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Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the "Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit" to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) associated myelopathy (HAM) can damage the spinal cord, causing paraplegia, spasticity, and gait disturbance. Currently, there are few effective treatments. OBJECTIVE: We investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) on gait disturbance in patients with HAM. METHODS: rTMS at 10 Hz was applied to HAM patients aged 30–80 years with an Osame's Motor Disability Score between 3 and 6. The stimulation site on the skull was the position where motor evoked potentials were most evidently elicited and leg motor areas were stimulated. Resting motor thresholds (minimum stimulation to induce motor evoked potential) were also determined. Each participant underwent 10 sessions of 2400 stimuli. Clinical measurements, including walking speed and stride length, were obtained. RESULTS: From 119 patients with HAM recruited, 12 were included in the rTMS group and 18 who did not undergo rTMS comprised the control group. rTMS significantly improved walking speed and stride length compared to controls. Particularly, resting motor thresholds decreased after 10 sessions of rTMS. CONCLUSIONS: rTMS improves walking speed in patients with HAM and may be an effective alternative for treating gait disturbance in patients with HAM. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Walking ability may be fairly well maintained after sciatic nerve resection combined with wide resection of soft tissue sarcoma, therefore, surgeons should not hesitate to perform sciatic nerve resection to achieve an adequate surgical margin. [ABSTRACT FROM AUTHOR]

Introduction: The reconstruction of bone defects of open lower leg fractures is challenging, and there is no established treatment strategy to date, especially in the acute phase. We report herein an 'acute Masquelet technique' for reconstructing bone defects of open lower limb fractures as the primary treatment in the acute phase. Patients and Methods: We retrospectively analyzed the outcomes of seven lower limbs of the seven Japanese patients (five males, two females, aged 24–76 years [mean 53 years]) who underwent the acute Masquelet technique for open fractures with bone defects. We evaluated postsurgical complications including deep infection, absorption of grafted bone, and the final result of the bone union. Results: Deep infection occurred in one of the seven limbs (14%). There was no case with absorption of grafted bone in our series. We have treated two patients who needed additional surgery for delayed bone union. Bone union was eventually obtained in all seven limbs. All of the patients became pain-free and could walk without a cane. Conclusion: The 'acute Masquelet technique' was quite useful for reconstructing bone defects of open lower limb fractures as the primary treatment in the acute phase. We believe that this is one of the options that might be successful in the treatment of open lower limb fractures. [ABSTRACT FROM AUTHOR]

RTMS is effective for treating brain fog and SPECT is a useful diagnostic technique and should be performed in patients presenting with symptoms suggestive of brain fog. IMP Single Photon Emission Computed Tomography (SPECT) showed cerebral blood flow decreased mainly in the right occipital lobe (Figure 1A). [Extracted from the article]

