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Mobility affects the ability of patients to live independently post-discharge. This study aimed to identify factors affecting the achievement of independent walking in patients after living donor liver transplantation (LDLT).This retrospective cohort study involved 40 patients who had undergone LDLT for severe hepatic dysfunction (Child-Pugh class C) in the Department of Transplant Surgery of our hospital between January 2010 and October 2019 and received physiotherapy during hospital admission. To identify factors associated with independent walking, we classified patients based on their ability to walk independently. We performed multiple logistic regression analyses with the patients' attributes, biochemical tests, and physical function, considering the achievement or non-achievement of independent walking as dependent variables, and factors that were significantly different between the 2 groups in the univariate analysis (P.05) as independent variables, after adjusting for age, sex, and body mass index. Moreover, we calculated cutoff values from the receiver operating characteristic (ROC) curves.All patients suffered from severe hepatic dysfunction (Child-Pugh class C). The mobility Functional Independence Measure score following rehabilitation was positively correlated with the psoas major muscle index within 1 month after LDLT and at the beginning of physiotherapy. The only factor associated with achieving independent walking at the end of physiotherapy (on discharge) was the psoas major muscle index within 1 month of LDLT (odds ratio = 35.03, P.05), and its cutoff value, calculated from the ROC curves curve, was 4.46.Psoas major skeletal muscle mass is a reliable index for independent walking after LDLT.

Aims Little is known about the relationship between medication adherence for oral hypoglycemic agents (OHAs) and glycemic control after adjusting healthy adherer effect in large scale study. Thus, adjusting for health-related behaviors, we investigated the clinical variables associated with medication adherence and the relationship between medication adherence and glycemic control using a large claims database. Methods Analyzed were 8805 patients with diabetes whose medication records for OHA were available for at least 1 year. Medication adherence was evaluated by the proportion of days covered (PDC). Multivariate logistic regression model was used to identify clinical variables significantly associated with non-adherence. Multiple regression analysis evaluated the relationship between PDC and HbA1c after adjusting for health-related behaviors. Results Mean PDC was 80.1% and 32.8% of patients were non-adherence. Logistic analysis indicated that older age and taking concomitant medications were significantly associated with adherence while skipping breakfast (odds ratio 0.66 [95% CI 0.57–0.76]), late-night eating (0.86 [0.75–0.98]), and current smoking (0.89 [0.80–0.99]) were significantly associated with non-adherence. Conclusions Skipping breakfast, late-night eating and current smoking were significantly associated with medication adherence, suggesting that clinicians pay attention to those health-related behaviors to achieve good medication adherence.

Aim To examine the association between treatment-achieved HbA1c values and incidence of both coronary artery disease (CAD) and severe eye disease with different diabetes treatments. Methods Associations of treatment-achieved HbA1c were investigated in various treatment groups [diet only; insulin; sulphonylurea (SU) alone; SU with glinides; and antihyperglycaemic agents other than glinides, SU or insulin] taken from a nationwide claims database of 14,633 Japanese diabetes patients. Cox’s regression analysis examined risks over a 5.1-year follow-up. Results A significant linear trend was associated with HbA1c levels and CAD events in the diet-only group, and CAD risks were significantly higher in insulin and SU groups with HbA1c ≤ 7.0% and > 8.0% than in the diet-only group with HbA1c ≤ 7.0%. In contrast to CAD, a linear association was observed regardless of treatment modality between achieved HbA1c levels and risk of severe diabetic eye disease, but with no significant difference in eye disease risk between groups with HbA1c ≤ 7.0% and 7.1–8.0% in those treated with either SU alone, SU with glinides, or insulin. Conclusion These findings suggest that the relationship between treatment-achieved HbA1c and incidence of both CAD and severe diabetic eye disease differed according to treatment, based on a large-scale real-life database. More research is now needed to confirm these findings and to further investigate the underlying mechanisms.

