Isocitrate dehydrogenase 1 upregulation in urinary extracellular vesicles from proximal tubules of type 2 diabetic rats.

Diabetic nephropathy (DN) is a major cause of chronic kidney disease. Microalbuminuria is currently the most common non-invasive biomarker for the early diagnosis of DN. However, renal structural damage may have advanced when albuminuria is detected. In this study, we sought biomarkers for early DN diagnosis through proteomic analysis of urinary extracellular vesicles (uEVs) from type 2 diabetic model rats and normal controls. Isocitrate dehydrogenase 1 (IDH1) was significantly increased in uEVs from diabetic model rats at the early stage despite minimal differences in albuminuria between the groups. Calorie restriction significantly suppressed the increase in IDH1 in uEVs and 24-hour urinary albumin excretion, suggesting that the increase in IDH1 in uEVs was associated with the progression of DN. Additionally, we investigated the origin of IDH1-containing uEVs based on their surface sugar chains. Lectin affinity enrichment and immunohistochemical staining showed that IDH1-containing uEVs were derived from proximal tubules. These findings suggest that the increase in IDH1 in uEVs reflects pathophysiological alterations in the proximal tubules and that IDH1 in uEVs may serve as a potential biomarker of DN in the proximal tubules.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Endoscopic Artificial Intelligence for Image Analysis in Gastrointestinal Neoplasms.

BACKGROUND: Artificial intelligence (AI) using deep learning systems has recently been utilized in various medical fields. In the field of gastroenterology, AI is primarily implemented in image recognition and utilized in the realm of gastrointestinal (GI) endoscopy. In GI endoscopy, computer-aided detection/diagnosis (CAD) systems assist endoscopists in GI neoplasm detection or differentiation of cancerous or noncancerous lesions. Several AI systems for colorectal polyps have already been applied in colonoscopy clinical practices. In esophagogastroduodenoscopy, a few CAD systems for upper GI neoplasms have been launched in Asian countries. The usefulness of these CAD systems in GI endoscopy has been gradually elucidated. SUMMARY: In this review, we outline recent articles on several studies of endoscopic AI systems for GI neoplasms, focusing on esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cancer (GC), and colorectal polyps. In ESCC and EAC, computer-aided detection (CADe) systems were mainly developed, and a recent meta-analysis study showed sensitivities of 91.2% and 93.1% and specificities of 80% and 86.9%, respectively. In GC, a recent meta-analysis study on CADe systems demonstrated that their sensitivity and specificity were as high as 90%. A randomized controlled trial (RCT) also showed that the use of the CADe system reduced the miss rate. Regarding computer-aided diagnosis (CADx) systems for GC, although RCTs have not yet been conducted, most studies have demonstrated expert-level performance. In colorectal polyps, multiple RCTs have shown the usefulness of the CADe system for improving the polyp detection rate, and several CADx systems have been shown to have high accuracy in colorectal polyp differentiation. KEY MESSAGES: Most analyses of endoscopic AI systems suggested that their performance was better than that of nonexpert endoscopists and equivalent to that of expert endoscopists. Thus, endoscopic AI systems may be useful for reducing the risk of overlooking lesions and improving the diagnostic ability of endoscopists.

Decrease in electrolyte after vitrectomy surgery may affect the results of forensic investigations using vitreous humor.

PURPOSE: Vitreous humor (VH) is used for postmortem biochemical studies because it is well protected in an uncontaminated state even after death. The goal of this research was to investigate electrolyte concentrations in the VH from human eyes with and without a history of vitrectomy surgery. METHODS: We analyzed the sodium (Na), potassium (K), chloride (Cl) and magnesium (Mg) concentrations from 34 VH samples from 34 patients. Eleven samples were from eyes with a history of vitrectomy, and the remaining 23 eyes had no history of vitrectomy. The correlations of Na, K, Cl and Mg concentrations with patient age, interval between first and second vitrectomy, and lens status (history of cataract surgery) were also evaluated. RESULTS: The Na, K, Cl and Mg concentrations in VH from vitrectomized eyes were 134.1 ± 7.9 mmol/L, 3.7 ± 0.2 mmol/L, 99.7 ± 6.7 mmol/L and 0.59 ± 0.09 mmol/L, respectively; all were significantly lower than the corresponding concentrations in VH from control eyes (lower by 5.0%, 11.0%, 11.7%, and 22.6%, respectively). Na, K, Cl and Mg concentrations in VH from vitrectomized eyes did not show significant correlations with patient ages or the interval between their first and second vitrectomies. There were no significant differences in Na, K, Cl and Mg concentrations in VH between phakic eyes and intraocular lens-implanted eyes. CONCLUSIONS: With the increasing number of vitrectomies being performed, it is necessary to consider the history of vitrectomy when using a subject's VH in forensic examination.

