Estimating Blood Pressure during Exercise with a Cuffless Sphygmomanometer.

Accurately measuring blood pressure (BP) is essential for maintaining physiological health, which is commonly achieved using cuff-based sphygmomanometers. Several attempts have been made to develop cuffless sphygmomanometers. To increase their accuracy and long-term variability, machine learning methods can be applied for analyzing photoplethysmogram (PPG) signals. Here, we propose a method to estimate the BP during exercise using a cuffless device. The BP estimation process involved preprocessing signals, feature extraction, and machine learning techniques. To ensure the reliability of the signals extracted from the PPG, we employed the skewness signal quality index and the RReliefF algorithm for signal selection. Thereafter, the BP was estimated using the long short-term memory (LSTM)-based neural network. Seventeen young adult males participated in the experiments, undergoing a structured protocol composed of rest, exercise, and recovery for 20 min. Compared to the BP measured using a non-invasive voltage clamp-type continuous sphygmomanometer, that estimated by the proposed method exhibited a mean error of 0.32 ± 7.76 mmHg, which is equivalent to the accuracy of a cuff-based sphygmomanometer per regulatory standards. By enhancing patient comfort and improving healthcare outcomes, the proposed approach can revolutionize BP monitoring in various settings, including clinical, home, and sports environments.

Experimental study platform for electrocatalysis of atomic-level controlled high-entropy alloy surfaces.

High-entropy alloys (HEAs) have attracted considerable attention to improve performance of various electrocatalyst materials. A comprehensive understanding of the relationship between surface atomic-level structures and catalytic properties is essential to boost the development of novel catalysts. In this study, we propose an experimental study platform that enables the vacuum synthesis of atomic-level-controlled single-crystal high-entropy alloy surfaces and evaluates their catalytic properties. The platform provides essential information that is crucial for the microstructural fundamentals of electrocatalysis, i.e., the detailed relationship between multi-component alloy surface microstructures and their catalytic properties. Nanometre-thick epitaxially stacking layers of Pt and equi-atomic-ratio Cr-Mn-Fe-Co-Ni, the so-called Cantor alloy, were synthesised on low-index single-crystal Pt substrates (Pt/Cr-Mn-Fe-Co-Ni/Pt(hkl)) as a Pt-based single-crystal alloy surface model for oxygen reduction reaction (ORR) electrocatalysis. The usefulness of the platform was demonstrated by showing the outperforming oxygen reduction reaction properties of high-entropy alloy surfaces when compared to Pt-Co binary surfaces.

Functionally integrated waveguide illuminator for common-path digital holographic microscopy through random media.

We designed and fabricated a functionally integrated optical waveguide illuminator specially for common-path digital holographic microscopy through random media. The waveguide illuminator creates two point sources with desired phase shifts, which are located close to one another so that the common-path condition of the object and reference illumination is satisfied. Thereby, the proposed device permits phase-shift digital holographic microscopy free from bulky optical elements such as a beam splitter, an objective lens, and a piezoelectric transducer for phase shifting. Using the proposed device, microscopic 3D imaging through a highly heterogeneous double-composite random medium was experimentally demonstrated by means of common-path phase-shift digital holography.

Shape memory effect and aging behavior of Bi-added Ti-Cr alloys for biomedical applications.

For the further development of biocompatible metastable ß (bcc) Ti alloys, the purpose of this study is to evaluate the potential of bismuth (Bi) addition in terms of shape memory properties and phase stability. It was found that the shape memory effect appeared in Ti-5Cr-1.6Bi (mol%) alloy. However, permanent (unrecoverable) deformation due to dislocations or twinning was also introduced simultaneously from the early stage of deformation. Regarding the formation of isothermal ω phase and the resulting hardness change by aging, it was found that the hardness change was large and that the isothermal ω phase formed in Ti-5Cr-1.6Bi alloy, while age hardening was small and no isothermal ω phase formed in Ti-5Cr-6.1Bi alloy. These results indicate the suppression of not only athermal ω but also isothermal ω phase by Bi addition. However, considering the fact that the alloy becomes brittle when Bi addition is over 3 mol%, it can be concluded that 1-3 mol% Bi addition is worth for the improvement of shape memory effect, suppression of ω phase, X-ray imaging, magnetic resonance imaging, and biocompatibility in metastable ß Ti alloys.

