Four-dimensional computed tomography is useful for detection of apical sparing of cardiac amyloidosis.

A 73-year-old male was admitted because of recurrent syncope. He was diagnosed with transient bradycardia caused by a 2:1 atrioventricular block, and he underwent cardiac computed tomography (CT) using 320 detector-row CT to screen for coronary artery disease. Significant coronary artery stenosis was not detected, but diffuse late iodinate enhancement was found on the epi-myocardium and endo-myocardium of the interventricular septum, and endo-myocardium of the anterior and lateral left ventricular (LV) myocardium (LVM) on CT. The ejection fraction and global longitudinal strain (LS) of LVM were 53.97% and - 9.87% on CT. Apical sparing was present, meaning the LS of LV apical segments were preserved compared with basal segments on CT. Pathological findings of LVM demonstrated loss of myocardial cells and extra-cellular amyloid deposition on the direct fast scarlet staining. He was finally diagnosed with transthyretin amyloidosis.

Plasma Gel Matrix as a Promising Carrier of Epigallocatechin Gallate for Regenerative Medicine.

Plasma gel (PG) is a protein matrix prepared from platelet-poor plasma and can be utilized as a drug carrier for controlled release. We previously demonstrated its applicability as a carrier of polyphosphate. Epigallocatechin-3-gallate (EGCG) is the main flavonoid found in green tea and functions as a strong antioxidant. To explore the applicability of PG as an EGCG carrier, we examined the release of EGCG from the PG matrix using an in vitro system. Pooled platelet-poor plasma (PPP) was prepared from four healthy adult male donors, mixed with EGCG, and heated at 75 °C for 10 or 20 min to prepare the PG matrix. The PG-EGCG matrix was incubated in PBS at 37 °C, and the EGCG released into PBS was determined using spectrophotometry. The antioxidant capacity was determined based on the principle of the iodine decolorization reaction. EGCG precipitated and incorporated into the PG matrix during thermal preparation. Trypsin, used to simulate the in vivo degradation of PG, released EGCG from the PG matrix over time. The released EGCG maintained its antioxidant capacity during incubation. These results indicate that thermally prepared PG matrices can be utilized as a promising EGCG carrier in the fields of tissue engineering and regenerative medicine.

Successful Treatment of Rosai-Dorfman Disease with Cutaneous Involvement and Arthritis with Methotrexate and Infliximab.

Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder characterized by lymphadenopathy and extra-nodal manifestations. Some patients with RDD require systemic treatment, but there is no consensus on the treatment strategy owing to its extreme rarity. Overexpression of tumor necrosis factor α (TNF-α) has been reported in lesions of patients with RDD and is thought to be involved in its pathogenesis. We herein report the first case of RDD with cutaneous involvement and arthritis that was successfully treated with methotrexate and infliximab. This case highlights the potential efficacy of anti-TNF-α therapy for RDD, offering a novel treatment option for this rare condition.

Strong Diagnostic Performance of Single Energy 256-row Multidetector Computed Tomography with Deep Learning Image Reconstruction in the Assessment of Myocardial Fibrosis.

Objective Although magnetic resonance imaging (MRI) is the gold standard for evaluating abnormal myocardial fibrosis and extracellular volume (ECV) of the left ventricular myocardium (LVM), a similar evaluation has recently become possible using computed tomography (CT). In this study, we investigated the diagnostic accuracy of a new 256-row multidetector CT with a low tube-voltage single energy scan and deep-learning-image reconstruction (DLIR) in detecting abnormal late enhancement (LE) in LVM. Methods We evaluated the diagnostic performance of CT for detecting LE in LVM and compared the results with those of MRI as a reference. We also measured the ECV of the LVM on CT and compared the results with those on MRI. Patients or Materials We analyzed 50 consecutive patients who underwent cardiac CT, including a late-phase scan and MRI, within three months of suspected cardiomyopathy. All patients underwent 256-slice CT (Revolution CT Apex; GE Healthcare) with a low tube-voltage (70 kV) single energy scan and DLIR for a late-phase scan. Results In patient- and segment-based analyses, the sensitivity, specificity, and accuracy of detection of LE on CT were 94% and 85%, 100% and 95%, and 96% and 93%, respectively. The ECV of LVM per patient on CT and MRI was 33.0% ±6.2% and 35.9% ±6.1%, respectively. These findings were extremely strongly correlated, with a correlation coefficient of 0.87 (p <0.0001). The effective radiation dose on late-phase scanning was 2.4±0.9 mSv. Conclusion The diagnostic performance of 256-row multislice CT with a low tube voltage and DLIR for detecting LE and measuring ECV in LVM is credible.