Selenide [Se(-II)] Immobilization in Anoxic, Fe(II)-Rich Environments: Coprecipitation and Behavior during Phase Transformations.

The radionuclide selenium-79 (Se-79) is predicted to be a key contributor to the long-term radiologic hazards associated with geological high-level waste (HLW) repositories; hence its release is of pertinent concern in the safety assessment of repositories. However, interactions of reduced Se species with aqueous Fe(II) species and solid phases arising from the corrosion of a steel overpack could play a role in mitigating its migration to the surrounding environment. In this study, we examined the immobilization mechanisms of Se(-II) during its interaction with aqueous Fe(II) and freshly precipitated Fe(OH)2 at circumneutral and alkaline conditions, respectively, its response to changes in pH, and its behavior during aging at 90 °C. Using microscopic and spectroscopic techniques, we observed ß-FeSe precipitation, regardless of whether Se(-II) reacts with aqueous species or solid phases, and that modifying the pH following initial immobilization did not remobilize Se(-II). These observations indicate that Se(-II) migration beyond the overpack can be effectively and rapidly retarded via interactions with Fe(II) species arising from overpack corrosion. Thermodynamic calculations, however, showed that iron selenides became metastable at alkaline conditions and will dissolve in the long term. Aging experiments at 90 °C showed that Se(-II) can be completely retained via the crystallization of ferroselite at circumneutral conditions, while it will be largely remobilized at alkaline conditions. Our results show that Se(-II) mobility can be significantly influenced by its interactions with the corrosion products of the steel overpack and that these behaviors will have to be considered in repository safety assessments.

Apolipoprotein E binds to and reduces serum levels of DNA-mimicking, pyrrolated proteins.

Lysine N-pyrrolation, converting lysine residues to Nϵ-pyrrole-l-lysine, is a recently discovered post-translational modification. This naturally occurring reaction confers electrochemical properties onto proteins that potentially produce an electrical mimic to DNA and result in specificity toward DNA-binding molecules such as anti-DNA autoantibodies. The discovery of this unique covalent protein modification provides a rationale for establishing the molecular mechanism and broad functional significance of the formation and regulation of Nϵ-pyrrole-l-lysine-containing proteins. In this study, we used microbeads coupled to pyrrolated or nonpyrrolated protein to screen for binding activities of human serum-resident nonimmunoglobin proteins to the pyrrolated proteins. This screen identified apolipoprotein E (apoE) as a protein that innately binds the DNA-mimicking proteins in serum. Using an array of biochemical assays, we observed that the pyrrolated proteins bind to the N-terminal domain of apoE and that oligomeric apoE binds these proteins better than does monomeric apoE. Employing surface plasmon resonance and confocal microscopy, we further observed that apoE deficiency leads to significant accumulation of pyrrolated serum albumin and is associated with an enhanced immune response. These results, along with the observation that apoE facilitates the binding of pyrrolated proteins to cells, suggest that apoE may contribute to the clearance of pyrrolated serum proteins. Our findings uncover apoE as a binding target of pyrrolated proteins, providing a key link connecting covalent protein modification, lipoprotein metabolism, and innate immunity.

Adductome-based identification of biomarkers for lipid peroxidation.

Lipid peroxidation is an endogenous source of aldehydes that gives rise to covalent modification of proteins in various pathophysiological states. In this study, a strategy for the comprehensive detection and comparison of adducts was applied to find a biomarker for lipid peroxidation-modified proteins in vivo This adductome approach utilized liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) methods designed to detect the specific product ions from positively ionized adducts in a selected reaction monitoring mode. Using this procedure, we comprehensively analyzed lysine and histidine adducts generated in the in vitro oxidized low-density lipoproteins (LDL) and observed a prominent increase in several adducts, including a major lysine adduct. Based on the high resolution ESI-MS of the adduct and on the LC-ESI-MS/MS analysis of the synthetic adduct candidates, the major lysine adduct detected in the oxidized LDL was identified as Nϵ-(8-carboxyoctanyl)lysine (COL). Strikingly, a significantly higher amount of COL was detected in the sera from atherosclerosis-prone mice and from patients with hyperlipidemia compared with the controls. These data not only offer structural insights into protein modification by lipid peroxidation products but also provide a platform for the discovery of biomarkers for human diseases.

