Explore the vast range of titles available.

Ultrasonography (US) is a major, sustainable hepatocellular carcinoma (HCC) surveillance method as it provides inexpensive, real-time, and noninvasive detection. Since US findings are based on pathological features, knowledge of pathological features is essential for delivering a correct US diagnosis. Recent advances in US equipment have made it possible to provide more information, such as malignancy potential and accurate localization diagnosis of HCC. Evaluation of malignancy potential is important to determine the treatment strategy, especially for small HCC. Diagnosis of blood flow dynamics using color Doppler and contrast-enhanced US is one of the most definitive approaches for evaluating HCC malignancy potential. Recently, a new Doppler microvascular imaging technique, superb microvascular imaging, which can detect Doppler signals generated by low-velocity blood flow, was developed. A fusion imaging system, another innovative US technology, has already become an indispensable technology over the last few years not only for US-guided radiofrequency ablation but also for the detection of small, invisible HCC. This article reviews the evidence on the use of ultrasound and contrast-enhanced ultrasound with Sonazoid for the practical management of HCC.

Background/Objectives: Brick dust molecules exhibit high melting points and ultralow solubility. Overcoming this solubility issue is challenging. Previously, we formulated a co-amorphous system for a neuropeptide Y5 receptor antagonist (NP) as a brick dust drug using sodium taurocholate (ST) to improve its dissolution profile. In this study, we have designed a ternary amorphous system involving polymer addition to further improve a co-amorphous system. Methods: The amorphous samples were prepared by the ball milling. The thermal and spectroscopic analyses were performed, and the isothermal crystallization and dissolution profiles were evaluated. Results: The ball milling of NPs, ST, and each of the three types of polymers successfully converted crystalline NPs to amorphous NPs. Thermal analysis confirmed the formation of a single amorphous phase. The infrared spectra revealed a specific interaction between an NP and ST in the co-amorphous system. Moreover, the intermolecular interactions of NP-ST were maintained in the ternary amorphous systems, suggesting the miscible dispersion of the co-amorphous system into the polymer via weak interactions as co-amorphous solid dispersions. The dissolution profile of co-amorphous NP-ST was 4.1- and 6.7-fold higher than that of crystalline NPs in pH 1.2 and 6.8 buffers, respectively. The drug concentration in the ternary amorphous system in pH 1.2 and 6.8 buffers became 1.1–1.2- and 1.4–2.7-fold higher than that seen in the co-amorphous system, respectively. Conclusions: Co-amorphous solid dispersion is a promising method for enhancing the solubility of brick dust molecules.

BackgroundNot only obesity but also sarcopenia is associated with NAFLD. The influence of altered body composition on the pathophysiology of NAFLD has not been fully elucidated. The aim of this study is to determine whether skeletal muscle mass to visceral fat area ratio (SV ratio) affects NAFLD pathophysiology.MethodsA total of 472 subjects were enrolled. The association between SV ratio and NAFLD pathophysiological factors was assessed in a cross-sectional nature by stratification analysis.ResultsWhen the SV ratio was stratified by quartiles (Q1–Q4), the SV ratio showed a negative relationship with the degree of body mass index, HOMA-IR, and liver stiffness (Q1, 8.9 ± 7.5 kPa, mean ± standard deviation; Q2, 7.5 ± 6.2; Q3, 5.8 ± 3.7; Q4, 5.0 ± 1.9) and steatosis (Q1, 282 ± 57 dB/m; Q2, 278 ± 58; Q3, 253 ± 57; Q4, 200 ± 42) measured by transient elastography. Levels of leptin and biochemical markers of liver cell damage, liver fibrosis, inflammation and oxidative stress, and hepatocyte apoptosis were significantly higher in subjects in Q1 than in those in Q2, Q3, or Q4. Moreover, fat contents in femoral muscles were significantly higher in subjects in Q1 and the change was associated with weakened muscle strength. In logistic regression analysis, NAFLD subjects with the decreased SV ratio were likely to have an increased risk of moderate-to-severe steatosis and that of advanced fibrosis.ConclusionsDecreased muscle mass coupled with increased visceral fat mass is closely associated with an increased risk for exacerbating NAFLD pathophysiology.

[This corrects the article DOI: 10.1371/journal.pone.0291096.].

Purpose In Japan, the number of distal gastrectomy for patients ≥ 80 years old is increasing, whereas that of total gastrectomy is decreasing. Surgeons seem to avoid total gastrectomy for elderly patients. Total gastrectomy is reported to have a poorer prognosis than distal gastrectomy, and postoperative pneumonia may be involved in the cause. Methods The medical records of 39 and 108 patients ≥ 80 years old who underwent total and distal gastrectomy, respectively, at 2 affiliated institutions between 2010 and 2019 were retrospectively reviewed. Prognoses were compared between the two groups, focusing on death from pneumonia. Results The median overall survival time after total and distal gastrectomy was 21.3 and 74.1 months, respectively, with a significantly poorer prognosis after total gastrectomy than after distal gastrectomy ( p  < 0.01, hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.37–3.53). The gastric cancer-specific survival time was significantly worse after total gastrectomy than after distal gastrectomy ( p  < 0.01, HR 2.73, 95% CI 1.29–5.79). The pneumonia-specific survival time was also significantly worse after total gastrectomy than after distal gastrectomy ( p  = 0.01, HR 3.44, 95% CI 1.25–9.48). Conclusions Patients who underwent total gastrectomy had a poorer prognosis than those who underwent distal gastrectomy, because many patients died of pneumonia early after total gastrectomy.

