Effects of melatonin receptor expression on prognosis and survival in oral squamous cell carcinoma patients.

Melatonin receptors can inhibit breast and prostate cancers; however, little is known regarding their effects on oral squamous cell carcinoma. In this study, we collected specimens from 81 patients with oral squamous cell carcinoma and analysed clinicopathological data retrospectively. In addition, the expression of the melatonin receptor was analysed immunohistochemically. Survival rates were calculated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed based on the Cox proportional-hazards model. Further, an in vitro study was performed using YD15 cells. The cells were transfected with siRNA targeting melatonin receptor 1A and 1B for evaluating the malignancy of melatonin receptors by western blotting, trypan blue-exclusion, colony-forming, wound-healing, and invasion assays. Survival decreased as melatonin receptor expression and clinical and pathological tumour-node-metastasis stages increased. A Cox proportional-hazard model showed that melatonin receptor 1A may serve as a significant predictor of the survival rate of patients with oral squamous cell carcinoma [hazard ratio = 1.423, 95% confidence interval (CI) = 1.019-1.988, p = 0.038]. Melatonin receptor 1A and 1B knockdown significantly suppressed proliferation, migration ability, and invasion ability of YD15 cells in vitro. Our findings reveal that inhibiting melatonin receptor expression may suppress oral squamous cell carcinoma development.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Surfactant protein D alleviates eosinophil-mediated airway inflammation and remodeling in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Surfactant protein D (SPD) is a member of the collectin family that lines the airway epithelial cells with host defense. However, the role of SPD in the pathogenesis of aspirin-exacerbated respiratory disease (AERD) is still unclear. METHODS: The serum SPD level was measured in patients with AERD (n = 336), those with aspirin-tolerant asthma (ATA, n = 442), and healthy controls (HC, n = 104). Polymorphisms of SFTPD in the study subjects were analyzed. The effect of LTE4 on SPD production through eosinophil infiltration was investigated in BALB/c mice. The protective function of SPD against eosinophils inducing inflammation and remodeling was assessed in vitro/vivo. The potential efficacy of nintedanib against airway remodeling through the production of SPD was evaluated. RESULTS: The serum SPD level was significantly lower (P < .001) in AERD compared with ATA patients, and negatively correlated with fall in FEV1 (%) after lysine-aspirin bronchoprovocation test and/or the urinary LTE4 level. In addition, polymorphism of SFTPD at rs721917 was significantly different in the study subjects (odds ratio, 1.310; 95% confidence intervals, 2.124-3.446; P = .002). LTE4-exposed mice showed an increased eosinophil count with a decreased SPD level in bronchoalveolar lavage fluid. Eosinophils increased α-smooth muscle actin expression in airway epithelial cells, which was attenuated by SPD treatment. Furthermore, nintedanib protected the airway epithelial cells against eosinophils by enhancing the production of SPD. CONCLUSION: The decreased level of SPD in AERD was associated with airway inflammation/remodeling under the eosinophilic condition, suggesting that modulation of SPD may provide a potential benefit in AERD.

Expression of the glutamine metabolism-related proteins glutaminase 1 and glutamate dehydrogenase in canine mammary tumours.

Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumour growth and glutamine metabolism. Because of their similarities, canine mammary carcinomas are useful for studying human breast cancer. Accordingly, we investigated the correlations between the expression of glutamine metabolism-related proteins and the pathological features of canine mammary tumours. We performed immunohistochemical and western blot analysis of 39 mammary tumour tissues. In immunohistochemical analysis, the expression of glutaminase 1 (GLS1) in the epithelial region increased according to the histological grade (P < .005). In the stromal region, complex-type tumours displayed significantly higher GLS1 intensity than simple-type tumours. However, glutamate dehydrogenase expression did not show the same tendencies as GLS1. The western blot results were consistent with the immunohistochemical findings. These results suggest that the expression of GLS1 is correlates with clinicopathological factors in canine mammary tumours and shows a similar pattern to human breast cancer.

Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly.

BACKGROUND: Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. OBJECTIVE: We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. METHODS: A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE concentrations were significantly higher in patients with asthma than in controls [median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001]. Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of covariables [SE-IgE-high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86-30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly.

