To establish an appropriate steroid treatment regimen for autoimmune pancreatitis (AIP).
A retrospective survey of AIP treatment was conducted in 17 centres in Japan. The main outcome measures were ...rate of remission and relapse.
Of 563 patients with AIP, 459 (82%) received steroid treatment. The remission rate of steroid-treated AIP was 98%, which was significantly higher than that of patients without steroid treatment (74%, 77/104; p<0.001). Steroid treatment was given for obstructive jaundice (60%), abdominal pain (11%), associated extrapancreatic lesions except the biliary duct (11%), and diffuse enlargement of the pancreas (10%). There was no relationship between the period necessary to achieve remission and the initial dose (30 mg/day vs 40 mg/day) of prednisolone. Maintenance steroid treatment was given in 377 (82%) of 459 steroid-treated patients, and steroid treatment was stopped in 104 patients. The relapse rate of patients with AIP on maintenance treatment was 23% (63/273), which was significantly lower than that of patients who stopped maintenance treatment (34%, 35/104; p = 0.048). From the start of steroid treatment, 56% (55/99) relapsed within 1 year and 92% (91/99) relapsed within 3 years. Of the 89 relapsed patients, 83 (93%) received steroid re-treatment, and steroid re-treatment was effective in 97% of them.
The major indication for steroid treatment in AIP is the presence of symptoms. An initial prednisolone dose of 0.6 mg/kg/day, is recommend, which is then reduced to a maintenance dose over a period of 3-6 months. Maintenance treatment with low-dose steroid reduces but dose not eliminate relapses.
•The primary motor cortex (M1) is crucial in sequential finger tapping learning.•We utilized preparatory activity as the measure of activated engram.•The learning included both speed-stressed and ...accuracy stressed modes.•The M1 showed training-related increase in preparatory activity in both modes.•The M1 encodes and retrieves the engram irrespective of training modes' difference.
The primary motor cortex (M1) is crucial in motor learning. Whether the M1 encodes the motor engram for sequential finger tapping formed by an emphasis on speed is still inconclusive. The active states of engrams are hard to discriminate from the motor execution per se. As preparatory activity reflects the upcoming movement parameters, we hypothesized that the retrieval of motor engrams generated by different learning modes is reflected as a learning-related increase in the preparatory activity of the M1. To test this hypothesis, we evaluated the preparatory activity during the learning of sequential finger-tapping with the non-dominant left hand using a 7T functional MRI. Participants alternated between performing a tapping sequence as quickly as possible (maximum mode) or at a constant speed of 2 Hz paced by a sequence-specifying visual cue (constant mode). We found a training-related increase in preparatory activity in the network covering the bilateral anterior intraparietal sulcus and inferior parietal lobule extending to the right M1 during the maximum mode and the right M1 during the constant mode. These findings indicate that the M1, as the last effector of the motor output, integrates the motor engram distributed through the networks despite training mode differences.
•Motor engrams of human at dormant states are hard to depict by fMRI.•We applied eigenvector centrality to networks to evaluate information accumulation.•An M1-centered parietal–premotor network ...represents early-phase motor engram.
Neural substrates of motor engrams in the human brain are hard to identify because their dormant states are difficult to discriminate. We utilized eigenvector centrality (EC) to measure the network information that accumulates as an engram during learning. To discriminate engrams formed by emphasis on speed or accuracy, we conducted functional MRI on 58 normal volunteers as they performed a sequential finger-tapping task with the non-dominant left hand. Participants alternated between performing a tapping sequence as quickly as possible (maximum mode) or at a constant speed of 2 Hz, paced by a sequence-specifying visual cue (constant mode). We depicted the formation of the motor engram by characterizing the dormant state as the increase in EC of the resting epoch throughout the training course, and the ecphory, or activated state, as the increment in EC during the task epoch relative to the alternated resting epoch. We found that a network covering the left anterior intraparietal sulcus and inferior parietal lobule represented the engram for the speed of execution, whereas bilateral premotor cortex and right primary motor cortex represented the sequential order of movements. This constitutes the first demonstration of learning-mode specific motor engrams formed by only 30 min of training.
