Frequency analysis of heart rate variability: a useful assessment tool of linearly polarized near-infrared irradiation to stellate ganglion area for burning mouth syndrome.

BACKGROUND: Burning mouth syndrome (BMS) is characterized by the following subjective complaints without distinct organic changes: burning sensation in mouth or chronic pain of tongue. BMS is also known as glossodynia; both terms are used equivalently in Japan. Although the real cause of BMS is still unknown, it has been pointed out that BMS is related to some autonomic abnormality, and that stellate ganglion near-infrared irradiation (SGR) corrects the autonomic abnormality. Frequency analysis of heart rate variability (HRV) is expected to be useful for assessing autonomic abnormality. OBJECTIVES: This study investigated whether frequency analysis of HRV could reveal autonomic abnormality associated with BMS, and whether autonomic changes were corrected after SGR. SUBJECTS AND METHODS: Eight subjects received SGR; the response to SGR was assessed by frequency analysis of HRV. RESULTS: No significant difference of autonomic activity concerning low-frequency (LF) norm, high-frequency (HF) norm, and low-frequency/high-frequency (LF/HF) was found between SGR effective and ineffective groups. Therefore, we proposed new parameters: differential normalized low frequency (D LF norm), differential normalized high frequency (D HF norm), and differential low-frequency/high-frequency (D LF/HF), which were defined as differentials between original parameters just before and after SGR. These parameters as indexes of responsiveness of autonomic nervous system (ANS) revealed autonomic changes in BMS, and BMS seems to be related to autonomic instability rather than autonomic imbalance. CONCLUSIONS: Frequency analysis of HRV revealed the autonomic instability associated with BMS and enabled tracing of autonomic changes corrected with SGR. It is suggested that frequency analysis of HRV is very useful in follow up of BMS and for determination of the therapeutic efficacy of SGR.

TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.

Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.

Diffusion-weighted MRI as an adjunct to mammography in women under 50 years of age: an initial study.

PURPOSE: To evaluate diffusion-weighted magnetic resonance (DW) imaging as an adjunct to mammography for the detection of small invasive breast cancer. MATERIALS AND METHODS: Institutional review board standards were followed for this retrospective study. We performed both breast DW imaging and mammography on 25 women under 50 years of age with pathologically proven T1 breast cancer and on 21 healthy women under 50 years of age. Four offsite radiologists blind to the clinical information independently interpreted the mammograms and DW images and then classified their confidence level regarding the presence of breast cancer. The composite area under receiver operating characteristic curve (AUC), of mammography alone, DW imaging alone, and the combination of DW imaging and mammography (DWI/Cal) were calculated. RESULTS: The AUC of composite ROC curves of mammography, DW imaging, DWI/Cal combination, was 0.79 (95% CI, 0.72-0.87), 0.86 (95% CI, 0.84-0.87), and 0.96 (95% CI, 0.92-1.00), respectively. CONCLUSION: DW imaging may be a useful adjunct to mammography in the detection of small invasive breast cancer in women under 50 years of age.

Knot formation of a guidewire during subclavian venous catheterization: A case report.

Central venous catheters are used for a variety of purposes, including emergency care, parenteral nutrition, and chemotherapy, but their insertion can cause mechanical complications such as malposition, arterial puncture, and pneumothorax. Here, we describe a rare case of guidewire knot formation during subclavian vein catheterization. A 70-year-old woman presented to our facility for central venous port placement for chemotherapy after surgical resection of a retroperitoneal liposarcoma. The left subclavian vein was selected and punctured under ultrasound guidance, and a guidewire was introduced. However, strong resistance prevented both advancement and withdrawal of the guidewire. Radiograph revealed a knot like shadow near the tip of the guidewire. After placement of a central venous port in the opposite site, the knotted guidewire was surgically removed. Intraoperatively, the guidewire was found to penetrate the vein and form a knot on the outside of the posterior wall. Although the guidewire was able to be removed, a postoperative chest x-ray revealed a left pneumothorax, which required 10 days of treatment. If a knot forms in a guidewire during catheterization, surgical removal is recommended because forcible pulling can damage the vessel. In conclusion, guidewire knot formation is a very rare complication, but physicians performing central venous catheterization should be aware of it, and this report describes how to prevent and manage it.

Whole-liver transcatheter arterial chemoinfusion and bland embolization with fine-powder cisplatin and trisacryl gelatin microspheres for treating unresectable multiple hepatocellular carcinoma.

