Olfactory and taste dysfunctions caused by COVID-19: a nationwide study.

BACKGROUND: Olfactory dysfunctions (OD) and taste dysfunctions (TD) are widely recognized as characteristic symptoms of COVID-19; however, the frequency and mode of occurrence has varied depending on the viral mutation. The prevalence and characteristics of OD/TD in Japan have not been definitively investigated. The purpose of this study is to assess the prevalence of OD/TD in Japan during the Alpha variant epidemic, and measure symptom prolongation at 6 months and 1 year later following initial infection. METHODS: Patients treated for COVID-19 between February to May 2021 were evaluated for OD/TD symptoms and provided with a QOL questionnaire. Olfactory tests and taste tests were performed using Open Essence and Taste Strips, respectively. RESULTS: Among the 251 COVID-19 patients who participated, 119 underwent both olfactory and taste tests. Prevalence of subjective OD and TD at the time of survey was 57.8% and 40.2%, respectively. After 12 months, the prevalence fell to 5.8% for OD and 3.5% for TD. Among the OD/TD patients, 36.6% experienced parosmia, and 55.4% experienced parageusia. Prevalence of parosmia and parageusia was higher at 6 and 12 months than at the time of survey. Patients with long-lasting disease reported qualitative dysfunctions and scored significantly higher in food-related QOL problems. Most patients who were aware of their hyposmia had low scores on the olfactory test (83.1%). In contrast, only 26.7% of patients who were aware of their hypogeusia had low scores on the taste test. CONCLUSIONS: The prevalence of COVID-19-related OD and TD at the time of survey was 57.8% and 40.2%, respectively. Subjective symptoms of OD and TD persisted for one year in 5.8% and 3.5% of patients, respectively. More than half of the patients with OD or TD complained of qualitative dysfunction and a decrease in their QOL related to eating and drinking. Most patients with TD did not have true TD, but rather developed flavour disorders associated with OD. This conclusion is supported by the finding that patients with subjective OD had low scores on the olfactory test, whereas most patients with subjective TD had normal scores on the taste test.

Surface nanostructures on Nb-doped SrTiO3irradiated with swift heavy ions at grazing incidence.

A single crystal of SrTiO3doped with 0.5 wt% niobium (Nb-STO) was irradiated with 200 MeV Au32+ions at grazing incidence to characterize the irradiation-induced hillock chains. Exactly the same hillock chains are observed by using atomic force microscopy (AFM) and scanning electron microscopy (SEM) to study the relation between irradiation-induced change of surface topography and corresponding material property changes. As expected, multiple hillocks as high as 5-6 nm are imaged by AFM observation in tapping mode. It is also found that the regions in between the adjacent hillocks are not depressed, and in many cases they are slightly elevated. Line-like contrasts along the ion paths are found in both AFM phase images and SEM images, indicating the formation of continuous ion tracks in addition to multiple hillocks. Validity of preexisting models for explaining the hillock chain formation is discussed based on the present results. In order to obtain new insights related to the ion track formation, cross-sectional transmission electron microscopy (TEM) observation was performed. The ion tracks in the near-surface region are found to be relatively large, whereas buried ion tracks in the deeper region are relatively small. The results suggest that recrystallization plays an important role in the formation of small ion tracks in the deep region, whereas formation of large ion tracks in the near-surface region is likely due to the absence of recrystallization. TEM images also show shape deformation of ion tracks in the near-surface region, suggesting that material transport towards the surface is the reason for the absence of recrystallization.

Impact of various intensities and frequencies of non-occupational physical activity on the risk of dementia among physically independent older adults: the Japan Gerontological Evaluation Study.

OBJECTIVES: The aim of this study was to investigate the association between different intensities and frequencies of non-occupational physical activity (PA) and the risk of dementia among Japanese older adults. STUDY DESIGN: This was a prospective cohort study. METHODS: A total of 2194 participants aged ≥65 years from the Japan Gerontological Evaluation Study were followed up between 2010 and 2016. The standardised dementia scale of the long-term care insurance system was used to identify incident dementia, whereas non-occupational PA (<2 or ≥2 times/week on each intensity: light, moderate and vigorous) was assessed using a questionnaire. Cox regression was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia. RESULTS: After adjustment for sociodemographic and medical characteristics, the following frequencies and intensities of non-occupational PA, compared with no non-occupational PA at all, were associated with a reduced risk of dementia: light PA ≥2 times/week (HR = 0.61, 95% CI: 0.38-0.97), moderate PA <2 times/week (HR = 0.46, 95% CI: 0.28-0.76), moderate PA ≥2 times/week (HR = 0.57, 95% CI: 0.36-0.91), vigorous PA <2 times/week (HR = 0.40, 95% CI: 0.21-0.74) and vigorous PA ≥2 times/week (HR = 0.29, 95% CI: 0.15-0.57). In the sex-specific analysis, moderate PA <2 times/week and vigorous PA ≥2 times/week were associated with a reduced risk of dementia in men, whereas light and moderate PA ≥2 times/week and all frequencies of vigorous PA were associated with a reduced risk of dementia in women. CONCLUSIONS: Practicing non-occupational PA was associated with a reduced risk of dementia among Japanese older adults.

