Supraspinal Activation Induced by Visual Kinesthetic Illusion Modulates Spinal Excitability.

Repetitive passive movement (RPM) enhances reciprocal inhibition. RPM is more effective when performed rapidly and at wide joint angles. However, patients with limited joint range of motion may not receive the most effective RPM. Therefore, having an alternative method for performing RPM in patients who cannot perform actual exercise due to limited joint motion is necessary. This study investigated the effects of RPM on spinal excitability using a visual kinesthetic illusion. Participants included 17 healthy adults (7 women). Measurements were taken before, during, and immediately after the intervention. We established two intervention conditions: the control condition, in which participants focused their attention forward, and the illusion condition, in which participants watched a video about RPM. F-waves from the tibialis anterior and soleus muscles were measured, and F-wave persistence and F/M amplitude ratios were analyzed. Under the illusion condition, compared with the preintervention condition, the F/M amplitude ratio of the tibialis anterior increased by approximately 44% during the intervention (p < 0.05), whereas the F-wave persistence of the soleus decreased by approximately 23% from the immediate start of the intervention (p < 0.05). This study suggests that a visual kinesthetic illusion can increase the spinal excitability of the tibialis anterior, whereas reciprocal inhibition can decrease the spinal excitability of the soleus.

Chromosomal missegregation and aberrant embryo development in repro57 female mice with Rnf212 homozygous mutation.

In brief: Repro57 mice, bearing an Rnf212 gene mutation, exhibit infertility in both homozygous mutant males and females, revealing arrested spermatogenesis in males and investigating unclear mechanisms in females. The study highlights aneuploidy and altered kinetochore patterns in repro57 homozygous mutant oocytes, which impact later stages of embryo development. Abstract: Repro57 mice, induced with N-ethyl-N-nitrosourea and harboring a mutation in the Rnf212 gene, exhibit infertility in both homozygous mutant males and females. Rnf212 plays a crucial role in recombination and crossover designation. In male repro57 homozygous mutants, spermatocytes often degenerate during late prophase, and mature spermatozoa are absent in the seminiferous epithelium, indicating arrested spermatogenesis as the cause of infertility. Despite reports of infertility in Rnf212-knockout female mice, the specific mechanisms underlying infertility in female repro57 homozygous mutants remain elusive. This study investigates the chromosomal and kinetochore patterns of mature oocytes and their developmental potential following in vitro fertilization in female repro57 homozygous mutant mice. While all wild-type oocytes progress to metaphase II and exhibit euploidy, all repro57 homozygous mutant mouse oocytes display aneuploidy. Additionally, kinetochore distances in repro57 homozygous mutant oocytes exceed those observed in wild-type counterparts. Although no significant differences are noted in fertilization and early embryo development rates between wild-type and repro57 homozygous mutant mice, embryos derived from repro57 homozygous mutants exhibit significantly lower morula and blastocyst rates, accompanied by frequent cytokinesis failure and vacuole formation. These findings suggest that the premature segregation of sister chromatids in repro57 homozygous mutant mice adversely impacts the later stages of embryo development.

Successful Childbirth During Satralizumab Treatment in Neuromyelitis Optica Spectrum Disorder.

A 40-year-old woman with neuromyelitis optica spectrum disorder (NMOSD) and anti-aquaporin 4 antibodies suffered three NMOSD episodes between 35 and 37 years of age. Despite treatment with prednisolone and azathioprine, her condition repeatedly relapsed. We introduced satralizumab, targeting interleukin-6 receptors, which stabilized her condition. At the age of 38, she became pregnant and delivered a healthy baby at 38 weeks. Post delivery, both mother and child stayed healthy with no NMOSD relapses. This case illustrates the efficacy and safety of satralizumab in managing NMOSD, especially for women in their reproductive years who are planning pregnancy.

Case Report: Intraventricular Cerliponase Alfa Treatment in a Patient with Advanced Neuronal Ceroid Lipofuscinosis Type 2.

Neuronal ceroid lipofuscinosis type 2 (CLN2) is an autosomal recessive lysosomal disease caused by decreased activity of the enzyme tripeptidyl peptidase 1 (TPP1) due to pathogenic variants in the TPP1 gene. Cerliponase alfa, a recombinant proenzyme form of TPP1, has shown efficacy in preventing motor and language function decline in early-stage CLN2. However, the safety and effects of this therapy in advanced-stage CLN2 are unclear. We herein report a case of intraventricular cerliponase alfa treatment for over a year in a patient with advanced-stage CLN2. The results suggest the safety and potential efficacy of treatment at an advanced stage of CLN2.