TLR2-dependent amelioration of allergic airway inflammation by parasitic nematode type II MIF in mice.

In our previous studies, the recombinant type II macrophage migration inhibitory factor homologue (rAs-MIF) secreted from Anisakis simplex suppressed experimental inflammation mouse model through IL-10 production and CD4(+)CD25(+)Foxp3(+) T-cell recruitment. Also, TLR2 gene expression was significantly increased following rAs-MIF treatment. To know the relation between TLR2 and amelioration mechanisms of rAs-MIF, we induced allergic airway inflammation by ovalbumin and alum with or without rAs-MIF under TLR2 blocking systems [anti-TLR2-specific antibody (α-mTLR2 Ab) treatment and using TLR2 knockout mice]. As a result, the amelioration effects of rAs-MIF in allergic airway inflammation model (diminished inflammation and Th2 response in the lung, increased IL-10 secretion, CD4(+)CD25(+)Foxp3(+) T-cell recruitment) were diminished under two of the TLR2 blocking model. The expression of TLR2 on the surface of lung epithelial cell was significantly elevated by rAs-MIF treatment or Pam3CSK (TLR2-specific agonist) treatment, but they might have some competition effect on the elevation of TLR2 expression. In addition, the elevation of IL-10 gene expression by rAs-MIF treatment was significantly inhibited by α-mTLR2 Ab or Pam3CSK pretreatment. In conclusion, anti-inflammatory effects of the rAs-MIF on OVA-induced allergic airway inflammation might be closely related to TLR2.

Two cases of cytarabine syndrome successfully resolved by desensitization

No disponible

Electroporation markedly improves Sleeping Beauty transposon-induced tumorigenesis in mice.

The Sleeping Beauty (SB) transposon system is an important tool for genetic studies. It is used to insert a gene of interest into the host chromosome, thus enabling permanent gene expression. However, this system is less useful in higher eukaryotes because the transposition frequency is low. Efforts to improve the efficacy of the SB transposon system have focused on the method of gene delivery, but although electroporation has recently attracted much attention as an in vivo gene delivery tool, the simultaneous use of electroporation and the SB transposon system has not been studied for gene transfer in mice. In this study, electroporation was used in a model of SB transposon-induced insertional tumorigenesis. Electroporation increased the rate of tumor development to three times that of the control group. There was no difference in phenotype between tumors induced with the SB transposon system alone and those induced by the SB transposon and electroporation. Electroporation therefore may be an efficient means of improving the efficacy of gene transfer via the SB transposon system.

Effects of celecoxib on hematoma and edema volumes in primary intracerebral hemorrhage: a multicenter randomized controlled trial.

BACKGROUND AND PURPOSE: We investigated the effect of celecoxib, a selective inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a multicenter, randomized, controlled, and open with blinded end-point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end-point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut-off value, 20%). RESULTS: The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end-point analysis using cut-off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end-points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow-up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058). CONCLUSIONS: In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.

Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy.

Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.

Association of CXCL1 promoter polymorphism with ischaemic stroke in Korean population.

This is a pilot study analysing association of chemokine gene polymorphisms (CXCL1, rs3117604; CXCL2, rs3806792; CCL2, rs2857656 and rs3760396; CCL5, rs2107538) in Korean patients with ischemic stroke (IS) (n = 120) and age-matched controls (n = 267). The CXCL1 gene and particularly T allele of rs3117604 was associated with IS.

Oral health status of male adolescent smokeless tobacco users in Saudi Arabia.

Few studies have evaluated the oral effects of smokeless tobacco use in adolescents. This study described the oral health status of adolescents who were daily users of local smokeless tobacco (shamma) in Saudi Arabia. A convenience sample of 270 middle-school male students completed a questionnaire and received an oral examination and a saliva cotinine test. Among the students, 96% had plaque deposits (mean plaque index score 1.66); 41% had gingivitis (mean clinical attachment loss 1.1 mm); 56% had dental caries (mean decayed, missing, filled teeth score 2.1) and 86% had at least I mucosal lesion. The levels of plaque, gingivitis, dental caries and periodontitis among smokeless tobacco users were similar to those of most adolescents regardless of tobacco use. Almost 9/10 students had a mucosal lesion that could be related to smokeless tobacco use. Strong measures should be taken to increase students' awareness of the adverse health effects of tobacco use and to control their access to tobacco.