Impact of high-density lipoprotein 3 cholesterol subfraction on periprocedural myocardial injury in patients who underwent elective percutaneous coronary intervention.

BACKGROUND: Periprocedural myocardial injury (PMI) is a major complication of percutaneous coronary intervention (PCI) and is associated with atherosclerotic coronary plaque and worse clinical outcomes. High-density lipoprotein cholesterol (HDL-C) is a protective factor for cardiovascular disease. However, the role of HDL-C subfractions, such as HDL2 cholesterol (HDL2-C) or HDL3 cholesterol (HDL3-C), in cardiovascular disease remains unclear. The purpose of the study was to investigate the relationship between HDL2-C and HDL3-C subfractions and the incidence of PMI in patients who underwent elective PCI. METHODS: We enrolled 129 patients who underwent elective PCI for stable angina pectoris. PMI was defined as an increase in high-sensitivity troponin T levels > 5 times the upper normal limit (> 0.070 ng/mL) at 24 h after PCI. Serum HDL-C subfractions (HDL2-C and HDL3-C) were assessed using ultracentrifugation in patients with and those without PMI. RESULTS: HDL3-C levels were significantly lower in patients with PMI than in those without (15.1 ± 3.0 mg/dL vs. 16.4 ± 2.9 mg/dL, p = 0.016) and had an independent and inverse association with PMI (odds ratio, 0.86; 95% confidence interval, 0.74-0.99; p = 0.038). When divided by the cut-off value of HDL3-C for PMI (14.3 mg/dL), the incidence of PMI was significantly higher in low HDL3-C patients than in high HDL3-C patients (51.2% vs. 30.2%, p = 0.020). CONCLUSIONS: HDL3-C was an independent inverse predictor of PMI in patients who underwent elective PCI.

Secreted Frizzled-related Protein 5 Diminishes Cardiac Inflammation and Protects the Heart from Ischemia/Reperfusion Injury.

Wnt signaling has diverse actions in cardiovascular development and disease processes. Secreted frizzled-related protein 5 (Sfrp5) has been shown to function as an extracellular inhibitor of non-canonical Wnt signaling that is expressed at relatively high levels in white adipose tissue. The aim of this study was to investigate the role of Sfrp5 in the heart under ischemic stress. Sfrp5 KO and WT mice were subjected to ischemia/reperfusion (I/R). Although Sfrp5-KO mice exhibited no detectable phenotype when compared with WT control at baseline, they displayed larger infarct sizes, enhanced cardiac myocyte apoptosis, and diminished cardiac function following I/R. The ischemic lesions of Sfrp5-KO mice had greater infiltration of Wnt5a-positive macrophages and greater inflammatory cytokine and chemokine gene expression when compared with WT mice. In bone marrow-derived macrophages, Wnt5a promoted JNK activation and increased inflammatory gene expression, whereas treatment with Sfrp5 blocked these effects. These results indicate that Sfrp5 functions to antagonize inflammatory responses after I/R in the heart, possibly through a mechanism involving non-canonical Wnt5a/JNK signaling.

Glutaredoxin-1 up-regulation induces soluble vascular endothelial growth factor receptor 1, attenuating post-ischemia limb revascularization.

Glutaredoxin-1 (Glrx) is a cytosolic enzyme that regulates diverse cellular function by removal of GSH adducts from S-glutathionylated proteins including signaling molecules and transcription factors. Glrx is up-regulated during inflammation and diabetes, and Glrx overexpression inhibits VEGF-induced EC migration. The aim was to investigate the role of up-regulated Glrx in EC angiogenic capacities and in vivo revascularization in the setting of hind limb ischemia. Glrx-overexpressing EC from Glrx transgenic (TG) mice showed impaired migration and network formation and secreted higher levels of soluble VEGF receptor 1 (sFlt), an antagonizing factor to VEGF. After hind limb ischemia surgery Glrx TG mice demonstrated impaired blood flow recovery, associated with lower capillary density and poorer limb motor function compared with wild type littermates. There were also higher levels of anti-angiogenic sFlt expression in the muscle and plasma of Glrx TG mice after surgery. Noncanonical Wnt5a is known to induce sFlt. Wnt5a was highly expressed in ischemic muscles and EC from Glrx TG mice, and exogenous Wnt5a induced sFlt expression and inhibited network formation in human microvascular EC. Adenoviral Glrx-induced sFlt in EC was inhibited by a competitive Wnt5a inhibitor. Furthermore, Glrx overexpression removed GSH adducts on p65 in ischemic muscle and EC and enhanced NF-κB activity, which was responsible for Wnt5a-sFlt induction. Taken together, up-regulated Glrx induces sFlt in EC via NF-κB-dependent Wnt5a, resulting in attenuated revascularization in hind limb ischemia. The Glrx-induced sFlt explains part of the mechanism of redox-regulated VEGF signaling.