PURPOSE: To evaluate the safety and effectiveness of whole-liver transcatheter arterial chemoinfusion and bland embolization (TACBE) with fine-powder cisplatin and trisacryl gelatin microspheres for the treating unresectable multinodular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The medical records of all patients who underwent TACBE sessions were retrospectively reviewed. 15 patients (11 men, 4 women; mean age, 72.5 years) and 22 procedures (BCLC B;17 C;5) were included in the analysis. The cisplatin resulting solution and microspheres were infused through a microcatheter placed nonselectively. Overall survival (OS) was defined as the time from commencement of initial TACBE until any cause of death. Toxicity was assessed by the CTCAE version 5.0, and the tumor response was evaluated by the mRECIST. Liver function was assessed by the albumin-bilirubin (ALBI) score. RESULTS: The 1-year OS rate was 64.6% (95% CI 0.438-0.955). Severe adverse effects were not observed except for grade 3 increase in the ALT, ALT, vasovagal episode. The objective response and disease control rare were 54.5% and 68.2%, respectively. The ALBI scores from pre-treatment to the follow-up ranged from - 2.39 to - 2.26 (p = 0.38). CONCLUSION: Whole-liver TABCE with fine-powder cisplatin and trisacryl gelatin microspheres was well tolerated and effective in patients with multinodular HCC.

Pulmonary surfactant itself must be a strong defender against SARS-CoV-2.

Pulmonary surfactant is considered to be one of the soaps. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the other enveloped viruses become very weak against surfactant. The SARS virus binds to angiotensin-converting enzyme (ACE2) receptor and causes pneumonia. In the lung, the ACE2 receptor sits on the top of lung cells known as alveolar epithelial type II (AE2) cells. These cells play an important role in producing surfactant. Pulmonary surfactant is believed to regulate the alveolar surface tension in mammalian lungs. To our knowledge, AE2 cells are believed to act as immunoregulatory cells; however, pulmonary surfactant itself has not been believed to act as a defender against the enveloped viruses. This study hypothesises that pulmonary surfactant may be a strong defender of enveloped viruses. Therefore, old coronaviruses merely cause pneumonia. On the contrary, new SARS-CoV-2 can suppress the production of surfactant that binds to the ACE2 of AE2 cells. The coronavirus can survive in the lung tissue because of the exhaustion of pulmonary surfactant.

Imaging spectrum of abnormal subcutaneous and visceral fat distribution.

Adipose tissue plays multiple and complex roles not only in mechanical cushioning and energy storage but also as an important secretory organ that regulates energy balance and homeostasis multilaterally. Fat tissue is categorized into subcutaneous fat tissue (SCAT) or visceral fat tissue (VSA) depending on its distribution, with the two having different metabolic functions. Near-total lack of fat in congenital/acquired generalized lipodystrophy, cachexia, or any other severe malnutrition condition induces severe multi-organ dysfunction due to lack of production of leptin and other adipokines. Increased visceral fat tissue secondary to obesity, hypercortisolism, or multiple symmetric lipomatosis raises the risk of insulin resistance, cardiac complications, and airway or spinal canal stenosis, although the fat distribution pattern differs in each condition. Partial abnormal fat distribution conditions such as HIV/HAART therapy-associated lipodystrophy, familial partial lipodystrophies, and acquired partial lipodystrophy frequently show a mixture of lipoatrophy and lipohypertrophy with metabolic dysfunction. Characteristic imaging features in conditions with local abnormal fat distribution can provide information about a patient's co-existent/unrecognized disease(s), past medical history, or lifestyle. Knowledge of characteristic abnormal fat distribution patterns can contribute to proper and timely therapeutic decision-making and patient education.

Histological evaluation of apatite cement containing atelocollagen.

Tissue response to apatite cement (AC) containing atelocollagen (AC (ate)) was evaluated using conventional AC (c-AC) as a control material. At one week, the only difference between AC (ate) and c-AC was found in the soft tissue response. With c-AC, a moderate inflammatory response was exhibited: small particles of c-AC were scattered in the cutaneous tissue and many foreign body giant cells were aggregated around the scattered c-AC, whereas AC (ate) showed only a slight inflammatory response with few foreign body giant cells. In terms of bone tissue response, difference between AC (ate) and c-AC was observed at four weeks. New bone formation was observed along the cement at the edge of the pre-existing cortical bone in both c-AC and AC (ate). However, in the case of AC (ate), more abundant and thicker new bone was formed along the cement in the bone marrow when compared with c-AC.