A Case of Methimazole-Induced Acute Pancreatitis With an HLA Allele Causing Antithyroid Drug-Induced Agranulocytosis.

Among the side effects of methimazole (MMI) for the treatment of Graves' disease, MMI-induced acute pancreatitis (MIP) is a rare adverse reaction, with only 7 cases being reported to date. However, 2 large-scale population-based studies recently revealed that the risk of MIP was significantly higher, ranging from 0.02% to 0.56%. Although MIP is common in middle-aged and elderly Asian women, its pathogenesis remains largely unknown. We herein present a case of a 72-year-old Japanese woman with Graves' disease who developed MIP 12 days after the initiation of MMI. The MMI was discontinued, the patient was switched to propylthiouracil (PTU) therapy, and pancreatitis gradually resolved. Serological human leukocyte antigen (HLA) typing identified HLA-DRB1*08:03:02. This HLA allele was previously detected in a patient with MIP and is one of the major risk factors for agranulocytosis induced by antithyroid drugs, including PTU as well as MMI. In cases of MIP, PTU is being considered as an alternative to MMI; however, its safety needs further investigation and patients require close monitoring after the switch to PTU. Further studies are warranted, particularly on the relationship between MIP and the presence of HLA alleles causing antithyroid drug-induced agranulocytosis.

Thrombotic Microangiopathy, Podocytopathy, and Damage to the Renal Tubules with Severe Proteinuria and Acute Renal Dysfunction Induced by Lenvatinib.

Lenvatinib, a tyrosine kinase inhibitor (TKI), is a stronger inhibitor of vascular endothelial growth factor receptor, fibroblast growth factor receptors 1 to 4, and platelet-derived growth factor receptor (PDGFR) than other TKIs. We herein report a 77-year-old Japanese woman who received the minimum dose of lenvatinib for treatment of hepatocellular carcinoma. Within one month of starting treatment, she developed severe proteinuria, hypertension, and renal dysfunction. A kidney biopsy showed drug-induced thrombotic microangiopathy, podocytopathy, and polar vasculosis. We also observed damage to the renal tubules, where PDGFR is located. To our knowledge, this is the first report of lenvatinib-induced damage to the renal tubules.

Mendelson's syndrome complicated by bacterial aspiration pneumonia triggered by right putamen bleeding: A case report.

We present the case of an 80-year-old woman with Mendelson's syndrome complicated by bacterial aspiration pneumonia caused by consciousness loss followed by vomiting resulting from putamen bleeding. Her condition worsened rapidly to develop respiratory failure, within a few hours; thereafter, she was intubated. Streptococcus agalactiae and Klebsiella oxytoca were detected from the aspirated sputum sample culture. She was diagnosed with acute respiratory distress syndrome with Mendelson's syndrome complicated by bacterial aspiration pneumonia. Corticosteroid and antibiotic administration improved her condition and led to successful extubation; therefore, these treatment modalities were invaluable. We suggest the clinical considerations for the corticosteroid and antibiotic use in such cases.

Solid pseudopapillary neoplasm of the pancreas in a young male with main pancreatic duct dilatation: A case report.

BACKGROUND: Solid pseudopapillary neoplasms (SPNs) are rare tumors of the pancreas. Typically, they occur in young females, often have characteristic imaging features, such as cystic components and calcification, and have few effects on the pancreatic duct. CASE SUMMARY: A 31-year-old man was admitted to our hospital with the chief complaint of epigastric pain. There was only mild tenderness in his upper abdomen, and blood tests showed only a slight increase in alkaline phosphatase. Contrast-enhanced computed tomography showed a 40-mm-diameter, hypovascular mass in the head of the pancreas, and the main pancreatic duct upstream of the mass was severely dilated. Magnetic resonance imaging showed low intensity on T1-weighted images, with high intensity on T2-weighted image in some parts. Pancreatic ductal adenocarcinoma was the primary differential diagnosis. Portal vein infiltration could not be ruled out, so this case was a candidate for neoadjuvant chemotherapy. Subsequently, endoscopic ultrasound-guided fine needle aspiration was performed, and pathological evaluation and immunostaining suggested a diagnosis of SPN. Thus, pancreatoduodenectomy was performed. One year after the operation, the patient is alive with no recurrence. CONCLUSION: Main pancreatic duct dilatation is usually a finding of suspected pancreatic cancer. However, pancreatic duct dilatation can occur in SPN depending on the location and growth speed. Therefore, SPN should be considered in the differential diagnosis of tumors with pancreatic duct dilatation, and pathological evaluation by endoscopic ultrasound-guided fine needle aspiration should be actively performed.