Antiangiogenic actions of vascular endothelial growth factor-A165b, an inhibitory isoform of vascular endothelial growth factor-A, in human obesity.

BACKGROUND: Experimental studies suggest that visceral adiposity and adipose tissue dysfunction play a central role in obesity-related cardiometabolic complications. Impaired angiogenesis in fat has been implicated in the development of adipose tissue hypoxia, capillary rarefaction, inflammation, and metabolic dysregulation, but pathophysiological mechanisms remain unknown. In this study, we examined the role of a novel antiangiogenic isoform of vascular endothelial growth factor-A (VEGF-A), VEGF-A165b, in human obesity. METHODS AND RESULTS: We biopsied paired subcutaneous and visceral adipose tissue in 40 obese subjects (body mass index, 45±8 kg/m(2); age, 45±11 years) during bariatric surgery and characterized depot-specific adipose tissue angiogenic capacity using an established ex vivo assay. Visceral adipose tissue exhibited significantly blunted angiogenic growth compared with subcutaneous fat (P<0.001) that was associated with marked tissue upregulation of VEGF-A165b (P=0.004). The extent of VEGF-A165b expression correlated negatively with angiogenic growth (r=-0.6, P=0.006). Although recombinant VEGF-A165b significantly impaired angiogenesis, targeted inhibition of VEGF-A165b with neutralizing antibody stimulated fat pad neovascularization and restored VEGF receptor activation. Blood levels of VEGF-A165b were significantly higher in obese subjects compared with lean control subjects (P=0.02), and surgical weight loss induced a marked decline in serumVEGF-A165b (P=0.003). CONCLUSIONS: We demonstrate that impaired adipose tissue angiogenesis is associated with overexpression of a novel antiangiogenic factor, VEGF-A165b, that may play a pathogenic role in human adiposopathy. Moreover, systemic upregulation of VEGF-A165b in circulating blood may have wider-ranging implications beyond the adipose milieu. VEGF-A165b may represent a novel area of investigation to gain further understanding of mechanisms that modulate the cardiometabolic consequences of obesity.

T-cadherin is essential for adiponectin-mediated revascularization.

Adipose tissue secretes protein factors that have systemic actions on cardiovascular tissues. Previous studies have shown that ablation of the adipocyte-secreted protein adiponectin leads to endothelial dysfunction, whereas its overexpression promotes wound healing. However, the receptor(s) mediating the protective effects of adiponectin on the vasculature is not known. Here we examined the role of membrane protein T-cadherin, which localizes adiponectin to the vascular endothelium, in the revascularization response to chronic ischemia. T-cadherin-deficient mice were analyzed in a model of hind limb ischemia where blood flow is surgically disrupted in one limb and recovery is monitored over 28 days by laser Doppler perfusion imaging. In this model, T-cadherin-deficient mice phenocopy adiponectin-deficient mice such that both strains display an impaired blood flow recovery compared with wild-type controls. Delivery of exogenous adiponectin rescued the impaired revascularization phenotype in adiponectin-deficient mice but not in T-cadherin-deficient mice. In cultured endothelial cells, T-cadherin deficiency by siRNA knockdown prevented the ability of adiponectin to promote cellular migration and proliferation. These data highlight a previously unrecognized role for T-cadherin in limb revascularization and show that it is essential for mediating the vascular actions of adiponectin.

Mitofusins 1 and 2 are essential for postnatal metabolic remodeling in heart.

