Analysis of local invasion and regional spread in malignant sublingual gland tumour: Implications for surgical planning.

Malignant tumours arising from the sublingual glands are very rare, and the extent and frequency of local invasion or regional spread in malignant sublingual gland tumour (MSLT) has not been fully studied due to the disease rarity. To provide comprehensive features of local and regional spread of MSLT, we reviewed 20 surgical cases for detailed pathological analyses among 26 cases diagnosed as having primary MSLT. Adenoid cystic carcinoma (ACC) was the most common pathological subtype, followed by mucoepidermoid carcinoma. Disease-free and overall survivals at 5 years were 76.1 % and 77.7 %, respectively. High-grade malignant tumours and grade 2-3 ACC accounted for 41.7 % and 85.7 %. Clinical and pathological extraparenchymal extensions were found in 34.6 % and 80.0 %, respectively. Tumour invasion to the lingual nerve and submandibular gland/ductal system were also detected in 40.0 % and 28.6 %. The incidences of lingual nerve invasion in ACC and ACC ≥4 cm were 30.8 % and 42.9 %. Regional nodal involvement occurred in seven of 26 cases, and all metastatic lymph nodes were found in neck levels Ib and IIa. In summary, a significant portion of MSLT cases consisted of high-grade tumours and grade 2-3 ACC; therefore local invasion into adjacent structures should be cautiously evaluated in cases of MSLT.

Astrocytic water channel aquaporin-4 modulates brain plasticity in both mice and humans: a potential gliogenetic mechanism underlying language-associated learning.

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.

STAT3 activation in endothelial cells is important for tumor metastasis via increased cell adhesion molecule expression.

Metastasis is a life-threatening feature of cancer and is primarily responsible for cancer patient mortality. Cross talk between tumor cells and endothelium is important for tumor progression and metastasis. However, very little is known about the mechanisms by which endothelial cells (ECs) that are close to tumor cells, respond to the tumor cells during tumor progression and metastasis. In this study, we exploited the use of EC-specific signal transducer activator of transcription 3 (STAT3) knockout mice to investigate the role of STAT3 in ECs in tumor progression and metastasis. We found that the loss of STAT3 in ECs did not affect primary Lewis lung carcinoma (LLC) tumor growth, but it reduced in vivo LLC metastasis in experimental and spontaneous metastasis models. Mechanistically, STAT3 activation upregulated cell adhesion molecule expression, including E-selectin and P-selectin, in murine endothelial MS-1 cells treated with tumor cell-conditioned media in vitro and in pre-metastatic lungs of tumor-bearing mice in vivo. We also found that both E-selectin and P-selectin were, at least in part, responsible for STAT3-induced adhesion and invasion of LLC cells through an EC monolayer. However, tumor cell-conditioned media from B16F10 melanoma cells did not activate STAT3 in MS-1 cells. As a result, EC STAT3 knockout did not affect B16F10 melanoma cell metastasis. In addition, various human cancer cells activated STAT3 in human ECs (HUVECs), resulting in increased cell adhesion molecule expression. Collectively, our findings demonstrate that STAT3 activation in ECs promotes tumor metastasis through the induction of cell adhesion molecules, demonstrating a role for ECs in response to tumor cells during tumor metastasis.

Changes in cognitive function and brain glucose metabolism in elderly women with subjective memory impairment: a 24-month prospective pilot study.

OBJECTIVES: Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI. MATERIALS AND METHODS: Clinical evaluation, comprehensive neuropsychological test, and 18 F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. RESULTS: All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: -0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (ß = 0.43, P = 0.02). CONCLUSIONS: Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time.

Concurrent Post-Transplantation Diabetes Mellitus in Renal Allograft Recipients With Immunoglobulin A Nephropathy.

