How surface roughness affects the interparticle interactions at a liquid interface.

HYPOTHESIS: Colloidal particles can be trapped at a liquid interface, which reduces the energetically costly interfacial area. Once at an interface, colloids undergo various self-assemblies and structural transitions due to shape-dependent interparticle interactions. Particles with rough surfaces receive increasing attention and have been applied in material design, such as Pickering emulsions and shear-thickening materials. However, the roughness effects on the interactions at a liquid interface remain less understood. EXPERIMENTS: Experimentally, particles with four surface roughnesses were designed and compared via isotherm measurements upon a uniaxial compression. At each stage of the compression, micrographic observations were conducted via the Blodgett method. Numerically, the compression of monolayer was simulated by using Langevin dynamics. Rough colloids were modelled as particles with capillary attraction and tangential constraints. FINDINGS: Sufficiently rough systems exhibit a non-trivial intermediate state between a gas-like state and a close-packed jamming state. This state is understood as a gel state due to roughness-induced capillary attraction. Roughness-induced friction lowers the jamming point. Furthermore, the tangential contact force owing to surface asperities can cause a gradual off-plane collapse of the compressed monolayer.

Active colloid with externally induced periodic bipolar motility and its cooperative motion.

Active matter physics has been developed with various types of self-propelled particles, including those with polar and bipolar motility and beyond. However, the bipolar motions experimentally realized so far have been either random along the axis or periodic at intrinsic frequencies. Here we report another kind of bipolar active particles, whose periodic bipolar self-propulsion is set externally at a controllable frequency. We used Quincke rollers-dielectric particles suspended in a conducting liquid driven by an electric field-under an AC electric field instead of the usually used DC field. Reciprocating motion of a single particle at the external frequency was observed experimentally and characterized theoretically as stable periodic motion. Experimentally, we observed not only the reciprocating motion but also non-trivial active Brownian particle (ABP)-like persistent motion in a long time scale. This resulted in a Lorentzian spectrum around zero frequency, which is not accounted for by a simple extension of the conventional model of Quincke rollers to the AC field. It was found that ABP-like motion can be reproduced by considering the top-bottom asymmetry in the experimental system. Moreover, we found a rotational diffusion coefficient much larger than the thermal one, as also reported in previous experiments, which may have resulted from roughness of the electrode surface. We also found self-organized formation of small clusters, such as doublets and triplets, and characterized cooperative motion of particles therein. The AC Quincke rollers reported here may serve as a model experimental system of bipolar active matter, which appears to deserve further investigations.

Successful excision of a giant subcarinal bronchogenic cyst by video-assisted thoracoscopic surgery.

Mediastinal bronchogenic cysts, regarded as congenital foregut abnormalities, are uncommon. These cysts can compress adjacent structures, causing obstructive symptoms and complications. A 57-year-old man was admitted to our hospital with complaints of tachycardia, dyspnea, and chest pain. Enhanced computed tomography revealed a 90 × 90 mm, well-defined subcarinal cystic mass causing significant compression and stenosis of the right main bronchus, right pulmonary artery, and right inferior pulmonary vein. The mass was successfully excised using one window and two-port video-assisted thoracoscopic surgery with partial resection and repair of pulmonary artery, and the postoperative course was good with no recurrence.

Machine Learning Prediction of the Three Main Input Parameters of a Simplified Physiologically Based Pharmacokinetic Model Subsequently Used to Generate Time-Dependent Plasma Concentration Data in Humans after Oral Doses of 212 Disparate Chemicals.

Physiologically based pharmacokinetic (PBPK) modeling has the potential to play significant roles in estimating internal chemical exposures. The three major PBPK model input parameters (i.e., absorption rate constants, volumes of the systemic circulation, and hepatic intrinsic clearances) were generated in silico for 212 chemicals using machine learning algorithms. These input parameters were calculated based on sets of between 17 and 65 chemical properties that were generated by in silico prediction tools before being processed by machine learning algorithms. The resulting simplified PBPK models were used to estimate plasma concentrations after virtual oral administrations in humans. The estimated absorption rate constants, volumes of the systemic circulation, and hepatic intrinsic clearance values for the 212 test compounds determined traditionally (i.e., based on fitting to measured concentration profiles) and newly estimated had correlation coefficients of 0.65, 0.68, and 0.77 (p < 0.01, n = 212), respectively. When human plasma concentrations were modeled using traditionally determined input parameters and again using in silico estimated input parameters, the two sets of maximum plasma concentrations (r = 0.85, p < 0.01, n = 212) and areas under the curve (r = 0.80, p < 0.01, n = 212) were correlated. Virtual chemical exposure levels in liver and kidney were also estimated using these simplified PBPK models along with human plasma levels. These results indicate that the PBPK model input parameters for humans of a diverse set of compounds can be reliability estimated using chemical descriptors calculated using in silico tools.