Endothelial dysfunction is an early pathophysiological feature and independent predictor of a poor prognosis in most forms of cardiovascular disease. We evaluated the effect of brown rice crackers (BR-C) on endothelial function.Effect of heat-moisture treated (HMT) -BR-C on postprandial flow-mediated dilation (FMD) in adults with mild endothelial dysfunction was compared with that of BR-C and white rice crackers (WR-C) in 12 adults with mild endothelial dysfunction (less than 7.0% of FMD) by a randomized, single-blind, three-treatment three-period crossover trial (UMIN 000034898). Since we considered that the FMD increase was associated with the treatment of HMT-BR-C, we examined the effect of three possible factors: postprandial glucose levels, polyphenol content, and polyphenol release from the food matrix.Mean pre-intake baseline FMD values of HMT-BR-C, BR-C, and WR-C were 4.9%, 5.1%, and 4.9%, respectively, and those values 1 h post-intake were 6.3%, 5.1%, and 4.8%, respectively. There was no difference in intergroup comparisons of FMD using Dunnett's multiple comparison test. There was a significant increase in FMD only in HMT-BR-C in intragroup comparisons (HMT-BR-C intake increased the postprandial FMD response.

Summary Background & aims High intake of fruit and vegetables is recommended for cardiovascular health. However, there have been persistent beliefs that fruits having high concentrations of fructose elevate the level of triglycerides (TG) in blood unlike vegetables. This meta-analysis aims to clarify the relationship between fruit intake and TG or hypertriglyceridemia. Methods Electronic literature searches were conducted for observational studies that investigated the relationship between fruit intake and hypertriglyceridemia or intervention studies that investigated the effect of increasing fruit intake on TG. Each effect size was pooled with an inverse-variance method. Results Five cross-sectional studies and only 2 intervention studies were eligible. The pooled odds ratio (OR) (95% confidence interval (CI)) of the 5 cross-sectional studies for the highest vs. the lowest fruit intake category was 0.79 (0.72–0.87). In these studies, the pooled OR for the highest vs. the lowest vegetable intake category was not significant (OR = 0.92; 95% CI, (0.82–1.03)). A linear dose–response association was observed between increases in fruit intake and ORs for hypertriglyceridemia; the OR (95% CI) for an incrementally increased intake of fruit by 1 serving/day was 0.91 (0.84–0.98). Conclusion This meta-analysis suggests that high intake of fruit but not vegetables is inversely associated with hypertriglyceridemia. More trials are needed to clarify whether increasing fruit intake would reduce the level of TG and/or incident hypertriglyceridemia.

AIM Hepatic insulin clearance (HIC) is important in regulating plasma insulin levels. Diminished HIC causes inappropriate hyperinsulinaemia, and both obesity and fatty liver (FL), which are known to decrease HIC, can be found either together in the same patient or on their own. The mechanism by which obesity reduces HIC is presumed to be mediated by FL. However, few reports have examined the role of FL in the relationship between obesity and HIC in type 2 diabetes (T2D) patients. Therefore, our study investigated the association of HIC with clinical factors, including insulin sensitivity indices, focusing on the presence or absence of FL and obesity in T2D patients. METHOD Baseline data from 419 patients with T2D (279 men, 140 women; mean age: 57.6 years; body mass index: 25.5kg/m2) controlled by diet and exercise were analyzed. HIC was calculated from the ratio of fasting c-peptide to fasting insulin levels (HICCIR). Correlation analyses between HICCIR and clinical variables were performed using Pearson's product-moment correlation coefficients and single regression analysis in all participants and in those with obesity and FL either alone or in combination. RESULTS HICCIR was significantly correlated with whole-body insulin sensitivity indices and influenced by FL, but only in the FL group was obesity independently influenced HIC level. HICCIR decreased in those with both FL and obesity compared with those with only one such complication. CONCLUSION HICCIR may be used to evaluate whole-body insulin sensitivity in T2D. Also, compared with obesity, the influence of FL strongly contributed to a reduced HIC. TRIAL REGISTRATION NUMBER These trials were registered by the Japan Pharmaceutical Information Centre clinical trials information (JapicCTI) as 101349 and 101351.

