy young male performed a 30-min cycling exercise protocol at 50% of the maximal oxygen uptake (VO2 max) in the recumbent and supine positions. Near-infrared spectroscopy (NIRS) was used to measure exercise-induced O2Hb and HHb changes in the right (R-PMA) and left premotor areas (L-PMA), supplementary motor area (SMA), and primary motor cortex (M1). In R-PMA, L-PMA and SMA, the O2Hb obtained during supine cycling was significantly higher than that during recumbent cycling (R-PMA, 0.031 ± 0.01 vs. 0.693 ± 0.01; L-PMA, 0.027 ± 0.01 vs. 0.085 ± 0.013; SMA, 0.041 ± 0.011 vs. 0.076 ± 0.008 mM·cm, recumbent vs. supine position; p < 0.05). These results suggest that supine cycling exercise increases R-PMA, L-PMA, and SMA O2Hb levels in healthy young men.

Atomic resolution electron microscopy in a magnetic field free environment.

Atomic-resolution electron microscopes utilize high-power magnetic lenses to produce magnified images of the atomic details of matter. Doing so involves placing samples inside the magnetic objective lens, where magnetic fields of up to a few tesla are always exerted. This can largely alter, or even destroy, the magnetic and physical structures of interest. Here, we describe a newly developed magnetic objective lens system that realizes a magnetic field free environment at the sample position. Combined with a higher-order aberration corrector, we achieve direct, atom-resolved imaging with sub-Å spatial resolution with a residual magnetic field of less than 0.2 mT at the sample position. This capability enables direct atom-resolved imaging of magnetic materials such as silicon steels. Removing the need to subject samples to high magnetic field environments enables a new stage in atomic resolution electron microscopy that realizes direct, atomic-level observation of samples without unwanted high magnetic field effects.

Cancer survivors exhibit a different relationship between muscle strength and health-related quality of life/fatigue compared to healthy subjects.

We investigated the difference in relationship between muscle strength and quality of life (QOL)/fatigue in long-term cancer survivors and healthy subjects. Thirty-six cancer survivors and 29 healthy subjects were assessed for body composition and bone status at the calcaneus using the Osteo Sono Assessment Index. Muscle strength was evaluated via handgrip and knee extensor strength. Health-related QOL was assessed using the Medical Outcome Study 36-item Short-Form Health Survey. Fatigue was measured using the brief fatigue inventory. Cancer survivors exhibited lower QOL scores in the physical functioning, physical role function, bodily pain and general health domains (p < .05). Grip and knee extension muscle strength in cancer survivors was positively correlated with the physical function and bodily pain of QOL (p < .05). The usual fatigue subscale score was only significantly higher in cancer survivors than in healthy subjects (p < .05). However, there were no correlations between muscle strength and fatigue in cancer survivors. Our results showed that muscle strength was an important factor for improving QOL in cancer survivors. We believe that the findings of this study will be relevant in the context of planning rehabilitation for cancer survivors.

Clinical and mutational spectrum of Charcot-Marie-Tooth disease type 2Z caused by MORC2 variants in Japan.

BACKGROUND AND PURPOSE: The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of Charcot-Marie-Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring MORC2 mutations in Japan. METHODS: We analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next-generation sequencing, and samples from 434 mutation-negative patients were subjected to whole-exome sequencing. We extracted MORC2 variants from these whole-exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines. RESULTS: We identified MORC2 variants in 13 patients. As the second most common causative gene of CMT type 2 after MFN2, MORC2 variants were detected in 2.7% of patients with CMT type 2. The mean age of onset was 10.3 ± 8.7 years, and the inheritance pattern was mostly sporadic (11/13 patients, 84.6%). The clinical phenotype was typically length-dependent polyneuropathy, and electrophysiological studies revealed sensory-dominant axonal neuropathy. Mental retardation was identified in 4/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys. CONCLUSIONS: Our study is the largest report of patients harboring MORC2 variants. We revealed a clinical and mutational spectrum of Japanese patients with MORC2 variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.

Relationship of physical activity with physical function and health-related quality of life in patients having undergone allogeneic haematopoietic stem-cell transplantation.