Plasma Concentration Profiles for Hepatotoxic Pyrrolizidine Alkaloid Senkirkine in Humans Extrapolated from Rat Data Sets Using a Simplified Physiologically Based Pharmacokinetic Model.

AIM: The main aim of the current study was to obtain forward dosimetry assessments of pyrrolizidine alkaloid senkirkine plasma and liver concentrations by setting up a human physiologically based pharmacokinetic (PBPK) model based on the limited information available. BACKGROUND: The risks associated with plant-derived pyrrolizidine alkaloids as natural toxins have been assessed. OBJECTIVE: The pyrrolizidine alkaloid senkirkine was investigated because it was analyzed in a European transcriptomics study of natural hepatotoxins and in a study of the alkaloidal constituents of traditional Japanese food plants Petasites japonicus. The in silico human plasma and liver concentrations of senkirkine were modeled using doses reported for acute-term toxicity in humans. METHODS: Using a simplified PBPK model established using rat pharmacokinetic data, forward dosimetry was conducted. Since in vitro rat and human intrinsic hepatic clearances were similar; an allometric scaling approach was applied to rat parameters to create a human PBPK model. RESULTS: After oral administration of 1.0 mg/kg in rats in vivo, water-soluble senkirkine was absorbed and cleared from plasma to two orders of magnitude below the maximum concentration in 8 h. Human in silico senkirkine plasma concentration curves were generated after virtual daily oral administrations of 3.0 mg/kg senkirkine (the dose involved in an acute fatal hepatotoxicity case). A high concentration of senkirkine in the culture medium caused in vitro hepatotoxicity as evidenced by lactate dehydrogenase leakage from human hepatocyte-like HepaRG cells. CONCLUSION: Higher virtual concentrations of senkirkine in human liver and plasma than those in rat plasma were estimated using the current rat and human PBPK models. Current simulations suggest that if P. japonicus (a water-soluble pyrrolizidine alkaloid-producing plant) is ingested daily as food, hepatotoxic senkirkine could be continuously present in human plasma and liver.

Abnormal Urine Outflow from the Ureteral Orifice on Cystoscopy Following Vaginal Stump Suture in Total Laparoscopic Hysterectomy.

OBJECTIVES: Ureteral injuries may occur subsequent to abdominal or laparoscopic hysterectomy. In total laparoscopic hysterectomy (TLH), we usually check for ureteral damage by confirming urinary outflow from the bilateral ureteral orifices by cystoscopy after vaginal stump suture. In this work, we investigated the causes of urine outflow disruption after TLH. MATERIALS AND METHODS: We conducted a retrospective review of all TLHs performed for benign diseases at our hospital from February 2012 to March 2016. There were 11 cases with no or poor urine outflow from the ureteral orifice after vaginal stump suture. For these cases, we assessed the treatment to recover urine outflow and examined the cases with intraoperative manipulation. EZR version 1.25 was used for statistical analysis. Correlation coefficients were calculated with Spearman's rank correlation coefficient test. RESULTS: The abnormality was on the right and left sides in seven and four cases, respectively. In all cases, apart from one, urine outflow was recovered by removing the sutures at the affected side, where the initial suture had included a small amount of the connective tissue near the urinary bladder. It was inferred that ureteral deviation due to vaginal stump sutures that picked up the connective tissue near the ureter caused ureteral peristaltic disorder and abnormal ureteral orifice outflow. CONCLUSION: TLH without ureter isolation requires sufficient separation of the bladder from the anterior vaginal wall and careful vaginal stump suture without involving the bladder-side tissue to avoid ureteral injury.

Repeat epidural blood patch at the level of unintentional dural puncture and its neurologic complications: a case report.

BACKGROUND: Autologous epidural blood patch (AEBP) is effective for post-dural-puncture headache (PDPH). In some cases, repeat procedures are required for complete cure. In rare instances, severe adverse effects can occur. We present a case of neurologically complicated AEBPs, one of which was performed at the interspace of unintentional dural puncture (UDP). CASE PRESENTATION: A 40-year-old primigravida sustained UDP at the L2-3 interspace during combined spinal-epidural anesthesia for a scheduled cesarean section. She developed PDPH and underwent a single AEBP at L3-4. The PDPH recurred and she required another AEBP at L2-3, after which she reported radicular pains. A diagnosis of subdural hematoma and adhesive arachnoiditis was made. Her symptoms partially resolved in the following months. CONCLUSION: It may be prudent to reconsider the use of repeated AEBP and to avoid the interspace of UDP. A thorough evaluation is warranted to exclude treatable lesions when adverse effects occur.