RATIONALE: At birth, there is a switch from placental to pulmonary circulation and the heart commences its aerobic metabolism. In cardiac myocytes, this transition is marked by increased mitochondrial biogenesis and remodeling of the intracellular architecture. The mechanisms governing the formation of new mitochondria and their expansion within myocytes remain largely unknown. Mitofusins (Mfn-1 and Mfn-2) are known regulators of mitochondrial networks, but their role during perinatal maturation of the heart has yet to be examined. OBJECTIVE: The objective of this study was to determine the significance of mitofusins during early postnatal cardiac development. METHODS AND RESULTS: We genetically inactivated Mfn-1 and Mfn-2 in midgestational and postnatal cardiac myocytes using a loxP/Myh6-cre approach. At birth, cardiac morphology and function of double-knockout (DKO) mice are normal. At that time, DKO mitochondria increase in numbers, appear to be spherical and heterogeneous in size, but exhibit normal electron density. By postnatal day 7, the mitochondrial numbers in DKO myocytes remain abnormally expanded and many lose matrix components and membrane organization. At this time point, DKO mice have developed cardiomyopathy. This leads to a rapid decline in survival and all DKO mice die before 16 days of age. Gene expression analysis of DKO hearts shows that mitochondria biogenesis genes are downregulated, the mitochondrial DNA is reduced, and mitochondrially encoded transcripts and proteins are also reduced. Furthermore, mitochondrial turnover pathways are dysregulated. CONCLUSIONS: Our findings establish that Mfn-1 and Mfn-2 are essential in mediating mitochondrial remodeling during postnatal cardiac development, a time of dramatic transitions in the bioenergetics and growth of the heart.

Volatile anticancer drug determination by thermal desorption technique with polydimethylsiloxane-coated macroporous silica adsorbent in gas chromatography-mass spectrometry.

An analytical method for quantifying the volatile anticancer drugs ifosfamide (IF) and cyclophosphamide (CP) in air was developed on the basis of thermal desorption (TD)-gas chromatography-mass spectrometry. Polydimethylsiloxane-coated macroporous silica was used as the adsorbent. The extraction tube was prepared by packing 0.2 g of adsorbent particles into a glass tube. The extraction and desorption efficiencies of the proposed method were quantitatively investigated in this study. The limits of detection of the proposed method for IF and CP were 3.3 ng L-1 at an air sampling volume of 3.0 L (30 min). The sensitivity of the proposed method was compared with using a Tenax TA packed tube that is widely used as the extraction medium in TD analysis. Finally, detection of IF and CP that evaporated from aqueous standard solution was investigated.

Changes in antibody titer after four and five doses of the SARS-CoV-2 vaccine in Japanese post-kidney transplant patients.

INTRODUCTION: Immunosuppressed patients exhibit low antibody acquisition rates following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Kidney transplant recipients previously exhibited low antibody acquisition rates after two vaccine doses, which increased after the third dose. We evaluated antibody titers of Japanese post-kidney transplant patients after the fourth and fifth vaccinations. METHODS: Antibody titers for SARS-CoV-2 spike protein were measured between 3 weeks and 3 months after the fourth or fifth vaccination. RESULTS: Increased antibody acquisition rates were observed after the fourth (75.0% antibody-positive) and fifth (81.5% antibody-positive) vaccinations. The antibody-acquired group after the fourth vaccination exhibited a higher body mass index and estimated glomerular filtration rate (eGFR) than the non-acquired group. A higher eGFR was associated with antibody acquisition after the fifth vaccination. CONCLUSION: In Japanese post-kidney transplant patients, the antibody acquisition rate increased with each vaccine additional dose. Additional vaccinations are recommended to protect against SARS-CoV-2 infection.

Variability in combinations of APTT reagent and substrate plasma for a one-stage clotting assay to measure factor VIII products.

INTRODUCTION: An investigation of the suitability of reagents for measuring FVIII products in a one-stage clotting assay (OSA) showed variations in their FVIII activity (FVIII:C). Most studies have focused on the activated partial thromboplastin time (APTT) reagent rather than FVIII-deficient plasma (F8DP), even though the APTT-based OSA is comprised of APTT reagents and factor-deficient plasma. AIM: A single-centre study was conducted to clarify variations in measurements of FVIII products in an OSA using a total of 12 reagent combinations, including four APTT reagents and three types of F8DP. METHODS: FVIII:C in nine types of FVIII product-spiked plasma was measured using an OSA with four different APTT reagents and three types of F8DP. RESULTS: F8DP-dependent variations were found in addition to differences derived from APTT reagents. Variations in target recovery (TR) were observed for NovoEight®, Eloctate®, and Jivi®. Reduced TR for Jivi was found only for Pathromtin SL in combination with congenital F8DP (F8DP-3). This lower TR was not observed with alternative manufacturing lots of F8DP-3. The reduced TR for Jivi might be related to impaired contact activation due to lower factor XI activity in F8DP-3. CONCLUSION: In addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur.