Enhanced electrochemical hydrogen oxidation reaction and suppressed hydrogen peroxide generation properties on Pt/Ir(111) bimetallic surfaces.

Simultaneous accomplishment of high hydrogen oxidation reaction (HOR) activity and suppressed hydrogen peroxide (H2O2) generation is desired for anode catalysts of polymer electrolyte fuel cells. 0.3 monolayer-thick-Pt-deposited Ir(111) showed three-fold higher HOR activity than Pt(111) and suppressed H2O2 generation under the detection limit, providing insights for effective catalyst development.

Cerebral blood flow abnormalities with central sparing on arterial spin labeling in mild encephalopathy associated with excitotoxicity: a case report.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX) are the most frequent acute encephalopathies in pediatric patients in Japan. AESD typically presents with biphasic seizures and delayed reduced diffusion in the subcortical area, called bright tree appearance (BTA), on radiological examination. In patients with AESD, arterial spin labeling (ASL) shows decreased cerebral blood flow (CBF) in the hyperacute stage and increased CBF in the acute stage, suggesting the usefulness of ASL for the early diagnosis of AESD. Additionally, proton magnetic resonance spectroscopy (MRS) shows elevated glutamate (Glu) and glutamine (Gln) in AESD. MEEX is a group of mild encephalopathies with transient elevation of Gln on MRS similar to that in AESD; however, MEEX does not include any clinical biphasic course or abnormalities, including BTA on diffusion-weighted imaging. Although the usefulness of ASL for AESD has been reported, there are no reports for patients with MEEX. In this study, we report our experience with a 4-year-old girl diagnosed with MEEX who showed unique findings on ASL. CASE PRESENTATION: The patient was a 4-year-old girl admitted to the emergency room with febrile status epilepticus. Considering the possibility of AESD, vitamin therapy was initiated. ASL-MR imaging (MRI) of the brain performed on the second day showed increased blood flow in the frontal, temporal, and occipital regions with spared central sulcus, which indicated AESD with central sparing. The patient was diagnosed with AESD, and the treatment included pulse steroid therapy and immunoglobulin therapy from day 3. The patient remained mildly unconscious but gradually became conscious by day 7 with no seizures. Brain MRI performed on day 8 did not show any characteristic AESD findings, such as BTA. Furthermore, MRS showed elevated Gln, which, along with the clinical course, led to the diagnosis of MEEX. The patient was discharged on day 16 without obvious sequelae. CONCLUSIONS: ASL may be useful in the early diagnosis of MEEX as well as AESD, facilitating early intervention.

Hydrogen peroxide generation and hydrogen oxidation reactions of vacuum-prepared Ru/Ir(111) bimetallic surfaces.

From the viewpoint of the application of Ir-Ru alloys for the anode of proton exchange membrane fuel cells (PEMFCs), hydrogen peroxide (H2O2) generation and the hydrogen oxidation reaction (HOR) properties of well-defined Ir-Ru bimetallic surfaces (Ru/Ir(111)) have been investigated using scanning electrochemical microscopy (SECM). Using thermal inter-diffusion of vacuum-deposited Ru and substrate Ir atoms, the topmost surface atomic ratios of Ru/Ir(111) were controlled via changing the substrate temperature (x) during the deposition of 1 monolayer (ML)-thick Ru. Low-energy ion scattering spectroscopy (LE-ISS) estimated the Ru/Ir ratio to be 1 : 1 (x = 673 K), 1 : 2 (x = 773 K), and 1 : 4 (x = 873 K). The H2O2 generation property of Ru/Ir(111) was similar to that of clean Ir(111) and under the detection limit in the potential region of 0.06-0.3 V, while clean Ru(0001) generated H2O2 in this potential region. The results suggest that the Ir sites contribute to the reduction of H2O2 intermediates generated at neighboring Ru sites. In contrast, the HOR activity of Ru/Ir(111) correlated with the probabilities of ensembles, such as Ir2 dimers and Ir3 trimers: the ensemble probabilities were calculated under the assumption of random solute Ir and Ru atoms at the topmost surfaces. Such a close correlation suggests that the Ir ensemble sites strongly contribute to the HOR. In conclusion, the Ir sites play a key role in the suppression of H2O2 generation and high HOR activity, which is essential for next-generation PEMFC anode catalysts.

