Favorable changes in the eGFR slope after dapagliflozin treatment and its association with the initial dip.

BACKGROUND: Renoprotective effects of sodium glucose transporter 2 (SGLT2) inhibitors, including dapagliflozin, were observed in randomized controlled trials (RCTs). The suspected underlying mechanism is a correction of hyperfiltration, observed as an "initial dip". Whether SGLT2 inhibitors can attenuate the rate of decline in the estimated glomerular filtration rate (eGFR) in clinical settings, even when considering the pre-treatment decline rate, is unknown. Although several RCTs identified an association between the initial dip and long-term renal prognoses, a conclusion has not been reached. METHODS: We collected the eGFR data of patients for whom dapagliflozin was initiated in our hospital and then calculated their eGFR slopes before and after the start of the treatment. We investigated the changes in the eGFR slopes (ΔeGFR slope) and the association between the ΔeGFR slope and the initial dip. Risks for rapid eGFR decliners (eGFR slope < - 3 mL/min/1.73 m2/year) were also examined. RESULTS: The eGFR slope was significantly milder after dapagliflozin treatment (p < 0.01). A deeper initial dip was associated with a milder rate of eGFR decline (adjusted beta: - 0.29, p < 0.001). Dapagliflozin treatment reduced the proportion of rapid eGFR decliners from 52.9 to 14.7%, and a smaller initial dip was identified as a significant risk for post-treatment rapid eGFR decline (adjusted odds ratio: 1.73, p < 0.05). CONCLUSIONS: Compared to before the administration of dapagliflozin, the rate of eGFR decline was significantly milder after its administration. The initial dip was significantly associated with long-term renoprotective effects and may be a useful predictor of treatment response.

ATP2B1 gene polymorphisms associated with resistant hypertension in the Japanese population.

Single-nucleotide polymorphisms (SNP) of ATP2B1 gene are associated with essential hypertension but their association with resistant hypertension (RHT) remains unexplored. The authors examined the relationship between ATP2B1 SNPs and RHT by genotyping 12 SNPs in ATP2B1 gene of 1124 Japanese individuals with lifestyle-related diseases. Patients with RHT had inadequate blood pressure (BP) control using three antihypertensive drugs or used ≥4 antihypertensive drugs. Patients with controlled hypertension had BP controlled using ≤3 antihypertensive drugs. The association between each SNP and RHT was analyzed by logistic regression. The final cohort had 888 (79.0%) and 43 (3.8%) patients with controlled hypertension and RHT, respectively. Compared with patients homozygous for the minor allele of each SNP in ATP2B1, a significantly higher number of patients carrying the major allele at 10 SNPs exhibited RHT (most significant at rs1401982: 5.8% vs. 0.8%, p = .014; least significant at rs11105378: 5.7% vs. 0.9%, p = .035; most nonsignificant at rs12817819: 5.1% vs. 10%, p = .413). After multivariate adjustment for age, sex, systolic BP, and other confounders, the association remained significant for rs2681472 and rs1401982 (OR: 7.60, p < .05 and OR: 7.62, p = .049, respectively). Additionally, rs2681472 and rs1401982 were in linkage disequilibrium with rs11105378. This study identified two ATP2B1 SNPs associated with RHT in the Japanese population. rs1401982 was most closely associated with RHT, and major allele carriers of rs1401982 required significantly more antihypertensive medications. Analysis of ATP2B1 SNPs in patients with hypertension can help in early prediction of RHT and identification of high-risk patients who are more likely to require more antihypertensive medications.

Efficacy of StepAdd, a Personalized mHealth Intervention Based on Social Cognitive Theory to Increase Physical Activity Among Patients With Type 2 Diabetes Mellitus: Protocol for a Randomized Controlled Trial.