The dorsal premotor cortex (PMd) plays an essential role in visually guided goal-directed motor behavior. Although there are several planning processes for achieving goal-directed behavior, the ...separate neural processes are largely unknown. Here, we created a new visuo-goal task to investigate the step-by-step planning processes for visuomotor and visuo-goal behavior in humans. Using functional magnetic resonance imaging, we found activation in different portions of the bilateral PMd during each processing step. In particular, the activated area for rule-based visuomotor and visuo-goal mapping was located at the ventrorostral portion of the bilateral PMd, that for action plan specification was at the dorsocaudal portion of the left PMd, that for transformation was at the rostral portion of the left PMd, and that for action preparation was at the caudal portion of the bilateral PMd. Thus, the left PMd was involved throughout all of the processes, but the right PMd was involved only in rule-based visuomotor and visuo-goal mapping and action preparation. The locations related to each process were generally spatially separated from each other, but they overlapped partially. These findings revealed that there are functional subregions in the bilateral PMd in humans and these subregions form a functional gradient to achieve goal-directed behavior.
Background
Although 7T functional MRI (fMRI) provides better signal‐to‐noise ratio and higher spatial resolution than 3T fMRI, geometric distortions become more challenging because fMRI is more ...susceptible to distortions than structural MRI. Accurate alignment of 7T fMRI to structural MRI data is critical for precise cortical surface‐based analysis.
Purpose
To quantify the effectiveness of distortion corrections of 7T fMRI data.
Study Type
Prospective.
Subjects
Fifteen healthy individuals aged 19–26 years (mean: 21.9 years).
Field Strength/Sequence
Multiband gradient‐echo echo‐planar imaging sequence at 7T; 3D T1/T2‐weighted sequences (magnetization prepared rapid acquisition with gradient echo MPRAGE and sampling perfection with application optimized contrast using different flip angle evolution SPACE) at 3T.
Assessment
fMRI data at 7T were registered to cortical surfaces reconstructed from 3T structural data acquired in the same subjects. Distortions induced by B0 inhomogeneity and gradient nonlinearity (B0 and gradient distortions) were evaluated as cortical fallout (misregistration of noncortical areas) and displacement (misregistration along gray matter).
Statistical Tests
Repeated measures analyses of variance with post‐hoc t‐tests with Bonferroni correction.
Results
The accuracy of fully corrected fMRI images based on the intensity distribution was 89.2%. Without any corrections, 9.7% of vertices in the whole surfaces were fallout and the average displacement was 0.96 mm for the rest of the vertices. B0 and gradient distortion corrections significantly reduced the fallout (to 2.1% and 8.7%) and displacement (to 0.29 mm and 0.86 mm). These corrections were effective even around regions with moderate distortions (the somatosensory and visual cortices for B0 distortion, and the anterior frontal, inferior temporal, and posterior occipital cortices for gradient distortion).
Data Conclusion
B0 distortion correction is crucial for surface‐based analysis of fine‐resolution fMRI at 7T. Gradient distortion correction should be considered when regions of interest include regions distant from the isocenter of scanners.
Evidence Level
1
Technical Efficacy Stage
1
How coherent neural oscillations are involved in task execution is a fundamental question in neuroscience. Although several electrophysiological studies have tackled this issue, the brain-wide task ...modulation of neural coherence remains uncharacterized. Here, with a fast fMRI technique, we studied shifts of brain-wide neural coherence across different task states in the ultraslow frequency range (0.01–0.7 Hz). First, we examined whether the shifts of the brain-wide neural coherence occur in a frequency-dependent manner. We quantified the shift of a region's average neural coherence by the inter-state variance of the mean coherence between the region and the rest of the brain. A clustering analysis based on the variance's spatial correlation between frequency components revealed four frequency bands (0.01–0.15 Hz, 0.15–0.37 Hz, 0.37–0.53 Hz, and 0.53–0.7 Hz) showing band-specific shifts of the brain-wide neural coherence. Next, we investigated the similarity of the inter-state variance's spectra between all pairs of regions. We found that regions showing similar spectra correspond to those forming functional modules of the brain network. Then, we investigated the relationship between identified frequency bands and modules’ inter-state variances. We found that modules showing the highest variance are those made up of parieto-occipital regions at 0.01–0.15 Hz, while it is replaced with another consisting of frontal regions above 0.15 Hz. Furthermore, these modules showed specific shifting patterns of the mean coherence across states at 0.01–0.15 Hz and above 0.15 Hz, suggesting that identified frequency bands differentially contribute to neural interactions during task execution. Our results highlight that usage of the fast fMRI enables brain-wide investigation of neural coherence up to 0.7 Hz, which opens a promising track for assessment of the large-scale neural interactions in the ultraslow frequency range.