In this study, we investigated the differences in physical activity before and after transplantation, and the relationship between physical activity and physical function and health-related quality of life (QOL) in 30 patients who underwent allogeneic haematopoietic stem cell transplantation (allo-HSCT). Duration and intensity of physical activity were quantified using a three-dimensional accelerometer. Physical function was quantified by handgrip and knee-extensor strength, with the 6-minute walk test (6MWT) used as a measure of exercise capacity. Health-related QOL was assessed using the 36-item Short-Form Health Survey. The proportion of daily activities performed at an intensity >3.0 metabolic equivalents (METs) increased significantly after allo-HSCT (p < .05). Daily activity time performed at an intensity of 1.6-2.9 METs significantly correlated only with left knee strength (p < .05). In contrast, the total number of daily steps and the proportion of activity performed at 1.6-2.9 METs and >3.0 METs were positively correlated with the 6MWT (p < .05). Additionally, physical functioning and general health subscales in health-related QOL positively correlated with daily activities performed at >3.0 METs (p < .05). Physical activity was associated with 6MWT and health-related QOL. These findings have implications for rehabilitation planning for patients undergoing allo-HSCT.

Negative predictive value of multiparametric MRI for prostate cancer detection: outcome of 5-year follow-up in men with negative findings on initial MRI studies.

OBJECTIVE: To assess the clinical negative predictive value (NPV) of multiparametric MRI (mp-MRI) for prostate cancer in a 5-year follow-up. MATERIALS AND METHODS: One hundred ninety-three men suspected of harboring prostate cancer with negative MRI findings were included. Patients with positive transrectal ultrasound (TRUS)-guided biopsy findings were defined as false-negative. Patients with negative initial TRUS-guided biopsy findings were followed up and only patients with negative findings by digital rectal examination, MRI, and repeat biopsy and no increase in PSA at 5-year follow-up were defined as "clinically negative". The clinical NPV of mp-MRI was calculated. For quantitative analysis, mean signal intensity on T2-weighted images and the mean apparent diffusion coefficient value on ADC maps of the initial MRI studies were compared between peripheral-zone (PZ) cancer and the normal PZ based on pathologic maps of patients who had undergone radical prostatectomy. RESULTS: The clinical NPV of mp-MRI was 89.6% for significant prostate cancer. Small cancers, prostatitis, and benign prostatic hypertrophy masking prostate cancer returned false-negative results. Quantitative analysis showed that there was no significant difference between PZ cancer and the normal PZ. CONCLUSION: The mp-MRI revealed a high clinical NPV and is a useful tool to rule out clinically significant prostate cancer before biopsy.

Reduction in radiation and contrast medium dose via optimization of low-kilovoltage CT protocols using a hybrid iterative reconstruction algorithm at 256-slice body CT: phantom study and clinical correlation.

AIM: To optimize low-kilovoltage (kV) computed tomography (CT) protocols using a hybrid iterative reconstruction (HIR) algorithm at 256-detector-row body CT. MATERIALS AND METHODS: Based on preliminary phantom studies, three different tube voltage protocols with an equal contrast-to-noise ratio (CNR) were developed. They were a conventional 120 kV protocol with filtered back-projection (FBP), an 80 kV protocol with HIR (a 160% increase in the tube current-time product and a 40% reduction in the contrast medium dose), and a 100 kV protocol with HIR (a 20% reduction in the tube current-time product and the contrast medium dose). The clinical study included 70 patients (34 women, 36 men; mean age 70.5 ± 9.1 years, range 44-92 years) who had undergone CT at 120 kV a mean of 148 ± 137 days before undergoing low kV contrast-enhanced body CT (80 kV with HIR, n = 35; 100 kV with HIR, n = 35). The estimated effective radiation dose (ED), image noise, and CNR were calculated and the visual image quality was scored on a four-point scale. RESULTS: Mean ED was 12.3, 8.4, and 15.4 mSv for the 80, 100, and 120 kV protocol, respectively, and significantly lower using the low kV protocols. There was no significant difference in the image noise and CNR between the low kV protocols with HIR and the 120 kV protocol with FBP, or in the visual scores among the three protocols. CONCLUSION: Without ensuing image-quality degradation, the radiation and contrast medium dose can be reduced with optimal contrast-enhanced CT protocols using a low kV technique and an HIR algorithm.

Safety and feasibility of physical therapy in cytopenic patients during allogeneic haematopoietic stem cell transplantation.

This study aimed to investigate the safety and feasibility of physical therapy in cytopenic patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to investigate the effect of physical therapy on physiological functions and quality of life (QOL) in allo-HSCT patients. The study cohort included 321 patients who underwent allo-HSCT. To investigate the safety and feasibility of physical therapy during cytopenia, patients were assigned to the physical therapy group (n = 227) or the control group (n = 94). To determine the effects of physical therapy, patients were divided according to the frequency with which they underwent physical therapy (n = 51 per group). Handgrip strength, knee extensor strength and a 6-min walk test were used as measures of physiological function. Short-Form 36 was used to assess QOL. The physical therapy group had higher rate of achieving engraftment and lower death rate than the control group (P < 0.05). After HSCT, the high-frequency physical therapy group showed significantly less decline than the low-frequency physical therapy group with respect to physical functioning of QOL (P < 0.01). Physical therapy is quite beneficial and can be performed safely and feasibly in cytopenic patients during allo-HSCT.