Oral health status of male adolescent smokeless tobacco users in Saudi Arabia

Few studies have evaluated the oral effects of smokeless tobacco use in adolescents. This study described the oral health status of adolescents who were daily users of local smokeless tobacco [shamma] in Saudi Arabia. A convenience sample of 270 middle-school male students completed a questionnaire and received an oral examination and a saliva cotinine test. Among the students, 96% had plaque deposits [mean plaque index score 1.66]; 41% had gingivitis [mean clinical attachment loss 1.1 mm]; 56% had dental caries [mean decayed, missing, filled teeth score 2.1] and 86% had at least 1 mucosal lesion. The levels of plaque, gingivitis, dental caries and periodontitis among smokeless tobacco users were similar to those of most adolescents regardless of tobacco use. Almost 9/10 students had a mucosal lesion that could be related to smokeless tobacco use. Strong measures should be taken to increase students' awareness of the adverse health effects of tobacco use and to control their access to tobacco

Potential effects of tooth-brushing on human dentin wear following exposure to acidic soft drinks.

This study used scanning electron microscopy and atomic force microscopy to examine the short-term potential effects of brushing time and the start-time of tooth-brushing after demineralization on primary dentin wear in vitro. Thirty-six noncarious primary central incisors were assigned to 12 experimental groups. Exposure to cola drinks was used to initiate the demineralization process. Three brushing times (5, 15 and 30 s) and four start-times of brushing (0, 30, 60 and 120 min) after an erosive attack were used for the abrasion process. Tooth-brushing the softened dentin surface led to increases in the open tubular fraction and microstructural changes on the dentin surface. Brushing immediately after exposure to cola resulted in the greatest irreversible dentin loss, whereas brushing 60 or 120 min after pretreatment resulted in the least irreversible dentin loss. However, brushing time had no effect on the irreversible loss of dentin wear. Based on these experimental results, tooth-brushing should be performed at least 60 min after consuming a cola drink to achieve the desired tooth cleaning and avoid the introduction of surface lesions on dentin.

Marker-free registration for the accurate integration of CT images and the subject's anatomy during navigation surgery of the maxillary sinus.

OBJECTIVE: This study compared three marker-free registration methods that are applicable to a navigation system that can be used for maxillary sinus surgery, and evaluated the associated errors, with the aim of determining which registration method is the most applicable for operations that require accurate navigation. METHODS: The CT digital imaging and communications in medicine (DICOM) data of ten maxillary models in DICOM files were converted into stereolithography file format. All of the ten maxillofacial models were scanned three dimensionally using a light-based three-dimensional scanner. The methods applied for registration of the maxillofacial models utilized the tooth cusp, bony landmarks and maxillary sinus anterior wall area. The errors during registration were compared between the groups. RESULTS: There were differences between the three registration methods in the zygoma, sinus posterior wall, molar alveolar, premolar alveolar, lateral nasal aperture and the infraorbital areas. The error was smallest using the overlay method for the anterior wall of the maxillary sinus, and the difference was statistically significant. CONCLUSION: The navigation error can be minimized by conducting registration using the anterior wall of the maxillary sinus during image-guided surgery of the maxillary sinus.

Evaluation of overnight storage conditions for autologous peripheral blood stem cell products: comparison of three different conditions.