The primary motor cortex (M1) is crucial for motor learning; however, its interaction with other brain areas during motor learning remains unclear. We hypothesized that the fronto-parietal execution ...network (FPN) provides learning-related information critical for the flexible cognitive control that is required for practice. We assessed network-level changes during sequential finger tapping learning under speed pressure by combining magnetic resonance spectroscopy and task and resting-state functional magnetic resonance imaging. There was a motor learning-related increase in preparatory activity in the fronto-parietal regions, including the right M1, overlapping the FPN and sensorimotor network (SMN). Learning-related increases in M1-seeded functional connectivity with the FPN, but not the SMN, were associated with decreased GABA/glutamate ratio in the M1, which were more prominent in the parietal than the frontal region. A decrease in the GABA/glutamate ratio in the right M1 was positively correlated with improvements in task performance (p = 0.042). Our findings indicate that motor learning driven by cognitive control is associated with local variations in the GABA/glutamate ratio in the M1 that reflects remote connectivity with the FPN, representing network-level motor sequence learning formations.
Summary
This study showed that bisphosphonate was safe and effective for the treatment of bone disorders in stage 4 chronic kidney disease (CKD) rats. Intermittent teriparatide therapy showed an ...anabolic action on bone even under secondary hyperparathyroidism conditions without having an adverse effect on mineral metabolism in late-stage CKD.
Introduction
Patients with late-stage CKD are at high risk for fragility fractures. However, there are no consensus on the efficacy and safety of osteoporosis medications for patients with late-stage CKD. In the present study, we aimed to examine the efficacy and safety of alendronate (ALN) and teriparatide (TPD) for treating bone disorder in late-stage CKD with pre-existing secondary hyperparathyroidism using a rat model of CKD.
Methods
Male 10-week-old Sprague-Dawley rats were subjected to a 5/6 nephrectomy or sham surgery and randomized into the following four groups: sham, vehicle (saline subcutaneous (sc) daily), ALN (50 μg/kg sc daily), and TPD (40 μg/kg sc daily). Medications commenced at 24 weeks of age and continued for 4 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum assays were performed.
Results
Nephrectomized rats developed hyperphosphatemia, secondary hyperparathyroidism (SHPT), and high creatinine, equivalent to CKD stage 4 in humans. ALN suppressed the bone turnover and increased the degree of mineralization in cortical bone, resulting in an improvement in the mechanical properties. TPD further increased the bone turnover and significantly increased the degree of mineralization, micro-geometry, and bone volume, resulting in a significant improvement in the mechanical properties. Both ALN and TPD had no adverse effect on renal function and mineral metabolism.
Conclusions
BP is safe and effective for the treatment of bone disorders in stage 4 CKD rats. Intermittent TPD therapy showed an anabolic action on bone even under SHPT conditions without having an adverse effect on mineral metabolism in late-stage CKD.
Autoimmune pancreatitis is characterised by raised serum levels of IgG4 and IgG4-bearing plasma cells in the inflammatory tissue. 1 Similar pathology can also occur in the larger bile ducts, ...resembling sclerosing cholangitis. 2 We report a patient with hepatitis and chronic cholecystitis, raised IgG4 level, and IgG4-bearing plasma cells in the liver and gall bladder wall, but no evident pancreatic disease. Raised serum IgG4 concentration and IgG4-bearing plasma cell infiltrates have a high sensitivity and specificity for the diagnosis of autoimmune pancreatitis 1 and associated diseases, including sclerosing cholangitis. 2 In the present case, the clinical and histological criteria for definite autoimmune hepatitis were met and, additionally, both biopsies showed hepatitis with abundant IgG4-bearing plasma cells in the liver and gallbladder.
State self-esteem, the momentary feeling of self-worth, functions as a sociometer involved in maintenance of interpersonal relations. How others' appraisal is subjectively interpreted to change state ...self-esteem is unknown, and the neural underpinnings of this process remain to be elucidated. We hypothesized that changes in state self-esteem are represented by the mentalizing network, which is modulated by interactions with regions involved in the subjective interpretation of others' appraisal. To test this hypothesis, we conducted task-based and resting-state fMRI. Participants were repeatedly presented with their reputations, and then rated their pleasantness and reported their state self-esteem. To evaluate the individual sensitivity of the change in state self-esteem based on pleasantness (i.e., the subjective interpretation of reputation), we calculated evaluation sensitivity as the rate of change in state self-esteem per unit pleasantness. Evaluation sensitivity varied across participants, and was positively correlated with precuneus activity evoked by reputation rating. Resting-state fMRI revealed that evaluation sensitivity was positively correlated with functional connectivity of the precuneus with areas activated by negative reputation, but negatively correlated with areas activated by positive reputation. Thus, the precuneus, as the part of the mentalizing system, serves as a gateway for translating the subjective interpretation of reputation into state self-esteem.
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