Mach-Zehnder interferometric engineering in silicon optical modulators: towards extrinsic OMA enhancement.

The realization of a high dynamic extinction ratio (ER) and optical modulation amplitude (OMA) while keeping the optical and radio-frequency (RF) signal losses low is a major issue for carrier-depletion Mach-Zehnder (MZ) silicon optical modulators. However, there is still room to improve modulator performance by applying the information gained from recent advanced testing technology to the modulator design. In this study, the extrinsic OMA (E-OMA) enhancement effect, which was discovered through the evaluation process and by revisiting the physics of the MZ interferometer (MZI), is investigated. First, we raise the issue of a periodic ripple observed on an MZI spectrum that has previously been overlooked but can affect modulator performance and attribute it to optical resonance between the multi-mode interferometers that compose an MZI. We show that, although having the effect of reducing the dynamic ER in the push-pull regime, as demonstrated experimentally, this resonance can take them beyond the realm of modulation efficiency and generate an E-OMA enhancement effect in the single-arm-drive regime without involving any optical and RF signal losses. By comparing two modulator structures that generate resonance internally, we successfully identify the factors that are responsible for increasing the E-OMA enhancement effect. We reveal that theoretically the OMA can easily be increased by 0.45 dB or more.

High-temperature and high-efficiency operation of a membrane optical link with a buried-ridge-waveguide bonded on a Si substrate.

We demonstrate a membrane photonic integrated circuit (MPIC) that includes a membrane distributed feedback (DFB) laser and a p-i-n photodiode with a buried-ridge-waveguide (BRW) on a Si substrate, using a-Si nanofilm-assisted room-temperature surface activated bonding (SAB) for on-chip optical interconnection. The BRW structure enhanced the lateral optical confinement compared with that of the conventional flat structure. The directly bonded membrane DFB laser using SAB had a lower thermal resistance and higher output power than the previous structure using a benzocyclobutene (BCB) bonding layer. The DFB laser had a low threshold current of 0.27 mA at 25 °C. The maximum detected photocurrent and slope efficiency were 0.95 mA and 0.203 mA/mA, respectively, at 25 °C. The MPIC was successfully operated at temperatures up to 120 °C. The 3-dB bandwidths of 16.8 GHz and 10.1 GHz were achieved at 25 °C and 80 °C, respectively, and 25 Gbps and 15 Gbps non-return-to-zero (NRZ) 215-1 pseudo-random bit sequence signals were recorded at 25 °C and 80 °C, respectively.

Combined treatment with glucagon-like peptide-1 receptor agonist exendin-4 and metformin attenuates breast cancer growth.

Cancer is a major cause of death in patients with diabetes. Incretin therapy has received much attention because of its tissue-protective effects. We have previously reported an anti-breast cancer effect of glucagon-like peptide-1 receptor agonist exendin-4 (Ex-4). An anti-cancer effect of metformin is well recognized. Therefore, we examined the effect of combined treatment with Ex-4 and metformin in breast cancer cells. In human breast cancer cell lines MCF-7, MDA-MB-231, and KPL-1, 0.1-10 mM metformin significantly reduced the cell number in growth curve analysis in a dose-dependent manner. Furthermore, combined treatment with 0.1 mM metformin and 10 nM Ex-4 additively attenuated the growth curve progression of breast cancer cells. In a bromodeoxyuridine (BrdU) assay, Ex-4 or metformin significantly decreased breast cancer cell proliferation and further reduction of BrdU incorporation was observed by combined treatment with Ex-4 and metformin, which suggested that Ex-4 and metformin additively decreased DNA synthesis in breast cancer cells. Although apoptotic cells were not observed among Ex-4-treated breast cancer cells, apoptotic cells were clearly detected among metformin-treated breast cancer cells by apoptosis assays. Furthermore, metformin decreased BCL-2 expression in MCF-7 cells. In vivo experiments using a xenograft model showed that Ex-4 and metformin significantly decreased the breast tumor weight and Ki67-positive proliferative cancer cells, and metformin reduced the serum insulin level in mice. These data suggested that Ex-4 and metformin attenuated cell proliferation and metformin induced apoptosis in breast cancer cells. Combined treatment of Ex-4 and metformin may be an optional therapy to inhibit breast cancer progression.