Neurogenic pulmonary edema following febrile status epilepticus in a 22-month-old infant with multiple respiratory virus co-detection: a case report.

BACKGROUND: Neurogenic pulmonary edema is a rare but serious complication of febrile status epilepticus in children. Comprehensive screening for viral pathogens is seldomly performed in the work-up of febrile children. CASE PRESENTATION: A 22-month-old girl presented with her first episode of febrile status epilepticus, after which she developed acute pulmonary edema and respiratory failure. After the termination of seizure activity, the patient was intubated and managed on mechanical ventilation in the emergency room. The resolution of respiratory failure, as well as the neurological recovery, was achieved 9 h after admission, and the patient was discharged 6 days after admission without any complications. Molecular biological diagnostic methods identified the presence of human coronavirus HKU1, influenza C virus, and human parainfluenza virus 2 from the patient's nasopharyngeal specimens. CONCLUSIONS: Neurogenic pulmonary edema following febrile status epilepticus was suspected to be the etiology of our patient's acute pulmonary edema and respiratory failure. Timely seizure termination and rapid airway and respiratory intervention resulted in favorable outcomes of the patient. Molecular biological diagnostic methods identified three respiratory viruses; however, their relevance and association with clinical symptoms remain speculative.

Risk-Based Monitoring Approach to Ensure the Quality of Clinical Study Data and Enable Effective Monitoring.

BACKGROUND: Following the Guidance for Industry by FDA, the concept of risk-based approach has spread rapidly in recent years. It facilitates more effective, efficient, and high-quality clinical study execution. METHOD: We carried out a pilot study that adopted risk-based monitoring. In the preparatory stage, the risks of this study (protocol level and program level) were assessed and mitigated as much as possible. During the study, centralized monitoring were conducted in parallel with site (on-site/off-site) monitoring, and study risks were assessed based on the results of both monitoring in accordance with the risk management plan. RESULTS: We found that average on-site monitoring frequency decreased as the study progressed. After study completion, we conducted a Pharmaceutical and Medical Devices Agency inspection but found no significant nonconformance that would have affected the study results and patient safety. CONCLUSIONS: The results indicate that a risk-based approach, which is an innovative monitoring approach, contributes to the reliability of study results and promotes efficient monitoring.

High-dose linaclotide is effective and safe in patients with chronic constipation: A phase III randomized, double-blind, placebo-controlled study with a long-term open-label extension study in Japan.

BACKGROUND: A previous phase II dose-ranging study of linaclotide in a Japanese chronic constipation (CC) population showed that 0.5 mg was the most effective dose. This study aimed to verify the hypothesis that 0.5 mg of linaclotide is effective and safe in Japanese CC patients. METHODS: This was a Japanese phase III randomized, double-blind, placebo-controlled (part 1), and long-term, open-label extension (part 2) study of linaclotide. CC patients (n = 186) diagnosed using the Rome III criteria were randomly assigned to linaclotide 0.5 mg (n = 95) or placebo (n = 91) for a 4-week double-blind treatment period in part 1, followed by an additional 52 weeks of open-label treatment with linaclotide in part 2. The primary efficacy endpoint was the change from baseline in weekly spontaneous bowel movement (SBM) frequency at the first week. Secondary endpoints included responder rate for complete SBM (CSBM), changes in stool consistency, and severity of straining. KEY RESULTS: Part 1: Change in weekly mean SBM frequency in the first week of treatment with linaclotide (4.02) was significantly greater than that with placebo (1.48, P < 0.001). Linaclotide produced a higher CSBM responder rate (52.7%) compared to placebo (26.1%, P < 0.001). Part 2: Patients continued to show improved SBM frequency with linaclotide. Through parts 1 and 2, the most common drug-related adverse event was mild and occasionally moderate diarrhea. CONCLUSIONS AND INFERENCES: The results of this study indicate that a linaclotide dose of 0.5 mg/day is effective and safe in Japanese CC patients.

