Search Results (105)

Human milk oligosaccharides (HMOs) have garnered significant attention as one of the bioactive components in human milk, with growing applications in infant formula and food products. HMOs enhance butyrate production, which is produced by butyrate-producing bacteria such as Faecalibacterium prausnitzii and contributes to gut health through its diverse biological functions. However, the specific mechanisms by which individual HMOs promote butyrate production remain unclear. In this study, we conducted in vitro co-culture experiments of F. prausnitzii and Bifidobacterium bifidum, examining their relative abundance, fatty acid production, residual sugar levels, and gene expression. Our results revealed that B. bifidum utilizes HMOs and provides the constituent sugars to F. prausnitzii, thereby promoting butyrate production by F. prausnitzii. Furthermore, we found that the underlying mechanisms vary depending on the structure of the HMOs. Specifically, 2′-fucosyllactose and 3′-sialyllactose enhance the butyrate production efficiency of F. prausnitzii, while 6′-sialyllactose primarily promotes the growth of F. prausnitzii. These findings not only deepen our understanding of how HMOs influence infant gut health but also suggest new directions for developing nutritional products that leverage the distinct functional properties of each HMO. Full article

Abnormalities in plasma lipoproteins observed in patients with diabetes promote atherosclerosis. However, the association between various lipid species and classes and atherosclerosis remains unclear. Here, we aimed to identify the plasma lipid characteristics associated with atherosclerosis progression in patients with diabetes. We performed semi-targeted lipidomic analysis of fasting plasma samples using supercritical fluid chromatography coupled with mass spectrometry in two independent patient groups with type 2 diabetes (n = 223 and 31) and evaluated cross-sectional associations between plasma lipids and carotid intima-media thickness (CIMT). Ten plasma lipid species, including eight diacylglycerols (DGs), and total DG levels were significantly associated with CIMT in both groups. Patients of the former group were partly observed for 5 years, and we investigated associations between DGs and CIMT progression in these patients (n = 101). As a result, 22 DGs among the 26 identified DGs and total DG (β = 0.398, p < 0.001) were significantly associated with the annual change in CIMT. Furthermore, plasma DG levels improved the predictive ability for CIMT progression, with an adjusted R-squared increase of 0.105 [95% confidence interval: 0.010, 0.232] in the models. Plasma DGs are associated with CIMT progression in patients with type 2 diabetes. Measurement of total plasma DG levels may be beneficial in assessing the risk of atherosclerosis progression. Full article

Background: Hemodialysis patients, due to impaired kidney function and compromised immune responses, face increased risks from SARS-CoV-2. Anti-nucleocapsid IgG (anti-IgG N) antibodies are a commonly used marker to assess prior infection in the general population; however, their efficacy for hemodialysis patients remains unclear. Methods: A retrospective study of 361 hemodialysis patients evaluated anti-IgG N antibodies for detecting prior SARS-CoV-2 infection. Antibody levels were measured using a chemiluminescence immunoassay (CLIA) over the four time points. Boxplots illustrated antibody distribution across sampling stages and infection status. Logistic regression and receiver operating characteristic (ROC) curve analysis determined diagnostic accuracy, sensitivity, specificity, and optimal cutoff values. Results: Among the 361 hemodialysis patients, 36 (10.0%) had SARS-CoV-2 infection. Sex distribution showed a trend toward significance (p = 0.05). Boxplot analysis showed that anti-IgG N levels remained low in non-infected patients but increased in infected patients, peaking at the third sampling. Anti-IgG N demonstrated high diagnostic accuracy (AUC: 0.973–0.865) but declined over time (p = 0.00525). The optimal cutoff at C1 was 0.01 AU/mL (sensitivity 1.00, specificity 0.94). Adjusted models had lower predictive value. Conclusions: Anti-IgG N antibodies showed high diagnostic accuracy for detecting prior SARS-CoV-2 infection in hemodialysis patients, though performance declined over time. These findings highlight the need for tailored diagnostic strategies in this vulnerable population. Full article

