Development of Cu application using dual-energy computed tomography for detecting medication-related osteonecrosis of the jaw.

INTRODUCTION: The present study developed an application using dual-energy computed tomography (DECT) focused on Cu for detecting medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: First, we performed two types of phantom studies using a Cu wire syringe and pig mandible with Cu wire to detect Cu on DECT. Second, DECT examinations of 44 patients with MRONJ were performed to compare lesion and normal bone sites using single-energy CT, DECT-virtual non-calcium (VNCa), and DECT-Cu applications. Quantitative analyses of VNCa CT and CT values were performed, and a cut-off value was calculated using receiver operating characteristic analysis. Third, we compared the Cu content in the MRONJ and normal bone groups using inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: The material-specific differences in attenuation between the two different energies enabled the accurate separation of Cu from Ca in phantom studies. The sensitivity and specificity for single-energy CT, DECT-VNCa, and DECT-Cu applications were 97.7% and 2.3%, 86.4% and 81.8%, and 88.6% and 97.7%, respectively. Thus, VNCa CT values obtained on DECT-Cu application images showed the highest area under the curve value and maximal diagnostic efficacy in differentiating lesion sites from normal bone sites. On ICP-AES analyses, the Cu content was significantly higher in the MRONJ group than in the normal bone group. CONCLUSION: DECT-Cu application demonstrated better diagnostic performance in detecting MRONJ compared with single-energy CT or DECT-VNCa.

Chiral Benzo[b]silole-Fused 9,9'-Spirobi[fluorene]: Synthesis, Chiroptical Properties, and Transformation to π-Extended Polycyclic Arene.

Chiral spiro π-conjugated compounds have emerged as a new class of circularly polarized luminescent organic materials. Here we report the synthesis and (chir)optical properties of a chiral benzo[b]silole-fused 9,9'-spirobi[fluorene] (SBF) and π-extended spiro polycyclic arene. The benzo[b]silole-fused SBF was successfully synthesized by a rhodium-catalyzed intramolecular silylative cyclization. It was further transformed to the chiral π-extended spiro polycyclic arene by an annulative π-extension reaction. Less effective spiroconjugation was observed for these spiro compounds through UV-Vis absorption spectroscopy and theoretical calculations. They exhibit circularly polarized luminescence with the dissymmetry factors of up to 0.76×10-3 . Theoretical calculations demonstrate that emission of the benzo[b]silole-fused SBF occurs from one subunit, the structure of which is slightly different from that in the Frank-Condon state.

Alzheimer-type dementia prediction by sparse logistic regression using claim data.

This study aimed to predict the risk of Alzheimer-type dementia for persons aged over 75 years old without receiving long-term care services using regularly collected claim data. A refined dataset including 48,123 persons was prepared from claim data of health insurance and long-term care insurance in a large city in the metropolitan area in Japan. The utilized features include the age and sex of subjects, 502 diseases based on ICD-10 diagnosis codes, and 107 prescription drugs based on therapeutic classes. The most important challenge in this work was feature selection form a large number of features. We adopted sparse logistic regression models with L0 regularization (SLR-L0) and L1 regularization (SLR-L1) as classification models based on machine learning. These regularizations enable feature selection by estimating sparse solution of non-zero coefficients in the model optimization. Predictions were performed by integrating 100 predictors trained by bootstrap samples. As a result, the area under the ROC curves (AUCs) were 0.663 for SLR-L0 and 0.660 for SLR-L1. These performances were similar, however, the average numbers of selected features were 13 out of a total of 611 for SLR-L0 and 253 for SLR-R1. The results indicate that SLR-L1 tended to include less useful features, whereas SLR-L0 narrowed down influential features. SLR-L0 might be more useful than SLR-L1 for practical use or the discussion of risk factors with medical experts.

Solvent-sensitive circularly polarized luminescent compounds bearing a 9,9'-spirobi[fluorene] skeleton.

A series of chiral 9,9'-spirobi[fluorene] (SBF) derivatives with diphenylamino donor and cyano acceptor units were designed as a new family of circularly polarized luminescent materials. The designed SBF derivatives were successfully synthesized from 7,7'-dibromo-9,9'-spirobi[fluorene]-2,2'-diol. No racemization occurred in the synthetic sequence. Therefore, each enantiomer of the SBF derivatives can be prepared from the enantiomerically pure starting material. Absorption and fluorescence spectroscopy and theoretical calculations revealed that the phenylene linker between the donor/acceptor units and the SBF core has a great impact on their photophysical properties. In particular, the phenylene linker was found to induce a red shift in their emission bands. The obtained chiral SBF derivatives exhibited solvent-dependent circularly polarized luminescence owing to their donor-π-acceptor structures.

Wearable and low-stress ambulatory blood pressure monitoring technology for hypertension diagnosis.

We propose a highly wearable, upper-arm type, oscillometric-based blood pressure monitoring technology with low-stress. The low-stress is realized by new developments in the hardware and software design. In the hardware design, conventional armband; cuff, is almost halved in volume thanks to a flexible plastic core and a liquid bag which enhances the fitness and pressure uniformity over the arm. Reduced air bag volume enables smaller motor pump size and battery leading to a thinner, more compact and more wearable unified device. In the software design, a new prediction algorithm enabled to apply less stress (and less pain) on arm of the patient. Proof-of-concept experiments on volunteers show a high accuracy on both technologies. This paper mainly introduces hardware developments. The system is promising for less-painful and less-stressful 24-hour blood pressure monitoring in hypertension managements and related healthcare solutions.

Insulin sensitization by a novel partial peroxisome proliferator-activated receptor γ agonist with protein tyrosine phosphatase 1B inhibitory activity in experimental osteoporotic rats.

The pharmacological profile of (S)-7-(2-{2-[(E)-2-cyclopentylvinyl]-5-methyloxazol-4-yl}-ethoxy)-2-[(2E,4E)-hexadienoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (KY-201), a peroxisome proliferator-activated receptor (PPAR) γ agonist, was compared with that of rosiglitazone in ovariectomized rats. The serum triglyceride and non-esterified fatty acid reducing effects of KY-201 at 3 and 10 mg/kg per day for 6 weeks were similar to those of rosiglitazone despite its weaker PPARγ agonistic activity. KY-201 had no effects on body weight gain, blood volume, or heart and adipose weights, while rosiglitazone at 10 mg/kg per day increased them. KY-201 had few effects on bone mineral density (BMD) or fat in marrow (FM), whereas rosiglitazone strongly decreased BMD and increased FM. The PPARγ agonistic activity of KY-201 was weaker than that of rosiglitazone in ST-2 cells, and KY-201 reduced osteoblast differentiation and increased adipocyte differentiation less potently than rosiglitazone in rat bone marrow-derived mesenchymal stem cells. KY-201, but not rosiglitazone inhibited protein tyrosine phosphatase 1B (PTP1B) and increased phosphorylation of the insulin receptor in HepG2 cells. These results suggest that the hypolipidemic effects of KY-201 are similar to those of rosiglitazone, but with less adverse effects, due to the combination of PPARγ partial activation and PTP1B inhibition. KY-201 would be useful for treatments of diabetic patients at high risk of osteoporosis, cardiovascular disease, and/or obesity.

Subarachnoid-subarachnoid bypass: a new surgical technique for posttraumatic syringomyelia.

OBJECT: The origin of posttraumatic syringomyelia is not completely understood. With respect to posttraumatic syringomyelia, the optimum management strategy for patients with spinal cord injury has also not been established. The authors hypothesized that reconstruction of the subarachnoid channels would reestablish CSF flow, thereby addressing the underlying cause of the syrinx formation. The authors performed a new type of surgery, subarachnoid-subarachnoid bypass (S-S bypass), in which an attempt was made to reestablish normal CSF circulation around the spinal cord. The purpose of this study was to evaluate the effectiveness of S-S bypass for posttraumatic syringomyelia. METHODS: Twenty consecutive patients with symptomatic posttraumatic syringomyelia who had progressive neurological symptoms and underwent S-S bypass were included in the study. The surgical procedure was as follows: a laminectomy was performed at the level of trauma, and a midline dural opening was made under a microscope. The arachnoid was exposed up to the area of normal arachnoid mater with normal CSF circulation. After dissection of the normal arachnoid mater at the cephalic and caudal sites, 1 or 2 tubes made of medical-grade silicone were inserted into the cephalic and caudal ends of the normal subarachnoid space. Bypass tubes were laid in the subdural space, and a watertight dural closure was accomplished using running sutures. The mean follow-up period was 48.2 months (range 12-93 months). The preoperative status and postoperative clinical course were assessed according to 3 grading systems: the Frankel grading system for global neurological status, the American Spinal Injury Association motor score for motor weakness, and the Klekamp system for bladder function. The major presenting symptoms or signs were assessed in terms of symptom improvement, stabilization, or deterioration. Preoperative and postoperative MRI was used to analyze the size and craniocaudal extension of the cavity. RESULTS: Twelve patients showed clinical improvement, 4 were stable, and 4 showed deterioration. The mean length of the syrinx observed on preoperative MRI was 9.9 spinal levels, and the mean Vaquero index was 62.3%. The mean length of the syrinx observed on postoperative MRI was 5.3 spinal levels, and the mean Vaquero index was 28.4%. These values were significantly lower than the preoperative values (p = 0.01 and p < 0.01, respectively). CONCLUSIONS: This study showed that interference with CSF flow was the major cause of syrinx development and that reconstruction of CSF flow is the most important treatment strategy based on the cause of the syrinx. Subarachnoid-subarachnoid bypass, which can be performed without myelotomy, was not only a safe and effective surgical technique, but may also be a more physiological way of treating posttraumatic syringomyelia.

Inhibitory effects of osemozotan, a serotonin 1A-receptor agonist, on methamphetamine-induced c-Fos expression in prefrontal cortical neurons.

Psychostimulants induce hyperlocomotion in normal subjects, although, they are effective in producing a calming effect in hyperactive subjects. This paradoxical effect has been related to changes in serotonin (5-HT) neurotransmission in hyperactive dopamine transporter-knockout mice. In addition, we observed that hyperlocomotion in mice lacking pituitary adenylate cyclase-activating polypeptide was attenuated by amphetamine dependent on 5-HT(1A) receptor signaling and that amphetamine, when co-administered with a 5-HT(1A) agonist, produced a calming effect in wild-type mice. Here, in an attempt to address how 5-HT(1A) receptor signaling exerts the calming action of psychostimulants, we examined c-Fos expression in several brain regions after administration of methamphetamine and osemozotan, a selective 5-HT(1A) receptor agonist. The number of c-Fos-positive cells was increased in the medial prefrontal cortex, striatum and nucleus accumbens in methamphetamine (3 mg/kg body weight)-injected mice. Osemozotan (1 mg/kg) significantly reduced the methamphetamine-induced c-Fos expression in the medial prefrontal cortex and striatum, but not in the nucleus accumbens. This osemozotan action was completely blocked by the 5-HT(1A) receptor antagonist WAY-100635 (1 mg/kg). As the prefrontal cortex is considered to be involved in the beneficial actions of psychostimulant medications for attention-deficit/hyperactivity disorder, the present result showing 5-HT(1A)-mediated inhibition of corticostriatal activity may partly be related to this psychostimulant action.

An antihyperkinetic action by the serotonin 1A-receptor agonist osemozotan co-administered with psychostimulants or the non-stimulant atomoxetine in mice.

It has been demonstrated that treatment of hyperactive mice with psychostimulants produced a calming effect depending on serotonergic neurotransmission. Our previous study also showed that hyperactivity in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) was ameliorated by amphetamine in a serotonin (5-HT)(1A)-dependent manner and that amphetamine calmed wild-type mice given the 5-HT(1A) agonist 8-OH-DPAT. Here, we examined if 5-HT(1A)-mediated pathways can be a determinant of the action of other psychostimulants as well as the non-stimulant atomoxetine by examining locomotor activity in mice co-administered with the 5-HT(1A) agonist osemozotan. Co-administration of osemozotan with either methamphetamine or amphetamine was not only antihyperkinetic, but also decreased locomotion to below basal levels. In contrast, osemozotan just nullified methylphenidate-induced hyperactivity. The non-stimulant atomoxetine did not induce hyperactivity, but co-administration of atomoxetine with osemozotan produced a calming effect. The adjunctive effect of osemozotan added to the psychostimulants was blocked by the 5-HT(1A) antagonist WAY-100635 at a low dose (0.1 mg/kg), suggesting the involvement of a presynaptic 5-HT(1A)-mediated mechanism. However, WAY-100635 (up to 1 mg/kg) did not block the effect of atomoxetine plus osemozotan. The present results may provide insights into the therapeutic mechanisms of the psychostimulants and atomoxetine for hyperkinetic disorders.

[Case with renal pelvic carcinoma with giant hydronephrosis].

A 62-year-old man consulted us for further examination of left giant hydronephrosis which was accidentally found by abdominal ultrasonography. The patient chose observation instead of left nephrectomy. One year later, he re-visited us with a complaint of sudden abdominal pain. Computed tomography (CT) revealed left giant hydronephrosis containing high-density fluid which was suspected of hemorrhage in the renal pelvis. Percutaneous nephrostomy yielded discharge of 7000 ml of hemorrhagic fluid and urine cytology revealed class V. Systemic examination by CT and magnetic resonance imaging (MRI) showed renal pelvic tumors in the left kidney as well as multiple metastatic lesions in the lung, liver and bone. Pathological examination of the left renal pelvic tumors obtained by biopsy showed high-grade urothelial carcinoma. Although systemic and intra-arterial chemotherapy showed partial response in the metastatic lesions, he died of cancer 1 year and 3 months after the first diagnosis.