Objective This study aimed to examine the impact of obesity, as defined by body mass index (BMI), and a metabolically unhealthy phenotype on the development of coronary artery disease (CAD) according to glucose tolerance status. Methods This population-based retrospective cohort study included 123,746 Japanese men aged 18–72years (normal glucose tolerance: 72,047; prediabetes: 39,633; diabetes: 12,066). Obesity was defined as a BMI≥25kg/m 2 . Metabolically unhealthy individuals were defined as those with one or more of the following conditions: hypertension, hypertriglyceridaemia and/or low HDL cholesterol. A Cox proportional hazards regression model identified variables related to CAD incidence. Results The prevalences of obese subjects with normal glucose tolerance, prediabetes and diabetes were 21%, 34% and 53%, whereas those for metabolically unhealthy people were 43%, 60% and 79%, respectively. Multivariate analysis showed that a metabolically unhealthy phenotype increases hazard ratios (HRs) for CAD compared with a metabolically healthy phenotype, regardless of glucose tolerance status (normal glucose tolerance: 1.98, 95% CI: 1.32–2.95; prediabetes: 2.91, 95% CI: 1.85–4.55; diabetes: 1.90, 95% CI: 1.18–3.06). HRs for CAD among metabolically unhealthy non-obese diabetes patients and obese diabetes patients with a metabolically unhealthy status were 6.14 (95% CI: 3.94–9.56) and 7.86 (95% CI: 5.21–11.9), respectively, compared with non-obese subjects with normal glucose tolerance and without a metabolically unhealthy status. Conclusion A metabolically unhealthy state can associate with CAD independently of obesity across all glucose tolerance stages. Clinicians may need to consider those with at least one or more conditions indicating a metabolically unhealthy state as being at high risk for CAD regardless of glucose tolerance status.

Olfactory neuroblastoma (ONB) is a relatively rare nasal or paranasal malignant tumor. This tumor is rarely accompanied by paraneoplastic syndromes such as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Here, we report a 31-year-old female with histologically confirmed ONB who had been diagnosed with SIADH three years prior. She was treated with surgery followed by concurrent chemoradiotherapy. SIADH resolved immediately after surgical tumor resection. Immunohistochemically, both biopsy and resected specimens from the nasal cavity had been negative for ADH. Although extremely rare, ONB may be associated with SIADH, and the possibility of this cancer should be taken into account during the follow-up of idiopathic SIADH.

Aims To examine the impact of glucose tolerance status on the development of coronary artery disease (CAD) in working-age men in Japan. Methods This population-based retrospective cohort study included 111,621 men aged 31–60 years [63,558 with normal glucose tolerance (NGT); 37,126 with prediabetes; 10,937 with diabetes]. The Cox proportional-hazards regression model was used to identify variables related to the incidence of CAD. Results Multivariate analysis showed that, compared with NGT, diabetes increased the risk of CAD by 17.3 times (95% CI: 6.36–47.0) at ages 31–40 years, by 2.74 times (95% CI: 1.85–4.05) at ages 41–50 years and by 2.47 times (95% CI: 1.69–3.59) at ages 51–60 years. The HRs for CAD in men with diabetes aged 31–40 equaled that of men with NGT aged 51–60 [18.2 (7.15–46.4) and 19.4 (8.28–45.4), respectively]. Conclusion The impact of diabetes on CAD was markedly greater in men aged 31–40 years compared with those aged 41–60 years.

Objective Acute otitis media (AOM) is one of the most common infectious diseases in children. Nontypeable Haemophilus influenzae (NTHi) is Gram-negative bacteria that are considered major pathogens of AOM and respiratory tract infections. In this study, we used monophosphoryl lipid A (MPL), a toll-like receptor (TLR) 4 agonist, as an adjuvant to induce mucosal immune responses against NTHi to enhance bacterial clearance from the nasopharynx. Methods Mice were administered 10 μg outer membrane protein (OMP) from NTHi and 0, 10, or 20 μg MPL intranasally once a week for 3 weeks. Control mice were administered phosphate-buffered saline alone. After immunization, these mice were challenged with NTHi. At 6 and 12 h after bacterial challenge, the mice were killed and nasal washes and sera were collected. The numbers of NTHi- and OMP-specific antibodies were quantified by enzyme-linked immunosorbent assay. Results The MPL 10 and 20 μg group produced a significant reduction in the number of bacteria recovered from the nasopharynx at 12 h after bacterial challenge compared to the control group. OMP-specific IgA titers were also augmented in the MPL groups compared to the control and OMP groups. Conclusion MPL is suitable for eliciting effective mucosal immune responses against NTHi in the nasopharynx. These results demonstrate the possibility of an adjuvant that involves stimulation of the innate immune system by TLR4 agonists such as MPL for mucosal vaccination.

Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually arises from the pleura. Recently, SFTs have been reported in the head and neck region located in subsites such as the orbit. SFTs of the lacrimal sac are extremely rare, with only six cases reported in the English literature. We describe a SFT arising from the right lacrimal sac and extending along the nasolacrimal duct into the nasal cavity. Although, the tumor could not be removed by endoscopic-modified medial maxillectomy (EMMM) alone, combined approach with EMMM and a small external incision achieved the complete removal of the tumor. The patient has remained disease-free 24 months after surgery.