Risk of disease flares after SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus.

This study aims to elucidate the effectiveness and safety of SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus (SLE). We enrolled uninfected SLE patients who received two vaccine doses (BNT162b2 or mRNA-1273) and historical unvaccinated patients. Neutralizing antibodies, adverse reactions, and disease flares were evaluated 4 weeks after the second vaccination. Ninety patients were enrolled in each group. Among the vaccinated patients, SLE Disease Activity Index (SLEDAI), and prednisolone doses before vaccination were 2, and 5 mg/d, respectively. After the second vaccination, 19 (21.1%) had no neutralizing antibodies. Adverse reactions occurred in 88.9% within 3 d. Negative antibodies were associated with anemia and mycophenolate mofetil administration. SLEDAI increased modestly but significantly after vaccination, with 13 (14.4%) experiencing flares and 4 (4.4%) severe flares (nephritis in three and vasculitis in one). The flare rate was higher in vaccinated patients than unvaccinated controls. The mean duration between the second vaccination and flares was 35 d, and flares occurred at least 8 days after vaccination. Multivariable analysis showed that high SLEDAI and anti-dsDNA antibodies were associated with flares. The vaccine type, neutralizing antibody titer, and adverse reaction frequency did not affect flares. Therefore, residual disease activity before vaccination increases flare risk.

Elevated IL-1ß and Comparable IL-1 Receptor Antagonist Levels Are Characteristic Features of L-PRP in Female College Athletes Compared to Male Professional Soccer Players.

Autologous platelet-rich plasma (PRP) therapy has been becoming popular for the treatment of musculotendinous injuries among athletes. However, for individual and practical variations, clinical success is hardly predictable. To overcome this difficulty, we have been exploring possible criterion candidates for monitoring its clinical effectiveness. In this study, we focused on sex-based differences in young elite athletes and compared the biochemical compositions of their PRP. Leukocyte-rich PRP (L-PRP) was manually prepared from blood samples collected from male professional soccer players (mPSPs) (n = 25) and female college athletes (fCAs) (n = 36). Platelet-derived growth factor-BB (PDGF-BB), transforming-growth factor-ß1 (TGFß1), platelet factor-4 (PF4), interleukin-1ß (IL-1ß), and IL-1 receptor antagonist (IL-1RA) were quantified using an enzyme-linked immunosorbent assay. The levels of PDGF-BB, TGFß1, and PF4 in L-PRP were significantly higher in mPSPs than in fCAs. Conversely, IL-1ß and IL-1RA were detected at significantly and slightly higher levels, respectively, in fCAs than in mPSPs. Our findings suggest that, even though L-PRP from fCAs may have lower potential to induce cell growth and differentiation than that of mPSPs, due to the latter's higher capacity to control inflammation, it does not necessarily imply that PRP treatment in fCAs is less effective. Thus, these cytokine levels should be checked before PRP therapy.

Dietary amino acid intake and sleep duration are additively involved in future cognitive decline in Japanese adults aged 60 years or over: a community-based longitudinal study.

BACKGROUND: Sleep duration and amino acid intake are independently associated with cognitive decline. This study aimed to determine the longitudinal association between sleep duration and cognitive impairment incidence and to examine the involvement of diet, particularly amino acid intake, in these associations in community dwellers. METHODS: In this longitudinal study in a community-based setting, we analyzed data from 623 adults aged 60-83 years without cognitive impairment at baseline. Sleep duration was assessed using a self-report questionnaire. Amino acid intake was assessed using 3-day dietary records. Cognitive impairment was defined as a Mini-Mental State Examination score ≤ 27. Participants were classified into short-, moderate-, and long-sleep groups according to baseline sleep duration (≤ 6, 7-8, and > 8 h, respectively). Using moderate sleep as a reference, odds ratios (ORs) and 95% confidence intervals (CIs) of short- and long-sleep for cognitive-impairment incidence were estimated using the generalized estimating equation. Participants were classified according to sex-stratified quartiles (Q) of 19 amino acid intake: Q1 and Q2-Q4 were low- and middle to high-intake groups, respectively. Using middle- to high-intake as a reference, ORs and 95% CIs of low intake for cognitive impairment incidence were estimated using the generalized estimating equation in each sleep-duration group. Follow-up period, sex, age, body mass index, depressive symptoms, education, smoking status, employment status, sleep aids use, physical activity, medical history, and Mini-Mental State Examination score at baseline were covariates. RESULTS: Mean follow-up period was 6.9 ± 2.1 years. Adjusted ORs (95% CIs) for cognitive impairment in short- and long-sleep groups were 0.81 (0.49-1.35, P = 0.423) and 1.41 (1.05-1.87, P = 0.020), respectively. Particularly in long sleepers (i.e., > 8 h), cognitive impairment was significantly associated with low cystine, proline, and serine intake [adjusted ORs (95% CIs) for cognitive impairment were 2.17 (1.15-4.11, P = 0.017), 1.86 (1.07-3.23, P = 0.027), and 2.21 (1.14-4.29, P = 0.019), respectively]. CONCLUSIONS: Community-dwelling adults aged ≥ 60 years who sleep longer are more likely to have cognitive decline, and attention should be paid to the low cystine, proline, and serine intake.

Characterization of Leukocyte- and Platelet-Rich Plasma Derived from Female Collage Athletes: A Cross-Sectional Cohort Study Focusing on Growth Factor, Inflammatory Cytokines, and Anti-Inflammatory Cytokine Levels.

Platelet-rich plasma (PRP) has been increasingly used in sports medicine owing to its various advantages. The purpose of our project was to standardize the parameters before performing large-scale clinical trials in the near future to precisely evaluate individual PRP quality. To examine the effects of regular exercise on PRP quality, this study focused on young female athletes, who have been relatively less studied. Blood samples were obtained from female college athletes (n = 35) and ordinary healthy adults (n = 30), which were considered as controls, and leukocyte-rich PRP (L-PRP) was prepared manually. Body composition indices were determined using a bathroom weight scale equipped with an impedance meter. Growth factors and cytokines were quantified using ELISA kits. Platelet-derived growth factor-BB (PDGF-BB) and Transforming-growth factors ß1 (TGFß1) levels (per platelet) in L-PRP were significantly lower in female athletes than in controls. In contrast, Interleukin-1ß and Interleukin 1 receptor antagonist (IL-1RA) levels (per platelet and L-PRP) in L-PRP were significantly higher in athletes, and this difference was more prominent in IL-1RA. These findings suggest that L-PRP from athletes may facilitate the inflammatory phase of the healing process by regulating the pro-inflammatory and anti-inflammatory balance. These chemical compositions can be adopted as "must-check" parameters to characterize individual PRP preparations prior to clinical trials.

Diet-related factors strongly shaped the gut microbiota of Japanese macaques.

Although knowledge of the functions of the gut microbiome has increased greatly over the past few decades, our understanding of the mechanisms governing its ecology and evolution remains obscure. While host genetic distance is a strong predictor of the gut microbiome in large-scale studies and captive settings, its influence has not always been evident at finer taxonomic scales, especially when considering among the recently diverged animals in natural settings. Comparing the gut microbiome of 19 populations of Japanese macaques Macaca fuscata across the Japanese archipelago, we assessed the relative roles of host genetic distance, geographic distance and dietary factors in influencing the macaque gut microbiome. Our results suggested that the macaques may maintain a core gut microbiome, while each population may have acquired some microbes from its specific habitat/diet. Diet-related factors such as season, forest, and reliance on anthropogenic foods played a stronger role in shaping the macaque gut microbiome. Among closely related mammalian hosts, host genetics may have limited effects on the gut microbiome since the hosts generally have smaller physiological differences. This study contributes to our understanding of the relative roles of host phylogeography and dietary factors in shaping the gut microbiome of closely related mammalian hosts.

Strategic analysis of body composition indices and resting platelet ATP levels in professional soccer players for better platelet-rich plasma therapy.

Background: Autologous platelet-rich plasma (PRP) therapy is ambiguously thought to be more effective in elite athletes than in sedentary patients, although the possible importance of recipient responsiveness remains poorly understood. To address this issue, along with the well-known PRP quality, in this initial study, we evaluated two candidate biomarkers: body composition indices (BCIs), which reflect systemic physical conditions, and resting platelet ATP levels, which reflect platelet energy expenditure and the mass of energy generation units. Methods: In this cross-sectional cohort study, blood samples were collected from male professional soccer players (PSPs) on a local professional team during the off-season and platelet ATP levels were quantified using an ATP luminescence assay kit. BCIs were measured using the body mass impedance method. Age-matched male sedentary participants were used as the controls. Results: Among the BCIs, the body mass index, basal metabolic rate (BMR), and skeletal muscle weight levels were higher in the PSPs than in the controls. The platelet ATP levels in the PSPs group were significantly lower than those in the control group. The correlation between BMR and platelet ATP levels was moderately negative in the control group, but weakly positive in the PSPs group. Conclusion: Owing to regular physical exercise, PSPs had higher BMR levels and lower platelet ATP levels without a significant mutual correlation compared to sedentary controls. This study did not indicate the influence of these biomarkers on the success of PRP therapy but provided evidence for a better understanding of PRP therapy, particularly for elite athletes.

Effect of imbalance in dietary macronutrients on blood hemoglobin levels: a cross-sectional study in young underweight Japanese women.

Background: Iron deficiency and underweight are common nutritional problems among young Japanese women, many of whom show unhealthy dietary patterns owing to a desire for thinness. We conducted a cross-sectional analysis of the relationship between iron status, nutritional status, and dietary intake among young Japanese women with underweight to identify dietary risk factors for iron deficiency. Methods: Of the 159 young women (18-29 years of age) enrolled, 77 underweight and 37 normal-weight women were included in the study. They were further categorized into four groups based on quartiles of hemoglobin levels among all participants. Dietary nutrient intake was ascertained using a brief self-administered diet history questionnaire. Blood level of hemoglobin and nutritional biomarkers such as total protein, albumin, insulin-like growth factor-1 (IGF-1), and essential amino acids were measured. Results: In underweight, the multiple comparison test showed that dietary intakes of fat, saturated fatty acid, and monosaturated fatty acid were significantly higher and carbohydrate intake was significantly lower in the group with the lowest hemoglobin level, whereas intakes of iron were the same across groups. Multivariate regression coefficients suggested that replacing fat with protein or carbohydrates increased hemoglobin levels under isocaloric conditions. Additionally, significant positive correlations were observed between hemoglobin levels and nutritional biomarkers. Conclusion: Dietary iron intake did not change across different hemoglobin groups among Japanese underweight women. However, our results suggested that an imbalanced dietary macronutrient induces anabolic status and hemoglobin synthesis deterioration among them. Especially, a higher fat intake may be a risk factor for lower hemoglobin.

Optimized Protocol for Preservation of Human Platelet Samples for Fluorometric Polyphosphate Quantification.

Platelet polyphosphate (polyP) can be conveniently quantified by exploiting a recent methodological breakthrough using 4',6-diamidino-2-phenylindole (DAPI). However, the preservation of these biological samples has not yet been standardized. In a preliminary study, potential protocols were screened, while accepted protocols were further tested in this study. Pure-platelet-rich plasma (P-PRP) samples and washed platelet suspensions were prepared using blood obtained from non-smoking healthy male donors and were fixed with ThromboFix for 20-24 h at 4 °C. Mass polyP levels were determined using a fluorometer at wavelengths of 425 and 525 nm. Platelet polyP levels were normalized to platelet counts. Statistical analyses were performed using non-parametric tests. Platelet polyP levels significantly decreased by 20% after 7 days in the platelet suspension maintained under fixed conditions at 4 °C (control). In contrast, the platelet polyP levels in both the P-PRP and washed platelet suspensions were maintained without a significant reduction for up to 6 weeks by removing ThromboFix after fixation and subsequent freezing in pure water at -80 °C. Fluorometric polyP quantification often interferes with the low specificity of DAPI binding and the wavelength used. Our validated protocols will enable long-term preservation and high-throughput polyP quantification and can be applied to relatively large cohort studies.

