Surgical Treatment for Congenital Kyphosis Correction Using Both Spinal Navigation and a 3-dimensional Model

An 11 year-old girl had 66 degrees of kyphosis in the thoracolumbar junction. For the purpose of planning for kyphosis correction, we created a 3-D, full-scale model of the spine and consulted spinal navigation. Three-dimensional models are generally used as tactile guides to verify the surgical approach and portray the anatomic relations specific to a given patient. We performed posterior fusion from Th10 to L3, and vertebral column resection of Th12 and L1. Screw entry points, directions, lengths and diameters were determined by reference to navigation. Both tools were useful in the bone resection. We could easily detect the posterior element to be resected using the 3D model. During the anterior bony resection, navigation helped us to check the disc level and anterior wall of the vertebrae, which were otherwise difficult to detect due to their depth in the surgical field. Thus, the combination of navigation and 3D models helped us to safely perform surgery for a patient with complex spinal deformity

15-Deoxy-Δ12,14-prostaglandin J2 inhibits IL-1β–induced cyclooxygenase-2 expression in mesangial cells

15-Deoxy-Δ12,14-prostaglandin J2 inhibits IL-1β–induced cyclooxygenase-2 expression in mesangial cells.BackgroundCyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, is induced in mesangial cells in response to proinflammatory cytokines. Recently, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the natural ligands of peroxisome proliferator-activated receptor γ (PPARγ), has been reported to have an anti-inflammatory effect. Therefore, we examined the effect of 15d-PGJ2 on COX-2 expression in cultured rat mesangial cells.MethodsMesangial cells were incubated with 15d-PGJ2 for 30 minutes and then exposed to interleukin-1β (IL-1β). The expression of COX-2 mRNA and proteins was determined by Northern blot and immunoblot analyses, respectively. Accumulation of prostaglandin E2 (PGE2) was measured by an enzyme-linked immunosorbent assay (ELISA). Activities of mitogen-activated protein kinases (MAPKs) were evaluated by an immunoblot analysis. DNA binding activities of activator protein-1 (AP-1) or nuclear factor-κB (NF-κB) were examined by an electrophoretic mobility shift assay (EMSA). The activities of PPAR responsive elements (PPRE) and COX-2 promoter were measured by a luciferase reporter assay.Results15D-PGJ2 significantly suppressed IL-1β–induced COX-2 expression and PGE2 production, but thiazolidinediones, synthetic PPARγ ligands, did not affect COX-2 expression. Moreover, the cells transfected with a PPRE luciferase reporter did not respond to 15d-PGJ2. IL-1β rapidly activated extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), which were involved in the up-regulation of COX-2 induction, but 15d-PGJ2 inhibited the activation of these kinases. 15d-PGJ2 inhibited the IL-1β–induced increase in binding activities of nuclear proteins to consensus AP-1 site and AP-1–like site of COX-2 promoter but not of NF-κB. IL-1β was unable to activate the COX-2 promoter when the AP-1–like site was mutated.ConclusionsThese data suggest that 15d-PGJ2 inhibits IL-1β–induced COX-2 expression, independent of PPARγ activation, by suppression of ERK and JNK pathways and AP-1 activation in mesangial cells. Thus, 15d-PGJ2 may play an important role in the negative feedback mechanism of COX-2 expression in renal inflammation and may be useful as an anti-inflammatory agent

Reactive 2-Quinolones Dearomatized by Steric Repulsion between 1-Methyl and 8-Substited Groups

Usual 1-methyl-2-quinolone (MeQone) derivatives are not reactive because of aromatic property in the heterocyclic ring. On the other hand, 8-substituted MeQones have been proved to be highly reactive, which is caused by steric repulsion between the 1-methyl and the 8-substituted groups. When 1-methyl-3,6,8-trinitro-2-quinolone was treated with potassium (or trimethylsilyl) cyanide, cyanation proceeded at the 4-position regioselectively as a result of cine-substitution. This reaction is initiated with addition of cyanide species, and the cyanoquinolone is formed by the protonation of the resultant anionic intermediate followed by elimination of nitrous acid. The high reactivity was maintained even when one of the nitro groups on the benzene moiety was replaced by a methyl group, which afforded corresponding cine-substituted products upon treatment with potassium cyanide

Promoter Polymorphism of RGS2 Gene Is Associated with Change of Blood Pressure in Subjects with Antihypertensive Treatment: The Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study

