Measuring congestion with a non-invasive monitoring device in heart failure and haemodialysis: CONGEST-HF.

Aims: We examined the effectiveness of a novel cardiopulmonary management wearable sensor (worn for less than 5 mins) at measuring congestion and correlated the device findings with established clinical measures of congestion.

Methods And Results: We enrolled three cohorts of patients: (1) patients with heart failure (HF) receiving intravenous diuretics in hospital; (2) patients established on haemodialysis, and (3) HF patients undergoing right heart catheterization (RHC). The primary outcomes in the respective cohorts were a Spearman correlation between (1) change in weight and change in thoracic impedance (TI) (from enrolment, 24 h after admission to discharge) in patients hospitalized for HF; (2) lung ultrasound B-lines and volume removed during dialysis with device measured TI, and (3) pulmonary capillary wedge pressure (PCWP) and sub-acoustic diastolic, third heart sound (S3) in the patients undergoing RHC.

Intracerebroventricular enzyme replacement therapy in patients with neuronopathic mucopolysaccharidosis type II: Final report of 5-year results from a Japanese open-label phase 1/2 study.

Intravenous idursulfase is standard treatment for mucopolysaccharidosis II (MPS II) in Japan. In the interim analysis of this open-label, phase 1/2 study (Center for Clinical Trials, Japan Medical Association: JMA-IIA00350), intracerebroventricular (ICV) idursulfase beta was well tolerated, suppressed cerebrospinal fluid (CSF) heparan sulfate (HS) levels, and stabilized developmental decline over 100 weeks in Japanese children with MPS II. Here, we report the final study results, representing 5 years of ICV idursulfase beta treatment.

Identifying Key Residues in Lysine Decarboxylase for Soluble Expression Using Consensus Design Soluble Mutant Screening (ConsenSing).

Although recent advances in deep learning approaches for protein engineering have enabled quick prediction of hot spot residues improving protein solubility, the predictions do not always correspond to an actual increase in solubility under experimental conditions. Therefore, developing methods that rapidly confirm the linkage between computational predictions and empirical results is essential to the success of improving protein solubility of target proteins. Here, we present a simple hybrid approach to computationally predict hot spots possibly improving protein solubility by sequence-based analysis and empirically explore valuable mutants using split GFP as a reporter system.

Screening of Carbofuran-Degrading Bacteria sp. BSC2-3 and Unveiling the Change in Metabolome during Carbofuran Degradation.

Carbofuran is one of the most commonly used N-methylcarbamate-based pesticides and is excellent for controlling pests; however, carbofuran also causes soil and water pollution. Although various studies have been conducted on the bioremediation of pesticide-contaminated soil, the changes occurring in the metabolome during the bioremediation of carbofuran are not fully understood. In this study, the intracellular and extracellular metabolites of the sp.

A high temperature cell for investigating interfacial structure on the molecular scale in molten salt/alloy systems.

In this work, we describe the design and development of an in situ neutron reflectometry cell for high temperature investigations of structural changes occurring at the interface between inorganic salts, in their molten state up to 800 °C, and corrosion resistant alloys or other surfaces. In the cell, a molten salt is confined by an annular ring of single crystal sapphire constrained between the sample substrate and a sapphire plate using two gold O-rings, enclosing a liquid salt volume of 20 ml, along with a dynamic cell volume to accommodate expansion of the liquid with heating. As a test case for the cell, we report on an in situ neutron reflectometry measurement of the interface between a eutectic salt mixture of MgCl-KCl (32:68 molar ratio) and a single crystal sapphire substrate at 450 °C, resulting in the formation of a 60 Å layer having a scattering length density of 1.

Impact of intracerebroventricular enzyme replacement therapy in patients with neuronopathic mucopolysaccharidosis type II.

This open-label, phase 1/2 study (JMACCT CTR JMA-IIA00350) evaluated the efficacy and safety of intracerebroventricular idursulfase beta in patients with mucopolysaccharidosis II (MPS II). Herein, we report the 100-week results. Six patients with severe MPS II aged 23-65 months were enrolled.

Natural history of cognitive development in neuronopathic mucopolysaccharidosis type II (Hunter syndrome): Contribution of genotype to cognitive developmental course.

The natural history of cognitive growth in the neuronopathic form of Mucopolysaccharidosis type II (MPS II) is not well defined especially their patterns of development and decline. The ability to predict the developmental course of the neurologically impaired patient is necessary to assess treatment outcomes aimed at the brain. Thirteen intravenous enzyme replacement therapy-treated Japanese patients with neuronopathic MPSII who had mutation analysis were followed on one standard measure of cognitive development over time.

Non-Invasive Evaluation of a Carotid Arterial Pressure Waveform Using Motion-Tolerant Ultrasound Measurements During the Valsalva Maneuver.