Therapy with propylthiouracil for T3-predominant neonatal Graves' disease: a case report.

This case report describes a male neonate with Graves' disease. The mother's pregnancy was complicated by poorly controlled Graves' disease. The neonate was diagnosed with thyroxine (T3)-predominant Graves' disease with low free triiodothyronine (T4) and high free T3 during antithyroid drug therapy. The patient also presented with persistent pulmonary hypertension of the newborn due to hyperthyroidism and airway stenosis caused by goiter. It was difficult to control thyroid function and maintain free T4 levels with inorganic iodine, thiamazole, and levothyroxine sodium hydrate. We successfully controlled thyroid function using the previous treatments in combination with propylthiouracil. Propylthiouracil suppresses type 1 iodothyronine deiodinase, and its pharmacological action suppresses the conversion of T4 to T3. Therefore, we used propylthiouracil at an earlier stage of intervention in this case. We ceased administration of antithyroid drugs on day 85 of life. Subsequently, as the TRH loading test revealed central hypothyroidism, oral administration of levothyroxine sodium hydrate was continued. Its administration was discontinued at the age of 1 yr. Thyroid-stimulating hormone recovered to normal values, and his development had progressed without complications by the age of 2 yr.

Spatial arrangement of proteins using scCro-tag: application for an in situ enzymatic microbead assay.

In natural systems, various metabolic reactions are often spatially organized to increase enzyme activity and specificity. Thus, by spatially arranging enzyme molecules in synthetic systems to imitate these natural systems, it is possible to promote a high rate of enzymatic turnover. In this present study, a normal and mutant form of the scCro DNA-binding protein were shown to bind orthogonally to specific recognition sequences under appropriate conditions. Furthermore, these DNA-binding tags were used to establish an enzyme assay system based on the spatial arrangement of transglutaminase and its substrate at the molecular level. Together, the results of the present study suggest that the scCro-tag may be a powerful tool to facilitate the synthetic spatial arrangement of proteins on a DNA ligand.

Streptococcal toxic shock syndrome caused by the dissemination of an invasive emm3/ST15 strain of Streptococcus pyogenes.

BACKGROUND: Streptococcus pyogenes (group A Streptococcus [GAS]) is a major human pathogen that causes a wide spectrum of clinical manifestations. Although invasive GAS (iGAS) infections are relatively uncommon, emm3/ST15 GAS is a highly virulent, invasive, and pathogenic strain. Global molecular epidemiology analysis has suggested that the frequency of emm3 GAS has been recently increasing. CASE PRESENTATION: A 14-year-old patient was diagnosed with streptococcal toxic shock syndrome and severe pneumonia, impaired renal function, and rhabdomyolysis. GAS was isolated from a culture of endotracheal aspirates and designated as KS030. Comparative genome analysis suggested that KS030 is classified as emm3 (emm-type) and ST15 (multilocus sequencing typing [MLST]), which is similar to iGAS isolates identified in the UK (2013) and Switzerland (2015). CONCLUSIONS: We conclude that the global dissemination of emm3/ST15 GAS strain has the potential to cause invasive disease.

Chaotic dynamics of a swirling flame front instability generated by a change in gravitational orientation.

