Serum albumin redox state as an indicator of dietary protein intake among community-dwelling older adults.

BACKGROUND AND AIMS: Serum markers capable of detecting mild levels of undernutrition, such as insufficient dietary protein intake (IDPI), have not been established among community-dwelling older adults. Although the serum albumin redox state, expressed as the ratio of reduced albumin (Alb) to total Alb (the reduced albumin ratio), has the potential to overcome this challenge, empirical epidemiological data are lacking. This study aimed to investigate the association between a serum reduced Alb ratio and dietary protein intake among community-dwelling older adults. METHODS: This study analyzed cross-sectional data from 1,005 community dwelling population (572 males and 433 females) aged 70-84 years who participated in the Itabashi Longitudinal Study on Aging. Exclusion criteria included participants with incomplete data, individuals with a history of kidney disease and high C-reactive protein (CRP) levels. The dietary protein intake was estimated using validated food frequency questionnaires. The IDPI was defined as not meeting the level recommended by the Dietary Reference Intakes for Japanese (Men ≥60 g/day, Women ≥50 g/day). RESULTS: IDPI was observed in 14.1% of the study population. Logistic regression analyses adjusted for sex, age, body weight and malnutrition showed that a serum reduced Alb ratio was significantly associated with IDPI (odds ratio = 0.962, 95% confidence interval = 0.926-0.999), whereas serum albumin concentration was not (odds ratio = 0.549, 95% confidence interval = 0.285-1.061). CONCLUSIONS: A serum reduced Alb ratio would be a useful indicator of protein insufficiency among community-dwelling older adults.

Comparison of protein digestibility of human milk and infant formula using the INFOGEST method under infant digestion conditions.

Many improvements have been made to bring infant formula (IF) closer to human milk (HM) regarding its nutritional and biological properties. Nevertheless, the protein components of HM and IF are still different, which may affect their digestibility. This study aimed to evaluate and compare the protein digestibility of HM and IF using the infant INFOGEST digestion method. Pooled HM and a commercial IF were subjected to the infant INFOGEST method, which simulates the physiological digestion conditions of infants, with multiple directions, i.e., the curd state, SDS-PAGE, molecular weight distribution, free amino acid concentration, and in vitro protein digestion rate. HM underwent proteolysis before digestion, and tended to have a higher protein digestion rate with finer curds during gastric digestion, than the IF. However, multifaceted analyses showed that the protein digestibility of HM and IF was not significantly different after gastrointestinal digestion. In conclusion, the infant INFOGEST method showed that the digestibility of HM and IF proteins differed to some extent before digestion and after gastric digestion, but not at the end of gastrointestinal digestion. The findings of this study will contribute to the refinement of IFs with better protein digestibility in infant stomach.

Guidance for performance, utilization, and education of cardiac and lung point-of-care ultrasonography from the Japanese Society of Echocardiography.

In recent years, bedside ultrasound examinations have been used in many clinical departments and are called point-of-care ultrasound (POCUS). Regarding POCUS in the cardiac field, a protocol called focus (focused) cardiac ultrasound (FoCUS) has been developed in Europe and the United States, is being used clinically, and an educational syllabus has been created. According to them, FoCUS is defined as a point-of-care cardiac ultrasound examination using standardized limited sections and protocols. FoCUS is primarily intended to be performed by non-cardiologists, and in order to avoid making mistakes in judgment, it is important to be familiar with its limitations and it is necessary to understand pathological conditions that can only be diagnosed using conventional comprehensive echocardiography. The Japanese Society of Echocardiography has edited this clinical guideline because we believe that FoCUS should be used effectively and appropriately in Japan, and that appropriate education is essential to popularize FoCUS in Japan. Furthermore, lung POCUS has recently come into clinical use. Lung POCUS is useful for the diagnosis and follow-up of heart failure when used in conjunction with FoCUS, and is especially useful in primary care where chest X-rays are not available. The working group that created this manual agreed that it is desirable to educate patients about lung POCUS in conjunction with FoCUS, so we decided to include the basic techniques of lung POCUS and how to use them in this manuscript.

A Heart Failure Smartphone Application That Nudges Patients/Physicians Toward Optimal Medical Therapy　- Development and Usability Study.

Background: The low implementation rate of guideline-directed medical therapy for heart failure (HF) remains a problem worldwide. To address this issue, we hypothesized that a smartphone application (app) based on behavioral economics that nudges physicians and patients towards optimal medical therapy would be a scalable approach. Methods and Results: The app prototype was developed, and its usability was tested with 5 HF patients in the outpatient setting. Adherence to the app was outstanding, with a high usability rating from the patients. Conclusions: It appears feasible to further study our app in a larger cohort to evaluate its efficacy.

