Novel Screening Tool Using Non-linguistic Voice Features Derived from Simple Phrases to Detect Mild Cognitive Impairment and Dementia.

Appropriate intervention and care in detecting cognitive impairment early are essential to effectively prevent the progression of cognitive deterioration. Diagnostic voice analysis is a noninvasive and inexpensive screening method that could be useful for detecting cognitive deterioration at earlier stages such as mild cognitive impairment. We aimed to distinguish between patients with dementia or mild cognitive impairment and healthy controls by using purely acoustic features (i.e., nonlinguistic features) extracted from two simple phrases. Voice was analyzed on 195 recordings from 150 patients (age, 45-95 years). We applied a machine learning algorithm (LightGBM; Microsoft, Redmond, WA, USA) to test whether the healthy control, mild cognitive impairment, and dementia groups could be accurately classified, based on acoustic features. Our algorithm performed well: area under the curve was 0.81 and accuracy, 66.7% for the 3-class classification. Thus, our vocal biomarker is useful for automated assistance in diagnosing early cognitive deterioration.

Endothelin-1 Elicits TRP-Mediated Pain in an Acid-Induced Oral Ulcer Model.

Oral ulcer is the most common oral disease and leads to pain during meals and speaking, reducing the quality of life of patients. Recent evidence using animal models suggests that oral ulcers induce cyclooxygenase-dependent spontaneous pain and cyclooxygenase-independent mechanical allodynia. Endothelin-1 is upregulated in oral mucosal inflammation, although it has not been shown to induce pain in oral ulcers. In the present study, we investigated the involvement of endothelin-1 signaling with oral ulcer-induced pain using our proprietary assay system in conscious rats. Endothelin-1 was significantly upregulated in oral ulcers experimentally induced by topical acetic acid treatment, while endothelin-1 production was suppressed by antibacterial pretreatment. Spontaneous nociceptive behavior in oral ulcer model rats was inhibited by swab applications of BQ-788 (ETB receptor antagonist), ONO-8711 (prostanoid receptor EP1 antagonist), and HC-030031 (TRPA1 antagonist). Prostaglandin E2 production in the ulcers was suppressed by BQ-788. Mechanical allodynia in the model was inhibited not only by BQ-788 and HC-030031 but also by BQ-123 (ETA receptor antagonist), SB-366791 (TRPV1 antagonist), and RN-1734 (TRPV4 antagonist). In naive rats, submucosal injection of endothelin-1 caused mechanical allodynia that was sensitive to HC-030031 and SB-366791 but not to RN-1734. These results suggest that endothelin-1 production following oral bacterial invasion via ulcerative regions elicits TRPA1-mediated spontaneous pain. This pain likely occurs through an indirect route that involves ETB receptor-accelerated prostanoid production. Endothelin-1 elicits directly TRPA1- and TRPV1-mediated mechanical allodynia via both ETA and ETB receptors on nociceptive fibers. The TRPV4-mediated allodynia component seems to be independent of endothelin signaling. These findings highlight the potential of endothelin signaling blockers as effective analgesic approaches for oral ulcer patients.

Difference in voice analysis result by pre- and post- processing of telephone line.

The purpose of this study is to verify the impact of a deterioration of the sound quality of voice by a telephone line on estimating Vitality as the extent of depressive tendency based on voice analysis using MIMOSYS. First, the voices of about 1,000 people recorded using a recorder were prepared. Next, each voice was coded and resampled in preparation for transmission over a phone line. Vitalities obtained by analyzing the voices before and after these processes were compared. The results showed high correlation between the Vitality after coding and Vitality before coding, revealing that using a telephone would be an effective way to obtain voices.

Reconstruction of knee ligaments with a free tensor fascia lata myocutaneous flap transfer.

A 26-year-old woman suffered a grinding injury of the thigh and knee, resulting in the loss of a large amount of soft tissue and some of the femur. A contralateral tensor fascia lata myocutaneous free flap was used to reconstruct the soft tissues and the lateral ligament compartment around the knee. Later, a ceramic artificial bone was implanted. The patient was able to walk, and a stress radiograph showed that the implanted artificial bone and the knee joint were stable. There was no donor-site morbidity. The functional and cosmetic results were satisfactory.