Whether early stages of kidney dysfunction assessed by the estimated glomerular filtration rate from cystatin C measurements (eGFRCysC) rather than from creatinine measurements (eGFRCr) would more precisely reflect the risk of developing type 2 diabetes (T2D) has not been clarified. We compared the risk of developing T2D associated with renal dysfunction indicated by eGFRCysC or eGFRCr measurements.Studied were 2131 Japanese individuals without diabetes. Hazard ratios (HRs) for the development of T2D over 3-5 y were calculated across categories of eGFRCysC and eGFRCr, respectively.Reduced levels of eGFRCysC were associated with a step-wise increase in the cumulative incidence rate of T2D (p=0.007). In comparison with the eGFRCysC85th percentile group (≥ 117.4 ml/min/1.73 m(2)), the lowest group, which was the eGFRCysC15th percentile group (86.2 ml/min/1.73 m(2)), had an adjusted HR of 2.30 (95% CI 1.13, 4.68) for T2D. Compared with the eGFRCr85th percentile group, the lowest eGFRCr group (15th percentile) had an HR of 1.19 (0.63, 2.24) for T2D. However, individuals with eGFRCr60 ml/min/1.73 m(2) had a significantly increased risk of T2D. Clustering of both low eGFRCysC and low eGFRCr further elevated the HR for T2D compared with the presence of either.Although eGFRCr in ranges indicating chronic kidney disease reflected an elevated risk of developing diabetes, earlier stages of kidney dysfunction indicated by reduced eGFRCysC, which could not be captured by reduced eGFRCr, would be a marker for an elevated risk of developing T2D.

Aim and objective Insulin-induced moderate or severe hypoglycemia (MH or SH) impairs cognition and SH causes neuronal death. On the contrary, alternate day fasting (ADF) protects the brain during excitotoxic stress and improves cognitive function. Unlike the scenario in the periphery, insulin and its relationship towards brain glucose uptake and metabolism are considered to be less significant. Yet, the hypoglycemia associated brain metabolism is not clearly understood. The authors broadly investigated the brain metabolism in various hypoglycemic models such as insulin-induced MH, SH, SH with glucose reperfusion, 24 h fasting and ADF in the cortex or hippocampus of C57BL6/J mice. The authors analyzed the protein expression of insulin signaling kinases (plays a key role in neuronal survival and memory), Bcl-2 associated death promoter (p-BADser155) (dephosphorylation inhibits glucokinase activity and reduces glucose or increases ketone body metabolism in the brain), neuronal-specific glucose transporter 3 (GLUT 3) and nitrotyrosine (marker of nitric oxide which is involved in neuronal glucose uptake via GLUT 3) using western blotting analysis. Results Insulin-induced MH or SH differentially regulated the brain insulin signaling kinases. The expression of p-BADser155 decreased in all hypoglycemic models except the insulin-induced MH in hippocampus. The trended higher GLUT 3 and increased nitrotyrosine expression of insulin-induced SH were restored after glucose reperfusion. The trended higher or increased GLUT 3 and nitrotyrosine expression of ADF were positively correlated with serum beta-hydroxybutyrate levels. Conclusion During hypoglycemia, it can be suggested that the brain might decrease glucose metabolism via glycolysis or prefer ketone body metabolism (except the insulin-induced MH in hippocampus) by modifying the p-BADser155 expression. In addition to the ketone body metabolism, the brain might adapt to uptake glucose in insulin-induced SH or ADF by modifying the GLUT 3 or nitrotyrosine expression.

Summary Background & aims Some foods rich in cholesterol are associated with high risk of type 2 diabetes (T2D). To confirm the association between dietary cholesterol intake and T2D risk, we performed a meta-analysis of observational studies. Methods We searched for longitudinal studies that provided data on the relative risk (RR) for T2D in relation to the cholesterol intake level using MEDLINE (from 1950 for July 10, 2013) and EMBASE (from 1974 to July 10, 2013). The RR for the highest vs. lowest cholesterol intake category or for an increment of 100 mg/day in cholesterol consumption was pooled with an inverse-variance method. Results Five studies met the inclusion criteria. Compared with the lowest category, the highest category had a significantly higher association with T2D risk (RR [95% confidence interval (CI)], 1.25 [1.16–1.36]). The pooled RR for a 100-mg/day increment was also significant (RR [95% CI], 1.11 [1.06–1.15]). Conclusion Current meta-analysis suggested that high intake of cholesterol was positively associated with future T2D risk.