ACE2, TMPRSS2, and Furin expression in the nose and olfactory bulb in mice and humans.

No abstract available.

Effect of Small Focus on Electron Heating and Proton Acceleration in Ultrarelativistic Laser-Solid Interactions.

Acceleration of particles from the interaction of ultraintense laser pulses up to 5×10^{21} W cm^{-2} with thin foils is investigated experimentally. The electron beam parameters varied with decreasing spot size, not just laser intensity, resulting in reduced temperatures and divergence. In particular, the temperature saturated due to insufficient acceleration length in the tightly focused spot. These dependencies affected the sheath-accelerated protons, which showed poorer spot-size scaling than widely used scaling laws. It is therefore shown that maximizing laser intensity by using very small foci has reducing returns for some applications.

Increased Survival Benefit of Adjuvant Intra-arterial Infusion Chemotherapy in HCC Patients with Portal Vein Infiltration after Hepatectomy.

BACKGROUND: The role of adjuvant hepatic intra-arterial infusion chemotherapy (HAI) is considered to be a promising option. METHODS: We examined treatment effects of adjuvant HAI using cisplatin in 37 hepatocellular carcinoma (HCC) patients with portal vein infiltration (PVI) who underwent hepatectomy in comparison with those in 85 patients who did not. RESULTS: PVI in 89 patients. Increased levels of aspartate transaminase, tumor markers, size and microvessel tumor infiltration (MVI) or cirrhosis, poorly differentiation, non-adjuvant HAI was associated with lower overall survival (p = 0.09). Poor differentiation, MVI and HAI were independently risk factors associated with tumor-free and overall survivals by the multivariate analysis (p < 0.05). Adjuvant HAI tended to show longer survivals in comparison with no-HAI (p = 0.08) and the multivariate analysis revealed significant efficacy of HAI for better prognosis. CONCLUSION: Adjuvant HAI showed effectiveness on prolonging tumor-free and patient survival in HCC with PVI and is a promising option in the daily clinical practice.

Detection of the Metastable Ice Phase during Water Crystallization.

BACKGROUND: Under atmospheric pressure, the identifiable phases of ice crystals are hexagonal (stable) and cubic (metastable). OBJECTIVE: This study aimed to test the hypothesis that water crystallizes into the cubic phase at the beginning and then changes to the hexagonal phase. MATERIALS AND METHODS: Aqueous solutions of 40% (w/w) and 50% (w/w) glucose, and 40% (w/w) ammonium hydrogen sulfate, as well as emulsified water, were investigated. RESULTS: The cubic-to-hexagonal ice phase transition was detected in 40% (w/w) glucose solution within a 1 s integration interval, whereas the cubic ice formed in 50% (w/w) glucose solution did not transition to the hexagonal phase. The cubic phase was also confirmed in the 40% (w/w) ammonium hydrogen sulfate solution, but not in emulsified water. CONCLUSION: The cubic-to-hexagonal ice phase transition was detected in three aqueous solutions tested upon freezing. It was not possible to clearly capture the transition process in emulsified water under the study condition.

Laser-Particle Collider for Multi-GeV Photon Production.

As an alternative to Compton backscattering and bremsstrahlung, the process of colliding high-energy electron beams with strong laser fields can more efficiently provide both a cleaner and brighter source of photons in the multi-GeV range for fundamental studies in nuclear and quark-gluon physics. In order to favor the emission of high-energy quanta and minimize their decay into electron-positron pairs, the fields must not only be sufficiently strong, but also well localized. We here examine these aspects and develop the concept of a laser-particle collider tailored for high-energy photon generation. We show that the use of multiple colliding laser pulses with 0.4 PW of total power is capable of converting more than 18% of multi-GeV electrons passing through the high-field region into photons, each of which carries more than half of the electron initial energy.