Aminopeptidase N (APN), an enzyme expressed in the small intestinal mucosa, is involved in dietary protein digestion. Previous studies have shown that oral administration of fermented milk containing lactic acid bacteria (LAB) enhances mucosal APN activity in young mice. This study aimed to investigate whether LAB strains stimulate mucosal APN activity in aged mice and to evaluate its relevance to age-related changes in body composition. The underlying molecular mechanisms were also explored in vitro. Experiment 1: Aged C57BL/6J mice were fed diets supplemented with heat-killed LAB strains—Enterococcus faecalis OU-23 (EF), Leuconostoc mesenteroides OU-03 (LM), or Lactiplantibacillus plantarum SNK12 (LP). Compared to the aged Control group, the ileal APN activity was significantly higher in the LP group. LP administration also elevated serum Gla-osteocalcin levels and decreased serum CTX-1 levels. Experiment 2: IEC-6 cells were co-cultured with LP that had been treated with RNase, DNase, or lysozyme. APN activity was significantly lower in cells co-cultured with DNase- or lysozyme-treated LP compared to those co-cultured with untreated LP. A specific LAB strain may enhance mucosal APN activity in the aged intestine, potentially contributing to improved bone metabolism. This effect may be mediated by bacterial DNA and peptidoglycan. Full article

Objectives: The objective of this study is to investigate the two-year continuous efficacy, risk factors, and safety profile of selective laser trabeculoplasty (SLT) in Japanese individuals diagnosed with normal-tension glaucoma (NTG) who underwent SLT as either a first-line or second-line treatment. Methods: A retrospective chart review was conducted of patients with NTG who underwent SLT as either an initial or secondary therapy at 26 medical institutions in Japan between January 2020 and December 2021 with a 2-year follow-up. The primary endpoint was a reduction in the rate of intraocular pressure (IOP) over 2 years after SLT. To estimate the time-varying effect of IOP reduction, a linear mixed-effects model was employed. The secondary endpoints were numerical IOP reduction, treatment success rates shown by a Kaplan–Meier analysis, and complications. Success was defined as an outflow pressure improvement rate (ΔOP) ≥ 20% (definition A) or an IOP reduction rate ≥ 20% (definition B) without further treatment. A Cox proportional hazards regression analysis was used to identify the risk factors to successful SLT treatment. The study was registered with UMIN-CTR (ID: UMIN R000064045). Results: A total of 230 eyes from 230 individuals participated in this study, with 148 eyes receiving SLT as an initial (first-line) therapy and 82 eyes undergoing SLT as a secondary (second-line) intervention. In the first-line group, the mean IOP dropped from 16.7 ± 2.3 mmHg to 13.7 ± 2.4 mmHg at two years post-treatment, reflecting a 16.8% reduction. In the second-line group, the average IOP declined from 15.9 ± 2.5 mmHg to 13.2 ± 2.0 mmHg, marking a 14.4% decrease over the same period. The treatment success rate according to definition A (ΔOP ≥ 20%) was 73.7% at 2 years. Analysis using a linear mixed-effects model identified time (p < 0.001), age (p = 0.044), baseline IOP (p < 0.001), and central corneal thickness (CCT) (p < 0.001) as statistically significant contributors to IOP reduction following SLT. However, neither the Group (first-line vs. second-line) variable (p = 0.386) nor the Time × Group interaction (p = 0.298) reached statistical significance. A lower baseline IOP and a thicker CCT were confirmed as significant predictors of SLT treatment failure. Conclusions: Both initial and secondary SLT treatments for NTG proved to be effective and safe over a two-year period, although the extent of IOP reduction was smaller in cases with a lower baseline IOP. Our findings indicate that the IOP-lowering effect of SLT in NTG is influenced by pretreatment IOP levels, aligning with previous studies on primary open-angle glaucoma and ocular hypertension. However, in contrast to those earlier findings, our research identified pretreatment central corneal thickness as a statistically significant factor influencing SLT efficacy in NTG. These results support the role of SLT as a reliable and safe therapeutic option for managing NTG. Full article