Results of epidemiologic studies that investigated the significance of pulse pressure (PP) and mean arterial pressure (MAP) in terms of risk of cardiovascular disease (CVD) in patients with diabetes mellitus are inconsistent. We performed a quantitative meta-analysis to estimate CVD risk in relation to PP or MAP. Electronic literature search was conducted for prospective studies providing data on CVD risk for an increment in baseline MAP or PP in patients with diabetes mellitus. The pooled CVD risk for a 10-mm Hg increase in each blood pressure (BP) index was estimated with a random-effects model. There were 17 eligible studies consisting of 52,647 patients and 5,112 CVD cases. The pooled relative risk (95% confidence interval) of CVD for an increment of 10 mm Hg was 1.10 (1.04 to 1.16) for PP and 1.09 (0.98 to 1.21) for MAP. Significant between-study heterogeneity was observed (I(2) [p value]; 76.5% [p0.001] for PP, 67.8% [p = 0.005] for MAP). In studies concurrently investigating CVD risk for the 4 indexes (i.e., PP, MAP, systolic BP, and diastolic BP), the pooled relative risk (95% confidence interval) was 1.17 (1.09 to 1.26) for PP, 1.11 (1.06 to 1.15) for MAP, 1.14 (1.06 to 1.22) for systolic BP, and 1.06 (0.94 to 1.19) for diastolic BP. In conclusion, the current meta-analysis suggested that PP was the strongest indicator among the 4 commonly used BP indexes. However, the large heterogeneity urged cautious interpretation of the study results.

To evaluate the effect of elevated fasting plasma glucose (FPG) and hemoglobin A(1c) (HbA(1c)) concentrations on lung dysfunction and to prospectively investigate whether reduced lung function would be independently predictive of diabetes.From January 6, 1997, through December 22, 2008, we observed 5346 men with no history of diabetes or lung dysfunction. Hazard ratios (HRs) for incident diabetes (FPG ≥126 mg/dL, HbA(1c) ≥6.5%, or self-reported clinician-diagnosed diabetes) were estimated for spirometry indices as continuous and categorical variables.Elevated HbA(1c) concentrations within the normal range were significantly and more strongly associated with reduced forced vital capacity and forced expiratory volume in the first second after expiration (FEV(1)) than were FPG concentrations. During a 4.0-year follow-up, diabetes developed in 214 individuals. A 10-point decrease in percentage of FEV(1) predicted value was associated with an increased HR of 1.21 (95% confidence interval [CI], 1.09-1.34; P=.001) for diabetes after adjustment for demographic factors and body mass index. This association remained significant even after adjustment for metabolic factors, smoking status, and FPG or HbA(1c) concentrations but was attenuated substantially after adjustment for baseline HbA(1c) values (HR, 1.13; 95% CI, 1.01-1.26; P=.03). Lower quartile (Q) categories of percentage of FEV(1) predicted value were associated with increased risk of diabetes independently of known predictors including HbA(1c) (HR, 1.73; 95% CI, 1.14-2.62 for Q1; and HR, 1.76; 95% CI, 1.15-2.69 for Q2).Reduced lung function was significantly related to chronic glycemic exposure within a normal range. Relatively low pulmonary function was an independent risk factor for diabetes in apparently healthy Japanese men.

Objective To evaluate the impact of HbA1c for diagnosis of diabetes and investigate whether cardiovascular risks profiles differ among individuals with diabetes diagnosed by HbA1c or fasting plasma glucose (FPG). Methods This cross-sectional study involved 26,884 participants (30.6% women; aged 20–91 years) without known diabetes. Subjects were categorized into 4 groups according to the presence or absence of FPG ≥7.0 mmol/L and/or HbA1c ≥6.5%, which were American Diabetes Association criteria. Oral glucose tolerance test data were not available. Results Prevalence of undiagnosed diabetes was 3.6%. Of those individuals, 47.5% fulfilled both two criteria and 26.0% fulfilled only HbA1c criterion. Individuals with diabetes according to FPG ≥7.0 mmol/L alone were characterized as having poorly controlled hypertension while those with HbA1c ≥6.5% alone were characterized as older, female, and having lower blood pressure and γ-glutamyltransferase values. Persons with newly diagnosed diabetes by HbA1c had low HDL cholesterol and high LDL or non-HDL cholesterol levels. Conclusions Introducing HbA1c into the diagnosis allowed detection of many previously undiagnosed cases of diabetes in Japanese individuals. Those diagnosed by FPG were characterized by hypertension and those diagnosed by HbA1c had unfavorable lipid profiles, reflecting an atherosclerotic trait.