We have intensively examined the dynamic behavior of flame front instability in a lean swirling premixed flame generated by a change in gravitational orientation [H. Gotoda, T. Miyano, and I. G. Shepherd, Phys. Rev. E 81, 026211 (2010)PLEEE81539-375510.1103/PhysRevE.81.026211] from the viewpoints of complex networks, symbolic dynamics, and statistical complexity. Here, we considered the permutation entropy in combination with the surrogate data method, the permutation spectrum test, and the multiscale complexity-entropy causality plane incorporating a scale-dependent approach, none of which have been considered in the study of flame front instabilities. Our results clearly show the possible presence of chaos in flame front dynamics induced by the coupling of swirl-buoyancy interaction in inverted gravity. The flame front dynamics also possesses a scale-free structure, which is reasonably shown by the probability distribution of the degree in ε-recurrence networks.

Probing and exploiting the chaotic dynamics of a hydrodynamic photochemical oscillator to implement all the basic binary logic functions.

The convective motions within a solution of a photochromic spiro-oxazine being irradiated by UV only on the bottom part of its volume, give rise to aperiodic spectrophotometric dynamics. In this paper, we study three nonlinear properties of the aperiodic time series: permutation entropy, short-term predictability and long-term unpredictability, and degree distribution of the visibility graph networks. After ascertaining the extracted chaotic features, we show how the aperiodic time series can be exploited to implement all the fundamental two-inputs binary logic functions (AND, OR, NAND, NOR, XOR, and XNOR) and some basic arithmetic operations (half-adder, full-adder, half-subtractor). This is possible due to the wide range of states a nonlinear system accesses in the course of its evolution. Therefore, the solution of the convective photochemical oscillator results in hardware for chaos-computing alternative to conventional complementary metal-oxide semiconductor-based integrated circuits.

Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study.

BACKGROUND: The long-term safety of administration of ramosetron in female patients with irritable bowel syndrome with diarrhea (IBS-D) is unknown. The aim of this study was to assess the long-term safety, tolerability, and outcomes with the use of ramosetron in female patients with IBS-D. METHODS: This was a phase III, open-label, uncontrolled, long-term safety trial of the treatment of female Japanese patients with IBS-D, diagnosed according to the Rome III criteria. A total of 151 patients were given 2.5 µg of ramosetron for 4 weeks, and responders continued the same dose for another 48 weeks. Non-responders at 4 weeks were given 5 µg of ramosetron for 48 weeks. At the end of week 52, 106 patients receiving 2.5 µg and 17 patients receiving 5 µg had completed the study. Safety and efficacy including symptoms and quality of life (QOL) were evaluated. RESULTS: Concerning safety, no serious adverse event related to ramosetron, specifically ischemic colitis, was observed in patients with either dose of ramosetron. However, constipation occurred in 19.7 % of patients given 2.5 µg and 10.5 % of patients given 5 µg of ramosetron. Ramosetron-treated patients showed high rates of global improvement. Stool consistency, abdominal pain and discomfort, and IBS-QOL were also improved at the last evaluation point. CONCLUSIONS: The results provide evidence of the long-term safety and efficacy of treatment with 2.5 and 5 µg of ramosetron in female patients with IBS-D. Clinicians should be aware that one-fifth of women with IBS-D receiving ramosetron may suffer from constipation during treatment (ClinicalTrials.gov ID: NCT01736423).

Characterization of degeneration process in combustion instability based on dynamical systems theory.

We present a detailed study on the characterization of the degeneration process in combustion instability based on dynamical systems theory. We deal with combustion instability in a lean premixed-type gas-turbine model combustor, one of the fundamentally and practically important combustion systems. The dynamic behavior of combustion instability in close proximity to lean blowout is dominated by a stochastic process and transits to periodic oscillations created by thermoacoustic combustion oscillations via chaos with increasing equivalence ratio [Chaos 21, 013124 (2011); Chaos 22, 043128 (2012)]. Thermoacoustic combustion oscillations degenerate with a further increase in the equivalence ratio, and the dynamic behavior leads to chaotic fluctuations via quasiperiodic oscillations. The concept of dynamical systems theory presented here allows us to clarify the nonlinear characteristics hidden in complex combustion dynamics.

