Successful Termination of Insulin Therapy in Transient Neonatal Diabetes Mellitus.

A sensor-augmented pump (SAP) therapy is used to treat neonatal diabetes mellitus (NDM). We treated a case for which SAP therapy was successful and prevented hypoglycemia. The patient was a baby boy who was small for his gestational age. He had hyperglycemia at 4 days of age, and a diagnosis of NDM had previously been made at another hospital. A continuous intravenous insulin infusion was initiated. At 29 days of age, the patient was transferred to our hospital for further treatment. SAP therapy was initiated at 39 days, which was successful and prevented hypoglycemia. Gradually, blood glucose levels improved. The insulin infusion was stopped to determine if any potential pump issues arose prior to discharge; the patient's blood glucose level did not increase. The decision was therefore made to discharge the patient from the hospital at 58 days of age with discontinued insulin. After discharge, genetic analysis showed hypomethylation on one of the alleles within 6q24, leading to a diagnosis of 6q24-related diabetes mellitus. Although almost all 6q24-related NDM cases are transient, no evidence exists for the appropriate timing of insulin discontinuation. Retrospective continuous glucose monitoring (CGM) analysis showed improved standard deviation (SD) values as well as improved blood glucose variability. This experience suggested SD values of CGM may be used as an index for tapering and discontinuing insulin in SAP therapy. However, future collaborative studies at other centers that focus on SD values as a guide for insulin discontinuation in SAP are required.

Prediction of delayed union of tibial shaft fracture treated with intramedullary nailing: multicenter-study analysis and literature review -the TRON study.

PURPOSE: We aimed to 1) identify predictors of delayed and nonunion of tibial shaft fractures in patients treated with intramedullary nailing (IMN), including patient demographics and surgical factors, and 2) determine whether the nail/shaft ratio is associated with delayed and nonunion. METHODS: This retrospective, multicenter study included 315 patients with tibial shaft fracture treated with IMN between 2014 and 2019 and excluded patients with insufficient follow-up for 12 months, lost data and inadequate radiographs. Finally, we analyzed 258 patients (184 males; 74 females). Main outcome measurements were delayed union at 6 and nonunion at 12 months after surgery as determined on anteroposterior and lateral radiographs. We extracted the following as risk factors of delayed and nonunion: age, sex, BMI, fracture site, fracture type, injury energy, smoking history, and nail/shaft ratio. We conducted logistic regression analysis to investigate risk factors of delayed and nonunion using these extracted items as explanatory variables. RESULTS: Type C fracture was independently associated with delayed union (odds ratio 2.9, 95% confidential interval: 1.04-8.09, P = 0.04). Nail/shaft ratio was not an independent factor of delayed union. No independent explanatory factors were related to nonunion. CONCLUSIONS: Type C fractures, which were unstable and fragmented, was associated with delayed union in tibia fractures treated with IMN, whereas nail thickness was not associated with delayed or nonunion fractures.

Aphasia testing (auditory comprehension domain) using a new eye-tracking system in healthy participants.

Sakai R, Koike Y, Saito K, Matsunaga T, Shimada Y, Miyakoshi N. Aphasia testing (auditory comprehension domain) using a new eye-tracking system in healthy participants. Jpn J Compr Rehabil Sci 2022; 13: 31-35. Objective: We administered a conventional pointing-method test with eye-tracking to evaluate items associated with auditory comprehension and examined the concordance between the obtained results. Methods: The enrolled participants were 10 healthy volunteers. We performed tests after extracting auditory comprehension items from the SLTA, the WAB, and the Supplementary tests for the SLTA using the eye-tracking system and the pointing method. Results: The mean test duration was 9 min 51 s ± 1 min 41 s (mean ± SD), and the percentage of correct answers was 100% and in perfect agreement for the pointing method and the eye-tracking system. The mean response time was 0.96 ± 0.36 s for the pointing method and -0.39 ± 0.21 s for the eye-tracking system. Hence, the latter was faster than the former, and examinees completed their responses before listening to the end of the questions. Conclusion: The new eye-tracking system makes it possible to perform aphasia tests (auditory comprehension items) comparable to the conventional pointing method.

Early versus delayed weight bearing after intramedullary nailing for tibial shaft fracture: A multicenter, propensity score-matched study, the TRON study.