Proliferation and differentiation of cultured MC3T3-E1 osteoblasts on surface-layer modified hydroxyapatite ceramic with acid and heat treatments.

Effects of functionally gradient calcium phosphate consisting of hydroxyapatite (HAP) and alpha-tricalcium phosphate (alpha-TCP) on proliferation and differentiation of osteoblasts were evaluated using MC3T3-E1 cells. There were no significant differences in the proliferation of MC3T3-E1 cells among HAP-alpha-TCP functionally gradient calcium phosphate, pure HAP, and cell culture plastic wells. mRNA expressions of type I collagen, alkaline phosphate, and osteocalcine were evaluated as indexes of initial; mid-stage, and late-stage osteoblastic differentiation. Basically, HAP-alpha-TCP functionally gradient calcium phosphate and pure HAP enhanced the expressions of the three markers when compared with that of cell culture plastic wells. For type I collagen and alkaline phosphate expressions, HAP-alpha-TCP functionally gradient calcium phosphate showed the same expression level as pure HAP. For osteocalcine expression, HAP-alpha-TCP functionally gradient calcium phosphate showed a higher level than pure HAP. We concluded, therefore, HAP-alpha-TCP functionally gradient calcium phosphate has good potential to be a bone filler material with high osteoconductivity.

γ-Tocotrienol prevents 5-FU-induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5-FU-induced activation of Nrf2.

Chemotherapy-induced oral mucositis is a common adverse event in patients with oral squamous cell carcinoma, and is initiated through a variety of mechanisms, including the generation of reactive oxygen species (ROS). In this study, we examined the preventive effect of γ-tocotrienol on the 5-FU-induced ROS production in human oral keratinocytes (RT7). We treated RT7 cells with 5-FU and γ-tocotrienol at concentrations of 10 µg/ml and 10 nM, respectively. When cells were treated with 5-FU alone, significant growth inhibition was observed as compared to untreated cells. This inhibition was, in part, due to the ROS gene-rated by 5-FU treatment, because N-acetyl cysteine (NAC), a ROS scavenger, significantly ameliorated the growth of RT7 cells. γ-tocotrienol showed no cytotoxic effect on the growth of RT7 cells. Simultaneous treatment of cells with these agents resulted in the significant recovery of cell growth, owing to the suppression of ROS generation by γ-tocotrienol. Whereas 5-FU stimulated the expression of NF-E2-related factor 2 (Nrf2) protein in the nucleus up to 12 h after treatment of RT7 cells, γ-tocotrienol had no obvious effect on the expression of nuclear Nrf2 protein. Of note, the combined treatment with both agents stabilized the 5-FU-induced nuclear Nrf2 protein expression until 24 h after treatment. In addition, expression of Nrf2-dependent antioxidant genes, such as heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1), was significantly augmented by treatment of cells with both agents. These findings suggest that γ-tocotrienol could prevent 5-FU-induced ROS generation by stabilizing Nrf2 activation, thereby leading to ROS detoxification and cell survival in human oral keratinocytes.

Orthostatic Dysregulation during Postural Change on the Dental Chair and Intraoperative Monitoring by Heart Rate Variability Analysis.

This is the first case report of orthostatic dysregulation (OD) manifested during postural change on the dental chair and intraoperatively monitored by heart rate variability (HRV) analysis. OD-associated autonomic dysfunction is induced by postural changes and easily leads to disturbance in circulatory dynamics; however, most dental practices have not yet realized the importance of managing OD. We measured autonomic activity in a patient with OD during dental therapy and assessed the clinical significance of HRV analysis for OD. The patient was a 17-year-old Japanese female. She was diagnosed with impacted wisdom teeth and had no previous history of a distinct systemic disease. A surgical procedure to extract the teeth was safely performed under both local anesthesia and sedation with nitrous oxide and midazolam. After the surgery, her postural change to sitting induced orthostatic hypotension. HRV variables showed parasympathetic dominance due to the upright position. Subsequently, her posture was returned to supine, and atropine sulfate administration for the immediate treatment of OD returned her blood pressure to normal levels. HRV variables showed relative sympathetic dominance due to an atropine-derived parasympathetic blockade. HRV analysis revealed OD-associated autonomic dysfunction and should become a standard tool for safe and secure dental management of OD.