Enhanced salt tolerance mediated by AtHKT1 transporter-induced Na unloading from xylem vessels to xylem parenchyma cells.

AtHKT1 is a sodium (Na+) transporter that functions in mediating tolerance to salt stress. To investigate the membrane targeting of AtHKT1 and its expression at the translational level, antibodies were generated against peptides corresponding to the first pore of AtHKT1. Immunoelectron microscopy studies using anti-AtHKT1 antibodies demonstrate that AtHKT1 is targeted to the plasma membrane in xylem parenchyma cells in leaves. AtHKT1 expression in xylem parenchyma cells was also confirmed by AtHKT1 promoter-GUS reporter gene analyses. Interestingly, AtHKT1 disruption alleles caused large increases in the Na+ content of the xylem sap and conversely reduced the Na+ content of the phloem sap. The athkt1 mutant alleles had a smaller and inverse influence on the potassium (K+) content compared with the Na+ content of the xylem, suggesting that K+ transport may be indirectly affected. The expression of AtHKT1 was modulated not only by the concentrations of Na+ and K+ but also by the osmolality of non-ionic compounds. These findings show that AtHKT1 selectively unloads sodium directly from xylem vessels to xylem parenchyma cells. AtHKT1 mediates osmolality balance between xylem vessels and xylem parenchyma cells under saline conditions. Thus AtHKT1 reduces the sodium content in xylem vessels and leaves, thereby playing a central role in protecting plant leaves from salinity stress.

Intraoperative measurements of nerve root blood flow during discectomy for lumbar disc herniation.

STUDY DESIGN: Nerve root blood flow was intraoperatively measured before and after discectomy for lumbar disc herniation and compared with clinical features. OBJECTIVE: To investigate the relation between nerve root blood flow changes and symptoms associated with lumbar disc herniation. SUMMARY OF BACKGROUND DATA: Several authors have reported that recovery of intraneural blood flow, which restores the supply of oxygen and other nutrients to the nerve tissue, is strongly related to the rapid improvement of nerve function after discectomy for lumbar disc herniation. However, no previous study has quantitatively assessed blood flow in the human nerve root. METHODS: Nerve root blood flow was monitored in 21 patients with lumbar disc herniation using laser Doppler flowmetry (ALF 21 N; ADVANCE, Tokyo, Japan) during discectomy. Possible correlations were investigated between the blood flow rates and the following clinical features: age, duration of sciatica, presence or absence of neurologic deficits, latency to pain relief, and morphology of herniated discs. RESULTS: The blood flow rate in 16 patients who reported immediate relief after discectomy was much greater than in 5 patients whose pain was not relieved immediately after surgery (141% 8%, = 0.0364). The increase in the blood flow rate after discectomy was five times greater in patients with neurologic deficits than in patients without neurologic deficits (158% 36%, = 0.0638). CONCLUSIONS: The results of the current study suggest that immediate relief from pain and resolution of neurologic deficits soon after surgery are the result of early recovery from nerve root ischemia after discectomy, and that ischemia caused by mechanical nerve root compression is mainly related to the mechanisms underlying sciatic pain production and neurologic deficits.

Altered shoot/root Na+ distribution and bifurcating salt sensitivity in Arabidopsis by genetic disruption of the Na+ transporter AtHKT1.

Sodium (Na+) is toxic to most plants, but the molecular mechanisms of plant Na+ uptake and distribution remain largely unknown. Here we analyze Arabidopsis lines disrupted in the Na+ transporter AtHKT1. AtHKT1 is expressed in the root stele and leaf vasculature. athkt1 null plants exhibit lower root Na+ levels and are more salt resistant than wild-type in short-term root growth assays. In shoot tissues, however, athkt1 disruption produces higher Na+ levels, and athkt1 and athkt1/sos3 shoots are Na+-hypersensitive in long-term growth assays. Thus wild-type AtHKT1 controls root/shoot Na+ distribution and counteracts salt stress in leaves by reducing leaf Na+ accumulation.

Intestinal obstruction in autosomal dominant polycystic kidney disease.

A 42-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital on April 29, 1999, with complaints of abdominal pain. A diagnosis of intestinal obstruction was reached on the basis of clinical findings and X-ray evidence. A computed tomography scan of the abdomen showed massively enlarged kidneys, especially the right kidney, which seemed to compress the small intestine. The patient underwent percutaneous aspiration of the largest cysts on the surface of the right kidney. The symptoms, in this rare case of intestinal obstruction by an enlarged kidney in ADPKD, were alleviated the day after the aspiration procedure.