Summary Background The clinical relevance of the diagnostic criteria for prediabetes to prediction of progression to diabetes has been little studied. We aimed to compare the prevalence of prediabetes when assessed by the new glycated haemoglobin A 1c (HbA 1c ) 5·7–6·4% criterion or by impaired fasting glucose, and assessed differences in progression rate to diabetes between these two criteria for prediabetes in a Japanese population. Methods Our longitudinal cohort study included 4670 men and 1571 women aged 24–82 years without diabetes at baseline (diabetes was defined as fasting plasma glucose ≥7·0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA 1c ≥6·5%) who attended Toranomon Hospital (Tokyo, Japan) for a routine health check between 1997 and 2003. Participants with a baseline diagnosis of prediabetes according to impaired fasting glucose (fasting plasma glucose 5·6–6·9 mmol/L) or HbA 1c 5·7–6·4%, or both, were divided into four groups on the basis of baseline diagnosis of prediabetes. Rate of progression to diabetes was assessed annually. Findings Mean follow-up was 4·7 (SD 0·7) years. 412 (7%) of 6241 participants were diagnosed with prediabetes on the basis of the HbA 1c 5·7–6·4% criterion. Screening by HbA 1c alone missed 1270 (61%) of the 2092 prediabetic individuals diagnosed by a combination of impaired fasting glucose and HbA 1c 5·7–6·4%. Overall cumulative probability of progression to diabetes did not differ significantly between participants with prediabetes discordantly diagnosed by either HbA 1c or impaired fasting glucose alone (incidence was 7% for HbA 1c alone [n=412 individuals and 30 incident cases] and 9% for impaired fasting glucose alone [n=1270, 108 cases]; log-rank test, p=0·3317). Multivariate-adjusted hazard ratios for incident diabetes were 6·16 (95% CI 4·33–8·77) for those diagnosed with prediabetes by impaired fasting glucose alone and 6·00 (3·76–9·56) for diagnosis by HbA 1c alone, and were substantially increased to 31·9 (22·6–45·0) for diagnosis by both impaired fasting glucose and HbA 1c compared with normoglycaemic individuals. Interpretation Diagnosis of prediabetes by both the new HbA 1c criterion and impaired fasting glucose identified individuals with an increased risk of progression to diabetes. Although the new HbA 1c criterion identified fewer individuals at high risk than did impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA 1c 5·7–6·4% was similar to that assessed by impaired fasting glucose alone. The two tests used together could efficiently target people who are most likely to develop diabetes and allow for early intervention. Funding Japan Society for the Promotion of Science; Ministry of Health Labor and Welfare, Japan.

Nasal vaccination is an effective therapeutic regimen for preventing upper respiratory infection, while DNA vaccines represent a new approach for controlling infectious diseases. Here, we examined the efficacy of nasally administered DNA vaccine on upper respiratory infections. A DNA plasmid encoding the P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) was constructed. Mice were immunized 3 times intranasally with the DNA plasmid and Matrix-M, an immunostimulatory complex adjuvant. P6-specific immune responses were examined using purified P6 protein. Nasal-associated lymphoid tissue (NALT) CD4 + T cells were purified and incubated with feeder cells in the presence of P6, and the expression of cytokine mRNA was examined. In addition, NTHi challenges were performed and the level of NTHi was quantified in nasal washes. P6-specific nasal wash IgA and serum IgG were elevated following immunization with the DNA plasmid and Matrix-M. The number of specific IgA-producing cells increased in the nasal passages of the immunized mice. In addition to Th1 and Th2 cytokine expression, IL-17 was detected in P6-specific NALT CD4 + T cells. Moreover, DNA vaccination enhanced bacterial clearance. These findings suggest that a successful DNA vaccination protocol has been developed for inducing in vivo immune responses against NTHi. Nasal vaccination with P6 DNA vaccine and Matrix-M might be a new effective regimen for the induction of specific protective immunity in the upper respiratory tract.