High-wattage pulsed irradiation of linearly polarized near-infrared light to stellate ganglion area for burning mouth syndrome.

The purpose of this study was to apply high-wattage pulsed irradiation of linearly polarized near-infrared light to the stellate ganglion area for burning mouth syndrome (BMS) and to assess the efficacy of the stellate ganglion area irradiation (SGR) on BMS using differential time-/frequency-domain parameters (D parameters). Three patients with BMS received high-wattage pulsed SGR; the response to SGR was evaluated by visual analogue scale (VAS) representing the intensity of glossalgia and D parameters used in heart rate variability analysis. High-wattage pulsed SGR significantly decreased the mean value of VAS in all cases without any adverse event such as thermal injury. D parameters mostly correlated with clinical condition of BMS. High-wattage pulsed SGR was safe and effective for the treatment of BMS; D parameters are useful for assessing efficacy of SGR on BMS.

γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products.

Taxanes, including docetaxel, are widely used for the treatment of squamous cell carcinoma of the head and neck. However, the gastrointestinal toxicity of docetaxel has limited its high-dose clinical use. In this study, we examined the synergistic anticancer effects of combined low-dose docetaxel and γ-tocotrienol treatment on human oral cancer (B88) cells. We treated B88 cells with docetaxel and γ-tocotrienol at concentrations of 0.5 nM and 50 µM, respectively. When cells were treated with either agent alone at a low dose, no significant cytotoxic effect was observed. However, the simultaneous treatment of cells with both agents almost completely suppressed cell growth. Whereas docetaxel stimulated the expression of nuclear factor-κB (NF-κB) p65 protein in B88 cells, γ-tocotrienol slightly inhibited the expression of constitutive nuclear p65 protein. Of note, the combined treatment with both agents inhibited docetaxel-induced nuclear p65 protein expression. Electrophoretic mobility shift assay (EMSA) revealed that the simultaneous treatment with these agents suppressed the NF-κB DNA binding activity in B88 cells. In addition, γ-tocotrienol downregulated the docetaxel-induced expression of NF-κB-regulated gene products associated with the inhibition of apoptosis. Furthermore, the activation of initiator caspases, caspases-8 and -9, and the effector caspase, caspase-3, was detected following treatment with both agents. Finally, apoptosis was also clearly observed as demonstrated by the cleavage of poly(ADP-ribose) polymerase (PARP) and nuclear fragmentation through the activation of caspase-3 by combined treatment with docetaxel and γ-tocotrienol. These findings suggest that the combination treatment with these agents may provide enhanced therapeutic response in oral cancer patients, while avoiding the toxicity associated with high-dose ß-tubulin stabilization monotherapy.

Can pretreatment ADC values predict recurrence of bladder cancer after transurethral resection?

OBJECTIVE: The aim of this retrospective study was to investigate the association between the pretreatment apparent diffusion coefficient (ADC) value and recurrence of bladder cancer after transurethral resection. METHODS: Patients with superficial bladder cancer were identified. Mean ADC values of the tumors were compared between patients with and without recurrence following trans-urethral resection. A receiver-operator characteristic curve was used for determining the optimal cutoff ADC value. Univariate and multivariate analyses were used to determine the effect of ADC values and other factors. RESULTS: With a mean follow-up period of 25 months, bladder cancer recurred in 14 of 44 patients (32%). The mean ADC value of tumors in patients with recurrence was lower than in those without recurrence (1.08 mm2/s vs. 1.28×10(-3) mm2/s; p=0.003). The optimal cutoff ADC value for predicting recurrence was determined to be 1.12×10(-3) mm2/s. A modest and significant negative correlation was observed between the ADC values and tumor size (r=-0.436, p=0.008). After adjustment for size and risk groups, an ADC value equal to or less than the optimal cutoff remained a significant predictor of recurrence (odds ratio 6.3, 95% CI 1.23-32.2, p=0.027). CONCLUSION: Pretreatment ADC values may be an independent predictor of bladder cancer recurrence.

A case of ventricular asystole without escape rhythm 4 days after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy with drug-resistant paroxysmal atrial fibrillation.