BACKGROUND: The prevalence of post-transplantation immunoglobulin A nephropathy (PTIgAN) and diabetes mellitus (PTDM) increases with time after transplantation, and recognition and management of these conditions is becoming more important in renal allograft recipients as graft survival increases. METHODS: We explored the influence of concurrent PTDM on renal allograft histology and function in 111 cases with PTIgAN diagnosed from 2000 to 2010 at our institution. RESULTS: Sixteen patients (14.4%) had PTDM at the time of diagnosis of PTIgAN, which increased to 28 patients (25.2%) at the last follow-up (10.4 years after transplantation). Donor ages were younger in PTIgAN patients with concurrent PTDM. However, other clinical and demographic data were not significantly different between PTIgAN patients with and without PTDM. Histologically, Banff "mm" scores were higher and "M1" of the Oxford classification was more frequent in PTIgAN patients with concurrent PTDM than in patients without PTDM, but the difference did not reach statistical significance. Serum creatinine levels and proteinuria at the time of biopsy and overall graft survival did not vary according to the presence of PTDM both at biopsy and at the last follow-up. CONCLUSIONS: Concurrent PTDM does not significantly influence graft function or outcome for 10 years after transplantation in PTIgAN patients.

Predisposition to and effects of methamphetamine use on the adolescent brain.

Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users. Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain. Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents.

First norovirus outbreaks associated with consumption of green seaweed (Enteromorpha spp.) in South Korea.

In February 2012, an outbreak of gastroenteritis was reported in school A; a successive outbreak was reported at school B. A retrospective cohort study conducted in school A showed that seasoned green seaweed with radishes (relative risk 7·9, 95% confidence interval 1·1-56·2) was significantly associated with illness. Similarly, a case-control study of students at school B showed that cases were 5·1 (95% confidence interval 1·1-24·8) times more likely to have eaten seasoned green seaweed with pears. Multiple norovirus genotypes were detected in samples from students in schools A and B. Norovirus GII.6 isolated from schools A and B were phylogenetically indistinguishable. Green seaweed was supplied by company X, and norovirus GII.4 was isolated from samples of green seaweed. Green seaweed was assumed to be linked to these outbreaks. To our knowledge, this is the first reported norovirus outbreak associated with green seaweed.

A case-controlled, retrospective, comparative study on the use of biodegradable synthetic polyurethane foam versus polyvinyl acetate sponge after nasal fracture reduction.

One of the most frequently used packing materials in closed reduction of a nasal bone fracture is the hydroxylated polyvinyl acetate sponge (PVAS; Merocel(®)); however this may cause synechia, epistaxis, and pain. Synthetic polyurethane foam (SPF; Nasopore(®) Forte) has recently been used in septoplasty to prevent synechia or restenosis and haematoma formation. The purpose of this study was to compare the effects of PVAS and SPF on postoperative appearance and discomfort following the reduction of nasal bone fractures. We retrospectively reviewed all patient questionnaires and medical histories, and clinical photographs and computed tomography scans obtained before and after surgery. Outcomes were assessed using the Global Aesthetic Improvement Scale (GAIS) score and visual analogue scale (VAS) scores, which were used to assess discomfort during the 6-month follow-up period. Postoperatively, there was no statistically significant difference in the GAIS for the two packing materials (P > 0.05). Postoperative epistaxis was observed at a significantly lower rate in the SPF group than in the PVAS group, whereas anterior rhinorrhea and posterior nasal drip occurred at significantly higher rates following removal of packing in the SPF group (P < 0.05). The results of this study suggest that synthetic dissolvable polyurethane may be a reliable alternative material for nasal packing and postoperative management following the reduction of nasal bone fractures.

Optical properties of white organic light-emitting devices fabricated utilizing a mixed CaAl12O19:Mn4+ and Y3Al5O12:Ce3+ color conversion layer.

White organic light-emitting devices (OLEDs) were fabricated by combining a blue OLED with a color conversion layer made of mixed Y3Al5O12:Ce3+ green and Ca2AlO19:Mn4+ red phosphors. The X-ray diffraction patterns showed that Ce3+ ions in the Y3Al5O12:Ce3+ phosphors completely substituted for the Y3+ ions and the Mn4+ ions in the CaAl12O19:Mn4+ phosphors completely substituted for the Ca2+ ions. Electroluminescence spectra at 11 V for the OLEDs fabricated utilizing a color conversion layer showed that the Commission Internationale de l'Eclairage coordinates for the Y3Al5O12:Ce3+ and CaAl12O19:Mn4+ phosphors mixed at the ratio of 1:5 and 1:10 were (0.31, 0.34) and (0.32, 0.37), respectively, indicative of a good white color.