Sodium-glucose cotransporter 2 inhibitor canagliflozin attenuates lung cancer cell proliferation in vitro.

Cancer is a major cause of death in patients with type 2 diabetes mellitus (T2DM) and lung cancer is one of the most prevalent cancers in patients with T2DM. In the present study, we examined the anti-cancer effect of the Sodium-glucose cotransporter 2 (SGLT2) inhibitor, canagliflozin, using a lung cancer model. In lung cancer tissues from non-T2DM human subjects, SGLT2 was detected by immunohistochemistry. SGLT2 mRNA and protein were also detected in A549, H1975 and H520 lung cancer cell lines by RT-PCR and immunohistochemistry, respectively. Canagliflozin at 1-50 µM significantly suppressed the growth of A549 cells in a dose-dependent manner. In BrdU assays, canagliflozin attenuated the proliferation of A549 cells, but did not induce apoptosis. In cell cycle analysis, S phase entry was attenuated by canagliflozin in A549 cells. In in vivo experiments, a xenograft model of athymic mice implanted with A549 lung cancer cells was treated with low and high dose oral canagliflozin. Despite the results of the in vitro experiments, tumor weight was not decreased by canagliflozin. In addition, the serum insulin level, but not body weight or blood glucose level, was decreased by canagliflozin. The number of cells positive for Ki67 was slightly decreased by canagliflozin, but this was not statistically significant. In conclusion, SGLT2 is expressed in human lung cancer tissue and cell lines, and the SGLT2 inhibitor, canagliflozin, attenuated proliferation of A549 lung cancer cells by inhibiting cell cycle progression in vitro but not in vivo.

Pemafibrate, a PPAR alpha agonist, attenuates neointima formation after vascular injury in mice fed normal chow and a high-fat diet.

Recently, the prevention of cardiovascular events has become one of the most important aims of diabetes care. Peroxisome proliferator-activated receptor (PPAR) agonists have been reported to have vascular protective effects. Here, we examined whether pemafibrate, a selective PPAR alpha agonist, attenuated neointima formation after vascular injury and vascular smooth muscle cell (VSMC) proliferation. We performed endothelial denudation injury in mice treated with a high-fat diet (HFD) or normal chow. Orally administered pemafibrate significantly attenuated neointima formation after vascular injury in HFD and normal chow mice. Interestingly, pemafibrate increased the serum fibroblast growth factor 21 concentration and decreased serum insulin concentrations in HFD mice. In addition, body weight was slightly but significantly decreased by pemafibrate in HFD mice. Pemafibrate, but not bezafibrate, attenuated VSMC proliferation in vitro. The knockdown of PPAR alpha abolished the anti-VSMC proliferation effect of pemafibrate. BrdU assay results revealed that pemafibrate dose-dependently inhibited DNA synthesis in VSMCs. Flow cytometry analysis demonstrated that G1-to-S phase cell cycle transition was significantly inhibited by pemafibrate. Pemafibrate attenuated serum-induced cyclin D1 expression in VSMCs. However, apoptosis was not induced by pemafibrate as assessed by the TUNEL assay. Similar to the in vitro data, VSMC proliferation was also decreased by pemafibrate in mice. These data suggest that pemafibrate attenuates neointima formation after vascular injury and VSMC proliferation by inhibiting cell cycle progression.

Efficacy and safety of a combination of an insulin secretagogue and a dipeptidyl peptidase-4 inhibitor in Japanese patients with type 2 diabetes mellitus; the repaglinide glucose oscillation study in Fukuoka (REGO-F).