Background/Objectives: Effective management of aneurysmal subarachnoid hemorrhage (aSAH) requires an evidence-based treatment protocol. This study examines the outcomes of a unified, multicenter protocol emphasizing postoperative clazosentan as the first-line treatment for vasospasm. Methods: A standardized protocol prioritizing systemic management with clazosentan for vasospasm was implemented in April 2023. Cases treated between April 2022 and March 2024 were categorized into four groups: preprotocol fasudil treatment (PrF), preprotocol clazosentan treatment (PrC), postprotocol fasudil treatment (PoF), and postprotocol clazosentan treatment (PoC); these groups were analyzed. Results: Among 407 registered cases, 322 were eligible for analysis (PrF, 128; PrC, 69; PoF, 28; PoC, 97). PoC exhibited significantly lower angiographic vasospasm rates and had a lower incidence of symptomatic vasospasm compared with PrF (p = 0.048, p = 0.057). Logistic regression identified the clazosentan protocol as a predictive factor for vasospasm reduction (p = 0.02, OR 0.46 [0.22–0.94]; p = 0.022, OR 0.38 [0.16–0.91]). PoC experienced less fluid retention than the PrC (p < 0.001). Logistic regression confirmed protocol adherence with protocol reduced complications (p < 0.001, OR 0.24 [0.11–0.52]), included fluid retention (p < 0.001, OR 0.088 [0.03–0.29]). In older patients, no significant differences in vasospasm or complications were observed between PrF and PoC, but a trend toward reduced complications was observed in World Federation of Neurosurgical Societies (WFNS) grade V cases. Conclusions: Clazosentan-first protocol effectively reduces vasospasm and complications in aSAH management. It is also safe for older patients and those with WFNS grade V, offering a promising treatment strategy. Full article

Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25, p < 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61, p = 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. Conclusions: These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) causes cellular senescence due to oxidative stress, endoplasmic reticulum stress, and ectopic fat deposition in the liver. Recently, dasatinib, an antitumor agent, and quercetin, a dietary supplement, were combined as a senolytic drug to eliminate senescent cells. Thus, this study aimed to examine the effects of dasatinib and quercetin administration on removing senescent cells and their therapeutic effects on MASLD in a medaka MASLD model. Dasatinib and quercetin were administered to a medaka MASLD model, which was fed a high-fat diet by dissolving them in aquarium water. The results revealed that senescent cells in the liver were increased in the HFD group but improved in the treatment group. Hematoxylin and eosin staining also showed that treatment improved fat deposition in hepatocytes. In addition, TGFβ1, a driver factor of fibrosis, was reduced in the treatment group. Dasatinib and quercetin eliminated senescent cells in MASLD, attenuated fat deposition, and suppressed fibrosis gene expression. The results indicate that dasatinib and quercetin as senolytic drugs are novel therapeutic agents that reduce MASLD. Full article

Background: Patients with adolescent idiopathic scoliosis (AIS) has been reported to exhibit impaired postural stability. Posterior correction and fusion using four-dimensional (4D) anatomical spinal reconstruction techniques may improve postural stability to correct the spine for optimal anatomical alignment. This prospective study aimed to determine the effect of posterior correction and fusion using a 4D anatomical spinal reconstruction technique on postural stability in the eye-open and eye-closed standing position in patients with thoracic AIS. Methods: Thirty-three patients with AIS, excluding those with Lenke type 5C AIS, participated in the study. The mean and standard deviation of the minimum values of the time-to-boundary (TTB) were determined. All patients were asked to perform the quiet standing position under the eye-open and eye-closed condition on a force plate preoperatively and at 1 week and 2 years postoperatively. The TTB value was calculated from the velocity and distance to the foot boundary of the acquired center-of-pressure data. Results: Under the eye-closed condition, the mean and standard deviation of the minimum TTB were significantly higher at 2 years postoperatively than preoperatively and at 1 week postoperatively. The mean and standard deviation of the minimum TTB values were significantly lower at 1 week postoperatively than preoperatively. Conclusions: The results of this study suggest that surgery using the 4D anatomical spinal reconstruction technique reduces postural stability immediately after surgery; however, it improves postural stability at 2 years compared to the preoperative values. Full article