A Methodological Basis for Estimating Human Mercaptalbumin in Serum and Plasma Using a Thiol-Binding Resin.

Human serum albumin is categorized into human mercaptalbumin (HMA) and human non-mercaptalbumin (HNA), according to the redox state of the cysteine residue at position 34. The ratio of HMA to total albumin (%HMA) is a novel biomarker of oxidative stress as well as protein nutritional status, but measuring %HMA normally requires an expensive analyzer such as HPLC and LC-MS, and can hardly be conducted in many clinical sites. To address this issue, we aimed to develop a methodological basis for estimating %HMA without these analyzers. An analytical method was investigated consisting of three steps, i.e., 1) removal of HMA from serum or plasma by using a thiol-binding resin (i.e., thereby obtaining a HNA fraction), 2) determination of both total albumin and HNA concentrations by a colorimetric assay or ELISA, and 3) calculation of %HMA. Proof-of-concept experiments, using serum and plasma samples of 4 adult volunteers, showed that the estimated value of %HMA obtained by this analytical method was significantly correlated with the theoretical value of %HMA determined by HPLC. The subsequent validation experiment, using 86 serum samples of pregnant women in the Japanese participants of SMILE Iwamizawa, also confirmed the significant association between the estimated and theoretical values of %HMA. This analytical method can be a basis to determine %HMA without using HPLC or LC-MS, contributing to the universalization of %HMA measurement as a clinical test.

Effects of pemafibrate on left ventricular diastolic function in patients with type 2 diabetes mellitus: a pilot study.

Aims/introduction: Diabetic cardiomyopathy (DCM) is characterized predominantly by diastolic dysfunction. The multiple mechanisms underlying DCM include altered energy substrate utilization. Recent studies indicate that PPARα plays an important role in the pathogenesis of lipotoxic cardiomyopathy. Pemafibrate is known to be a selective PPARα modulator (SPPARMα). We thus investigated the effects of pemafibrate on cardiac diastolic function in patients with type 2 diabetes. Materials and methods: Seventeen patients with type 2 diabetes (T2D) and hypertriglyceridemia were screened and treated with pemafibrate at a dose of 0.2 mg/day for 8-16 weeks. Fourteen patients were eligible for analysis. Echocardiography was used for assessment of diastolic function. Early diastolic filling velocity (E), late atrial filling velocity (A) and the E/A ratio were included in this study. Peak early diastolic annular velocities (e') were also assessed using color tissue Doppler images. The primary endpoints were changes in the ratio of E to A (E/A), e', and the ratio of E to e' (E/e') from baseline. Results: Pemafibrate significantly increased average e' (7.24 ± 0.58 vs 7.94 ± 0.67, p = 0.019) and a significant reduction in E/e' (9.01 ± 0.94 vs 8.20 ± 0.91, p = 0.041). The increase in e' was significantly related to increases in fasting blood glucose (r = 0.607, p = 0.021) and non-esterified fatty acid (r = 0.592, p = 0.026). Conclusion: Pemafibrate improved diastolic function in patients with T2D and hypertriglyceridemia, suggesting that PPARα activation by pemafibrate prevents the development of DCM at an early stage.

A lower ratio of reduced to total albumin in serum is associated with protein nutritional status of pregnant women in Japan.

Protein-energy undernutrition is potentially prevalent among Japanese pregnant women, and biomarkers that objectively indicate the protein nutritional status during pregnancy may help in implementing appropriate protein supplementation to these women. We hypothesized that a serum parameter of pregnant women, the ratio of reduced to total albumin (reduced ALB ratio), would be associated with protein intake during pregnancy. The serum reduced ALB ratio of pregnant women was compared with protein intake and with gestation outcomes (gestation length and infant birth weight) in an observational study of 115 Japanese pregnant women. The serum reduced ALB ratio in the third trimester tended to be positively correlated with gestation length (P = .07). Infant birth weights tended to be different between protein intake tertiles (P = .09); the mean infant birth weight was higher in the third tertile compared with the first and second tertiles. The protein intake of pregnant women was significantly and positively correlated with the serum reduced ALB ratio in the second trimester. The serum reduced ALB ratio reflects protein nutritional status during pregnancy and may contribute to healthier gestation outcomes.