ABSTRACT: Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are one of the most frequently prescribed anti-diabetic agents in Japan, and they are often used in combination with insulin secretagogues, such as sulfonylureas and glinides. In the present study, we determined the efficacy and safety of the use of repaglinide or glimepiride, a sulfonylurea, in combination with a DPP-4I, in Japanese patients with type 2 diabetes mellitus (T2DM). This study was an investigator-initiated, open-label, randomized, multi-center prospective study. Patients with T2DM, which was inadequately controlled using a DPP-4I, were randomized to a repaglinide group or a glimepiride group and treated for 48 weeks. The primary outcomes were the reductions in glycated hemoglobin (HbA1c) and glucose oscillation, identified using continuous glucose monitoring, after 12 weeks. The secondary outcome was the change in carotid intima-media thickness (IMT), measured by ultrasonography, after 48 weeks. A total of 61 patients were recruited and analyzed in the study. Twelve weeks of treatment with 1.5 mg repaglinide or 1 mg glimepiride significantly reduced HbA1c, and a larger reduction in HbA1c occurred in the repaglinide group than the glimepiride group. Mean subcutaneous glucose concentration was significantly reduced in both groups, but the glucose oscillation did not decrease. Interestingly, the mean left IMT significantly increased in the glimepiride group, but not in the repaglinide group. More hypoglycemic events were observed in the glimepiride group. These data suggest that repaglinide reduces HbA1c more effectively than glimepiride when used in combination with a DPP-4I, and causes fewer hypoglycemic events. TRAIL REGISTRY: This study is registered with UMIN-CTR (UMIN000018321).

Activation of overexpressed glucagon-like peptide-1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression.

AIMS/INTRODUCTION: Incretin therapy is a common treatment for type 2 diabetes mellitus. We have previously reported an anti-prostate cancer effect of glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4. The attenuation of cell proliferation in the prostate cancer cell line was dependent on GLP-1R expression. Here, we examined the relationship between human prostate cancer severity and GLP-1R expression, as well as the effect of forced expression of GLP-1R using a lentiviral vector. MATERIALS AND METHODS: Prostate cancer tissues were extracted by prostatectomy and biopsy. GLP-1R was overexpressed in ALVA-41 cells using a lentiviral vector (ALVA-41-GLP-1R cells). GLP-1R expression was detected by immunohistochemistry and quantitative polymerase chain reaction. Cell proliferation was examined by growth curves and bromodeoxyuridine incorporation assays. Cell cycle distribution and regulators were examined by flow cytometry and western blotting. In vivo experiments were carried out using a xenografted model. RESULTS: GLP-1R expression levels were significantly inversely associated with the Gleason score of human prostate cancer tissues. Abundant GLP-1R expression and functions were confirmed in ALVA-41-GLP-1R cells. Exendin-4 significantly decreased ALVA-41-GLP-1R cell proliferation in a dose-dependent manner. DNA synthesis and G1-to-S phase transition were inhibited in ALVA-41-GLP-1R cells. SKP2 expression was decreased and p27Kip1 protein was subsequently increased in ALVA-41-GLP-1R cells treated with exendin-4. In vivo experiments carried out by implanting ALVA-41-GLP-1R cells showed that exendin-4 decreased prostate cancer growth by activation of GLP-1R overexpressed in ALVA41-GLP-1R cells. CONCLUSIONS: Forced expression of GLP-1R attenuates prostate cancer cell proliferation by inhibiting cell cycle progression in vitro and in vivo. Therefore, GLP-1R activation might be a potential therapy for prostate cancer.

SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation.

Cancer is currently one of the major causes of death in patients with type 2 diabetes mellitus. We previously reported the beneficial effects of the glucagon-like peptide-1 receptor agonist exendin-4 against prostate and breast cancer. In the present study, we examined the anti-cancer effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin using a breast cancer model. In human breast cancer MCF-7 cells, SGLT2 expression was detected using both RT-PCR and immunohistochemistry. Ipragliflozin at 1-50 µM significantly and dose-dependently suppressed the growth of MCF-7 cells. BrdU assay also revealed that ipragliflozin attenuated the proliferation of MCF-7 cells in a dose-dependent manner. Because the effect of ipragliflozin against breast cancer cells was completely canceled by knocking down SGLT2, ipragliflozin could act via inhibiting SGLT2. We next measured membrane potential and whole-cell current using the patch clamp technique. When we treated MCF-7 cells with ipragliflozin or glucose-free medium, membrane hyperpolarization was observed. In addition, glucose-free medium and knockdown of SGLT2 by siRNA suppressed the glucose-induced whole-cell current of MCF-7 cells, suggesting that ipragliflozin inhibits sodium and glucose cotransport through SGLT2. Furthermore, JC-1 green fluorescence was significantly increased by ipragliflozin, suggesting the change of mitochondrial membrane potential. These findings suggest that the SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation via membrane hyperpolarization and mitochondrial membrane instability.