Objective: Abnormalities in neurotransmission via N-methyl-d-aspartic acid receptor (NMDAR) play a role in the pathophysiology of neuropsychiatric disorders. The impact of repetitive transcranial magnetic stimulation (rTMS) on NMDAR-related amino acids remains unknown. We aim to investigate the effects of rTMS on NMDAR-related amino acids in serum of post-stroke patients. Methods: Ninety-five consecutive post-stroke patients with upper limb hemiparesis were recruited. In 27 patients, the Beck Depression Inventory (BDI) score was 10 or higher. Twelve depressed patients underwent rehabilitation in combination with rTMS and 15 non-depressed patients underwent rehabilitation only without rTMS for 14 days. 1 Hz rTMS was applied to the primary motor area in the non-lesional hemisphere. BDI was conducted before and after treatment. Serum glutamine, glutamate, glycine, l-serine, and d-serine levels were measured before and after treatment. Results: There were no differences between depressed patients and non-depressed patients in clinical characteristics, levels of the five amino acids in serum, and the ratio of amino acids. However, in 27 depressed patients, there was a significant correlation between levels of glutamate in serum and BDI (ρ = 0.428, p = 0.026). BDI decreased significantly in depressed patients after treatment with or without rTMS. d-serine decreased in the rehabilitation with rTMS group, but increased in the rehabilitation without rTMS group. l-serine increased in the rehabilitation with rTMS group, but decreased in the rehabilitation without rTMS group. Conclusion: The results suggest that rTMS can modulate NMDAR-related amino acids in blood, producing beneficial effects. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia and osteoporosis reduce life quality and worsen prognosis in patients with liver cirrhosis (LC). When these two complications coexist, a diagnosis of osteosarcopenia is made. We aimed to investigate the actual situations of sarcopenia, osteoporosis, osteosarcopenia, and vertebral fracture, and to clarify the relationship among these events in patients with LC.Methods: We describe a cross-sectional study of 142 patients with LC. Sarcopenia was defined according to the Japan Society of Hepatology (JSH) criteria, Asian Working Group for Sarcopenia (AWGS) criteria, and European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. The skeletal muscle mass index (SMI) and handgrip strength were assessed using bioelectrical impedance analysis and a digital grip strength dynamometer, respectively. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and vertebral fracture was evaluated using spinal lateral X-rays. The severity of LC was assessed using the Child-Pugh classification.Results: Among the 142 patients, the prevalence of sarcopenia was 33.8% (48/142) according to the JSH and AWGS criteria and 28.2% (40/142) according to the EWGSOP2 criteria. The number of patients with osteoporosis, osteosarcopenia, and vertebral fracture was 49 (34.5%), 31 (21.8%), and 41 (28.9%), respectively. Multivariate analysis revealed a close association between sarcopenia and osteoporosis. Osteoporosis was independently associated with sarcopenia [odds ratio (OR) = 3.923, P = 0.010]. Conversely, sarcopenia was independently associated with osteoporosis (OR = 5.722, P < 0.001). Vertebral fracture occurred most frequently in patients with osteosarcopenia (19/31; 61.3%) and least frequently in those without both sarcopenia and osteoporosis (12/76; 15.8%). The SMI and handgrip strength values were significantly correlated with the BMD of the lumbar spine (r = 0.55 and 0.51, respectively; P < 0.001 for both), femoral neck, (r = 0.67 and 0.62, respectively; P < 0.001 for both), and total hip (r = 0.67 and 0.61, respectively; P < 0.001 for both).Conclusions: Sarcopenia, osteoporosis, osteosarcopenia, and vertebral fracture were highly prevalent and closely associated with one another in patients with LC. Specifically, patients with osteosarcopenia had the highest risk of vertebral fractures. Early diagnosis of these complications is essential for treatment intervention. [ABSTRACT FROM AUTHOR]

Objectives:The purpose of the present study was to investigate retrospectively the relationship between botulinum toxin type A plus multidisciplinary rehabilitation and muscle echo intensity in post-stroke patients with spasticity. The primary aim was to investigate whether the effects of the intervention on the improvement of spasticity depend on muscle echo intensity, and the secondary aim was to investigate whether the motor function of the lower limbs depends on muscle echo intensity. Methods:A 12-day inpatient protocol was designed for 102 post-stroke patients with spasticity due to lower limb paralysis. Muscle echo intensity of the triceps surae muscle was measured by ultrasonography, and the patients were categorized into four groups based on Heckmatt scale grades (Grades I–IV). Results:All four groups classified by the Heckmatt scale showed significant pre-to-post-intervention differences in the knee and ankle modified Ashworth scale scores (p< 0.05). Grades I–III patient groups showed a significant improvement in lower limb motor function following intervention. Grade IV patients did not show a significant improvement in lower limb motor function. Conclusions:We observed significant improvements in the modified Ashworth scale scores after botulinum toxin type A and multidisciplinary rehabilitation therapy on post-stroke patients with spasticity. Although patients with lower muscle echo intensity demonstrated improvements in motor function, the improvement was poor in those with higher muscle echo intensity. [ABSTRACT FROM AUTHOR]