A short-term intervention of ingesting iron along with methionine and threonine leads to a higher hemoglobin level than that with iron alone in young healthy women: a randomized, double-blind, parallel-group, comparative study.

PURPOSE: Enhancing iron absorption and utilization is important for amelioration iron status faster and thereby, for improving quality of life. Dietary protein and amino acids, including methionine and threonine, have been reported to facilitate the absorption and utilization of dietary iron. Here, we investigated the effect of combined ingestion of methionine, threonine, and iron on the improvement of iron status during a short-term intervention, by comparing that with iron ingestion alone in healthy young women. METHODS: This was a randomized, double-blind, parallel-group, comparative study with 45 participants (aged 20-39) randomly assigned to three groups (n = 15 each): one group was administered 200 mg methionine, 400 mg threonine, and 6 mg iron once daily (FEMT); another ingested 6 mg iron alone (FE); and the third group ingested a placebo (PCG). Blood samples and dietary nutrient data were collected before the intervention (week 0) and after 2, 4, and 6 weeks. Serum iron, hemoglobin, transferrin, and ferritin levels were measured. RESULTS: Blood hemoglobin levels were significantly higher in the FEMT than in the FE group (P < 0.05) at week 4. Serum iron, transferrin, and ferritin levels were not changed across groups. In addition, our analyses showed that the observed increase in hemoglobin levels was affected by the intervention rather than changes in dietary nutrient intake. CONCLUSIONS: Ingestion of methionine and threonine with low doses of iron leads to a higher hemoglobin levels than that with iron alone in a short period of 4 weeks. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN000046621).

LIN28 is essential for the maintenance of chicken primordial germ cells.

Understanding the mechanism of stem cell maintenance underlies the establishment of long-term and mass culture methods for stem cells that are fundamental for clinical and agricultural applications. In this study, we use chicken primordial germ cell (PGC) as a model to elucidate the molecular mechanisms underlying stem cell maintenance. The PGC is a useful experimental model because it is readily gene-manipulatable and easy to test gene function in vivo using transplantation. Previous studies to establish a long-term culture system have shown that secreted factors such as FGF2 are required to maintain the self-renewal capability of PGC. On the other hand, we know little about intracellular regulators responsible for PGC maintenance. Among representative stem cell factors, we focus on RNA-binding factors LIN28A and LIN28B as possible central regulators for the gene regulatory network essential to PGC maintenance. By taking advantage of the CRISPR/Cas9-mediated gene editing and a clonal culture technique, we find that both LIN28A and LIN28B regulate the proliferation of PGC in vitro. We further showed that colonization efficiency of grafted PGC at the genital ridges, rudiments for the gonads, of chicken embryos were significantly decreased by knockout (KO) of LIN28A or LIN28B. Of note, overexpression of human LIN28 in LIN28-KO PGC was sufficient to restore the low colonization rates, suggesting that LIN28 plays a key role in PGC colonization at the gonads. Transcriptomic analyses of LIN28-KO PGC reveal that several genes related to mesenchymal traits are upregulated, including EGR1, a transcription factor that promotes the differentiation of mesodermal tissues. Finally, we show that the forced expression of human EGR1 deteriorates replication activity and colonization efficiency of PGCs. Taken together, this work demonstrates that LIN28 maintains self-renewal of PGC by suppressing the expression of differentiation genes including EGR1.

Potent neutralizing broad-spectrum antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescents.

Several antibody therapeutics have been developed against SARS-CoV-2; however, they have attenuated neutralizing ability against variants. In this study, we generated multiple broadly neutralizing antibodies from B cells of convalescents, by using two types of receptor-binding domains, Wuhan strain and the Gamma variant as bait. From 172 antibodies generated, six antibodies neutralized all strains prior to the Omicron variant, and the five antibodies were able to neutralize some of the Omicron sub-strains. Structural analysis showed that these antibodies have a variety of characteristic binding modes, such as ACE2 mimicry. We subjected a representative antibody to the hamster infection model after introduction of the N297A modification, and observed a dose-dependent reduction of the lung viral titer, even at a dose of 2 mg/kg. These results demonstrated that our antibodies have certain antiviral activity as therapeutics, and highlighted the importance of initial cell-screening strategy for the efficient development of therapeutic antibodies.