Associations between Maternal Diet, Human Milk Macronutrients, and Breast-Fed Infant Growth during the First Month of Life in the SMILE Iwamizawa in Japan.

Maternal diet may affect human milk macronutrients, but it remains to be elucidated whether this is also influential in infant growth. This study aimed to examine (1) how maternal diet influences human milk macronutrients, and (2) to what extent the variation in milk macronutrients affects infant growth during the first month of life. In 71 Japanese lactating women, maternal dietary information was collected from the brief-type self-administered diet history questionnaire, and anthropometry of mother-infant dyads was collected from medical records. Macronutrients in milk were analyzed by a Human Milk Analyzer. Maternal retinol intake was associated with the carbohydrate content in human milk at 1-month postpartum (standardized ß coefficient: 0.287; p = 0.038). Moreover, the energy content in human milk was associated with an increase in the weight standard deviation score based on the WHO growth standard at 1 month of age (standardized ß coefficient: 0.399; p = 0.046). Nevertheless, the milk macronutrient was not associated with the risk of infant growth abnormalities. In conclusion, a part of the maternal diet impacts macronutrient contents in human milk, but milk macronutrients have a limited effect on infant growth only within the normal growth curve during the first month of life.

Nutritional Evaluation of Milk-, Plant-, and Insect-Based Protein Materials by Protein Digestibility Using the INFOGEST Digestion Method.

The INFOGEST method is a valuable tool for understanding and monitoring food digestion as an alternative to in vivo assays. However, few studies have compared animal and alternative protein sources in terms of protein quality using the INFOGEST method. This study aimed to evaluate the protein quality of milk-, plant-, and insect-based protein materials by in vitro protein digestibility and in vitro digestible indispensable amino acid score (DIAAS), following the INFOGEST method. Milk-based protein materials had the highest protein digestibility (86.1-90.8%), followed by soy (85.1%) and wheat (82.3%). These materials had significantly higher protein digestibility compared with zein (65.1%), cricket (63.6%), and mealworm (69.5%). Additionally, the mean values of in vitro DIAAS of milk-based protein materials (105.0-137.5) were higher than those of plant- and insect-based protein materials (1.9-91.0). Milk-based protein materials have higher protein quality than plant- and insect-based protein materials by the nutritional evaluation following the INFOGEST digestion method.

Prevalence and characteristics of transesophageal echocardiography-related esophageal mucosal injury in patients with atrial fibrillation who underwent pulmonary vein isolation.

BACKGROUND: Transesophageal echocardiography (TEE) is the gold standard for detecting thrombi in the left atrium (LA) and left atrial appendage (LAA) prior to pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). Although TEE has a good safety profile, it was recently reported that TEE preceding PVI can cause esophageal mucosal injuries (EMIs). The exact mechanism remains to be elucidated. In the present study, we investigated the incidence and risk factors of TEE-related EMI (TEE-EMI) among patients who underwent PVI for AF. METHODS AND RESULTS: This study included 262 consecutive patients who underwent PVI with preoperative TEE using a 3D TEE probe and postoperative esophagogastroduodenoscopy. TEE-EMIs were observed in 16 (6.1%) patients (18 lesions), whereas PVI-related EMIs were found in 5 (1.9%) patients (8 lesions). All TEE-EMIs were observed in the upper or middle esophagus and occurred more frequently in the right region of the upper esophagus and the left anterior region of the middle esophagus; only one patient experienced mild chest discomfort. In the multivariate analysis, advanced age was an independent risk factor for TEE-EMIs (odds ratio 1.08, 95% confidence interval 1.01-1.16; P = 0.0274). CONCLUSIONS: The incidence of TEE-EMIs with 3D TEE probes was relatively high in the upper or middle esophagus, anatomically close to the LA, among patients who underwent PVI. Advanced age could pose a significant risk. These findings may warrant consideration of other methods to rule out LA/LAA thrombi, especially in elderly patients.

Echocardiographic features of acute-phase microscopic polyangiitis in Japanese patients: A single-centre retrospective study.

OBJECTIVES: Microscopic polyangiitis (MPA) affects various organs. However, echocardiographic findings of MPA are unclear. We aimed to evaluate the echocardiographic features of acute-phase MPA in Japanese patients. METHODS: This single-centre retrospective study included 15 patients with MPA who underwent echocardiography within 2 weeks of commencing steroid therapy for induction or reinduction. The echocardiography parameters of thetients were compared with those of 30 age- and sex-matched controls. RESULTS: No significant differences in left ventricular (LV) diameter, LV ejection fraction, or e' were observed between the two groups. However, the MPA group showed a significantly higher left atrial (LA) diameter and LA volume index, as well as higher early diastolic filling velocity, diastolic pulmonary venous flow velocity, and trans-tricuspid pressure gradient, and a shorter deceleration time (DCT). Serum C-reactive protein levels were positively correlated with E wave, E/A, and DCT. These results may indicate that increased LV stiffness, rather than impairment of LV relaxation, contributed to LV diastolic function, resulting in LA enlargement. CONCLUSIONS: Patients with acute-phase MPA had LA dilatation associated with LV diastolic dysfunction. This finding indicates the importance of cardiac assessment in patients with MPA, especially in patients with a strong inflammatory reaction.

Maternal Serum Albumin Redox State Is Associated with Infant Birth Weight in Japanese Pregnant Women.

BACKGROUND: Plasma albumin (ALB) reflects protein nutritional status in rats, but it is not clear whether it is associated with dietary protein insufficiency in pregnant women and/or their risk of low birth weight delivery. This study aimed to investigate whether maternal serum ALB redox state reflects maternal protein nutritional status and/or is associated with infant birth weights. METHODS: The relationship between the serum reduced ALB ratio and infant birth weight was examined in an observational study of 229 Japanese pregnant women. A rat model simulating fetal growth restriction, induced by protein-energy restriction, was used to elucidate the relationship between maternal nutritional status, maternal serum ALB redox state, and birth weight of the offspring. RESULTS: In the human study, serum reduced ALB ratio in the third trimester was significantly and positively correlated with infant birth weight. In the rat study, serum reduced ALB ratio and birth weight in the litter decreased as the degree of protein-energy restriction intensified, and a significant and positive correlation was observed between them in late pregnancy. CONCLUSIONS: Maternal serum reduced ALB ratio in the third trimester is positively associated with infant birth weight in Japanese pregnant women, which would be mediated by maternal protein nutritional status.

Serum Albumin Redox States: More Than Oxidative Stress Biomarker.

Serum albumin is the most abundant circulating protein in mammals including humans. It has three isoforms according to the redox state of the free cysteine residue at position 34, named as mercaptalbumin (reduced albumin), non-mercaptalbumin-1 and -2 (oxidized albumin), respectively. The serum albumin redox state has long been viewed as a biomarker of systemic oxidative stress, as the redox state shifts to a more oxidized state in response to the severity of the pathological condition in various diseases such as liver diseases and renal failures. However, recent ex vivo studies revealed oxidized albumin per se could aggravate the pathological conditions. Furthermore, the possibility of the serum albumin redox state as a sensitive protein nutrition biomarker has also been demonstrated in a series of animal studies. A paradigm shift is thus ongoing in the research field of the serum albumin. This article provides an updated overview of analytical techniques for serum albumin redox state and its association with human health, focusing on recent findings.

1H NMR metabolomic and transcriptomic analyses reveal urinary metabolites as biomarker candidates in response to protein undernutrition in adult rats.

Protein undernutrition contributes to the development of various diseases in broad generations. Urinary metabolites may serve as non-invasive biomarkers of protein undernutrition; however, this requires further investigation. We aimed to identify novel urinary metabolites as biomarker candidates responsive to protein undernutrition. Adult rats were fed control (CT; 14 % casein) or isoenergetic low-protein (LP; 5 % casein) diets for 4 weeks. 1H NMR metabolomics was applied to urine, plasma and liver samples to identify metabolites responsive to protein undernutrition. Liver samples were subjected to mRNA microarray and quantitative PCR analyses to elucidate the mechanisms causing fluctuations in identified metabolites. Urinary taurine levels were significantly lower in the LP group than in the CT group at week 1 and remained constant until week 4. Hepatic taurine level and gene expression level of cysteine dioxygenase type 1 were also significantly lower in the LP group than in the CT group. Urinary trimethylamine N-oxide (TMAO) levels were significantly higher in the LP group than in the CT group at week 2 and remained constant until week 4. Hepatic TMAO level and gene expression levels of flavin-containing mono-oxygenase 1 and 5 were also significantly higher in the LP group than in the CT group. In conclusion, urinary taurine and TMAO levels substantially responded to protein undernutrition. Furthermore, changes in hepatic levels of these metabolites and gene expressions associated with their metabolic pathways were also reflected in their fluctuating urinary levels. Thus, taurine and TMAO could act as non-invasive urinary biomarker candidates to detect protein undernutrition.