We aimed to investigate plastic changes in cerebral white matter structures using diffusion tensor imaging following a 15-day stroke rehabilitation program. We compared the detection of cerebral plasticity between generalized fractional anisotropy (GFA), a novel tool for investigating white matter structures, and fractional anisotropy (FA). Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of 2400 pulses applied to the nonlesional hemisphere and 240 min intensive occupation therapy (OT) daily over 15 days. Motor function was evaluated using the Fugl-Meyer assessment (FMA) and Wolf Motor Function Test (WMFT). Patients underwent diffusion tensor magnetic resonance imaging (MRI) on admission and discharge, from which bilateral FA and GFA values in Brodmann area (BA) 4 and BA6 were calculated. Motor function improved following treatment (p<0.001). Treatment increased GFA values for both the lesioned and nonlesioned BA4 (p<0.05, p<0.001, resp.). Changes in GFA value for BA4 of the lesioned hemisphere were significantly inversely correlated with changes in WMFT scores (R2=0.363, p<0.05). Our findings indicate that the GFA may have a potentially more useful ability than FA to detect changes in white matter structures in areas of fiber intersection for any such future investigations. [ABSTRACT FROM AUTHOR]

Although repetitive transcranial magnetic stimulation (rTMS) for hemiparesis is beneficial, so far no study has examined the usefulness of rTMS for apathy. Thirteen patients with chronic stroke were assigned randomly to 2 groups: rTMS group (n = 7) and sham stimulation group (n = 6). The patients received 5 sessions of either high-frequency rTMS over the region spanning from the dorsal anterior cingulate cortex (dACC) to medial prefrontal cortex (mPFC) or sham stimulation for 5 days. The severity of apathy was evaluated using the Apathy Scale (AS) and the severity of depression was evaluated using the Quick Inventory of Depressive Symptomatology (QIDS) serially before and after the 5-day protocol. The AS and QIDS scores were significantly improved in the rTMS group, although they were not changed in the sham stimulation group. The degree of change in the AS score was significantly greater in the rTMS group than that in the sham stimulation group. The degree of change in the QIDS score was greater in the rTMS group than that in the sham stimulation group, although the difference was not statistically significant. The application of high frequency rTMS over the dACC and mPFC may be a useful intervention for apathy due to stroke. [ABSTRACT FROM AUTHOR]

Objectives. The purpose of this study was to examine the effects of combined botulinum toxin type A (BoNT-A) and inpatient multidisciplinary (MD) rehabilitation therapy on the improvement of upper and lower limb function in post-stroke patients. Methods. In this retrospective study, a 12-day inpatient treatment protocol was implemented on 51 post-stroke patients with spasticity. Assessments were performed on the day of admission, at discharge, and at 3 months following discharge. Results. At the time of discharge, all of the evaluated items showed a statistically significant improvement. Only the Functional Reach Test (FRT) showed a statistically significant improvement at 3 months. In subgroup analyses, the slowest walking speed group showed a significantly greater change ratio of the 10 Meter Walk Test relative to the other groups, from the time of admission to discharge. This group showed a greater FRT change ratio than the other groups from the time of admission to the 3-month follow-up. Conclusion. Inpatient combined therapy of simultaneous injections of BoNT-A to the upper and lower limbs and MD may improve motor function. [ABSTRACT FROM AUTHOR]

Purpose: To examine the efficacy of selective repetitive transcranial magnetic stimulation (rTMS) therapy guided by functional near-infrared spectroscopy (fNIRS) combined with intensive speech therapy (iST) on post-stroke patients with aphasia. Material and Methods: Eight right-handed patients with aphasia in the chronic stage after stroke were grouped into left and right hemisphere-activated for a language task based on pre-intervention fNIRS. Those with left hemisphere activation received 1-Hz TMS to the right inferior frontal gyrus (RtIFG; low-frequency rTMS [LFS] group), and those with right hemisphere activation received 10-Hz TMS to the RtIFG (high-frequency rTMS [HFS] group). The patients underwent an 11-day program of rTMS and iST. Results: Both groups showed a significant improvement in language function as measured by Standard Language Test of Aphasia (SLTA) total score at post-intervention relative to pre-intervention. Furthermore, the pre-to-post SLTA change scores were not statistically different between the groups. Comparison of pre- and post-intervention fNIRS revealed a resolution of the imbalance of interhemispheric inhibition in the LFS group and activation of the target hemisphere in the HFS group. Conclusions: The administration of fNIRS-guided selective rTMS therapy and iST to post-stroke patients with aphasia induced a significant improvement in language function, with both groups demonstrating a similar degree of improvement. [ABSTRACT FROM AUTHOR]