We performed a prospective study to examine the genetic effect on the response to a calcium (Ca) channel blocker, azelnidipine and an ACE inhibitor, temocapril treatment in patients with hypertension, as a part of the prior clinical trial, the Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study (ATTEST). Methods and Results. All subjects who gave informed consent for genetic research were divided into two groups: the subjects treated with azelnidipine or temocapril, for 52 weeks. We selected 18 susceptible genes for hypertension and determined their genotypes using TaqMan PCR method. RNA samples were extracted from peripheral blood, and quantitative real time PCR for all genes was performed using TaqMan method. One of the polymorphisms of the RGS2 gene was extracted as being able to influence the effect of these treatments to reduce BP. At eight weeks, BP change showed a significant interaction between the A-638G polymorphism of Regulator of G protein signaling-2 (RGS2) gene and treatment with azelnidipine or temocapril. There was no gene whose expression was associated with BP phenotypes or the polymorphisms of each gene. Conclusions. A-638G polymorphism of the RGS-2 gene could be a predictive factor for therapeutic performance of Ca channel blockers

Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats

Cerebral edema following cerebral infarction can be severe and directly affect mortality and mobility. Exercise therapy after cerebral infarction is an effective therapeutic approach; however, the molecular mechanism remains unclear. Myokines such as interleukin-1 receptor antagonist (IL-1RA) are released during skeletal muscle contraction with effects on other organs. We hypothesized that myokine release during exercise might improve brain edema and confirmed the hypothesis using transient middle cerebral artery occlusion (tMCAO) model rats. Rats subjected to tMCAO were divided according to the severity of illness and further assigned to exercise and non-exercise groups. Treadmill exercises were performed at a speed of 2–8 m/min for 10 min from 1–6 days post-reperfusion after tMCAO. Exercise significantly reduced edema and neurological deficits in severely ill rats, with a reduction in aquaporin-4 (AQP4) expression in the ischemic core and increased blood IL-1RA release from the stroke-unaffected hindlimb muscle after tMCAO. Administration of IL-1RA into the lateral ventricles significantly reduced edema and AQP4 expression in the ischemic core. In conclusion, treadmill exercise performed in the early phase of stroke onset alleviated the decrease in blood IL-1RA following ischemic stroke. IL-1RA administration decreased astrocytic AQP4 expression in the ischemic core, suppressing brain edema.Gono R., Sugimoto K., Yang C., et al. Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats. Journal of Cerebral Blood Flow and Metabolism, 43(5), 812-827. © 2023 SAGE Publishing. DOI: 10.1177/0271678X231151569

Prevalence of and Risk Factors for the Progression of Upper Cervical Lesions in Patients with Rheumatoid Arthritis

We investigated the prevalence of and risk factors for the progression of upper cervical lesions (UCLs) in patients with rheumatoid arthritis (RA). A retrospective analysis of 49 patients with RA (4 males, 45 females) was conducted. The UCLs included atlanto-axial subluxation and vertical subluxation. We investigated the clinical factors including the Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) and the modified Health Assessment Questionnaire-Disability Index as well as radiographic changes between the baseline (at May 2010 to April 2013) and final follow-up. Forty patients (81.6%) were classified as the non-progressive group, and the other 9 patients (18.4%) comprised the progressive group. The progressive group’s final CRP values, baseline or final MMP-3 levels, DAS28-CRP, and rate of pre-existing lesions at baseline were all significantly higher than those of the non-progressive group (p=0.017, p=0.043, p=0.002, p=0.008, p<0.001, and p=0.008 respectively). A multivariate logistic regression analysis demonstrated that DAS28-CRP at baseline was a risk factor for radiographic progression (p=0.018, odds ratio: 2.54, 95% confidence interval: 1.17-5.51). Our findings indicate that higher disease activity might influence the progression of UCLs in patients with RA

Transactive Relationship Phenomena

Healthcare for older adults is a significant problem in Japan and in other developed countries. To address this problem, healthcare robots, now realized, can assist and meet healthcare and welfare practice demands. The aim of this study was to clarify characteristics of Transactive Relationships (TR) in older adults, in care workers as intermediaries, and Pepper (Softbank Robotics Corporation) a robot equipped with the application program of Care Prevention Gymnastics Exercises for Pepper (Pepper-CPGE) made by Xing Company, Japan. Data were collected by observing TRs between Pepper and older patients in Kagawa Prefecture, Japan between from May 8 to August 1 2018. The Transactive Relationship Theory of Nursing (TRETON) was used to explain how Pepper-CPGE led the exercises with older adults as physical exercises. The role of Pepper-CPGE was to provide instructions for the older adults in performing gymnastic exercises. During the exercising activity, care workers were present to prevent falls of the older adults, and to operate and observe the video presentations by supporting and caring for the participants. In using Pepper-CPGE, it was possible to change the role of the healthcare providers, originally thought to contribute to increasing the quality of older adult care and their rehabilitation

PirB regulates asymmetries in hippocampal circuitry

Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B). By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI) proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB), an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry