Preoperative simulation using three-dimensional printer in four temporal bone surgeries.

Preoperative simulation using a three-dimensional printer is effective to perform safe surgery by knowing the range limit of drilling in the temporal bone. Moreover, simulations using models are thought to be useful for education of young surgeon.

Infection control for COVID-19 in hospital examination room.

Healthcare providers are vulnerable to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their close proximity to patients with coronavirus disease 2019. SARS-CoV-2 is mainly transmitted via direct and indirect contact with respiratory droplets, and its airborne transmission has also been identified. However, evidence for environmental factors is scarce, and evidence-based measures to minimize the risk of infection in clinical settings are insufficient. Using computational fluid dynamics, we simulated exhalation of large and small aerosol particles by patients in an otolaryngology examination room, where medical procedures require the removal of a face mask. The effects of coughing were analyzed, as well as those of humidity as a controllable environmental factor and of a suction device as an effective control method. Our results show that a suction device can minimize aerosol exposure of healthcare workers by efficiently removing both large (11.6-98.2%) and small (39.3-99.9%) aerosol particles. However, for coughing patients, the removal efficiency varies inversely with the particle size, and the humidity notably affects the aerosol behavior, indicating the need for countermeasures against smaller aerosols. Overall, these results highlight the potential and limitation of using a suction device to protect against SARS-CoV-2 and future respiratory infections.

A case of jugular bulb diverticulum causing pulsatile tinnitus.

If you suspect pulsatile tinnitus from a medical interview, you should check for jugular bulb diverticulum and cortical bone defects on temporal bone CT, in addition to thorough physical examination and contrast-enhanced imaging.

Deep sequencing-based microRNA expression signatures in head and neck squamous cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs.

We adopted into RNA-sequencing technologies to construct the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Our signature revealed that a total of 160 miRNAs (44 upregulated and 116 downregulated) were aberrantly expressed in cancer tissues. Expression of miR-150-5p (guide strand miRNA) and miR-150-3p (passenger strand miRNA) were significantly silenced in cancer tissues, suggesting both miRNAs act as antitumor miRNAs in HNSCC cells. Ectopic expression of mature miRNAs, miR-150-5p and miR-150-3p inhibited cancer cell aggressiveness. Low expression of miR-150-5p and miR-150-3p predicted significantly shorter overall survival in patients with HNSCC (P = 0.0091 and P = 0.0386) by Kaplan-Meier survival curves analyses. We identified that integrin α3 (ITGA3), integrin α6 (ITGA6), and tenascin C (TNC) were coordinately regulated by these miRNAs in HNSCC cells. Knockdown assays using siRNAs showed that ITGA3, ITGA6 and TNC acted as cancer promoting genes in HNSCC cells. Moreover, ITGA3, ITGA6, and TNC alterations were associated with significantly poorer overall survival (P = 0.0177, P = 0.0237, and P = 0.026, respectively). Dual strands of pre-150 (miR-150-5p and miR-150-3p) functioned as antitumor miRNAs based on the miRNA expression signature of HNSCC. Identification of antitumor miR-150-mediated RNA networks may provide novel insights into pathogenesis of HNSCC.

Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer.

Our recent studies of microRNA (miRNA) expression signatures of prostate cancer (PCa) showed that six miRNAs (specifically, miR-26a, miR-26b, miR-29a, miR-29b, miR-29c and miR-218) were markedly reduced in cancer tissues. Moreover, ectopic expression of these miRNAs suppressed PCa cell aggressiveness, indicating that these miRNAs acted in concert to regulate genes that promoted metastasis. Genome-wide gene expression analysis and in silico database analysis identified a total of 35 candidate genes that promoted metastasis and were targeted by these 6 miRNAs. Using luciferase reporter assays, we showed that the lysyl oxidase-like 2 (LOXL2) gene was directly controlled by these tumor-suppressive miRNAs in PCa cells. Overexpression of LOXL2 was confirmed in PCa tissues and knockdown of the LOXL2 gene markedly inhibited the migration and invasion of PCa cells. Aberrant expression of LOXL2 enhanced migration and invasion of PCa cells. Downregulation of antitumor miRNAs might disrupt the tightly controlled RNA networks found in normal cells. New insights into the novel molecular mechanisms of PCa pathogenesis was revealed by antitumor miRNA-regulated RNA networks.

The microRNA signatures: aberrantly expressed microRNAs in head and neck squamous cell carcinoma.

microRNAs (miRNAs) are responsible for fine tuning the normal expression of RNA networks in human cells. Accumulating studies have demonstrated that abnormally expressed miRNAs have pivotal roles in the development of head and neck squamous cell carcinoma (HNSCC). Specifically, expression signatures of miRNAs in HNSCC have revealed dysregulated production of miRNAs and the resultant abnormal production of mRNAs and proteins. In this review, we discuss current findings regarding aberrantly expressed miRNAs and their contribution to HNSCC molecular pathogenesis.

Dual-receptor (EGFR and c-MET) inhibition by tumor-suppressive miR-1 and miR-206 in head and neck squamous cell carcinoma.

Our studies of microRNA (miRNA) expression signatures have shown that microRNA-1 (miR-1) and microRNA-206 (miR-206) were downregulated in head and neck squamous cell carcinoma (HNSCC) clinical specimens. The seed sequences of these miRNAs are identical, suggesting that the identification of the molecular targets regulated by miR-1 and miR-206 will provide new insights into novel mechanisms of HNSCC pathogenesis. Our present data showed that restoration of miR-1 and miR-206 significantly inhibited HNSCC cells' aggressiveness. A combination of gene expression data and in silico analysis revealed that several pathways ('pathway in cancer', 'focal adhesion pathway', 'MAPK signaling pathway', 'regulation of actin cytoskeleton pathway' and 'ECM-receptor interaction pathway') were regulated by miR-1 and miR-206. Among them, we found that two growth factor receptors, epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET), were directly regulated by both miR-1 and miR-206 in HNSCC cells. Also, downstream oncogenic signaling of these receptors was reduced by restoration of miR-1 or miR-206 expression. Moreover, overexpression of EGFR and c-MET was observed in HNSCC clinical specimens. The identification of targets modulated by tumor-suppressive miR-1 and miR-206 may lead to a better understanding of molecular pathogenesis of HNSCC.

The tumor-suppressive microRNA-23b/27b cluster regulates the MET oncogene in oral squamous cell carcinoma.

Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that two clustered miRNAs, microRNA-23b (miR-23b) and microRNA-27b (miR­27b), were significantly reduced in cancer tissues. Few reports have provided functional analyses of these clustered miRNAs in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the functional significance of miR-23b and miR-27b in OSCC and to identify novel miR-23b/27b-mediated cancer pathways and target genes involved in OSCC oncogenesis and metastasis. Expression levels of miR-23b and miR-27b were significantly reduced in OSCC specimens. Restoration of miR-23b or miR-27b in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analyses and luciferase reporter assays showed that the receptor tyrosine kinase MET, was directly regulated by these miRNAs. Moreover, downregulating the MET gene by use of siRNA significantly inhibited cell migration and invasion by OSCC cells. The identification of novel molecular pathways regulated by miR-23b and miR-27b may lead to a better understanding of the oncogenesis and metastasis of this disease.

Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma.

Our recent studies of microRNA (miRNA) expression signatures in human cancers revealed that microRNA-26a (miRNA-26a) and microRNA-26b (miRNA-26b) were significantly reduced in cancer tissues. To date, few reports have provided functional analyses of miR-26a or miR-26b in renal cell carcinoma (RCC). The aim of the present study was to investigate the functional significance of miR-26a and miR-26b in RCC and to identify novel miR-26a/b-mediated cancer pathways and target genes involved in RCC oncogenesis and metastasis. Downregulation of miR-26a or miR-26b was confirmed in RCC clinical specimens. Restoration of miR-26a or miR-26b in RCC cell lines (786-O and A498) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our in silico analysis and luciferase reporter assays showed that lysyl oxidase-like 2 (LOXL2) and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were directly regulated by these miRNAs. Moreover, downregulating the PLOD2 gene significantly inhibited cell migration and invasion in RCC cells. Thus, our data showed that two genes promoting metastasis, LOXL2 and PLOD2, were epigenetically regulated by tumor-suppressive microRNAs, miR-26a and miR-26b, providing important insights into the molecular mechanisms of RCC metastasis.

Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.

Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration-resistant PCa has revealed that miRNA-223 is significantly downregulated in cancer tissues, suggesting that miR-223 acts as a tumor-suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR-223 and identify downstream oncogenic targets regulated by miR-223 in PCa cells. Functional studies of miR-223 were carried out to investigate cell proliferation, migration, and invasion using PC3 and PC3M PCa cell lines. Restoration of miR-223 significantly inhibited cancer cell migration and invasion in PCa cells. In silico database and genome-wide gene expression analyses revealed that ITGA3 and ITGB1 were direct targets of miR-223 regulation. Knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion in PCa cells by regulating downstream signaling. Moreover, overexpression of ITGA3 and ITGB1 was observed in PCa clinical specimens. Thus, our data indicated that downregulation of miR-223 enhanced ITGA3/ITGB1 signaling and contributed to cancer cell migration and invasion in PCa cells. Elucidation of the molecular pathways modulated by tumor-suppressive miRNAs provides insights into the mechanisms of PCa progression and metastasis.

Tumor-suppressive microRNAs (miR-26a/b, miR-29a/b/c and miR-218) concertedly suppressed metastasis-promoting LOXL2 in head and neck squamous cell carcinoma.

In spite of considerable advances in multimodality therapy, including surgery, radiotherapy and chemotherapy, the overall survival rate for patients with head and neck squamous cell carcinoma (HNSCC) is very poor (only 15-45%). Understanding the molecular mechanisms of metastatic pathways underlying HNSCC using currently available genomic approaches might improve therapies for and prevention of the disease. Our previous studies showed that three tumor-suppressive microRNAs (miRNAs), miR-26a/b, miR-29a/b/c and miR-218, significantly inhibited cancer cell migration and invasion. Therefore, we hypothesized that these miRNAs-regulated target genes deeply contributed to cancer metastasis. These tumor-suppressive miRNAs directly regulate LOXL2 expression in HNSCC cells by using in silico analysis and luciferase reporter assays. Overexpressed LOXL2 was confirmed in HNSCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in HNSCC cell lines. Our present data showed that tumor-suppressive miRNAs regulation of LOXL2 will provide new insights into the novel molecular mechanisms of HNSCC metastasis.

[Aggravation after Diagnosis of Sudden Sensorineural Hearing Loss].

Among 95 patients with sudden sensorineural hearing loss who received inpatient treatment at our hospital within the 27-month period between October 2009 and December 2011, those in whom hearing loss was aggravated after diagnosis were compared with a control group. Hearing loss aggravation was defined as a decrease by 10 dB or more in the mean hearing threshold at 5 frequencies from 250 to 4,000 Hz or decrease of 15 dB or more in the hearing threshold at 2 consecutive frequencies. Hearing loss was aggravated after diagnosis in 22 (23.2%) of the 95 patients, showing a similar tendency to that previously reported. Although the grades of hearing loss in these patients were higher than those in 73 control group patients, according to the sudden hearing loss severity classification, their outcomes were favorable. The hearing loss aggravation group consisted of those with steroid-dependent hearing loss (6) and those who had undergone perilymphatic fistula repair (4), in addition to a large number of patients with idiopathic hearing loss, including suspicious perilymphatic fistula (10). When hearing loss becomes aggravated after the diagnosis of sudden sensorineural hearing loss, it may be important to determine the most appropriate approach in each case, such as a careful and gradual decrease in the adenocortical steroid dose and the consideration of perilymphatic fistula repair.

MicroRNA-26a/b directly regulate La-related protein 1 and inhibit cancer cell invasion in prostate cancer.

Our past studies of microRNA (miRNA) expression signatures of cancers including prostate cancer (PCa) revealed that microRNA-26a and microRNA-26b (miR-26a and miR-26b) were significantly downregulated in cancer tissues. In the present study, we found that restoration of miR-26a or miR-26b significantly inhibited PCa cell invasion. Gene expression data and in silico analysis showed that the gene encoding La-related protein 1 (LARP1) was a putative candidate of miR-26a and miR-26b regulation. Moreover, luciferase reporter assays revealed that LARP1 was a direct target of both miR-26a and miR-26b. Overexpression of LARP1 was observed in PCa clinical specimens and knockdown of LARP1 inhibited cancer cell migration. Therefore, LARP1 acted as an oncogene in PCa cells. Moreover, 'ribosome', 'RNA transport' and 'mTOR signaling pathway' were identified as LARP1-regulated pathways. Our present data suggested that loss of tumor-suppressive miR-26a and miR-26b enhanced cancer cell invasion in PCa through direct regulation of oncogenic LARP1. Elucidation of the molecular networks regulated by tumor-suppressive miRNAs will provide insights into the molecular mechanisms of PCa oncogenesis and metastasis.

Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma.

Here, we found that members of the microRNA-29 family (miR-29a/b/c; "miR-29s") were significantly reduced in clear cell renal cell carcinoma (ccRCC) tissues, suggesting that they functioned as tumour suppressors. Restoration of all mature members of the miR-29 family inhibited cancer cell proliferation, migration and invasion. LOXL2 was a direct target gene of miR-29s, as shown by genome-wide gene expression analysis and luciferase reporter assay. Overexpressed LOXL2 was confirmed in ccRCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in ccRCC cell lines. Our data demonstrated that the miR-29s-LOXL2 axis contributed to cancer cell migration and invasion in ccRCC.

The tumor-suppressive microRNA-1/133a cluster targets PDE7A and inhibits cancer cell migration and invasion in endometrial cancer.

In developed countries, endometrial cancer (EC) is the most common malignancy among women. Unopposed estrogen therapy, obesity, nulliparity, diabetes mellitus and arterial hypertension have been linked to an increased risk of EC. However, the molecular mechanisms of EC oncogenesis and metastasis have not yet been fully elucidated. Our recent studies of microRNA (miRNA) expression signatures revealed that the microRNA-1/133a (miR­1/133a) cluster is frequently downregulated in various types of human cancers. However, the functional role of the miR­1/133a cluster in EC cells is still unknown. Thus, the aim of this study was to investigate the functional significance of the miR­1/133a cluster and its regulated molecular targets, with an emphasis on the contributions of miR­1/133a to EC oncogenesis and metastasis. We found that the expression levels of miR­1 and miR­133a were significantly reduced in EC tissues. Moreover, restoration of mature miR­1 or miR­133a miRNAs significantly inhibited cancer cell migration and invasion, suggesting that these clustered miRNAs act as tumor suppressors. Prediction of miRNA targets revealed that phosphodiesterase 7A (PDE7A) was a potential target gene regulated by both miR­1 and miR­133a. PDE7A was confirmed to be overexpressed in EC clinical specimens and silencing of PDE7A significantly inhibited cancer cell migration and invasion. Our data demonstrated that downregulation of the miR­1/133a cluster promoted cancer cell migration and invasion via overexpression of PDE7A in EC cells. Elucidation of the molecular networks regulated by tumor-suppressive miRNAs will provide insights into the molecular mechanisms of EC oncogenesis and metastasis.

microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma.

Our recent study of the microRNA (miRNA) expression signature of hypopharyngeal squamous cell carcinoma (HSCC) revealed that microRNA-504 (miR-504) is significantly downregulated in HSCC tissues, suggesting that this miRNA is a candidate tumor suppressor. However, several previous reports indicated that miR-504 has an oncogenic function through targeting TP53. The aim of this study was to investigate the functional significance of miR-504 in cancer cells and to identify novel targets regulated by this miRNA in HSCC cells. First, we confirmed the downregulation of miR-504 in HSCC clinical specimens (P<0.0001) by qPCR. Using two sources of miR-504 to restore function, we observed significant inhibition of cancer cell proliferation in head and neck SCC (HNSCC) cell lines (FaDu, SAS and HSC3) and HCT116 colon carcinoma cells (p53+/+ and p53-/-). In HNSCC cells, induction of cell cycle arrest was observed by miR-504 transfection. To identify the molecular targets of miR-504, we performed gene expression analysis of miR-504 transfectants and in silico database analyses. Our data showed that cell cycle-related genes (RB1, CDK6, CDC23 and CCND1) were candidate target genes of miR-504. In HSCC clinical specimens, the expression of cyclin-dependent kinase 6 (CDK6) was significantly higher in cancer tissues compared to non-cancer tissues (P=0.0004). A significant inverse correlation between CDK6 and miR-504 expression was found (r=-0.43, P=0.0039). Expression of miR-504 inhibited CDK6 expression in HNSCC cells. Loss of tumor-suppressive miR-504 enhanced HSCC cell proliferation through targeting CDK6. The identification of novel tumor-suppressive miR-504-mediated molecular pathways and targets provide new insights into HSCC oncogenesis.