Cranial-bone defects with depression deformity treated with ceramic implants and free-flap transfers.

Hydroxyapatite ceramic has many advantages in the treatment of cranial-bone defects. However, for large skull defects with severe depression deformities, it may be risky to use ceramic implants because an extradural dead space will be left and the overlying scalp will have to be closed under tension. In these cases microvascular free-flap transfers are a good solution. We have treated three patients for large skull defects with severe depression deformities after repeated local infections and several operations or irradiation. A latissimus dorsi myocutaneous flap was combined with a serratus anterior muscle flap to fill the extradural space under the ceramic implant in the first patient. A latissimus dorsi muscle flap was inserted under the ceramic implant in an irradiated site and a combined small serratus anterior muscle flap was used as a monitor in the second patient. A latissimus dorsi myocutaneous flap was used to cover the ceramic implant and fill the scalp defect in the third patient. The follow-up periods varied from 12 to 35 months (mean: 20.7 months). The clinical courses of all three patients were uneventful and no flap was lost. The extradural space can be reduced to some extent by making the ceramic implant slightly flatter or thicker, but in patients with severe depression deformities, whose brain expansion cannot be expected, a muscle flap should be transferred into the space.

Antinociceptive effect of U-50488H, a kappa-opioid agonist, in streptozotocin-induced diabetic mice.

We compared the antinociceptive activity of a kappa-opioid agonist, U-50488H, in streptozotocin-induced diabetic mice with that in non-diabetic mice. Subcutaneously administered U-50488H (3 and 10 mg kg(-1)) showed a more potent antinociceptive effect, as evaluated by the tail-pressure method, in diabetic mice than in non-diabetic mice. Increased antinociceptive activity of U-50488H observed in diabetic mice was also observed in mice given U-50488H intrathecally (3 and 10 microg). However, there were no differences observed between diabetic and non-diabetic mice given U-50488H intracerebroventricularly (3 and 10 microg). Although the antinociceptive effect of U-50488H (3 mg kg(-1), s.c.) in non-diabetic mice was increased by treatment with PD135158 (100 ng, i.c.v.), a cholecystokininB (CCKB) antagonist, the antinociceptive activity of U-50488H which was enhanced in diabetic mice was not influenced by PD135158. Moreover, the increased antinociceptive activity of U-50488H (3 mg kg(-1), s.c.) in diabetic mice diminished when desulfated octapeptide of cholecystokinin (3-100 ng, i.c.v.), a CCKB agonist, was administered. These results suggested that diabetic mice were selectively hyper-responsive to spinal kappa-opioid receptor-mediated antinociception. The function of the analgesia inhibitory system in which cholecystokinin is used as a transmitter might be diminished in diabetic mice.

Mandibular contour reconstruction with three-dimensional computer-assisted models.

Facial contours are thought to depend on the appropriate balance of hard and soft tissue. To obtain aesthetically good results in head and neck reconstruction, surgeons should know the exact three-dimensional shape and volume of both hard and soft tissue to be reconstructed. The authors used computer-assisted three-dimensional solid models of the mandible in 7 patients (4 women and 3 men) who underwent mandibular contour reconstruction. Scapular osteocutaneous flaps were used in all 7 patients. The follow-up periods ranged from 7 to 57 months (mean follow-up, 29 months). No flap was lost. One patient died of metastatic cancer. In 2 patients the aesthetic results were excellent and in 4 patients they were good. Computer-assisted three-dimensional models for mandibular contour reconstruction in head and neck reconstruction are quite useful.

Changes in analgesia-producing mechanism of repeated cold stress loading in mice.