Objectives The purpose of this meta-analysis is to summarize the estimated risk of atrial fibrillation (AF) related to alcohol consumption. Background Results from observational studies examining the relationship between alcohol consumption and AF are inconsistent. Methods A systematic electronic search of Medline (January 1966 to December 2009) and Embase (January 1974 to December 2009) databases was conducted for studies using key words related to alcohol and AF. Studies were included if data on effect measures for AF associated with habitual alcohol intake were reported or could be calculated. The effect measures for AF for the highest versus lowest alcohol intake in individual studies were pooled with a variance-based method. Linear and spline regression analyses were conducted to quantify the relationship between alcohol intake and AF risk. Results Fourteen eligible studies were included in this meta-analysis. The pooled estimate of AF for the highest versus the lowest alcohol intake was 1.51 (95% confidence interval: 1.31 to 1.74). A linear regression model showed that the pooled estimate for an increment of 10 g per day alcohol intake was 1.08 (95% confidence interval: 1.05 to 1.10; R 2 = 0.43, p Conclusions Results of this meta-analysis suggest that not consuming alcohol is most favorable in terms of AF risk reduction.

Schwannoma is a benign tumor arising from the sheath of myelinated nerve fibers and may occur in any part of the body. Ancient schwannoma, a variant of schwannomas, in the head and neck region is uncommon, and its occurrence in the nasal cavity and paranasal sinuses is extremely rare with only one case reported to date. Herein, we describe a rare case of sinonasal ancient schwannoma. The tumor arose from the nasal septum and extended to the sphenoid sinus. It was successfully treated by endoscopic sinus surgery, and the patient showed no evidence of recurrence 24 months postoperatively.

Nasal vaccination is an effective therapeutic regimen for preventing otitis media. In the development of nasal vaccine, an appropriate adjuvant is required. In the present study, we examined the efficacy of fms-like tyrosine kinase receptor-3 ligand (Flt3L) as a mucosal adjuvant. Flt3L was administered intranasally or peritoneally to mice, which were then immunized intranasally with P6 protein of nontypeable Haemophilus influenzae (NTHi), and P6-specific immune responses were examined. In addition, NTHi challenges were performed and the level of NTHi was quantified in nasal washes. Nasal application of Flt3L induced an increase in the number of dendritic cells in nasal-associated lymphoid tissue. P6-specific nasal wash immunoglobulin (Ig)A and serum IgG titers were elevated significantly after nasal immunization. Enhanced NTHi clearance from the nasopharynx was also observed. The effect of nasal vaccination with P6 combined with nasal Flt3L application was prolonged. These results indicate the potential of Flt3L as an effective mucosal adjuvant and suggest that nasal vaccination with P6 in combination with nasal Flt3L might be an effective regimen for the induction of NTHi-specific protective immunity.

Aspergillosis is a common fungal infection of the paranasal sinuses. Isolated frontal sinus aspergillosis is extremely rare, with only three cases reported in the literature. We report a case of isolated frontal sinus aspergillosis that was accompanied by a contralateral frontal sinus cyst enclosed osseously. The patient was treated successfully by an endoscopic modified Lothrop procedure that permitted complete removal of the fungus ball and wide opening of the frontal sinus. The patient is without evidence of disease 18 months after surgery.

Objectives Osteopontin (OPN) is associated with several human malignancies, but the role of OPN in head and neck cancer (HNC) remains unclear. We investigated the clinicopathologic relevance of serum OPN levels in HNC patients. Methods Serum OPN levels in HNC patients were determined by quantitative sandwich enzyme immunoassay (EIA). OPN levels and their correlation with clinical features were examined. In addition, serum squamous cell carcinoma (SCC) antigen was examined simultaneously. Results The mean OPN level was significantly higher in HNC patients (99.5 ng/ml) than in control subjects (55.3 ng/ml). OPN levels were significantly higher in patients with advanced stage HNC than in patients with early stage HNC. OPN levels did not correlate with SCC antigen levels. Conclusions OPN may play a role in the pathogenesis of head and neck cancer (HNC), and serum OPN may be a potential biomarker of HNC.