Decreased postoperative pain after reduction of fractured nasal bones using a nerve block of the anterior ethmoidal nerve.

There is consensus that all patients should experience minimal pain following reduction of a fractured nasal bone. The issue requiring further study is what technique will provide patients with the greatest pain relief following the reduction of nasal fractures. This study investigated the use of an anterior ethmoidal nerve block as preemptive analgesia for the management of postoperative pain associated with reduction of nasal bone fractures. The medical documents of 85 patients were reviewed for a retrospective case-controlled comparative study. Patients in the nerve block group (n=45) were injected with 2% lidocaine containing epinephrine into the anterior ethmoidal nerve and dorsal periosteum, and those in the control group (n=40) were not. The rate of patients requiring postoperative injectable analgesics was compared between the two groups. The rate of patients who received a postoperative analgesic injection was significantly lower in the nerve block group than in the control group (P=0.034). The use of an anterior ethmoidal nerve block and dorsal periosteal injection of anaesthetic solution during reduction of fractured nasal bones under general anaesthesia resulted in the effective reduction of postoperative pain. Thus, this is regarded as a good method for enhancing patient quality of care and compliance in the reduction of fractured nasal bones.

Effects of the mixing ratio of the CaAl12O19:mn and Zn2SiO4:mn color-conversion layer on the color tunable emissions of white organic light-emitting devices.

The optical properties of white organic light-emitting devices (WOLEDs) fabricated utilizing a CaAl12O19:Mn and Zn2SiO4:Mn phosphor layer were investigated. X-ray diffraction patterns for CaAl12O19:Mn and Zn2SiO4:Mn phosphors showed that Mn ions in the CaAl12O19:Mn phosphors were completely substituted into Ca ions and that Mn ions in the Zn2SiO4:Mn phosphors were completely substituted into Zn ions. Field emission scanning electron microscopy images showed that the size of the CaAl12O19:Mn phosphor was approximately between 0.1 and 3 microm, and that the size of the Zn2SiO4:Mn phosphor was smaller than 7 microm. The color coordinates of the electroluminescence spectra for WOLEDs with phosphor thicknesses of 0.25 and 0.35 mm shifted to the white emission side because the generated blue light from the blue OLEDs combined with the red and green lights was converted by the CaAl12O19:Mn and the Zn2SiO4:Mn phosphor down-conversion layers.

Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial.

AIMS: Prominent anxiety symptoms are related to poor clinical course and outcome in major depressive disorder (MDD). The aim of this randomised, open-label, controlled study is to compare the efficacy and tolerability of mirtazapine in the form of orally disintegrating tablets against paroxetine in treating MDD patients with anxiety symptoms. METHODS: A total of 60 MDD patients with a score above 18 on the Hamilton Anxiety Rating Scale (HARS) were randomly assigned to 8 weeks of fixed dosing treatment with mirtazapine (15-30 mg/day) and paroxetine (10-20 mg/day). Efficacy was primarily assessed with the HARS and with the 17-item Hamilton Depression Rating Scale (HDRS) at weeks 1, 2, 4 and 8 after treatment. Tolerability was assessed from adverse events. RESULTS: The generalised estimating equations (GEE) models showed that the rates of improvement in HDRS scores from baseline to week 8 were similar between mirtazapine and paroxetine groups. However, patients with mirtazapine exhibited earlier improvement in HARS scores at weeks 1 and 2. Week-by-week GEE models showed that these significant differences in improvement of HARS scores between the two treatment groups were detectable from the first evaluation after the treatment (week 1) and maintained through week 2. There was no difference in the overall frequency of adverse events experienced between the two treatment groups. The most common adverse event in the mirtazapine group was somnolence (n = 8), whereas that in the paroxetine group was gastrointestinal discomfort (n = 9). CONCLUSIONS: Mirtazapine and paroxetine were equally effective and well tolerated for the depressive symptoms in MDD patients with the high level of anxiety symptoms. Mirtazapine was, however, more effective in reducing the anxiety symptoms than paroxetine in the early weeks of treatment, suggesting that mirtazapine may have an earlier-onset action for the anxiety symptoms in MDD patients.