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Consistent increase in the prevalence and female ratio of multiple sclerosis over 15 years in northern Japan.

BACKGROUND AND PURPOSE: The prevalence of multiple sclerosis (MS) is considered to be lower in East Asia than in Western countries. An increasing trend has been reported globally for the prevalence of MS. We investigated the changes in the prevalence and clinical characteristics of MS in the Tokachi province of Hokkaido, northern Japan from 2001 to 2016. METHODS: Prevalence was determined on 31 March 2016. Data-processing sheets were collected from all MS-related institutions in Tokachi province. We applied Poser's diagnostic criteria for MS as used in our previous three studies. Cases of neuromyelitis optica spectrum disorders were excluded. RESULTS: In 2016, the crude MS prevalence was 18.6/100 000 (95% confidence interval, 14.3-23.8) in northern Japan. Over the last 15 years, the prevalence of MS in the same area was 8.1, 12.6 and 16.2 in 2001, 2006 and 2011, respectively. The female:male ratio was 3.57, which increased from 2.63 in 2001. The ratios of primary progressive, relapsing-remitting and secondary progressive MS types were 2%, 84% and 14%, respectively. CONCLUSION: Our results demonstrated a consistent increase in MS prevalence among the northern Japanese population, particularly in females, and relatively lower rates of progressive MS in northern Japan than in Western countries.

Characterization of micron-size hydrogen clusters using Mie scattering.

Hydrogen clusters with diameters of a few micrometer range, composed of 108-10 hydrogen molecules, have been produced for the first time in an expansion of supercooled, high-pressure hydrogen gas into a vacuum through a conical nozzle connected to a cryogenic pulsed solenoid valve. The size distribution of the clusters has been evaluated by measuring the angular distribution of laser light scattered from the clusters. The data were analyzed based on the Mie scattering theory combined with the Tikhonov regularization method including the instrumental functions, the validity of which was assessed by performing a calibration study using a reference target consisting of standard micro-particles with two different sizes. The size distribution of the clusters was found discrete peaked at 0.33 ± 0.03, 0.65 ± 0.05, 0.81 ± 0.06, 1.40 ± 0.06 and 2.00 ± 0.13 µm in diameter. The highly reproducible and impurity-free nature of the micron-size hydrogen clusters can be a promising target for laser-driven multi-MeV proton sources with the currently available high power lasers.

Evaluation of the relationship between salivary concentration of anti-heat shock protein immunoglobulin and clinical manifestations of Behçet's disease.

OBJECTIVE: This study investigated the relationship between the concentration of anti-heat shock protein (HSP) 60 antibody in resting saliva and the severity of Behçet's disease (BD). METHOD: Sixty-five patients diagnosed with BD at Tokyo Medical and Dental University Hospital were enrolled in this study. Based on clinical severity scores, patients were categorized as having mild, moderate, or severe BD. Periodontal status was evaluated with the Community Periodontal Index (CPI), and anti-HSP60 antibody concentrations in resting saliva were measured with an enzyme-linked immunosorbent assay. RESULTS: The mean antibody concentration in patients in the moderate group was significantly higher than concentrations in the mild and severe groups. No significant difference was found between the mild and severe groups. Gingival inflammation, identified with the CPI, was associated with a higher antibody concentration. The antibody concentration in patients who had stomatitis for more than 2 weeks was significantly higher than in those with stomatitis for less than 2 weeks. The antibody concentration in patients who had taken colchicine was significantly lower than that in subjects who had not. CONCLUSION: These results suggest that the concentration of anti-HSP60 antibody in resting saliva may be effective as a non-invasive indicator for the diagnosis (screening) and prognostication of BD.

Facial skin photo-aging and development of hyperpigmented spots from children to middle-aged Japanese woman.