Background: High- and low-frequency repetitive transcranial magnetic stimulation (HF-rTMS and LF-rTMS) has been shown to be beneficial for upper limb hemiparesis in patients with acute stroke. However, no study has examined the usefulness of bilateral application of HF- and LF-rTMS (BL-rTMS). Methods: Fifty-eight hemiparetic patients with acute stroke were randomly assigned into two groups: HF-rTMS group and BL-rTMS group. All patients were scheduled to receive five sessions of either HF-rTMS over the lesional hemisphere or BL-rTMS over both hemispheres for 5 days. Motor function of the affected upper limb was evaluated using the Brunnstrom Recovery Stage (BRS) for upper-limb and hand-fingers, grip strength and tapping frequency, before the first session and after the last session of rTMS. Results: Improvement of BRS for the upper limb and hand/finger was significantly greater in the BL-rTMS group than the HF-rTMS group ( p < 0.01). Improvement in grip strength and tapping frequency was also greater in the BL-rTMS group, although the differences were not statistically significant. Conclusions: The proposed BL-rTMS is safe and feasible and showed a greater improvement of BRS of the affected upper limb compared to HF-rTMS. This novel rTMS approach may be a useful intervention for hemiparetic patients with acute stroke. [ABSTRACT FROM AUTHOR]

Extracellular signal-regulated kinase 5 (ERK5), the newest member of the mitogen-activated protein (MAP) kinase family, is regulated differently than the other MAP kinases. Emerging evidence suggest the role of ERK5 signaling in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. The present study investigates whether suicide brain is associated with alterations in components of the ERK5 signaling cascade. In the prefrontal cortex (PFC) and hippocampus of suicide subjects (n=28) and nonpsychiatric control subjects (n=21), we examined the catalytic activities and protein levels of ERK5 and upstream MAP kinase kinase MEK5 in various subcellular fractions; mRNA levels of ERK5 in total RNA; and DNA-binding activity of myocyte enhancer factor (MEF)2C, a substrate of ERK5. In the hippocampus of suicide subjects, we observed that catalytic activity of ERK5 was decreased in cytosolic and nuclear fractions, whereas catalytic activity of MEK5 was decreased in the total fraction. Further, decreased mRNA and protein levels of ERK5, but no change in protein level of MEK5 were noted. A decrease in MEF2C-DNA-binding activity in the nuclear fraction was also observed. No significant alterations were noted in the PFC of suicide subjects. The observed changes were not related to a specific psychiatric diagnosis. Our findings of reduced activation and/or expression of ERK5 and MEK5, and reduced MEF2C-DNA-binding activity demonstrate abnormalities in ERK5 signaling in hippocampus of suicide subjects and suggest possible involvement of this aberrant signaling in pathogenic mechanisms of suicide.Neuropsychopharmacology (2007) 32, 2338–2350; doi:10.1038/sj.npp.1301372; published online 7 March 2007 [ABSTRACT FROM AUTHOR]