Efficacy and safety of sodium-glucose cotransporter 2 inhibitor ipragliflozin on glycemic control and cardiovascular parameters in Japanese patients with type 2 diabetes mellitus; Fukuoka Study of Ipragliflozin (FUSION).

Sodium-glucose co-transporter-2 inhibitors are newly established anti-diabetic agents with a unique glucose-lowering mechanism. In the present study, we investigated the efficacy and safety of the sodium-glucose co-transporter-2 inhibitor ipragliflozin (Ipra) for metabolic markers and cardiovascular parameters in Japanese patients with type 2 diabetes mellitus (T2DM). This study was an investigator-initiated, open-label, single-arm, multicenter prospective study. Patients with T2DM were treated with 50 mg Ipra for 24 and 52 weeks. The primary outcome investigated was the reduction of glycated hemoglobin (HbA1c) level. The secondary outcome was the change in other metabolic and cardiovascular parameters by 24 weeks. Before and after 52 weeks of treatment, carotid intima-media thickening (IMT) was measured by echography. A total of 134 patients were recruited in the study. A 24-week treatment with 50 mg Ipra daily significantly reduced HbA1c level (-0.6%, p < 0.01). Body mass index (BMI), blood pressure and serum C-peptide were reduced significantly (p < 0.05), while serum glucagon level was unchanged. Interestingly, the serum adiponectin and high-density lipoprotein (HDL) cholesterol levels were significantly increased by Ipra. However, 52 weeks of Ipra treatment did not change carotid IMT. Multiple regression analysis revealed that the only significant contributing factor for HbA1c reduction by Ipra was baseline HbA1c level. These data suggest that Ipra decreased not only glucose level but also BMI, blood pressure and serum C-peptide, and the contributing factor for HbA1c reduction by Ipra was baseline HbA1c level. Further, Ipra improved serum adiponectin and HDL cholesterol levels.

Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer Growth by Inhibiting NF-κB Activation.

Incretin therapies have received much attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients who have diabetes mellitus. We previously reported antiprostate cancer effects of the glucagonlike peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients who have type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer. GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL-1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce apoptosis, it attenuated breast cancer cell proliferation significantly and dose-dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not affect breast cancer cell proliferation. When MCF-7 cells were transplanted into athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry revealed that breast cancer cell proliferation was significantly reduced in tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly inhibited nuclear factor κB (NF-κB ) nuclear translocation and target gene expression. Furthermore, Ex-4 decreased both Akt and IκB phosphorylation. These results suggest that GLP-1 could attenuate breast cancer cell proliferation via activation of GLP-1R and subsequent inhibition of NF-κB activation.

Si-nanowire-based multistage delayed Mach-Zehnder interferometer optical MUX/DeMUX fabricated by an ArF-immersion lithography process on a 300 mm SOI wafer.

We report good phase controllability and high production yield in Si-nanowire-based multistage delayed Mach-Zehnder interferometer-type optical multiplexers/demultiplexers (MUX/DeMUX) fabricated by an ArF-immersion lithography process on a 300 mm silicon-on-insulator (SOI) wafer. Three kinds of devices fabricated in this work exhibit clear 1×4 Ch wavelength filtering operations for various optical frequency spacing. These results are promising for their applications in high-density wavelength division multiplexing-based optical interconnects.

Differential receivers with highly -uniform MSM Germanium photodetectors capped by SiGe layer.

Waveguide integrated MSM (metal-semiconductor-metal) Germanium (Ge) photodetectors (PDs) with a SiGe capping layer were exploited for silicon photonics integration. Under optimized epitaxial growth conditions, the capping layer passivated the Ge surface, resulting in sufficiently low dark current of the PDs. In addition, the PDs exhibited a narrower distribution of the dark current than PDs with a Si capping layer, probably due to the lower surface leakage current. Low-noise differential receivers with uniform MSM Ge PDs exhibiting 10 Gbps data transmission were realized.

50-Gb/s ring-resonator-based silicon modulator.