BACKGROUND/PURPOSE: Facial skin hyperpigmention caused by chronic sun exposure is a major skin complaint, however, its characteristics and influential factors are still limitedly known. METHODS: A cross-sectional survey in healthy Japanese women aged from 6 to 62 years (n=169) was conducted using a facial image analyzer VISIA™ for knowing onset age of hyperpigmented spot formation, its chronological changes, and influence of environmental factors. RESULTS: UV Pigmented Spot (PS) Score was positively correlated with age (R=.487, P=.000). Hyperpigmented spots appeared first around 18 years old in most subjects, and PS score remarkably increased at 20s then gradually increased by ages. The subjects with Skin Type I, one of the three grades of Japanese Skin Type (JST), whose melanin formation is genetically lower, showed higher PS score. A woman aged 31 years was subjected a weekly VISIA measurement for 2 years, and found no changes in the number, place, size and intensity of the pigment spots in this duration. CONCLUSION: Hyperpigmented spots developed in women over 20 years of age due to chronic sun exposure without sun protection during childhood and adolescent and it was stable afterwards, whose intensity was influenced by age and skin type.

Immunocytochemistry for Claudin-18 and Maspin in biliary brushing cytology increases the accuracy of diagnosing pancreatobiliary malignancies.

OBJECTIVE: Biliary brush cytology is an important diagnostic tool in the evaluation of pancreatobiliary malignancies. However, it is difficult to distinguish between malignant and benign cells. The present study evaluated the utility of immunocytochemical expression of Claudin-18 and Maspin in brushing cytology specimens of pancreatobiliary lesions in the diagnosis of pancreatobiliary malignancies. METHODS: The study retrospectively assessed biliary and pancreatic duct brushing cytology specimens of 43 patients whose pancreatobiliary lesions were histologically diagnosed at the University of Miyazaki Hospital. Scanty cellularity slides and cases with no histological confirmation were excluded. Alcohol-fixed and Papanicolaou-stained slides were immunostained with monoclonal antibodies to Claudin-18 and Maspin. RESULTS: Of the 43 patients, 35 (81.4%) were finally histologically diagnosed with invasive adenocarcinomas. The sensitivity of routine cytology for the detection of malignancy was 63%, and the specificity was 100%. The sensitivity of cytology in combination with immunocytochemical expression of Claudin-18 (89%) or Claudin-18 and/or Maspin (97%) was significantly higher than that of cytology alone (P < 0.01). CONCLUSION: Immunocytochemical staining for Claudin-18 and Maspin improved the diagnostic sensitivity for pancreatobiliary adenocarcinomas.

Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502.

BACKGROUND: While adjuvant chemotherapy is preferable for high-risk colon cancer, treatment duration is controversial. Oral uracil and tegafur (UFT)/leucovorin (LV) is widely used as a standard adjuvant chemotherapy for colon cancer in Japan. We conducted a phase III trial to investigate the optimal duration of adjuvant chemotherapy for stage IIB/III colon cancer. PATIENTS AND METHODS: Patients with curatively resected stage IIB/III colon cancer were eligible for enrollment in this trial. Patients were registered within 6 weeks after surgery and were randomly assigned to receive UFT/LV for 28 of 35 days for 6 months in the control group or for 5 consecutive days per week for 18 months in the study group. The primary end point was the disease-free survival (DFS), and the secondary end points were overall survival (OS) and safety. RESULT: A total of 1071 patients were registered from 233 centers. A statistically significant difference in DFS was not observed between the study group and the control group; the 5-year DFS was 69% in the study group and 69% in the control group. The 5-year OS was 85% in the study group and 85% in the control group. CONCLUSION: Eighteen-month treatment with UFT/LV did not improve DFS or OS compared with 6-month UFT/LV treatment in patients with stage IIB/III colon cancer. The important finding from this study is that not 18 months but 6 months of treatment is enough for postoperative UFT/LV for stage IIB/III colon cancer. CLINICAL TRIAL NUMBER: UMIN-CTR C000000245.

Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study.

BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.