The Maillard reaction that leads to the formation of advanced glycation end products (AGE) is considered to play an important role in the pathogenesis of Alzheimer’s disease (AD). Until now AGE derived from glucose (glucose-AGE) have been mainly investigated, so we established new AGE species derived from α-hydroxyaldehydes and dicarbonyl compounds. We have found that AGE derived from glyceraldehyde (glycer-AGE) and glycolaldehyde (glycol-AGE) showed strong neurotoxicity for primary cultured rat cortical neurons in vitro. In this study, we immunohistochemically examined the localization of glycer-AGE and glycol-AGE in the brains of AD patients and elderly controls. Most of the neurons in AD or control brains did not show any immunoreaction with glycol-AGE. In AD brains, glycer-AGE was mainly present in the cytosol of neuron in the hippocampus and para-hippocampal gyrus, but not in senile plaques and astrocytes. The pattern of immunopositivity was uniform and powdery, not dot-like. The distribution of glycer-AGE differed from that of glucose-AGE, which was detected at both intracellular and extracellular sites. This suggests that glycer-AGE has a pathological role different from glucose-AGE in AD. In the central nervous system, glyceraldehyde is generated via the glycolytic pathway from glyceraldehyde-3-phosphate by glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We hypothesize that perikaryal glycer-AGE immunopositivity of neurons reflects an increase of cytoplasmic glycer-AGE along with the decline of GAPDH activity. [ABSTRACT FROM AUTHOR]

The properties of a mutant hammerhead ribozyme system, which consists of two RNA oligomer strands and in which stem II is deleted (replaced with a UUUU loop), are described. The effects of temperature, pH, and metal ions on the cleavage reaction were similar to those for the parent ribozyme with stem II. The mutant ribozyme showed a much lower cleavage rate (kcat=0.04 min−1) in the presence of 10 mM MgCl2, where the parent ribozyme showed full cleavage activity. However, increasing the concentration of MgCl2 from 10 to 100 mM restored the cleavage activity of the mutant ribozyme to the original level (Kcat=0.2 min−1). CD titration experiments with MgCl2 using a noncleavable substrate were carried out. Deletion of stem II resulted in an about 20-fold reduction of the apparent Mg2+ binding affinity when the Mg2+ concentrations of half-saturation are compared. The results were analyzed by curve-fitting analysis and compared with those for the parent ribozyme. The analysis showed that the Mg2+ concentration dependence data in CD and cleavage experiments for the mutant enzyme can be explained by a two Mg2+ ion binding mechanism. These results suggest that stem II is important for maintaining the conformation of the catalytic core suitable for Mg2+ binding. [ABSTRACT FROM AUTHOR]

A real-time video signal processing LSI-Picot has been developed which processes dynamic images at video rate. Picot has an architecture which is suited to the image and video signal processing. By employing several internal buses and a new program control scheme, all operations are performed in one cycle 70 ns (=1/14.3 MHz). It has functions not only addition, subtraction, and multiplication but also the maximum, minimum and absolute value operations, which are indispensable to image processing. Its dedicated addressing units can concurrently perform the memory write/read and operation with a data memory of up to 16 Mw connected and it can cope with a large-size static image exceeding that of HDTV. Picot is constructed using 1.5 µm CMOS gate array technology and a 30,000 gate circuit integrated on a 14.95 mm x 14.95 mm chip, to be implemented in a 223-pin PGA. It operates on a 5-V single power supply with the power consumption of approximately 1 W. [ABSTRACT FROM AUTHOR]

Objectives: This study is a retrospective investigation of the effects of repetitive botulinum toxin A therapy (BoNT-A) and intensive rehabilitation (IR) on lower limb spasticity in post-stroke patients. Methods: Thirty-five post-stroke patients was included in this study and received BoNT-A for the first time. A 12-day inpatient protocol was with 4 cycles of the treatment protocol. The severity of spasticity, motor function and brace status were evaluated. Results: The modified Ashworth Scale (MAS) score of ankle dorsiflexors, range of motion, walking speed and balancing ability were significantly improved after cycle 1. The improvement of spasticity and motor function was persistent through cycles 2–4. One-third of brace users were able to discontinue the use of a brace. All of these brace users showed a forward gait pattern prior to therapy. Conclusions: Repeated BoNT-A combined with IR improved lower limb spasticity in post-stroke patients. Our results suggest that patients who show the forward gait pattern prior to therapy may be able to discontinue the use of their brace after therapy. [ABSTRACT FROM AUTHOR]