We achieved 50-Gb/s operation of a ring-resonator-based silicon modulator for the first time. The pin-diode phase shifter, which consists of a side-wall-grating waveguide, was loaded into the ring resonator. The forward-biased operation mode was applied, which exhibited a V(π)L as small as 0.28 V · cm at 25 GHz. The driving voltage and optical insertion loss at 50-Gb/s were 1.96 V(pp) and 5.2 dB, respectively.

Low-loss, flat-topped and spectrally uniform silicon-nanowire-based 5th-order CROW fabricated by ArF-immersion lithography process on a 300-mm SOI wafer.

We report superior spectral characteristics of silicon-nanowire-based 5th-order coupled resonator optical waveguides (CROW) fabricated by 193-nm ArF-immersion lithography process on a 300-mm silicon-on-insulator wafer. We theoretically analyze spectral characteristics, considering random phase errors caused by micro fabrication process. It will be experimentally demonstrated that the fabricated devices exhibit a low excess loss of 0.4 ± 0.2 dB, a high out-of-band rejection ratio of >40dB, and a wide flatband width of ~2 nm. Furthermore, we evaluate manufacturing tolerances for intra-dies and inter-dies, comparing with the cases for 248-nm KrF-dry lithography process. It will be shown that the 193-nm ArF-immersion lithography process can provide much less excess phase errors of Si-nanowire waveguides, thus enabling to give better filter spectral characteristics. Finally, spectral superiorities will be reconfirmed by measuring 25 Gbps modulated signals launched into the fabricated device. Clear eye diagrams are observed when the wavelengths of modulated signals are stayed within almost passband of the 5th-order CROW.

Demonstration of 12.5-Gbps optical interconnects integrated with lasers, optical splitters, optical modulators and photodetectors on a single silicon substrate.

One of the most serious issues in information industries is the bandwidth bottleneck in inter-chip interconnects. We propose a photonics-electronics convergence system to solve this issue. We fabricated a high density optical interposer to demonstrate the feasibility of the system by using silicon photonics integrated with an arrayed laser diode, an optical splitter, silicon optical modulators, germanium photodetectors, and silicon optical waveguides on a single silicon substrate. Error-free data transmission at 12.5 Gbps and a transmission density of 6.6 Tbps/cm2 were achieved with the optical interposer. We believe this technology will solve the bandwidth bottleneck problem in the future.

12.5-Gb/s operation with 0.29-V·cm V(π)L using silicon Mach-Zehnder modulator based-on forward-biased pin diode.

We present high-speed operation of pin-diode-based silicon Mach-Zehnder modulators that have side-wall gratings on both sides of the waveguide core. The use of pre-emphasis signals generated with a finite impulse response digital filter was examined in the frequency domain to show how the filter works for different filter parameter sets. In large signal modulation experiments, V(π)L as low as 0.29 V·cm was obtained at 12.5 Gb/s using a fabricated modulator and the pre-emphasis technique. Operation of up to 25-Gb/s is possible using basically the same driving configurations.

Difference between home and office blood pressures among treated hypertensive patients from the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

This study sought to clarify the factors associated with the magnitude of the difference between home and office blood pressures in treated hypertensive patients. Study subjects consisted of 3,308 essential hypertensive patients (mean age, 66 years; males, 44%) receiving antihypertensive treatment in primary care settings in Japan. Patients were classified into 3 groups (the home effect group, small difference group, and office effect group) according to tertiles of the magnitude of the office-home systolic blood pressure difference. Compared to the other two groups, the home effect group patients were significantly and independently older, were more often habitual drinkers, had a greater family history of cerebrovascular disease or personal history of ischemic heart disease, and were prescribed a greater number of antihypertensive drugs, non-amlodipine calcium channel blockers, and alpha-blockers as antihypertensive drugs. Compared to the other two groups, the office effect group patients were significantly and independently younger, included more females, less frequently had a family history of cerebrovascular disease or personal history of ischemic heart disease, and were less often prescribed alpha-blockers as antihypertensive drugs. The characteristics of home effect group patients and the factors negatively affecting the blood pressure difference were the same. Among treated hypertensive patients, compared to patients in the other groups, office effect group patients had a lower-risk profile, whereas home effect group patients had a higher-risk profile. These predictive factors might be useful clinically to help identify patients who may have a large difference between home and office blood pressures.