Molecular epidemiology and genetic diversity of human astrovirus in South Korea from 2002 to 2007.

The present study was conducted to survey the prevalence and genotypic distribution of human astrovirus (HAstV) circulating in South Korea. Of 160,027 patients with acute gastroenteritis, 2,057 (1.3%) were positive for HAstV antigen. We determined the genotypes of 187 HAstV strains collected from laboratories across the country. Genetic analysis revealed genotype 1 to be the most prevalent, accounting for 72.19% of the strains, followed by genotypes 8 (9.63%), 6 (6.95%), 4 (6.42%), 2 (3.21%) and 3 (1.60%). Our findings indicate that HAstV is less common but, even so, a potentially important viral agent of gastroenteritis in South Korea, with significant genetic diversity among circulating HAstV strains.

Genotypes of the circulating rotavirus strains in the seven prevaccine seasons from September 2000 to August 2007 in South Korea.

A Korean nationwide surveillance on circulating rotavirus strains was conducted from September 2000 to August 2007 aiming to obtain prevaccine data for predicting vaccine effectiveness. The predominant strains among the 2779 strains analyzed varied annually and only approximately 50% had either a G or a P antigen present in both RotaTeq (Merck & Co. Inc., Whitehouse Station, NJ, USA) and Rotarix (GlaxoSmithKline, Brentford, UK).

Genetic analysis of norovirus GII.4 variants circulating in Korea in 2008.

Noroviruses are the enteric pathogens most commonly responsible for infectious gastroenteritis and outbreaks of foodborne illness. The GII.4 norovirus, in particular, is responsible for the majority of epidemics. Here, we present data on the distribution of norovirus genotypes in Chungnam, Korea, in 2008, measure genetic variation among GII.4 strains, and compare Korean GII.4 variants with reference strains based on the 237-bp junction of ORF1 and ORF2. We detected 139 different strains, which formed two distinct genetic clusters with significant sequence diversity. One Korean cluster (2008-Korea_a) showed high similarity to the Sakai cluster that appeared in Japan and Europe in 2006. The other cluster (2008-Korea_b) was unique and unrelated to previously reported clusters. Genotype GII.4 was confirmed as the predominant cause of norovirus epidemics in Korea. Foodborne norovirus infections, on the other hand, were generally caused by emerging GII.4 genetic variants similar to those responsible for global epidemics.

Assessment of cell surface properties and adhesion potential of selected probiotic strains.

AIM: To evaluate the physicochemical cell surface and adhesive properties of selected probiotic strains for human use. METHODS AND RESULTS: Probiotic strains, Bifidobacterium longum B6, Lactobacillus acidophilus ADH, Lactobacillus paracasei, Lactobacillus rhamnosus GG, Lactobacillus brevis, Lactobacillus casei, Leuconostoc mesenteroides and Pediococcus acidilactici were tested for the physicochemical properties of cell surfaces and the adhesion abilities against foodborne pathogens. Bif. longum B6 (53.6%) and Lact. rhamnosus GG (46.5%) showed the highest hydrophobicity, while the least affinity to xylene was observed in Ped. acidilactici (10.4%). Bifidobacterium longum B6 showed the strongest coaggregation phenotype with Listeria monocytogenes (53.0%), Shigella boydii (42.0%) and Staphylococcus aureus (45.9%). Lactobacillus rhamnosus GG had the strong binding ability to Caco-2 cells and effectively inhibited the adhesion of L. monocytogenes, Salmonella Typhimurium, Sh. boydii and Staph. aureus to Caco-2 cells. The hydrophobicity was highly correlated with coaggregative abilities and competitive inhibition, suggesting a good relationship between in vitro adhesion and in vivo colonization. CONCLUSION: The results suggest that Bif. longum B6 and Lact. rhamnosus GG can be candidate probiotics available for human consumption. SIGNIFICANCE AND IMPACT OF THE STUDY: Because the use of probiotic strains has been more concerned with their beneficial effects in the GI tract, it is essential to examine the potential of probiotic strains based on the physicochemical properties in terms of bacterial-binding and adhesion capabilities.