Hemangioma of the nasal septum, known as "bleeding polyp," is an occasional lesion in adults. We report two cases of bleeding polyps, that were successfully treated by surgery using the Harmonic Scalpel (HS). Two women (aged 58 and 67 years) presented with unilateral nasal hemangioma, which was revealed by unilateral epistaxis. Both the women were treated by surgical excision using the HS under general and local anesthesia, respectively. Treatment involves surgical excision of the tumor including the mucosa and the underlying perichondrium. HS is an effective tool for the excision of bleeding polyps with less bleeding and less tissue injury.

The eustachian tube (ET) plays an important role in the pathogenesis of otitis media (OM). To better understand its biology and to develop a nasal vaccine for preventing OM, mucosal lymphocytes in the ET were analyzed, and the ET's immunological function was investigated. Mononuclear cells were isolated from murine ET, and lymphocyte subsets were analyzed by flow cytometry. Antibody-producing cells were determined by enzyme-linked immunospot assay. The expression of cytokine mRNA in ET CD4(+) T cells was determined by RT-PCR. Results in naive mice showed that the ET contained many immunocompetent cells, including a relative large number of IgA-producing cells and Th2 cytokine-expressing T cells. Next, we investigated antigen-specific immune responses in the ET. Mice were immunized intranasally with the P6 outer membrane of nontypeable Haemophilus influenzae (NTHi) and cholera toxin (CT), and P6-specific immune responses in the ET were examined. P6-specific IgA producing cells markedly increased in the ET. Moreover, in vitro stimulation with P6 of purified CD4(+) T cells from immunized mice resulted in the proliferation of CD4(+) T cells that expressed Th2 cytokine mRNA. These results indicate that the ET might be characterized as a mucosal effector site and that antigen-specific IgA and Th2 immune responses could be induced in the ET by intranasal immunization. These findings suggest that the ET might be a key immunological organ in the pathogenesis of OM, and in the development of a nasal vaccine.

Nontypeable Haemophilus influenzae (NTHi) is one of the leading pathogens in sinusitis. One of the outer membrane proteins of NTHi, P6, is a common antigen to all strains and is an attractive candidate for a subunit bacterial vaccine. In this study, we characterized normal sinus mucosa (SM) and investigated the potential of intranasal immunization with P6 and cholera toxin (CT) for induction of mucosal protective immunity against NTHi in the maxillary sinuses of rats. Intranasal immunization induced P6-specific sinus mucosal and systemic immunological responses, mainly of the IgA and IgG isotype. The protective effect of intranasal immunization was demonstrated by enhancement of sinus clearance of NTHi. The present study showed that unilateral intranasal immunization has a capacity to induce protective immunity against NTHi in the bilateral maxillary sinuses. Systemic administration of the vaccine did not affect sinus clearance of NTHi. These findings suggest that a nasal vaccine might be useful for preventing sinusitis.

Superior laryngeal neuralgia is a rare condition. We report a case of superior laryngeal neuralgia with deviated hyoid bone. A 50-year-old woman presented with paroxysmal and lancing pain localized to the area around the thyrohyoid membrane. Pain was induced and worsened by swallowing. A three-dimensional image showed deviation of the hyoid bone. General and neurological examinations were normal. After spraying of the larynx with 4% lidocaine, the pain improved. Superior laryngeal neuralgia was diagnosed, and the condition was treated with carbamazepine. Superior laryngeal neuralgia is rare but should be considered, particularly if no other pathologic findings are identified.

Nontypeable Haemophilus influenzae (NTHi) is a major pathogen of otitis media. P6 outer membrane protein is a common antigen to all strains and is considered as a candidate for mucosal vaccine. To elucidate the possibility of developing a nasal vaccine against NTHi and to investigate mucosal immune responses in the middle ear, mice were immunized intranasally with the P6 outer membrane protein of NTHi, and P6-specific immune responses in the middle ear mucosa were examined. P6-specific IgA antibody titre in ear wash was significantly elevated. Mononuclear cells were isolated from middle ear mucosa, and an increase in P6-specific IgA-producing cells was shown with ELISPOT assay. In addition, in vitro stimulation with P6 resulted in proliferation of purified CD4 + T cells from immunized mice, and these T cells expressed Th2 cytokine mRNA. Moreover, bacterial challenge with live NTHi into the middle ear was performed after immunization, and the clearance of NTHi from the middle ear was enhanced by nasal immunization. These results indicate that P6-specific protective immunity was induced in middle ear mucosa by nasal immunization. These findings suggest that nasal vaccine is useful for preventing otitis media.