BACKGROUND: Increasing physical activity improves glycemic control in patients with type 2 diabetes (T2D). Mobile health (mHealth) interventions have been proven to increase exercise, but engagement often fades with time. As the use of health behavior theory in mHealth design can increase effectiveness, we developed StepAdd, an mHealth intervention based on the constructs of social cognitive theory (SCT). StepAdd improves exercise behavior self-efficacy and self-regulation through the use of goal-setting, barrier-identifying, and barrier-coping strategies, as well as automatic feedback functions. A single-arm pilot study of StepAdd among 33 patients with T2D showed a large increase in step count (mean change of 4714, SD 3638 daily steps or +86.7%), along with strong improvements in BMI (mean change of -0.3 kg/m2) and hemoglobin A1c level (mean change of -0.79 percentage points). OBJECTIVE: In this study, we aim to investigate the efficacy and safety of StepAdd, an mHealth exercise support system for patients with T2D, via a large, long, and controlled follow-up to the pilot study. METHODS: This is a randomized, open-label, multicenter study targeting 160 patients with T2D from 5 institutions in Japan with a 24-week intervention. The intervention group will record daily step counts, body weight, and blood pressure using the SCT-based mobile app, StepAdd, and receive feedback about these measurements. In addition, they will set weekly step count goals, identify personal barriers to walking, and define strategies to overcome these barriers. The control group will record daily step counts, body weight, and blood pressure using a non-SCT-based placebo app. Both groups will receive monthly consultations with a physician who will advise patients regarding lifestyle modifications and use of the app. The 24-week intervention period will be followed by a 12-week observational period to investigate the sustainability of the intervention's effects. The primary outcome is between-group difference in the change in hemoglobin A1c values at 24 weeks. The secondary outcomes include other health measures, measurements of steps, measurements of other behavior changes, and assessments of app use. The trial began in January 2023 and is intended to be completed in December 2025. RESULTS: As of September 5, 2023, we had recruited 44 patients. We expect the trial to be completed by October 8, 2025, with the follow-up observation period being completed by December 31, 2025. CONCLUSIONS: This trial will provide important evidence about the efficacy of an SCT-based mHealth intervention in improving physical activities and glycemic control in patients with T2D. If this study proves the intervention to be effective and safe, it could be a key step toward the integration of mHealth as part of the standard treatment received by patients with T2D in Japan. TRIAL REGISTRATION: Japan Registry of Clinical Trials (JRCT) jRCT2032220603; https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2032220603. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53514.

Universality and Multiplication of Gigahertz-Operated Silicon Pumps with Parts Per Million-Level Uncertainty.

The universality of physical phenomena is a pivotal concept underlying quantum standards. In this context, the realization of a quantum current standard using silicon single-electron pumps necessitates the verification of the equivalence across multiple devices. Herein, we experimentally investigate the universality of pumped currents from two different silicon single-electron devices which are placed inside the cryogen-free dilution refrigerator whose temperature (mixing chamber plate) was ∼150 mK under the operation of the pump devices. By direct comparison using an ultrastable current amplifier as a galvanometer, we confirm that two pumped currents are consistent with ∼1 ppm uncertainty. Furthermore, we realize quantum-current multiplication with a similar uncertainty by adding the currents of two different gigahertz (GHz)-operated silicon pumps, whose generated currents are confirmed to be identical. These results pave the way for realizing a quantum current standard in the nanoampere range and a quantum metrology triangle experiment using silicon pump devices.

Ballistic Brownian Motion of Nanoconfined DNA.

Theoretical treatments of polymer dynamics in liquid generally start with the basic assumption that motion at the smallest scale is heavily overdamped; therefore, inertia can be neglected. We report on the Brownian motion of tethered DNA under nanoconfinement, which was analyzed by molecular dynamics simulation and nanoelectrochemistry-based single-electron shuttle experiments. Our results show a transition into the ballistic Brownian motion regime for short DNA in sub-5 nm gaps, with quality coefficients as high as 2 for double-stranded DNA, an effect mainly attributed to a drastic increase in stiffness. The possibility for DNA to enter the underdamped regime could have profound implications on our understanding of the energetics of biomolecular engines such as the replication machinery, which operates in nanocavities that are a few nanometers wide.

Single-Cell Electrochemical Aptasensor Array.

Despite several demonstrations of electrochemical devices with limits of detection (LOD) of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to the challenges of scaling up. In this study, we show that the recently introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array, based on Brownian-fluctuating redox species, opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Effect of the interaction between the visceral-to-subcutaneous fat ratio and aldosterone on cardiac function in patients with primary aldosteronism.

Primary aldosteronism is the most frequent secondary hypertensive disease and is characterized by an elevated risk for cardiovascular disease. The current standard treatments are adrenalectomy and/or administration of mineralocorticoid receptor blockers, both of which are effective at ameliorating hypertension via intervention for hyperaldosteronism. However, both of these approaches have side effects and contraindications, and mineralocorticoid receptor blockers also have limited preventive efficacy against cardiovascular events. Recently, in vitro experiments have shown that aldosterone regulation is closely related to abdominal fat accumulation and that there is crosstalk between aldosterone and visceral fat tissue accumulation. We previously reported that this interaction was clinically significant in renal dysfunction; however, its effects on the heart remain unclear. Here, we analyzed data from 49 patients with primary aldosteronism and 29 patients with essential hypertension to examine the potential effect of the interaction between the ratio of visceral-to-subcutaneous fat tissue volume and the plasma aldosterone concentration on echocardiographic indices, including the tissue Doppler-derived E/e' ratio. A significant interaction was found in patients with primary aldosteronism (p < 0.05), indicating that patients with the combination of a high plasma aldosterone concentration and high visceral-to-subcutaneous fat ratio show an increased E/e' ratio, which is a well-known risk factor for future cardiovascular events. Our results confirm the clinical importance of the interaction between aldosterone and abdominal fat tissue, suggesting that an improvement in the visceral-to-subcutaneous fat ratio may be synergistically and complementarily effective in reducing the elevated risk of cardiovascular disease in patients with primary aldosteronism when combined with conventional therapies for reducing aldosterone activity. A significant effect of the interaction between plasma aldosterone concentration and the visceral-to-subcutaneous fat ratio on the tissue Doppler-derived E/e' ratio in patients with primary aldosteronism.

The implication of calf circumference and grip strength in osteoporosis and bone mineral density among hemodialysis patients.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD), nutritional status, and uremia management have been emphasized for bone management in hemodialysis patients. Nevertheless, valuable data on the importance of muscle mass in bone management are limited, including whether conventional management alone can prevent osteoporosis. Thus, the importance of muscle mass and strength, independent of the conventional management in osteoporosis prevention among hemodialysis patients, was evaluated. METHODS: Patients with a history of hemodialysis 6 months or longer were selected. We assessed the risk for osteoporosis associated with calf circumference or grip strength using multivariable adjustment for indices of CKD-MBD, nutrition, and dialysis adequacy. Moreover, the associations between bone mineral density (BMD), calf circumference, grip strength, and bone metabolic markers were also evaluated. RESULTS: A total of 136 patients were included. The odds ratios (95% confidence interval) for osteoporosis at the femoral neck were 1.25 (1.04-1.54, P < 0.05) and 1.08 (1.00-1.18, P < 0.05) per 1 cm shorter calf circumference or 1 kg weaker grip strength, respectively. Shorter calf circumference was significantly associated with a lower BMD at the femoral neck and lumbar spine (P < 0.001). Weaker grip strength was also associated with lower BMD at the femoral neck (P < 0.01). Calf circumference or grip strength was negatively correlated with bone metabolic marker values. CONCLUSION: Shorter calf circumference or weaker grip strength was associated with osteoporosis risk and lower BMD among hemodialysis patients, independent of the conventional therapies.

Omega-3 Fatty Acids Reduce Remnant-like Lipoprotein Cholesterol and Improve the Ankle-Brachial Index of Hemodialysis Patients with Dyslipidemia: A Pilot Study.

Background and Objectives: Omega-3 fatty acids have potent lipid-lowering and antiplatelet effects; however, randomized controlled trials have yet to examine the effect of high-dose omega-3 fatty acid administration on peripheral artery disease (PAD) in hemodialysis patients with dyslipidemia. Therefore, this study aimed to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the ankle-brachial index (ABI) and remnant-like lipoprotein cholesterol (RLP-C) levels, which are indicators of PAD severity. Materials and Methods: Thirty-eight participants (mean age: 73.6 ± 12.7 years) were randomly assigned using stratified block randomization to either conventional therapy alone or conventional therapy supplemented with high-dose EPA/DHA (EPA: 1860 mg; DHA: 1500 mg) for a three-month intervention period. Patients in the conventional therapy alone group who opted to continue were provided with a low-dose EPA/DHA regimen (EPA: 930 mg; DHA: 750 mg) for an additional three months. The baseline and 3-month values for RLP-C, an atherogenic lipid parameter, and the ABI were recorded. Results: The results of the 3-month assessments revealed that the mean RLP-C changes were -3.25 ± 3.15 mg/dL and 0.44 ± 2.53 mg/dL in the EPA/DHA and control groups, respectively (p < 0.001), whereas the changes in the mean ABI values were 0.07 ± 0.11 and -0.02 ± 0.09 in the EPA/DHA and control groups, respectively (p = 0.007). In the EPA/DHA group, a significant negative correlation was found between the changes in RLP-C levels and the ABI (r = -0.475, p = 0.04). Additionally, the change in the RLP-C levels independently influenced the change in the ABI in the EPA/DHA group, even after adjusting for age, sex, and statin use (p = 0.042). Conclusions: Add-on EPA/DHA treatment improved the effectiveness of conventional therapy (such as statin treatment) for improving the ABI in hemodialysis patients with dyslipidemia by lowering RLP-C levels. Therefore, clinicians involved in dialysis should focus on RLP-C when considering residual cardiovascular disease risk in hemodialysis patients and should consider screening patients with elevated levels.

Efficacy of tolvaptan on advanced chronic kidney disease with heart failure: a randomized controlled trial.

BACKGROUND: Tolvaptan (TLV) is reported to improve diuretic effects in patients with chronic kidney disease (CKD) when furosemide (FUR) is not sufficiently effective. However, it is not clear whether TLV addition is effective for advanced CKD patients with heart failure. METHODS: An open-label, parallel-group randomized trial was performed. The subjects were 33 patients with CKD stage G3-G5 who had fluid overload despite taking 20-100 mg/day FUR. They were divided into two groups: a group administered 15 mg/day TLV plus their original FUR dose for 7 days (TLV group), and a group administered 120-200 mg/day FUR (i.e., 100 mg/day over their previous dose) for 7 days (FUR group). RESULTS: The mean change in urine volume was significantly higher in the TLV group compared to the FUR group (637 ml vs 119 ml; p < 0.05). The difference was greater when the urine osmolality before treatment was high. Serum creatinine was increased only in the FUR group. The incidence of worsening renal function (WRF) was significantly lower in the TLV group (18.8% vs 58.8%; p < 0.05). Serum sodium decreased significantly in the FUR group, but did not change in the TLV group. CONCLUSIONS: In patients with advanced CKD with fluid overload, the addition of TLV achieved a significantly higher urine volume with less adverse effects on renal function compared with increasing the dose of FUR. The efficacy and safety of TLV were higher in patients who had higher urine osmolality and lower serum sodium before treatment. CLINICAL TRIAL REGISTRATION: UMIN000014763.

LPIN1 is a new target gene for essential hypertension.

BACKGROUND: We previously showed Lipin1 (LPIN1) to be a candidate gene for essential hypertension by genome-wide association studies. LPIN1 encodes the Lipin 1 protein, which contributes to the maintenance of lipid metabolism and glucose homeostasis. However, little is known about the association between LPIN1 and blood pressure (BP). METHODS: We evaluated the BP of LPIN1-deficient [fatty liver dystrophy (fld)] mice and explored related mechanisms. RESULTS: Fld mice have very low expression of LPIN1 and exhibit fatty liver, hypertriglyceridemia, insulin resistance and peripheral neuropathy. Fld mice had significantly elevated SBP and heart rate (HR) throughout the day as measured by a radiotelemetric method. Diurnal variation of SBP and HR was also absent in fld mice. Furthermore, urinary excretion of adrenaline and noradrenaline by fld mice was significantly higher compared with that of control mice. The BP response of fld mice to clonidine (a centrally acting α2-adrenergic receptor agonist) was greater than that of control mice. However, levels of Angiotensinogen and Renin 1 mRNA and urinary nitric oxide excretion were comparable between the two groups. The decrease in SBP at 8 weeks after fat grafting surgery was significantly greater in the transplant group compared with the sham operated group. CONCLUSION: The elevated BP in fld mice may result from activation of the sympathetic nervous system through decreased levels of adipose cytokines. These results indicate that LPIN1 plays a crucial role in blood pressure regulation and that LPIN1 is a new target gene for essential hypertension.

Association of the ratio of visceral-to-subcutaneous fat volume with renal function among patients with primary aldosteronism.

Patients with primary aldosteronism have a higher risk of chronic kidney disease. Visceral fat tissue is hypothesized to stimulate the adrenal glands to overproduce aldosterone, and aldosterone promotes visceral fat tissue to produce inflammatory cytokines. However, it is unclear whether the volume of accumulated visceral fat tissue is associated with renal impairment among patients with hyperaldosteronism. We conducted a single-center cross-sectional study to assess the association between the estimated glomerular filtration rate and the ratio of the visceral-to-subcutaneous fat volume calculated by computed tomography. One hundred eighty patients with primary aldosteronism were enrolled. The mean ± SD age was 52.7 ± 11.0 years, and 60.0% were women. The ratio of visceral-to-subcutaneous fat volume was highly correlated with the estimated glomerular filtration rate (r = 0.49, p < 0.001). In multiple linear regression models, the ratio of visceral-to-subcutaneous fat tissue volume was significantly associated with the estimated glomerular filtration rate (estimates: -4.56 mL/min/1.73 m² per 1-SD), and there was an interaction effect between the plasma aldosterone concentration and the ratio of visceral-to-subcutaneous fat volume (p < 0.05). The group with a higher plasma aldosterone concentration exhibited a steeper decline in eGFR than the lower plasma aldosterone concentration group when the ratio increased. The ratio of visceral-to-subcutaneous fat tissue volume was an independent risk factor for renal dysfunction. This association increased in the presence of a high plasma aldosterone concentration. Clinicians should pay attention to the ratio of visceral-to-subcutaneous fat tissue volume and encourage primary aldosteronism patients to improve their lifestyle in addition to treating renin-aldosterone activity.

Clinical Intervention Using Body Shadows for a Patient with Complex Regional Pain Syndrome Who Reported Severe Pain and Self-Disgust Toward the Affected Site: A Case Report.

A woman in her thirties developed complex regional pain syndrome in her left shoulder due to a traffic accident. She demonstrated autonomic nervous symptoms (swelling, sweating, and skin color asymmetry) in her left hand, severe allodynia, neglect-like symptoms (NLS), impaired body image associated with impaired body awareness, and functional impairment of the left shoulder and elbow. She also reported physical self-disgust toward her affected limb, describing it as "reptilian," as well as aversion to touching others; this body awareness exacerbated her pain and NLS. We therefore conducted stepwise interventions using body shadows. The intervention did not trigger physical self-disgust, enabling formation of body ownership and a body image unaccompanied by pain. Consequently, the patient showed improvements in pain, NLS, and autonomic nervous symptoms.

Picosecond coherent electron motion in a silicon single-electron source.