Oligonucleotide microarray analysis of apoptosis induced by 15-methoxypinusolidic acid in microglial BV2 cells.

BACKGROUND AND PURPOSE: We conducted a genome wide gene expression analysis to explore the biological aspects of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis and tried to confirm the suitability of 15-MPA as a therapeutic candidate for CNS injuries focusing on microglia. EXPERIMENTAL APPROACH: Murine microglial BV2 cells were treated with 15-MPA, and their transcriptome was analysed by using oligonucleotide microarrays. Genes differentially expressed upon 15-MPA treatment were selected for RT-PCR (reverse transcription-polymerase chain reaction) analysis to confirm the gene expression. Inhibition of cell proliferation and induction of apoptosis by 15-MPA were examined by bromodeoxyuridine assay, Western blot analysis of poly-ADP-ribose polymerase and flow cytometry. KEY RESULTS: A total of 514 genes were differentially expressed by 15-MPA treatment. Biological pathway analysis revealed that 15-MPA induced significant changes in expression of genes in the cell cycle pathway. Genes involved in growth arrest and DNA damage [gadd45alpha, gadd45gamma and ddit3 (DNA damage-inducible transcript 3)] and cyclin-dependent kinase inhibitor (cdkn2b) were up-regulated, whereas genes involved in cell cycle progression (ccnd1, ccnd3 and ccne1), DNA replication (mcm4, orc1l and cdc6) and cell proliferation (fos and jun) were down-regulated. RT-PCR analysis for representative genes confirmed the expression levels. 15-MPA significantly reduced bromodeoxyuridine incorporation, increased poly-ADP-ribose polymerase cleavage and the number of apoptotic cells, indicating that 15-MPA induces apoptosis in BV2 cells. CONCLUSION AND IMPLICATIONS: 15-MPA induced apoptosis in murine microglial cells, presumably via inhibition of the cell cycle progression. As microglial activation is detrimental in CNS injuries, these data suggest a strong therapeutic potential of 15-MPA.

Anterior cricoid split procedure with transposition of cricoid cartilage segment.

OBJECTIVE: In order to improve the outcome and to reduce the post-operative care burden following the anterior cricoid split procedure, we modified the procedure to involve splitting only the cricoid cartilage, not the mucosa deep to the cartilage. In addition, we transposed the cricoid cartilage segment after division of the cricoid ring in the midline. CASE REPORT: We present the use of our modification in a 19-month-old boy with early-stage subglottic stenosis. RESULTS: The technique was performed in one surgical field, and the graft material obtained had the same thickness as the cricoid cartilage. Because there was no intraluminal break, this procedure allowed the patient to avoid the complications of prolonged stenting, and resulted in more rapid extubation. CONCLUSION: The anterior cricoid split procedure with transposition of the cricoid cartilage segment may be a useful treatment option for early-stage subglottic stenosis, with improved outcomes and a reduced post-operative care burden.

Extracorporeal oxygenation support for curative surgery in a patient with papillary thyroid carcinoma invading the trachea.

OBJECTIVE: Local extension of thyroid carcinoma can result in massive invasion of the trachea, causing severe airway compromise. The pre- and peri-operative management of such airway compromise is difficult but critical. We report the use of extracorporeal oxygenation support as an alternative peri-operative airway management option in such a situation. This approach facilitated curative surgery in a patient with papillary thyroid carcinoma invading the trachea. METHOD: We present a case report regarding extracorporeal oxygenation support in a patient with locally advanced thyroid carcinoma. RESULTS: The patient was a 68-year-old woman with aggressive thyroid papillary carcinoma invading the trachea. The airway was almost totally obstructed, and tracheal resection and end-to-end anastomosis was planned. A venovenous bypass catheter was placed for cardiopulmonary bypass, using the bilateral femoral veins. Curative surgery and reconstruction were then performed successfully, under general anaesthesia assisted by cardiopulmonary bypass oxygenation. CONCLUSION: Cardiopulmonary bypass oxygenation is a safe and effective alternative airway management option in patients with locally aggressive thyroid cancer.