BACKGROUND: Overnight (ON) storage of peripheral blood stem cell (PBSC) occurs frequently in clinical settings. However, there are no standard guidelines for optimal storage conditions of freshly harvested PBSC. The aim of this study was to investigate the influence of storage temperatures on the quality of autologous PBSC and establish optimal storage conditions before cryopreservation. METHODS: A retrospective analysis was performed on 260 PBSC harvests according to pre-cryopreservation conditions: immediate processing or ON storage at room temperature (RT). For direct comparison, 30 autologous PBSC products were collected prospectively and prepared under three different pre-cryopreservation conditions: immediate processing, ON storage at 4°C and ON storage at RT. The recovery of CD34(+) cells, post-thaw CFU-GM count and viability were analysed. RESULTS: Retrospective analysis revealed that post-thaw CFU-GM count was significantly lower when PBSC were stored ON at RT compared to when immediately processed (136·4 vs. 409·6/µl). Prospective analysis showed a mean recovery of CD34(+) cells of 65·5 ± 25·1%, 70·5 ± 27·4% and 35·9 ± 25·1% for immediate processing, ON storage at 4°C and ON storage at RT, respectively. Similarly, mean viability and CFU-GM counts were significantly reduced when stored ON at RT compared to when immediately processed or stored ON at 4°C (60·4 ± 25·6 vs. 84·1 ± 12·9 vs. 82·7 ± 12·6%, 15·7 ± 25·7 vs. 398·5 ± 906·2 vs. 350·0 ± 847·9/µl, respectively). CONCLUSIONS: ON storage of autologous PBSC at RT significantly decreased the quality of HPCs. These data indicate that ON storage of autologous PBSC at 4°C would be the most reasonable approach for maintaining the quality of HPCs when immediate processing is not possible.

Investigation of the hair of patients with scalp psoriasis using atomic force microscopy.

BACKGROUND: Psoriasis affects not only the soft keratin of the skin, but also hard keratin, such as nails and hair. However, few studies have described the changes induced in the hair of patients with psoriasis. AIM: Using atomic force microscopy (AFM), we investigated the morphological property of hair samples taken from the scalp of patients with psoriasis. METHODS: Lesional and nonlesional hairs taken from 15 patients with scalp psoriasis were investigated. Hairs from 15 healthy adults were also examined as controls. Using AFM, surface images were taken of an area of 20 × 20 µm(2), with 512 × 512 pixels and a scan speed of 0.8 lines/s. results: Pits were frequently seen in the hair shafts of patients with psoriasis, similar to those seen in their nail plates. Macropit number, scale thickness and surface roughness were all significantly increased in lesional hairs compared with both nonlesional and control hairs, and macropits and scale thickness were also increased in nonlesional hairs compared with control hairs. CONCLUSIONS: The hair shafts of patients with scalp psoriasis exhibited the same macropits seen in their nails. Both lesional and nonlesional hairs had similar changes in morphological structure compared with controls. This supports the generalized nature of psoriasis, with changes in hair structure being analogous to the changes seen in skin and nails.

Effects of self-ligating brackets on the surfaces of stainless steel wires following clinical use: AFM investigation.

In orthodontic treatment, the frictional force between the archwire and bracket reduces the effectiveness of orthodontic treatment. The frictional force is affected not only by the geometry of the self-ligating brackets but also by physical changes between the bracket slots and archwire surfaces during sliding movement. This study examined quantitatively the effect of self-ligating treatments on the surfaces of stainless steel (SS) archwires during tooth movement in vivo by atomic force microscopy. Orthodontic 0.019″ × 0.025″ SS archwires after clinical use with the first bicuspid-extraction treatment were employed using the Damon 3MX(®) SS self-ligating brackets, Clippy-C(®) ceramic self-ligating brackets, and Kosaka(®) SS brackets. Intact SS archwires were used as the control group. All SS archwires after clinical use showed severe scratches and significantly higher roughness caused by frictional interactions between the brackets and archwires (p < 0.0001 vs. control). The descending order of surface roughness was the SS archwires treated, with ceramic self-ligating brackets, with conventional SS brackets, and with SS self-ligating brackets (p < 0.001). These findings suggest that an orthodontic treatment with SS self-ligating brackets may require smaller orthodontic forces than that with ceramic self-ligating brackets or conventional SS brackets.

Patient with positional wheezing due to endobronchial lipomatous hamartoma.

Endobronchial hamartoma is a rare form of pulmonary hamartoma, and endobronchial lipomatous hamartomas are even rarer. We describe the case of a 39-year-old man who presented with a two-year history of dyspnea on exertion and wheezing over the left chest only while lying on his left side. The patient was diagnosed with endobronchial lipomatous hamartoma occluding the left main bronchus. He underwent a superior segmentectomy of the left lower lobe, which promptly relieved the dyspnea and positional wheezing. To our knowledge, fewer than 10 such cases are cited in the English literature, none of which presented with positional wheezing. This patient represents the first case of focal and positional wheezing resulting from endobronchial lipomatous hamartoma.