OBJECTIVES: The purpose of this multicenter study was to assess the differences in the rates of implant failure and bone union by X-ray examination, and walking ability between an early weight-bearing group (EWB) and a non-weight-bearing group (NWB) following treatment with intramedullary nailing (IMN) for tibial shaft fractures with a propensity score-matching method. MATERIAL AND METHODS: We collected data from 336 patients with tibia fractures that were treated surgically. We excluded patients lost to follow-up and polytrauma patients. Finally, 263 patients were included who were divided into two groups, the early weight-bearing (EWB) group, in which partial weight-bearing walking within four weeks was encouraged, and a non-weight-bearing (NWB) group, in which no weight bearing was allowed for more than four weeks. To adjust for baseline differences between groups, a propensity score algorithm was used to match the EWB group with the NWB group in a 1:1 ratio of 75 cases each. After matching, we compared the rate of implant failure, the rate of bone union at six months and one year after surgery, and walking ability at the last follow-up between the two groups. RESULT: Implant failure occurred in 0 of 75 patients in the EWB group vs. 1 of 75 in the NWB group (P = 1.0). Delayed bone union at six months occurred in 20 of 75 (26%) vs. 13 of 75 (17%) patients, and that at one year occurred in 5 of 75 (6.7%) vs. 3 of 75 (4%) patients. The median New Mobility Score was 9 (4-9) vs. 9 (0-9) points. CONCLUSIONS: There were no statistically significant differences in the rate of implant failure, the rates of the bone union at six months and one year after surgery, and walking ability between the EWB group and NWB group. We suggest that instruction in early weight-bearing after IMN nailing for tibial shaft fracture may not be harmful.

Toki-to protects dopaminergic neurons in the substantia nigra from neurotoxicity of MPTP in mice.

Parkinson's disease (PD) is a neurodegenerative disease of the brain characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). No clinically proven drugs that may halt or retard the progression of PD have been reported. This study examined the anti-PD effect of a traditional Japanese/Chinese herbal remedy Toki-to (TKT) using mice treated with a neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP). TKT showed improvement of MPTP-induced PD-like symptoms (bradykinesia) in a behavioral test (pole test). Histological studies of SNs from these mice demonstrated that TKT had a protective effect on dopaminergic neurons against MPTP neurotoxicity. Real-time RT-PCR analyses of mRNA from SNs demonstrated that expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) genes were decreased by MPTP treatment and that these decreases were reversed by TKT administration prior to MPTP treatment. DNA microarray analyses indicated that TKT per se suppressed gene expression of serum- and glucocorticoid regulated kinase (SGK) that is believed to be a molecule that drives the pathogenesis of PD. Hence, it is suggested that TKT may inhibit the activation of SGK at the transcriptional level and thusmay participate in halting the progression of MPTP-induced neurotoxicity.

Restoration of FcRgamma/Fyn signaling repairs central nervous system demyelination.

Disruption of myelin causes severe neurological diseases. An understanding of the mechanisms that control myelination and remyelination is needed to develop therapeutic strategies for demyelinating diseases such as multiple sclerosis (MS). Our previous finding indicating the critical involvement of the gamma chain of immunogloblin Fc receptors (FcRgamma) and Fyn signaling in oligodendrocyte differentiaion and myelination demands a fundamental revision of the strategies used for MS therapy, because antigen-antibody complexes in MS patients may induce the direct dysregulation of myelination process as well as the inflammatory destruction of myelin sheath. Here we show that the FcRgamma/Fyn signaling cascade is critically involved in cuprizone-induced demyelination/remyelination, with no lymphocytic response. The levels of phosphorylated myelin basic proteins (p-MBPs), especially the 21.5-kDa isoform, but not the levels of total MBPs, decreased markedly during demyelination induced by aging, cuprizone treatment, and double knockout of FcRgamma/Fyn genes. We also showed that the recovery from demyelination in cuprizone-treated and aged mice is achieved after administration of the herbal medicine Ninjin'yoeito, an effective therapy targeting the FcRgamma/Fyn-Rho (Rac1)-MAPK (P38 MAPK)-p-MBPs signaling cascade. These results suggest that the restoration of FcRgamma/Fyn signaling represents a new approach for the treatment of demyelinating diseases.