Background: Oxidative stress plays an important role in the pathophysiology of bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO), but its relevance has not been fully elucidated. The aim of this study was to measure the levels of oxidative stress and investigate its clinical significance in patients with BA, COPD, or ACO. Methods: We recruited 214 patients between June 2020 and May 2023 (109 patients with BA, 63 with COPD, and 42 with ACO). To assess clinical conditions, we evaluated patient characteristics, results of respiratory function tests and blood tests, and administered several questionnaires. We evaluated oxidative stress using the test for derivatives–reactive oxygen metabolites (d–ROMs) in serum. Results: The d–ROMs levels were significantly higher in patients with COPD or ACO than in patients with BA. There was no difference in serum d–ROMs levels between the COPD and ACO groups. In BA, d–ROMs levels were positively correlated with interleukin (IL)-6, IL-8, serum amyloid A (SAA), and C-reactive protein (CRP) levels; white blood cell (WBC) and neutrophil counts; and St. George’s Respiratory Questionnaire (SGRQ) scores, and they were negatively correlated with forced expiratory volume in 1 s (%FEV₁) and asthma control test (ACT) score. In COPD, d–ROMs levels were positively correlated with IL-6, SAA, and CRP levels; WBC, neutrophil, and eosinophil counts; and COPD assessment test (CAT) and SGRQ scores, and they were negatively correlated with forced vital capacity (%FVC), %FEV₁, and %FEV₁/FVC scores. In ACO, d–ROMs levels were positively correlated with IL-6, SAA, tumor necrosis factor alpha (TNF-α), and CRP levels; and CAT and SGRQ scores, and they were negatively correlated with %FVC and %FEV₁ scores. Conclusions: Serum d–ROMs levels may serve as a marker reflecting clinical conditions such as systemic inflammation, symptom severity, and airflow limitation in patients with BA, COPD, and ACO. Full article

Background/Objectives: Despite advancements in treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC), overall survival (OS) remains poor. The specific effects of varying heart and lung doses on OS in LA-NSCLC patients have not been thoroughly investigated, especially their combined impact on survival. This study aimed to examine the impact on OS of both individual and combined heart and lung doses in patients with LA-NSCLC treated with radiotherapy over a three-year follow-up period. Methods: A total of 120 patients who received definitive radiotherapy for LA-NSCLC (stage III, 92.5%) from January 2015 to January 2020 were retrospectively reviewed. The endpoint in this study was OS. Each patient was followed for a fixed period of three years. Results: Univariate Cox regression analysis showed that OS was significantly related to mean heart dose (MHD, hazard ratio [HR], 3.4 [1.8–6.3]; p < 0.001), pericardium V40 (HR, 3.2 [1.7–6.0]; p < 0.001), and total lung V20 (HR, 2.6 [1.4–5.0]; p = 0.003), and these were independent predictors for worse OS in multivariate analysis. Kaplan–Meier curve analysis with log-rank tests revealed that survival was significantly worse in patients with higher MHD (p < 0.001), pericardium V40 (p < 0.001), and total lung V20 (p = 0.002). Combining MHD and total lung V20, and pericardium V40 and total lung V20 provided enhanced risk stratification for OS (p < 0.001 for both combinations). Conclusions: The combination of heart and lung doses provided enhanced and more detailed risk stratification in prediction of OS for a fixed period of three years in LA-NSCLC patients treated with radiotherapy. Full article

Xerostomia induced by antidepressants such as imipramine has long been thought to be due to their anticholinergic effects. However, even antidepressants with low anticholinergic effects may have a high incidence of xerostomia. In salivary glands, norepinephrine activates alpha-adrenergic receptors in blood vessels and beta-adrenergic receptors in acinar cells, respectively, causing a decrease in the blood flow and an increase in the protein secretion, resulting in the secretion of viscous saliva with low water content and high protein content. A previous study demonstrated that perfusion of the submandibular glands of rats with serotonin significantly decreased saliva secretion. The results of the present study revealed the following: (1) that norepinephrine and serotonin, but not epinephrine nor dopamine, were detected in the interstitial fluids in rat submandibular glands; (2) that norepinephrine and serotonin concentrations in the dialysate was 4.3 ± 2.8 nM and 32.3 ± 19.6 nM at stable level, respectively; (3) that infusion with imipramine, a reuptake inhibitor of norepinephrine and serotonin, significantly and dose-dependently increased both norepinephrine and serotonin concentrations in the dialysate; and (4) that intraperitoneal administration of imipramine significantly increased both norepinephrine and serotonin concentrations in the dialysate. These results suggested that one of the mechanisms of xerostomia induced by reuptake inhibitors of norepinephrine and serotonin involves the activation of adrenergic and serotonin receptors in the salivary glands, respectively. Full article