This work details the non-invasive evaluation of a carotid arterial blood pressure (ABP) waveform during the Valsalva maneuver. Unfocused and wide acoustic beams are insonated on the carotid artery to achieve motion-tolerant measurements with a simple two-element ultrasound scanner. Arterial flow and distension waveforms are reliably estimated from spectral Doppler and M-mode ultrasound images whose qualities are consistently maintained in different phases of the maneuver despite possible displacements of the artery.

Biosynthesis of the human milk oligosaccharide 3-fucosyllactose in metabolically engineered Escherichia coli via the salvage pathway through increasing GTP synthesis and β-galactosidase modification.

3-Fucosyllactose (3-FL) is one of the major fucosylated oligosaccharides in human milk. Along with 2'-fucosyllactose (2'-FL), it is known for its prebiotic, immunomodulator, neonatal brain development, and antimicrobial function. Whereas the biological production of 2'-FL has been widely studied and made significant progress over the years, the biological production of 3-FL has been hampered by the low activity and insoluble expression of α-1,3-fucosyltransferase (FutA), relatively low abundance in human milk oligosaccharides compared with 2'-FL, and lower digestibility of 3-FL than 2'-FL by bifidobacteria.

Monitoring of Pulse Pressure and Arterial Pressure Waveform Changes during the Valsalva Maneuver by a Portable Ultrasound System.

This work presents non-invasive evaluation of the arterial blood pressure (ABP) waveform during the Valsalva maneuver. Ultrasound scanning is conducted to acquire blood flow and arterial distension signals. Motion-tolerant ultrasound measurement schemes are employed by using two wide rectangular transducers.

RiSLnet: Rapid identification of smart mutant libraries using protein structure network. Application to thermal stability enhancement.

A key point of protein stability engineering is to identify specific target residues whose mutations can stabilize the protein structure without negatively affecting the function or activity of the protein. Here, we propose a method called RiSLnet (Rapid identification of Smart mutant Library using residue network) to identify such residues by combining network analysis for protein residue interactions, identification of conserved residues, and evaluation of relative solvent accessibility. To validate its performance, the method was applied to four proteins, that is, T4 lysozyme, ribonuclease H, barnase, and cold shock protein B.

Characteristics of Japanese patients with X-linked adrenoleukodystrophy and concerns of their families from the 1st registry system.

Objective: Early diagnosis is critical in achieving the best outcome following hematopoietic stem cell transplantation (HSCT) for X-linked adrenoleukodystrophy (X-ALD). We used a questionnaire to gather detailed clinical information and information regarding the anxieties of patients' families using the registry system for X-ALD.

Methods: We and the patients' families established the registry system for X-ALD in Japan.

Improving catalytic activity of the Baeyer-Villiger monooxygenase-based Escherichia coli biocatalysts for the overproduction of (Z)-11-(heptanoyloxy)undec-9-enoic acid from ricinoleic acid.

Baeyer-Villiger monooxygenases (BVMOs) can be used for the biosynthesis of lactones and esters from ketones. However, the BVMO-based biocatalysts are not so stable under process conditions. Thereby, this study focused on enhancing stability of the BVMO-based biocatalysts.

Motion Tolerant Unfocused Imaging of Physiological Waveforms for Blood Pressure Waveform Estimation Using Ultrasound.

This paper details unfocused imaging using single-element ultrasound transducers for motion tolerant arterial blood pressure (ABP) waveform estimation. The ABP waveform is estimated based on pulse wave velocity and arterial pulsation through Doppler and M-mode ultrasound. This paper discusses approaches to mitigate the effect of increased clutter due to unfocused imaging on blood flow and diameter waveform estimation.

Characterization of regioselective flavonoid O-methyltransferase from the Streptomyces sp. KCTC 0041BP.

A flavonoid comprises polyphenol compounds with pronounced antiviral, antioxidant, anticarcinogenic, and anti-inflammatory effects. The flavonoid modification by methylation provides a greater stability and improved pharmacokinetic properties. The methyltransferase from plants or microorganisms is responsible for such substrate modifications in a regiospecific or a promiscuous manner.

Identification of (R)-selective ω-aminotransferases by exploring evolutionary sequence space.

Several (R)-selective ω-aminotransferases (R-ωATs) have been reported. The existence of additional R-ωATs having different sequence characteristics from previous ones is highly expected. In addition, it is generally accepted that R-ωATs are variants of aminotransferase group III.

Enzyme/whole-cell biotransformation of plant oils, yeast derived oils, and microalgae fatty acid methyl esters into n-nonanoic acid, 9-hydroxynonanoic acid, and 1,9-nonanedioic acid.

Oils and fatty acids are important renewable resources provided by nature. Therefore, biotransformation of renewable oils and fatty acids into industrially relevant C9 chemicals was investigated in this study. Olive oil, soybean oil, yeast derived oil, and microalgae fatty acid methyl esters were converted into n-nonanoic acid, 9-hydroxynonanoic acid, and 1,9-nonanedioic acid by a lipase and a recombinant Escherichia coli expressing oleate hydratase, long chain secondary alcohol dehydrogenase, Baeyer-Villiger monooxygenase, long chain primary alcohol dehydrogenase, and aldehyde dehydrogenase.