Interatrial dyssynchrony on tissue Doppler imaging predicts progression to chronic atrial fibrillation in patients with non-valvular paroxysmal atrial fibrillation.

OBJECTIVE: To determine prospectively whether interatrial dyssynchrony detected by tissue Doppler imaging (TDI) is useful for predicting the progression to chronic atrial fibrillation (CAF) in patients with non-valvular paroxysmal AF (PAF). METHODS: Thirty-seven patients with non-valvular PAF were prospectively followed after echocardiography. The interval of time from initiation of the P wave on the electrocardiogram (ECG) until the beginning of the late diastolic TDI signal at the lateral border of the mitral annulus (P-A'(M)) and the tricuspid annulus (P-A'(T)) was measured. Interatrial dyssynchrony was defined as the difference between the P-A'(M) and P-A'(T) intervals (A'(M)-A'(T)). The study endpoint was the onset of CAF (>6 months). RESULTS: During a follow-up period of 28 (SD 23) months, eight patients developed CAF. Compared with those without CAF, the patients who developed CAF had a significantly lower atrial systolic mitral (A'(M)) (7.7 (1.7) vs 10.7 (2.9) cm/s, p<0.01) and tricuspid (A'(T)) (12.9 (3.5) vs 16.6 (5.1) cm/s, p<0.05) annular tissue Doppler velocity, as well as a longer A'(M)-A'(T) interval (47 (13) vs 24 (10) ms, p<0.0001). Kaplan-Meier analysis, using cut-off values determined by analysis of receiver-operating characteristics curves, revealed that progression to CAF was significantly more frequent when the A'(M)-A'(T) interval was > or =34 ms (p<0.01), the A'(M) velocity was < or =9 cm/s (p<0.05) and the A'(T) velocity was < or =16 cm/s (p<0.05). CONCLUSIONS: This prospective study suggests that non-valvular PAF patients with a high risk of developing CAF have "interatrial dyssynchrony" and "atrial systolic dysfunction" on atrial TDI.

Retinal nerve fibre layer assessment in myopic glaucomatous eyes: comparison of GDx variable corneal compensation with GDx enhanced corneal compensation.

AIM: To compare the results of scanning laser polarimetry (GDx) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) when applied to myopic glaucomatous eyes. METHODS: Forty glaucoma eyes with moderate myopia (between -3 and -6 D) and 35 glaucoma eyes with high myopia (-8 D or greater) were enrolled in this study. GDx VCC, GDx ECC and standard automated perimetry (SAP) were performed. The prevalence of an atypical retardation pattern (ARP), the typical scan score (TSS) and retinal nerve fibre layer (RNFL) thickness were compared between VCC and ECC in both groups of myopic subjects. A correlation analysis between RNFL thickness and visual sensitivity was also conducted. RESULTS: In both myopic groups, the mean TSS is significantly lower (p<0.0001), and the prevalence of ARP was significantly higher (p<0.0001) by VCC scans than by ECC scans. Temporal, superior, nasal, inferior, temporal (TSNIT) average and temporal average thickness showed significantly higher values (p<0.001) by VCC than by ECC. A statistically significant association was observed between TSNIT average and mean deviation of SAP by ECC scan. CONCLUSIONS: ECC scans showed a better retardation pattern and structure-function relationship than did VCC, and ECC appeared to be more suitable for RNFL assessment in glaucomatous eyes that are moderately to highly myopic.

Usefulness of multi-detector row computed tomography for accurate preoperative assessment of pancreatic adenocarcinoma: report of a case.

A 74-year-old female underwent surgical treatment for adenocarcinoma of the pancreatic head. Preoperative multi-detector row computed tomography (MD-CT) demonstrated tumor invasion into the accessory right colic vein and the branch of the middle colic artery (MCA), which was not detected by digital subtraction angiography. MD-CT showed anatomical variants in the left hepatic artery arising from the left gastric artery, and the right posterior hepatic artery arising from the superior mesenteric artery. Three-dimensional reconstruction CT generated a clear picture of the anatomy of the region concerned, which is essential for a safe operation. The MD-CT findings were highly consistent with the intraoperative findings. We have demonstrated that MD-CT is an important and highly accurate modality for pancreatic surgery.