Local increase in IgE and class switch recombination to IgE in nasal polyps in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is generally characterized by local Th2 inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis (similar to chronic rhinosinusitis with nasal polyps in western countries) and non-eosinophilic chronic rhinosinusitis (characterized by Th1-dominant inflammation). OBJECTIVE: To investigate local IgE production and class switch recombination to IgE in these two subtypes of chronic rhinosinusitis with nasal polyps. METHODS: The identity of IgE-positive cells was determined using double-immunofluorescent staining for IgE and cell-type-specific molecular markers. To investigate the local class switch recombination to IgE and IgE synthesis in the mucosa, we performed real-time polymerase chain reaction to examine the mRNA expression of Th2 cytokines and class-switch-related molecules, including IL-4, IL-5, IL-13, ε germline gene transcripts, IgE mature transcript, IgG mature transcript, RAG1, RAG2 and activation-induced cytidine deaminase in eosinophilic polyps, non-eosinophilic polyps and controls. RESULTS: The concentrations of total IgE and number of IgE-positive cells were significantly higher in the eosinophilic polyps compared with control and non-eosinophilic polyps. IgE-positive cells were predominantly mast cells in eosinophilic polyps and significantly correlated with the number of FcεR1-positive cells in the subepithelial layer. IL-5 and IL-13 mRNA and ε germline gene transcripts expression levels were significantly higher in eosinophilic polyps compared with control and non-eosinophilic polyps. In contrast, the number of plasma cells and the expression of IgG mature transcripts were increased in non-eosinophilic polyps compared with eosinophilic polyps. RAG2 mRNA was significantly increased in both eosinophilic and non-eosinophilic polyps compared with control mucosa. CONCLUSION AND CLINICAL RELEVANCE: The current study suggests local class switching to IgE, production of IgE and IgE localization to the surface of mast cells in eosinophilic chronic rhinosinusitis in the Japanese population. The difference in the IgE-related profiles between eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Insertable pulse cleaning module with a saturable absorber pair and a compensating amplifier for high-intensity ultrashort-pulse lasers.

We demonstrate the performance of an efficient insertable pulse cleaning module (IPCM) that uses a saturable absorber (SA) pair with a compensating multi-pass amplifier. IPCM consists of a first SA, a grating compressor, a second SA, a stretcher and a compensating Ti:sapphire amplifier. It is implemented with a conventional chirped pulse amplification (CPA) Ti:sapphire laser system, resulting in a double CPA system architecture, and suppresses the amplified spontaneous emission (ASE) level of the pulse pedestal by about three orders of magnitude while preserving the output pulse energy and repetition-rate of the overall laser system. The duration of recompressed cleaned pulses is comparable to that obtained without the cleaning module. The effectiveness of the cleaning module is confirmed in laser-driven proton acceleration experiments. At the 10(9) W/cm2 pedestal level, the surface structure and electrical resistivity of an insulator target (100 nm silicon nitride) are preserved prior to the arrival of the intense ultrashort pulse.

Dynamic wavelength conversion in copropagating slow-light pulses.

Dynamic wavelength conversion (DWC) is obtained by controlling copropagating slow-light signal and control pulse trajectories. Our method is based on the understanding that conventional resonator-based DWC can be generalized, and is linked to cross-phase modulation. Dispersion-engineered Si photonic crystal waveguides produce such slow-light pulses. Free carriers generated by two-photon absorption of the control pulse dynamically shift the signal wavelength. Matching the group velocities of the two pulses enhances the shift, elongating the interaction length. We demonstrate an extremely large wavelength shift in DWC (4.9 nm blueshift) for the signal wavelength. Although DWC is similar to the Doppler effect, we highlight their essential differences.

Efficacy and safety of teneligliptin added to glimepiride in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study with an open-label, long-term extension.

AIMS: To assess the efficacy and safety of teneligliptin in combination with glimepiride in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with glimepiride monotherapy. METHODS: In the initial 12-week, double-blind, placebo-controlled, parallel-group period, 194 patients [haemoglobin A1c (HbA1c): 8.4 ± 0.8%; fasting plasma glucose (FPG): 164.2 ± 28.1 mg/dl] were randomized to either teneligliptin 20 mg or placebo once daily while continuing stable glimepiride therapy. This randomized period was then followed by a 40-week, open-label period, where all patients received teneligliptin once daily. The primary endpoint was the change in HbA1c from baseline to week 12. RESULTS: Teneligliptin reduced HbA1c significantly compared with placebo at week 12. The placebo-subtracted change in HbA1c was -1.0 ± 0.1% [least-squares (LS) mean ± s.e., p < 0.001]. Teneligliptin also significantly reduced FPG and 2-h postprandial glucose (PPG) as compared with placebo at week 12; the placebo-subtracted changes were -27.1 ± 3.2 and -49.1 ± 6.2 mg/dl (LS mean ± s.e., both p < 0.001), respectively. The blood glucose-lowering effects were sustained throughout the 40-week open-label period. The incidence rates of adverse events and adverse drug reactions, including hypoglycaemia, during the double-blind randomized period were similar in both groups. Therefore, teneligliptin was generally well tolerated when used in combination with glimepiride. CONCLUSIONS: The addition of teneligliptin was effective and generally well tolerated in Japanese patients with T2DM inadequately controlled with glimepiride monotherapy. The improvements in glycaemic control were maintained for up to 52 weeks.