An advanced understanding of ultrafast coherent electron dynamics is necessary for the application of submicrometre devices under a non-equilibrium drive to quantum technology, including on-demand single-electron sources1, electron quantum optics2-4, qubit control5-7, quantum sensing8,9 and quantum metrology10. Although electron dynamics along an extended channel has been studied extensively2-4,11, it is hard to capture the electron motion inside submicrometre devices. The frequency of the internal, coherent dynamics is typically higher than 100 GHz, beyond the state-of-the-art experimental bandwidth of less than 10 GHz (refs. 6,12,13). Although the dynamics can be detected by means of a surface-acoustic-wave quantum dot14, this method does not allow for a time-resolved detection. Here we theoretically and experimentally demonstrate how we can observe the internal dynamics in a silicon single-electron source that comprises a dynamic quantum dot in an effective time-resolved fashion with picosecond resolution using a resonant level as a detector. The experimental observations and the simulations with realistic parameters show that a non-adiabatically excited electron wave packet15 spatially oscillates quantum coherently at ~250 GHz inside the source at 4.2 K. The developed technique may, in future, enable the detection of fast dynamics in cavities, the control of non-adiabatic excitations15 or a single-electron source that emits engineered wave packets16. With such achievements, high-fidelity initialization of flying qubits5, high-resolution and high-speed electromagnetic-field sensing8 and high-accuracy current sources17 may become possible.

Effects of blood pressure lowering in patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis.

The efficacy and safety of blood pressure lowering in patients with heart failure with preserved ejection fraction (HFpEF) remain unknown. We systematically searched PubMed/Medline, ICHUSHI, EMBASE, and the Cochrane Central Library database for randomized controlled trials (RCTs) assessing the efficacy and safety of blood pressure lowering in patients with HFpEF that were published from January 1996 to July 2017. Our study included a total of 10 RCTs involving 13,091 patients with HFpEF that compared all-cause mortality, cardiovascular mortality, heart failure hospitalization, renal dysfunction, and/or hypotension between drug intervention and control groups. Then, we analyzed systolic blood pressure (SBP) before and during trials using the SBP from the RCTs data. SBP decreased in the intervention group (134.7-130.2 mmHg) more than that in the control group (134.4-133.3 mmHg), and heart failure hospitalization was reduced in the intervention group compared to that in the control group [RR 0.89 (0.82-0.97), P = 0.006]. There was no effect of treatment on all-cause mortality, cardiovascular mortality, and hypotension. However, in the studies that compared renal function, SBP decreased in the intervention group (134.3-129.6 mmHg) more than that in the control group (134.0-132.8 mmHg), and the occurrence of renal dysfunction increased in the intervention group compared to that in the control group [RR 1.52 (1.31-1.76), P < 0.00001)]. Blood pressure lowering that achieves SBP levels of ~130 mmHg may be related to the reduction in heart failure hospitalization in patients with HFpEF, but it also possibly leads to an increased risk of renal dysfunction.

Effects of lowering diastolic blood pressure to <80 mmHg on cardiovascular mortality and events in patients with coronary artery disease: a systematic review and meta-analysis.

The target of diastolic blood pressure (DBP) remains controversial in patients with coronary artery disease (CAD). We systematically searched PubMed/Medline and the Cochrane Central database for randomized controlled trials (RCTs) assessing the efficacy and safety of reducing DBP in CAD patients from January 1965 to July 2017. Seven placebo-controlled RCTs enrolling 34,814 CAD patients who achieved DBP <80 mmHg were included in the drug-intervention group. The average achieved blood pressures (BPs) were 126.3/75.1 and 131.5/77.8 mmHg in the drug-intervention and placebo-control groups, respectively. Drug intervention was associated with an 11% reduction in coronary revascularization and a 31% reduction in heart failure. In the drug-intervention group, all-cause death, myocardial infarction, angina pectoris, and stroke were reduced with marginal significance, whereas hypotension was increased by 123%. A meta-analysis of four RCTs, in which the achieved DBP was <75 mmHg, showed that the drug intervention was associated with a 22% reduction in heart failure. These results suggest that reducing DBP to 80 mmHg or less would significantly reduce coronary revascularization and heart failure but at the expense of causing hypotension in CAD patients. Further trials are warranted to prove this issue.

Angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers in hypertensive patients with myocardial infarction or heart failure: a systematic review and meta-analysis.

Angiotensin-converting enzyme inhibitors (ACEIs) are considered primary drugs for the secondary prevention of myocardial infarction (MI), and angiotensin receptor blockers (ARBs) are used when ACEIs cannot be tolerated. However, it is unclear whether ACEIs or ARBs are more appropriate first-line drugs in hypertensive patients with MI or heart failure (HF). The present study aimed to compare the effects of ACEIs and those of ARBs in these patients. Sixty randomized controlled trails (RCTs) that compared the effects of ACEIs and ARBs in patients with MI or HF were extracted by searching PubMed/MEDLINE, Cochrane Database, and the Medical Central Journal database according to the PRISMA guidelines. We finally selected six eligible RCTs and identified three systematic reviews and meta-analyses. The proportion of hypertensive patients ranged from 36 to 69%. Meta-analyses were performed for recurrence or new onset of MI (risk ratio 0.97 [95% confidence interval: 0.88, 1.06]), hospitalization for HF (0.98 [0.84, 1.14]), cardiovascular or total mortality (0.98 [0.91, 1.05]), cardiovascular events or stroke (1.02 [0.94, 1.11]), and adverse events (1.40 [1.11, 1.77]). There were no significant differences between ACEIs and ARBs for all outcomes, except adverse events. Study discontinuation owing to adverse events was significantly more common with ACEIs than with ARBs. Among hypertensive patients with MI or HF, it appears desirable to select the most appropriate drugs, ACEIs or ARBs, in each case by considering the function level, patient background, comorbidity presence, blood pressure target, drug price and other such factors comprehensively in addition to considering tolerability.

Electron aspirator using electron-electron scattering in nanoscale silicon.

Current enhancement without increasing the input power is a critical issue to be pursued for electronic circuits. However, drivability of metal-oxide-semiconductor (MOS) transistors is limited by the source-injection current, and electrons that have passed through the source unavoidably waste their momentum to the phonon bath. Here, we propose the Si electron-aspirator, a nanometer-scaled MOS device with a T-shaped branch, to go beyond this limit. The device utilizes the hydrodynamic nature of electrons due to the electron-electron scattering, by which the injected hot electrons transfer their momentum to cold electrons before they relax with the phonon bath. This momentum transfer induces an electron flow from the grounded side terminal without additional power sources. The operation is demonstrated by observing the output-current enhancement by a factor of about 3 at 8 K, which reveals that the electron-electron scattering can govern the electron transport in nanometer-scaled MOS devices, and increase their effective drivability.

Semaphorin 3F and Netrin-1: The Novel Function as a Regulator of Tumor Microenvironment.

Axon guidance molecules play an important role in regulating proper neuronal networking during neuronal development. They also have non-neuronal properties, which include angiogenesis, inflammation, and tumor development. Semaphorin 3F (SEMA3F), a member of the class 3 semaphorins, was initially identified as an axon guidance factor, that repels axons and collapses growth cones. However, SEMA3F has similar effects on endothelial cells (ECs) and tumor cells. In this review, we discuss the novel molecular mechanisms underlying SEMA3F activity in vascular and tumor biology. Recent evidence suggests that SEMA3F functions as a PI3K-Akt-mTOR inhibitor in mammalian cells, including T cells, ECs, and tumor cells. Therefore, SEMA3F may have broad therapeutic implications. We also discuss the key role of axon guidance molecules as regulators of the tumor microenvironment. Netrin-1, a chemoattractant factor in the neuronal system, promotes tumor progression by enhancing angiogenesis and metastasis. Moreover, our recent studies demonstrate that netrin-1/neogenin interactions augment CD4+ T cell chemokinesis and elicit pro-inflammatory responses, suggesting that netrin-1 plays a key role in modulating the function of a tumor and its surrounding cells in the tumor microenvironment. Overall, this review focuses on SEMA3F and netrin-1 signaling mechanisms to understand the diverse biological functions of axon guidance molecules.