A molecular analysis of the GAA gene and clinical spectrum in 38 patients with Pompe disease in Japan.

Pompe disease is an autosomal recessive disorder caused by acid α-glucosidase (GAA) deficiency, which results in the accumulation of glycogen in lysosomes in multiple tissues, including cardiac, skeletal, and smooth muscle cells. Thus far, 558 sequence variants of the GAA gene have been published in the Pompe Disease Mutation Database, and some mutations appear with considerable frequency in particular ethnic groups, such as Caucasians, Taiwanese, Chinese, and Koreans. However, the GAA mutation pattern in Japanese patients remains poorly understood.

Engineering of Baeyer-Villiger monooxygenase-based Escherichia coli biocatalyst for large scale biotransformation of ricinoleic acid into (Z)-11-(heptanoyloxy)undec-9-enoic acid.

Baeyer-Villiger monooxygenases (BVMOs) are able to catalyze regiospecific Baeyer-Villiger oxygenation of a variety of cyclic and linear ketones to generate the corresponding lactones and esters, respectively. However, the enzymes are usually difficult to express in a functional form in microbial cells and are rather unstable under process conditions hindering their large-scale applications. Thereby, we investigated engineering of the BVMO from Pseudomonas putida KT2440 and the gene expression system to improve its activity and stability for large-scale biotransformation of ricinoleic acid (1) into the ester (i.

Molecular diagnosis of 65 families with mucopolysaccharidosis type II (Hunter syndrome) characterized by 16 novel mutations in the IDS gene: Genetic, pathological, and structural studies on iduronate-2-sulfatase.

Mucopolysaccharidosis type II (MPS II: also called as Hunter syndrome) is an X-linked recessive lysosomal storage disorder characterized by the accumulation of extracellular glycosaminoglycans due to the deficiency of the enzyme iduronate-2-sulfatase (IDS). Previous observations suggested that MPS II can be classified into two distinct disease subtypes: (1) severe type of MPS II involves a decline in the cognitive ability of a patient and (2) attenuated type of MPS II exhibits no such intellectual phenotype. To determine whether such disease subtypes of MPS II could be explained by genetic diagnosis, we analyzed mutations in the IDS gene of 65 patients suffering from MPS II among the Japanese population who were diagnosed with both the accumulation of urinary glycosaminoglycans and a decrease in their IDS enzyme activity between 2004 and 2014.

Lysine ε-aminotransferases: kinetic constants, substrate specificities, and the variation in active site residues.

L-Lysine ε-aminotransferase (lysAT) is an important enzyme in tailoring the terminal amino group of L-lysine or L-ornithine and can be directed to the synthesis of various value-added chemicals such as adipic acid. Three lysATs, lysAT from Saccharopolyspora erythraea NRRL 2338 (lysAT_Sery), lysAT from Nocardia farcinica IFM 10152, and lysAT from Rhodococcus jostii RHA1, were cloned, and their kinetic values and substrate specificities were investigated. In the reaction using 5mM L-lysine and 10mM α-ketoglutarate, lysAT_Sery from S.

Carotid arterial blood pressure waveform monitoring using a portable ultrasound system.

This work presents a non-invasive arterial blood pressure (ABP) waveform monitoring technique using ultrasound. A portable ultrasound system to excite ultrasound transducers and acquire data is designed with off-the-shelf components. The insonation angles are identified using a vector Doppler technique based on the cosine dependency of the Doppler signals.

Adding value to plant oils and fatty acids: Biological transformation of fatty acids into ω-hydroxycarboxylic, α,ω-dicarboxylic, and ω-aminocarboxylic acids.

Not only short chain ω-hydroxycarboxylic acids, α,ω-dicarboxylic acids, and ω-aminocarboxylic acids but also medium to long chain carboxylic acids are widely used as building blocks and intermediates in the chemical, pharmaceutical, and food industries. Thereby, recent achievements in biological production of medium to long chain carboxylic acids are addressed here. ω-Hydroxycarboxylic and α,ω-dicarboxylic acids were synthesized via terminal CH bond oxygenation of fatty acids and/or internal oxidative cleavage of the fatty acid carbon skeletons.

Fatty acid hydration activity of a recombinant Escherichia coli-based biocatalyst is improved through targeting the oleate hydratase into the periplasm.

Whole-cell biotransformation of fatty acids can be influenced by the activities of catalytic enzymes and by the efficiency of substrate transport into host cells. Here, we improved fatty acid hydration activity of the recombinant Escherichia coli expressing an oleate hydratase of Stenotrophomonas maltophilia by targeting the catalytic enzyme into the periplasm instead of the cytoplasm. Recombinant E.