Optically Active Helical Lanthanide Complexes: Storable Chiral Lewis Acidic Catalysts for Enantioselective Diels-Alder Reaction of Siloxydienes.

Lanthanide triflates and a series of hexadentate chiral ligand complexes were synthesized. X-ray-quality crystals were obtained from mixtures of the lanthanide complexes, which were helical in shape. The complexes showed Lewis acidity and catalyzed the enantioselective Diels-Alder reaction of electron-rich siloxydienes. The complexes were stable enough to be stored at ambient temperature on a laboratory bench and retained their Lewis acidity even after a month.

Scaffold-fused riboregulators for enhanced gene activation in Synechocystis sp. PCC 6803.

Cyanobacteria are an attractive host for biofuel production because they can produce valuable chemical compounds from CO2 fixed by photosynthesis. However, the available genetic tools that enable precise gene regulation for the applications of synthetic biology are insufficient. Previously, we engineered an RNA-based posttranscriptional regulator, termed riboregulator, for the control of target gene expression in cyanobacterium Synechocystis sp. PCC 6803. Moreover, we enhanced the gene regulation ability of the riboregulators in Escherichia coli by fusing and engineering a scaffold sequence derived from naturally occurring E. coli noncoding small RNAs. Here, we demonstrated that the scaffold sequence fused to the riboregulators improved their gene regulation ability in Synechocystis sp. PCC 6803. To further improve gene regulation, we expressed an exogenous RNA chaperone protein that is responsible for noncoding small RNA-mediated gene regulation, which resulted in higher target gene expression. The scaffold sequence derived from natural E. coli noncoding small RNAs is effective for designing RNA-based genetic tools and scaffold-fused riboregulators are a strong RNA-tool to regulate gene expression in cyanobacteria.

Improving the gene-regulation ability of small RNAs by scaffold engineering in Escherichia coli.

Noncoding small RNAs are involved in transcriptional and post-transcriptional gene regulation of target mRNAs by modulating mRNA elongation, stability, or translational efficiency. Many natural trans-encoded small RNAs contain a scaffold that allows binding of the RNA chaperone protein Hfq for conditional gene regulation. Here, we improved the gene regulation abilities of small RNAs by directly fusing the natural Escherichia coli trans-encoded small RNA-derived scaffolds, including Hfq-binding and rho-independent transcription terminator sequences, to the 3' end of the small RNAs that mediate RNA-based gene regulation. As target small RNAs to improve their gene regulation abilities, we selected small RNAs of artificial post-transcriptional riboregulators and transcriptional attenuators. Four different small RNA scaffolds were fused to the riboregulator and attenuator-derived small RNAs. Mutations were introduced into the best small RNA scaffold to improve its gene-regulation ability further. As a result, mutations predicted to stabilize the secondary structures of the small RNA scaffolds dramatically increased its ability to regulate gene expression of both the post-transcriptional riboregulator and transcriptional attenuator systems. We believe our engineered small RNA scaffolds are applicable to other RNA regulators for improving regulatory activity, and engineered small RNA scaffolds may present a valuable strategy to regulate target gene expression strongly.

Design of riboregulators for control of cyanobacterial (Synechocystis) protein expression.

Cyanobacteria are attractive host bacteria for biofuel production because they can covert CO2 to biofuel lipids using only sunlight, water, and inorganic ions. For genetically engineering an ideal cyanobacterium, a synthetic biological approach is promising but few genetic components have been characterized in cyanobacteria. Here for controlling cyanobacterial protein expression, we constructed riboregulators, that one of the post-transcriptional regulators composed of RNAs. Riboregulators harboring a ribosome-binding site suitable for Synechocystis sp. were designed by trial and error using Escherichia coli as host bacteria. The designed riboregulators were effective in Synechocystis sp. as well as E. coli with slight interference on growth only observed in E. coli. They will therefore be useful tools for controlling target gene expression.