Background: The respiratory adjusted shock index (RASI) is a risk score whose usefulness in patients with sepsis and trauma has previously been reported. However, its relevance in elderly emergency patients with medical diseases is yet to be clarified. This study assessed the usefulness of the RASI, which can be evaluated without requiring special equipment, to provide objective and rapid emergency responses. Methods: In this retrospective study, we recruited patients with medical diseases, aged 65 years or older, who were transported to the emergency room from Tokushima Prefectural Kaifu Hospital and underwent arterial blood gas testing from 1 January 2022 to 31 December 2023. We investigated the association of the RASI with other indices, including the lactate level, National Early Warning Score 2 (NEWS2), Shock Index (SI), Sequential Organ Failure Assessment (SOFA) score, quick SOFA (qSOFA) score, and systemic inflammatory response syndrome (SIRS). Results: In this study, we included 260 patients (mean age, 86 years), of whom 234 were admitted to the hospital; 27 and 49 patients died within 7 and 30 days of admission, respectively. The RASI was positively correlated with the lactate level, NEWS2, SI, and increase in the SOFA score (p < 0.001). The RASI was higher in patients with a SIRS or qSOFA score ≥ 2 than in those without (p < 0.001). It predicted death within 7 and 30 days of admission with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.73–0.87), sensitivity of 96.3%, and specificity of 53.6% when the cutoff value was set to 1.58 and with an AUC of 0.73 (95% CI: 0.66–0.81), sensitivity of 69.4%, and specificity of 70.6% when the cutoff value was set to 1.83, respectively. Conclusions: The RASI is a simple indicator that can be used for predicting in-hospital outcomes in elderly emergency patients with medical diseases. Larger prospective studies based on this study are needed. Full article

Although hyperglycemia and hypertension are well-known risk factors for glomerular injury in individuals with type 2 diabetes (T2D), specific risk factors for tubular injury remain unclear. We aimed to clarify the differences between risk factors for glomerular injury and risk factors for tubular injury in individuals with T2D. We categorized 1243 subjects into four groups based on urinary biomarkers, including the albumin-to-creatinine ratio (uACR) and L-type fatty acid-binding protein-to-creatinine ratio (uL-ABPCR) as a normal (N) group (uACR < 30 mg/gCr and uL-FABPCR < 5 μg/gCr; n = 637), a glomerular specific injury (G) group (uACR ≥ 30 mg/gCr and uL-FABPCR < 5 μg/gCr; n = 248), a tubular specific injury (T) group (uACR < 30 mg/gCr and uL-FABPCR ≥ 5 μg/gCr; n = 90), and a dual injury (D) group (uACR ≥ 30 mg/gCr and uL-FABPCR ≥ 5 μg/gCr; n = 268). Logistic regression analysis referencing the N group revealed that BMI, current smoking, and hypertension were risk factors for the G group, creatinine (Cr) and Fibrosis-4 (FIB-4) index were risk factors for the T group, and BMI, hypertension, HbA1c, Cr, and duration of diabetes were risk factors for the D group. While hypertension was a distinct specific risk factor for glomerular injury, the FIB-4 index was a specific contributor to the prevalence of tubular injury. On the other hand, the logistic regression analysis revealed that the hepatic steatosis index (HSI) did not show any significant association with the G group, T group, or D group. Taken together, the development of liver fibrosis rather than liver steatosis is an inherent threat relating to tubular injury in individuals with T2D. Full article

This study reports on the magnetic hardening phenomenon of heavily helium ion-irradiated iron–chromium alloys. The alloys are important structural materials in next-generation nuclear reactors. In some cases, problems may arise when the magnetic properties of the materials change due to neutron irradiation. Therefore, it is necessary to understand the effects of irradiation on magnetism. Helium irradiation was conducted as a simulated irradiation, and the effect of cavity formation on magnetic properties was thoroughly investigated. High-quality single-crystal Fe-x%Cr (x = 0, 10, 20) films, with a thickness of 180–200 nm, were fabricated through ultra-high vacuum evaporation. Subsequently, irradiation of 19 dpa with 30 keV He⁺ ions was conducted at room temperature. X-ray diffraction measurements and electron microscopy observations confirmed significant lattice expansion and the formation of high-density cavities after irradiation. The magnetization curve of pure iron remained unchanged, while magnetic hardening was noticed in iron–chromium alloys. This phenomenon is believed to be due to the combined effect of cavity formation and changes in the atomic arrangement of chromium. Full article