[Automatic extraction of corpus callosum from midsagittal head MR image and examination of Alzheimer-type dementia objective diagnostic system in feature analysis].

We studied the objective diagnosis of Alzheimer-type dementia based on changes in the corpus callosum. We examined midsagittal head MR images of 40 Alzheimer-type dementia patients (15 men and 25 women; mean age, 75.4+/-5.5 years) and 31 healthy elderly persons (10 men and 21 women; mean age, 73.4+/-7.5 years), 71 subjects altogether. First, the corpus callosum was automatically extracted from midsagittal head MR images. Next, Alzheimer-type dementia was compared with the healthy elderly individuals using the features of shape factor and six features of Co-occurrence Matrix from the corpus callosum. Automatic extraction of the corpus callosum succeeded in 64 of 71 individuals, for an extraction rate of 90.1%. A statistically significant difference was found in 7 of the 9 features between Alzheimer-type dementia patients and the healthy elderly adults. Discriminant analysis using the 7 features demonstrated a sensitivity rate of 82.4%, specificity of 89.3%, and overall accuracy of 85.5%. These results indicated the possibility of an objective diagnostic system for Alzheimer-type dementia using feature analysis based on change in the corpus callosum.

A study on the rehabilitation of cognitive function and short-term memory in patients with Alzheimer's disease using transcutaneous electrical nerve stimulation.

In some previous studies, transcutaneous electrical nerve stimulation (TENS) to the back was shown to improve non-verbal short-term and long-term memory as well as verbal fluency in patients in the early stage of Alzheimer's disease (AD). Moreover, the patients' physical, social and affective functions were also improved. In this study, the effects of TENS applied to the face were studied in patients with mild and severe AD. Fourteen patients with probable AD were used as subjects. To evaluate the effects of treatment, the subjects underwent two kinds of neuropsychological tests as well as a pupillary light reflex test. The pupillary light reflex test was chosen because it has been proven to show poorer results in cases of senile dementia. These three tests were carried out before the treatment, immediately after the treatment and 6 months after the treatment. Improvements were seen in subjects in the TENS groups and the effects of treatment were more significant in mild AD patients than in severe AD patients. However, the improvements were not maintained 6 months after the treatment. The possible mechanisms underlying the beneficial effects of TENS in AD patients are discussed in this paper.

Image-based diagnosis of Alzheimer-type dementia: measurements of hippocampal and ventricular areas in MR images.

We studied the possibility of objective diagnosis of Alzheimer-type dementia through radiological findings by evaluating cerebral and hippocampal atrophy in magnetic resonance images of patients with dementia. A statistically significant difference was seen in the hippocampus area index (HAI) and the ventricle area index (VAI) of healthy elderly individuals. Discriminant analysis with these two indexes demonstrated a sensitivity of 90.2% and a specificity of 81.8%, with an overall accuracy of 87.7%. Multiple discriminant analysis with VAI and HAI by stage of dementia showed an overall accuracy of 61.6% for discrimination of four stages. These results indicate that quantitative magnetic resonance imaging measurements can be used as an objective diagnostic technique for Alzheimer-type dementia.

[Application of run length matrix to magnetic resonance imaging diagnosis of Alzheimer-type dementia].

To examine the possibility of diagnosing Alzheimer-type dementia, we studied this condition using the run length matrix, on head MR images of 29 Alzheimer-type dementia patients (8 men, 21 women, 78.7 +/- 6.7 years) and healthy elderly controls (10 men, 19 women, 72.3 +/- 8.7 years) . The results showed that differences in GLN (gray level nonuniformity) and RLN (run length nonuniformity) were statistically significant. Furthermore, discriminant analysis based on GLN and RLN showed a rate of sensitivity of 69.0%, specificity 86.2%, and correct classification 77.6%. Although this rate of correct classification is inferior to the planimetric and volumetric methods, run length matrix is only one method of texture analysis. The results of this study indicate the possibility of MR imaging-based diagnosis of Alzheimer-type dementia with texture analysis including a run length matrix.