Sitting maneuver to uncover latent left ventricular outflow tract obstruction in patients without hypertrophic cardiomyopathy.

BACKGROUND: Left ventricular outflow tract obstruction [LVOTO; pressure gradient (PG) ≥30 mmHg] is observed in some patients without hypertrophic cardiomyopathy (HCM), and it may develop especially in older patients without HCM (non-HCM). The aim of this study is to investigate if the Valsalva or an upright sitting maneuver can unveil latent LVOTO in patients with non-HCM. METHODS: A total of 33 non-HCM patients with a late peaking or dagger-shaped pulsed Doppler waveform of the LVOT and PG <30 mmHg were included. The Doppler flow velocity of the LVOT was measured at rest, after the Valsalva and a sitting maneuver. Peak PG of ≥30 mmHg after either maneuver was defined as latent LVOTO. The angle between the left ventricular septum and the aorta in the parasternal long-axis view and the apical three-chamber view was measured. RESULTS: Twenty (61 %) of the 33 patients (mean age 74 ±â€¯9 years) were diagnosed with latent LVOTO. Of these, five (25 %) patients were diagnosed after both the Valsalva and sitting maneuver, and 15 (75 %) were diagnosed only after the sitting maneuver. The latent LVOTO group had a significantly smaller angle than the no-LVOTO group between the ventricular septum and the aorta in the parasternal long axis views (107 ±â€¯8° vs. 117 ±â€¯8°, p < 0.01). CONCLUSION: The sitting maneuver is better than the Valsalva maneuver in unveiling latent LVOTO in older, non-HCM patients.

Long-term course of untreated asymptomatic esophageal eosinophilia and minimally symptomatic eosinophilic esophagitis.

Background and study aims The long-term course of untreated asymptomatic esophageal eosinophilia (aEE) and minimally symptomatic eosinophilic esophagitis (mEoE) are not well understood. This study aimed to clarify this course. Patients and methods A total of 36 patients with EE who were endoscopically followed up for more than 5 years, and who underwent more than one endoscopy evaluation after the first diagnosis, were investigated. These patients were divided into two groups according to the presence or absence of the continuous treatment: no treatment group (NT group, n=22) and proton pump inhibitor/potassium competitive acid blocker group (Tx group, n=14). Symptoms and endoscopic and histological findings were retrospectively reviewed according to endoscopic phenotypes. Endoscopic assessment was performed using the EoE endoscopic reference score (EREFS). Results The median follow-up period was 84.5 months in the Tx group and 92 months in the NT group. During the follow-up period, about half of the patients in the Tx-diffuse group persisted EREFS >3, while the remaining half had EREFS ≤2. The total EREFS in the NT-diffuse group remained almost unchanged (median: 2-4) without apparent exacerbation. In contrast, EREFS in the NT-localized group exhibited an unchanged or gradually decreasing trend, with statistical significance from the first diagnosis to 72 to 83 months after. Conclusions Untreated aEE and mEoE are not likely to worsen even without treatment at least for a median follow-up of 7 years. Instead, the localized type may spontaneously improve, implying a different pathogenesis in the presence of the diffuse type. Further studies should clarify the long-term prognosis.

Complete genome sequence of Pigmentibacter ruber isolated from a human patient in Japan.

Pigmentibacter ruber is a newly described bacterium belonging to the Silvanigrellaceae family that was isolated from human blood in 2021. We report the complete genome sequence of a clinical isolate of P. ruber (GTC16762) obtained from a human patient in Japan. Its genome contains a 3.6-Mb chromosome and three circular plasmids.

First Case of Necrotizing Fasciitis and Septicemia Caused by Pigmentibacter ruber.

We report the first case of necrotizing fasciitis caused by Pigmentibacter ruber. The isolated strain could not be identified by biochemical characterization or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry but was identified as P. ruber by 16S ribosomal RNA and whole-genome sequencing. Although much remains unknown about the pathogenicity of this bacterial species in humans, it has been shown to cause life-threatening infections such as septicemia and necrotizing fasciitis. Because the isolate was highly resistant to ß-lactams, it was difficult to treat with antimicrobial therapy. Thus, further documentation of cases and analyses are required.