Adaptive sampling dual terahertz comb spectroscopy using dual free-running femtosecond lasers.

Terahertz (THz) dual comb spectroscopy (DCS) is a promising method for high-accuracy, high-resolution, broadband THz spectroscopy because the mode-resolved THz comb spectrum includes both broadband THz radiation and narrow-line CW-THz radiation characteristics. In addition, all frequency modes of a THz comb can be phase-locked to a microwave frequency standard, providing excellent traceability. However, the need for stabilization of dual femtosecond lasers has often hindered its wide use. To overcome this limitation, here we have demonstrated adaptive-sampling THz-DCS, allowing the use of free-running femtosecond lasers. To correct the fluctuation of the time and frequency scales caused by the laser timing jitter, an adaptive sampling clock is generated by dual THz-comb-referenced spectrum analysers and is used for a timing clock signal in a data acquisition board. The results not only indicated the successful implementation of THz-DCS with free-running lasers but also showed that this configuration outperforms standard THz-DCS with stabilized lasers due to the slight jitter remained in the stabilized lasers.

Real-time absolute frequency measurement of continuous-wave terahertz radiation based on dual terahertz combs of photocarriers with different frequency spacings.

Real-time measurement of the absolute frequency of continuous-wave terahertz (CW-THz) radiation is required for characterization and frequency calibration of practical CW-THz sources. We proposed a method for real-time monitoring of the absolute frequency of CW-THz radiation involving temporally parallel, i.e., simultaneous, measurement of two pairs of beat frequencies and laser repetition frequencies based on dual THz combs of photocarriers (PC-THz combs) with different frequency spacings. To demonstrate the method, THz-comb-referenced spectrum analyzers were constructed with a dual configuration based on dual femtosecond lasers. Regardless of the presence or absence of frequency control in the PC-THz combs, a frequency precision of 10(-11) was achieved at a measurement rate of 100 Hz. Furthermore, large fluctuation of the CW-THz frequencies, crossing several modes of the PC-THz combs, was correctly monitored in real time. The proposed method will be a powerful tool for the research and development of practical CW-THz sources, and other applications.

[Three cases with high TARC levels of gastrointestinal food allergies in neonates and infants].

We measured serum TARC (Thymus and activation-regulated chemokine, CCL-17) levels in three patients of gastrointestinal food allergies in neonates and infants. Patient 1: 14-day-old girl. The chief complaints were poor feeding and weight loss. She tested peripheral eosinophilia (5820 /µL), high serum TARC levels (4730 pg/mL) and positive milk-specific IgE (1.53 UA/mL) at the time of onset. After change from cow' milk formula to hydrolyzed infant formulas and breast milk ahead of dairy products intake, the symptoms resolved. One month and a half later, she re-tested negative milk-specific IgE and normal serum TARC levels (198 pg/mL). Patient 2: 3-month-old girl. The chief complaint was vomiting after intake of cow' milk formula. She tested negative milk-specific IgE and very high serum TARC levels (25200 pg/mL) at the time of onset. After changing to hydrolyzed infant formulas and breast milk ahead of dairy products intake, the symptom resolved. Three months later, she re-tested positive milk-specific IgE (0.42 UA/mL) and normal serum TARC levels (1250 pg/mL). Patient 3: 21-day-old boy. The chief complaint was vomiting after intake of cow' milk formula. He tested peripheral eosinophilia (2923 /µL), very high serum TARC levels (49100 pg/mL) and positive milk-specific IgE (0.47 UA/mL) at the time of onset. After changing to hydrolyzed infant formulas and breast milk ahead of dairy products intake, the symptom resolved. Two weeks later, he re-tested negative milk-specific IgE and serum TARC levels (2210 pg/mL). Serum TARC may be related to the part of gastrointestinal food allergies in neonates and infants.