The current status of home and office blood pressure control among hypertensive patients with diabetes mellitus: the Japan Home Versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

Although self-measured blood pressure (BP) at home (HBP) has become popular in clinical practice, little information is available regarding the proportion of diabetic patients with properly controlled HBP. We evaluated the status of HBP control in diabetic hypertensives. HBP control status was cross-sectionally evaluated among 3400 essential hypertensives taking antihypertensive treatment. Of these, 466 (14%) had diabetes. Physicians evaluated the subjects' HBP control as "poor", "fairly good", or "excellent" using a self-administered questionnaire. When the HBP threshold in diabetic patients was set tentatively at 130/80 mmHg or 135/85 mmHg, HBP was properly controlled in 18% or 30% of diabetic patients, respectively. The same trend was observed in office BP. The average number of drugs prescribed for diabetic patients was 2.0 drugs. In the majority of diabetic patients with uncontrolled BP, the BP control status in two-thirds of those was evaluated as "excellent" or "fairly good" by their physicians. In Japan, HBP and office BP were not adequately controlled in most diabetic hypertensives. The main reason for this would appear to be a lack of intensive treatment and a lack of recognition by physicians that their patients' BP was insufficiently controlled.

Current usage of diuretics among hypertensive patients in Japan: the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

In the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study, we examined the current situation with respect to the prescription of diuretics, including the prevalence of diuretic treatment and the dosages used for patients with essential hypertension in primary care settings. Of the 3,400 hypertensive patients included in the study, 315 (9.3%) patients (mean age: 66.9+/-10.4 years; males: 43.5%) were prescribed diuretics. Compared with patients who were not using diuretics, those who were using diuretics were more obese and had more complications. The most commonly prescribed diuretic among the 331 prescriptions in the 315 diuretic users was trichlormethiazide (44%), followed by indapamide (15%) and spironolactone (14%). Among patients being treated with diuretics, monotherapy was used in only 5% of patients; in the majority of patients combination therapy including diuretics (95%) was used. Relatively low dosages of diuretics were generally used. There was a difference between the actual dosages prescribed and those recommended by the Japanese Society of Hypertension (JSH) guidelines or the product information approved in Japan. Compared with previous estimates of the prevalence of diuretic use in hypertensives in Japan (4.0-5.4%), the rate in the J-HOME study (9.3%) was higher. This may be attributable at least in part to the results of the many published, large-scale intervention trials confirming the clinical significance of diuretics. Although a relatively high dosage is recommended in the diuretic product information and in the JSH guidelines, dosages of diuretics should be reconsidered in Japan.

Prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure value: from the Japan Home versus Office Measurement Evaluation Study.

OBJECTIVE: To evaluate the prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure values. METHODS: The study population consisted of 3303 essential hypertensive outpatients receiving antihypertensive treatment in Japan. Information on the characteristics of the patients was collected by a physician's self-administrated questionnaire. The office blood pressure value was calculated as the average of the four readings in two visits. All patients were asked to measure their blood pressure once every morning and once every evening. In the study, we included patients with at least three measurements in the morning and in the evening, respectively. The average of all home blood pressure values was taken as the home blood pressure value. RESULTS: The mean value of home systolic/diastolic blood pressure was 136.8/79.3 mmHg, and the mean value of office systolic/diastolic blood pressure was 142.8/80.6 mmHg. Of the 3303 patients, 758 (23.0%) had controlled hypertension (home <135/85 mmHg and office <140/90 mmHg), 628 (19.0%) had masked uncontrolled hypertension (home > or =135/85 mmHg and office <140/90 mmHg), 640 (19.4%) had treated white-coat hypertension (home <135/85 mmHg and office > or =140/90 mmHg), and 1277 (38.7%) had uncontrolled hypertension (home > or =135/85 mmHg and office > or =140/90 mmHg). CONCLUSIONS: Treated white-coat hypertension and masked uncontrolled hypertension were often observed in clinical settings. Physicians need to understand the prevalence of such patients to prevent inadequate diagnosis and treatment in them.