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse‐transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR‐125b‐1 in cancer cells (P = 0.040), and miR‐378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR‐378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027–7.585; P = 0.044). In conclusion, miR‐125b‐1 and miR‐378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer. This is the first study to report that miR‐125b‐1 and miR‐378a might be novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer. In the present study of peptide vaccine in combination with standard chemotherapy for metastatic colorectal cancer patients, we reported that three miRNAs were negatively associated with OS: miR‐125b‐1 in cancer cells (P = 0.040), and miR‐378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001).

The mechanism of resistance to sorafenib in hepatocellular carcinoma (HCC) remains unclear. We analyzed miRNA expression profiles in sorafenib-resistant HCC cell lines (PLC/PRF5-R1/R2) and parental cell lines (PLC/PRF5) to identify the miRNAs responsible for resistance. Drug sensitivity, migration/invasion capabilities, and epithelial-mesenchymal transition (EMT) properties were analyzed by biochemical methods. The clinical relevance of the target genes to survival in HCC patients were assessed using a public database. Four miRNAs were significantly upregulated in PLC/PRF5-R1/-R2 compared with PLC/PRF5. Among them, miR-125b-5p mimic-transfected PLC/PRF5 cells (PLC/PRF5-miR125b) and showed a significantly higher IC50 for sorafenib compared with controls, while the other miRNA mimics did not. PLC/PRF5-miR125b showed lower E-cadherin and higher Snail and vimentin expression—findings similar to those for PLC/PRF5-R2—which suggests the induction of EMT in those cells. PLC/PRF5-miR125b exhibited significantly higher migration and invasion capabilities and induced sorafenib resistance in an in vivo mouse model. Bioinformatic analysis revealed ataxin-1 as a target gene of miR-125b-5p. PLC/PRF5 cells transfected with ataxin-1 siRNA showed a significantly higher IC50, higher migration/invasion capability, higher cancer stem cell population, and an EMT phenotype. Median overall survival in the low-ataxin-1 patient group was significantly shorter than in the high-ataxin-1 group. In conclusion, miR-125b-5p suppressed ataxin-1 and consequently induced Snail-mediated EMT and stemness, leading to a poor prognosis in HCC patients.

Early monitoring and feedback on the treatment of infectious diseases are some of the methods for optimising antimicrobial treatment throughout the treatment period. Prospective audits and feedback interventions have also been shown to improve antimicrobial use and reduce antimicrobial resistance. We examined the appropriate use of antimicrobials by focusing on the initial timing for audits and feedback intervention of antimicrobial prescription by Infection Control Team pharmacists. We conducted a retrospective observational study in a university hospital in Tokyo, Japan from 1 January 2019 to 31 May 2021. We retrospectively enrolled patients with infections and those patients suspected of having an infection, who were administered vancomycin and assessed at our hospital. The definition of primary outcome was the maintenance of target vancomycin trough blood concentrations of 10-20 μg/ml during treatment. Multivariable logistic regression and multivariate linear regression analyses were performed to test the effectiveness of the initial timing of the intervention by Infection Control Team pharmacists as the explanatory variable. A total of 638 patients were included in this study, with a median age of 69 years (interquartile range: 54-78 years). Multivariable logistic regression revealed that the maintenance of target vancomycin trough concentrations was not associated with the timing of the audit and the initiation of monitoring by Infection Control Team pharmacists (adjusted odds ratio: 0.99, 95% confidence interval: 0.99-1.00, p = 0.990). Multivariate linear regression revealed that the duration of vancomycin administration was significantly correlated with the timing of initiation of monitoring by Infection Control Team pharmacists (adjusted estimate: 0.0227, standard error: 0.0051, p = 0.012). Our study showed that early initiation of a comprehensive audit and monitoring by Infection Control Team pharmacists did not affect the maintenance of the target vancomycin trough blood concentration. However, it reduced the duration of vancomycin administration.

Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (Tg) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher Tg. A novel neuropeptide Y5 receptor antagonist (AntiY5R) and NaTC with Tg of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY5R and NaTC (AntiY5R-NaTC) at various molar ratios. Deviation from the theoretical Tg value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY5R and NaTC. AntiY5R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY5R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules.

Donepezil hydrochloride, used to treat Alzheimer's disease, is typically initiated at a low dose and titrated to minimize gastrointestinal side effects. Despite its favorable safety profile, the patient developed severe anorexia, dehydration, and electrocardiographic abnormalities. This case highlights the need for individualized dosing and careful monitoring of caregivers during pharmacotherapy.