A 42-year-old man with a more than 10-year history of hypertrophic obstructive cardiomyopathy, but no history of heart failure or syncope, had left ventricular outflow tract pressure gradient (LVOT-PG) of 50-80 mmHg on Doppler echocardiography. In June 2010, he experienced general malaise on effort, and LVOT-PG increased to 124 mmHg. Two months later, he suffered a transient ischemic attack, complicated with atrial fibrillation (AF). He underwent cardiac defibrillation and was prescribed amiodarone, but the arrhythmia recurred easily. Therefore, percutaneous transluminal septal myocardial ablation (PTSMA) was performed to prevent AF. The procedure entailed transient complete atrioventricular block (CAVB), which was resolved after a few hours. Four days later, CAVB recurred and advanced to fatal ventricular asystole without escape rhythm. The patient was resuscitated instantaneously and recovered without brain damage. Finally, a DDD permanent pacemaker was implanted 10 days after the procedure. Except for conduction problems, his cardiac condition was good after PTSMA, as paroxysmal AF disappeared and LVOT-PG was markedly decreased. CAVB is a well-known complication of PTSMA, but fatal ventricular asystole several days after the procedure is rare. Intensive care is required after PTSMA implementation.

Basic research on aw-AC/PLGA composite scaffolds for bone tissue engineering.

Recently, it has become important to develop effective material to be used as scaffolds for bone tissue engineering. Therefore, we fabricated new three-dimensional (3D) scaffolds consisting of biodegradable poly(D,L-lactide-co-glycolic acid)(PLGA)(75/25) with anti-washout type AC (aw-AC) particles. The aim of this study was to evaluate this new scaffold concerning its basic properties and biocompatibility. The obtained scaffolds were observed with scanning electron microscopy (SEM), and measured for porosity, shrinkage and biaxial compressive strengths. It was shown that PLGA with aw-AC composite scaffolds (aw-AC/PL) showed a greater strength and stability than PLGA scaffolds (PL). Also, the mass reduction of aw-AC/PL during incubation decreased compared to that of PL. The number of MC3T3-E1 cell in PL and aw-AC/PL was counted at 5 h, 1 week, and 2 weeks after cell seeding. As a result, aw-AC/PL exhibited a superior performance in terms of attachment and proliferation compared to PL. Histologically, aw-AC/PL showed an excellent response toward soft tissues. Therefore, it was shown that aw-AC/PL was more biocompatible than PL. In conclusion, it was strongly suggested that aw-AC/PL was more useful for cell transplantation than PL in bone tissue engineering.

Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma.

OBJECTIVE: The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. MATERIALS AND METHODS: Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. RESULTS: The primary lesions were in the thigh (n = 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. CONCLUSION: Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion.

Lymphadenopathy in the mesenteric pedicle of the free jejunal flap: reactive lymphadenopathy, not metastatic.

OBJECTIVE: Reconstructive surgery using the free jejunal flap is sometimes performed to close surgical defects in patients undergoing pharyngolaryngectomy for laryngeal or hypopharyngeal cancer. The clinical significance of lymph nodes in the flap was retrospectively examined. METHODS: Fifteen patients had undergone a laryngectomy with free jejunal flap reconstruction between March 1996 and October 1999. The appearance and size of lymph nodes of the flap were examined by 3 radiologists. RESULTS: Lymph nodes were observed in 10 patients. Size increases were noted within 1 year after surgery but not beyond 1 year. The pathologic diagnosis of the excised nodes was reactive lymphadenopathy. CONCLUSIONS: Lymph nodes may occasionally become apparent in the free jejunal flap. There was no suggestion of metastatic lymph nodes when examined retrospectively. We speculate that this reaction was the result of environmental changes attributable to surgery.

[Atypical takotsubo cardiomyopathy with preservation of apical contraction: a case report including pathological findings].

A 60-year-old woman presented with sudden chest and back pain. Electrocardiography suggested anterior myocardial infarction but coronary angiography revealed no significant stenosis in the coronary artery. Left ventriculography revealed akinesis of the mid ventricle and preserved contraction of the apical wall. The clinical condition of atypical left ventricular akinesia was suggested to be the same as conventionally reported typical takotsubo cardiomyopathy. Repeated left ventriculography revealed the abnormal wall motion had disappeared. The findings of endomyocardial biopsy were compatible with takotsubo cardiomyopathy. Although the clinical presentation of the left ventricle is atypical, the pathological findings may be the same as typical takatsubo cardiomyopathy.