Functional changes in opioid receptors involved in analgesia of repeated cold stress (RCS)-loaded mice were investigated. The antinociceptive potency of morphine (4 mg/kg, PO) was not affected in normal mice by norbinaltorphimine (10 mg/kg, SC), but treatment with this agent resulted in a lower level of morphine-induced antinociception in RCS-loaded animals. The antinociceptive activity of U-50488H (3 mg/kg, SC) was increased in RCS-loaded mice. In contrast to hypersensitivity to U-50488H (1 and 10 microg, IT) noted in RCS-loaded mice, the antinociception induced by DAMGO (0.1 and 1 microg, ICV) was reduced compared to that of normal animals. Diazepam (1 mg/kg/day SC) was given during RCS loading, and this agent prevented the development of hyperalgesia and the decrease in the antinociceptive activity of DAMGO (1 microg, ICV) in RCS-loaded mice, but there was no effect on the enhancement of the antinociceptive potency of U-50488H (10 microg, IT). These results indicate that the RCS-loaded mice were hyposensitive to supraspinal mu-opioid receptor-mediated antinociception, whereas their antinociceptive activities through kappa-opioid receptor in the spinal cord were increased. Hypofunction of the supraspinal mu-opioid receptor due to anxiety may explain the mechanism involved in the lowering of the nociceptive threshold in RCS-loaded animals.

Analgesia-producing mechanism of processed Aconiti tuber: role of dynorphin, an endogenous kappa-opioid ligand, in the rodent spinal cord.

The analgesia-producing mechanism of processed Aconiti tuber was examined using rodents whose nociceptive threshold was decreased by loading repeated cold stress (RCS). The antinociceptive effect of processed Aconiti tuber (0.3 g/kg, p.o.) in RCS-loaded mice was antagonized by pretreatment with a kappa-opioid antagonist, nor-binaltorphimine (10 mg/kg, s.c.), and was abolished by an intrathecal injection of anti-dynorphin antiserum (5 microg). The Aconiti tuber-induced antinociception was inhibited by both dexamethasone (0.4 mg/kg, i.p.) and a dopamine D2 antagonist, sulpiride (10 mg/kg, i.p.), in RCS-loaded mice, and it was eliminated by both an electric lesion of the hypothalamic arcuate nucleus (HARN) and a highly selective dopamine D2 antagonist, eticlopride (0.05 microg), administered into the HARN in RCS-loaded rats. These results suggest that the analgesic effect of processed Aconiti tuber was produced via the stimulation of kappa-opioid receptors by dynorphin released in the spinal cord. It was also shown that dopamine D2 receptors in the HARN were involved in the expression of the analgesic activity of processed Aconiti tuber.

A flap to monitor a temporoparietal fascial flap. Case report.

The temporoparietal fascial flap is useful in reconstructions of the hands and feet as tendon gliding material, but it is difficult to monitor its viability postoperatively. We have monitored such flaps by attaching a small preauricular skin flap 2 x 1 cm in size to the vascular pedicle. This preauricular island flap can be used as a "monitoring" flap.

Antinociceptive mechanism of the aconitine alkaloids mesaconitine and benzoylmesaconine.

We explored the possible role of the specific regions in the brain stem on the antinociceptive actions of mesaconitine (MA) and benzoylmesaconine (BM) by the microinjection of MA and BM into nucleus reticularis paragigantocellularis (NRPG), nucleus raphe magnus (NRM), and periaqueductal gray (PAG). MA microinjected into NRPG, NRM, or PAG elicited a dose-dependent antinociceptive action, whereas BM injected into NRM or PAG elicited a dose-dependent antinociceptive action but not in NRPG. The NRM appeared to be the most sensitive region among the three tested locations.

The analgesic mechanism of processed Aconiti tuber: the involvement of descending inhibitory system.

Tsumura-shuchi-bushi-matsu (TJ-3021) is a processed Aconiti tuber which has a potent antinociceptive action. The present study was undertaken to study the analgesic mechanism produced by TJ-3021. RCS (repeated cold stress) rats in hyperalgesia were markedly suppressed by oral administration of TJ-3021. Intrathecal and intraperitoneal administration of a selective alpha 2-adrenoreceptor antagonist, idazoxan (IDA), reduced significantly the analgesic effect of TJ-3021 in RCS rats. Methysergide (METH), a 5-HT receptor antagonist, demonstrated a similar effect, while intraperitoneal administration of opioid receptor antagonist, naloxone, did not produce the effect. Both oral and intracisternal administration of mesaconitine (MA) which is one of the main potent alkaloids contained in TJ-3021 produced analgesic effect in non-RCS rats.