Micronization and polymorphic conversion of tolbutamide and barbital by rapid expansion of supercritical solutions.

Rapid expansion of supercritical solutions (RESS) was applied to tolbutamide and barbital. The solubility in supercritical CO2 was determined to estimate the extraction efficiency roughly by a simple method and accurately by a direct spectrophotometric technique. The latter revealed that the solubility of tolbutamide was a function of applied pressure and temperature and was proportional to the pressure. No significant difference in solubility between polymorphic Forms I and II of tolbutamide was detected. Tolbutamide and barbital particles produced by the RESS were characterized by size distribution measurement, polymorph identification and morphological evaluation. Significant size reduction to micron or sub-micron level with narrow size distribution was achieved, while conventional mechanical grinding had only slight effect. The particle size was greatly affected by both extraction and expansion conditions. The lower the extraction temperature was, the smaller was the mean particle size. Higher extraction pressure resulted in smaller mean particle size when compared at the same extraction temperature. The mean particle size was reduced by lowering the spray nozzle temperature, by lowering the expansion chamber temperature, by increasing the CO2 amount per spray, and by increasing the exhaust gas flow rate. The RESS processing realized the polymorphic conversion as well. As for tolbutamide, three polymorphs (Forms I, II, and IV) out of four could be produced by changing the extraction conditions, and in the case of barbital, one polymorph (Form II) out of three was produced consistently.

Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic type and tumor cellularity.

BACKGROUND AND PURPOSE: On diffusion-weighted imaging (DWI), metastatic tumors of the brain may exhibit different signal intensities (SI) depending on their histology and cellularity. The purpose of our study was to verify the hypotheses (1) that SI on DWI predict the histology of metastases and (2) that apparent diffusion coefficient (ADC) values reflect tumor cellularity. MATERIALS AND METHODS: We assessed conventional MR images, DWI, and ADC maps of 26 metastatic brain lesions from 26 patients, 13 of whom underwent surgery after the MR examination. Two radiologists performed qualitative assessment by consensus of the SI on DWI in areas corresponding to their enhancing portions. We measured the contrast-to-noise ratio (CNR) on T2-weighted images and normalized ADC (nADC) values, and compared them with tumor cellularity. RESULTS: The mean SI on DWI and the CNR on T2-weighted images were significantly lower in well differentiated than in poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. The mean nADC value was significantly higher in well differentiated than poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. All 3 small-cell carcinomas and 1 large-cell neuroendocrine carcinoma exhibited high SI on DWI. The nADC value showed a significant inverse correlation with tumor cellularity. There was no significant correlation between the CNR and tumor cellularity. CONCLUSION: The SI on DWI may predict the histology of metastases; well differentiated adenocarcinomas tended to be hypointense, and small- and large-cell neuroendocrine carcinomas showed hyperintensity. Their ADC values reflect tumor cellularity.

Usefulness of multi-detector row computed tomography for accurate preoperative assessment of pancreatic adenocarcinoma: report of a case

A 74-year-old female underwent surgical treatment for adenocarcinoma of the pancreatic head. Preoperative multi-detector row computed tomography (MD-CT) demonstrated tumor invasion into the accessory right colic vein and the branch of the middle colic artery (MCA); which was not detected by digital subtraction angiography. MD-CT showed anatomical variants in the left hepatic artery arising from the left gastric artery; and the right posterior hepatic artery arising from the superior mesenteric artery. Three-dimensional reconstruction CT generated a clear picture of the anatomy of the region concerned; which is essential for a safe operation. The MD-CT findings were highly consistent with the intra-operative findings. We have demonstrated that MD-CT is an important and highly accurate modality for pancreatic surgery

Diverse transcriptional initiation revealed by fine, large-scale mapping of mRNA start sites.

Determination of the mRNA start site is the first step in identifying the promoter region, which is of key importance for transcriptional regulation of gene expression. The 'oligo-capping' method enabled us to introduce a sequence tag to the first base of an mRNA by replacing the cap structure of the mRNA. Using cDNA libraries made from oligo-capped mRNAs, we could identify the transcriptional start site of an individual mRNA just by sequencing the 5'-end of the cDNA. The fine mapping of transcriptional start sites was performed for 5880 mRNAs in 276 human genes. Contrary to our expectations, the majority of the genes showed a diverse distribution of transcriptional start sites. They were distributed over 61.7 bp with a standard deviation of 19.5. Our finding may reflect the dynamic nature of transcriptional initiation events of human genes in vivo.