Acute Abdomen due to Mutual Tangle of Two Small Paratubal Cysts.

A 30-year-old woman (gravida 0) visited our hospital with a complaint of right lower abdominal pain. Transvaginal ultrasonography revealed a 5-cm swollen right ovary, which was suspected to be a mature cystic teratoma. Pelvic examination revealed moderate pain. Contrast-enhanced computed tomography showed a 44-mm cystic mass containing fat and calcified material in the right pelvis. Since torsion was suspected, emergent laparoscopic surgery was performed. Intraoperative findings were a swollen right ovary without torsion or congestion. Two small pedunculated 1- and 2-cm diameter paratubal cysts that grew from almost the same place of the ampulla of the right fallopian tube were observed. The thin stalk of the 1-cm paratubal cyst was entangled around the stalk of the 2-cm paratubal cyst, with its head congested. Through a small abdominal laparoscopic incision, the tumor of the right ovary and the two paratubal cysts were excised. Histopathological examination revealed that the right ovarian tumor was a mature cystic teratoma, and the two paratubal cysts had no malignancy. This case showed that only a 2-cm tumor with congestion caused the acute abdomen.

Comparison of Sofosbuvir Plus Ribavirin Treatment with Pegylated Interferon Plus Ribavirin Treatment for Chronic Hepatitis C Genotype 2.

BACKGROUND: Sofosbuvir plus ribavirin (RBV) therapy showed higher sustained virological response at 12 weeks after treatment (SVR12) than pegylated interferon (peg-IFN) plus RBV; however, liver function, fibrosis, and hepatocellular carcinoma markers have not been assessed so far. SUMMARY: Patients (n = 21) receiving Sofosbuvir plus RBV and those (n = 24) receiving peg-IFN plus RBV were enrolled in this study. Changes in alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels, platelet (PLT) counts, FIB-4, and aspartate aminotransferase-to-platelet ratio index (APRI) in both groups were assessed in patients achieving SVR12. Also, fibrosis regression was assessed using pathophysiological biomarkers, such as hyaluronic acid, bone morphogenetic protein 7 (BMP-7), and connective tissue growth factor (CTGF) in the Sofosbuvir plus RBV group. In both groups, while the reduction in ALT levels was significant that of AFP was not. Compared with the baseline, although serum PLT count at the end of treatment (EOT) was significantly higher in the Sofosbuvir plus RBV group, it was significantly lower in the peg-IFN plus RBV group. Although a significant decline in fibrosis markers such as FIB-4 and APRI was observed between the baseline and at EOT in the Sofosbuvir plus RBV group, no significant change of these markers was observed in the peg-IFN plus RBV group. Moreover, BMP-7 and CTGF were significantly lower at EOT than the baseline in the Sofosbuvir plus RBV group. Key Message: The treatment with Sofosbuvir plus RBV results in not only a higher SVR, but also improves the liver function and the degree of fibrosis.

Design and Synthesis of Non-peptide RGD Mimics for Evaluation of Their Utility as Anti-platelet Agents.

Arg-Gly-Asp (RGD) mimics were synthesized and their anti-platelet activity was evaluated. A concise method was developed for the synthesis of the target compounds from dehydroepiandrosterone and Wieland-Miescher and Hajos-Parrish ketones, which are suitable for readily available platform. Among the synthesized compounds, the perhydronaphthalene framework with a 3-(4-piperidinyl)propoxyl structure 3e possessed the highest anti-aggregative activity. The IC50 values of 3e were 0.91 mM (ADP initiation) and 0.54 mM (collagen initiation).

Efficacy and Safety of Sofosbuvir Plus Ribavirin Treatment for Patients with Chronic Hepatitis C Genotype 2.

OBJECTIVES: The efficacy of sofosbuvir plus ribavirin (RBV) treatment for hepatitis C virus (HCV) genotype 2 focusing on virological response was compared with that of pegylated interferon (peg-IFN) plus RBV treatment. Safety of the former focusing on the decline in hemoglobin levels was compared with that of the latter and assessed in terms of age and inosine triphosphatase (ITPA). METHODS: Patients (n = 17) receiving sofosbuvir plus RBV and those (n = 24) receiving peg-IFN plus RBV diagnosed with chronic HCV genotype 2 were enrolled in this study, and the efficacy and safety of both treatments were assessed. RESULTS: Rapid virological response was attained with sofosbuvir plus RBV treatment compared with peg-IFN plus RBV treatment. All patients under sofosbuvir plus RBV treatment achieved end-of-treatment response compared with 70% who sustained viral response under the peg-IFN plus RBV treatment, with the former demonstrating greater virological response. The decline in hemoglobin levels under the former treatment was greater than that under the latter and in patients over 65 years of age with ITPA gene major. CONCLUSION: Efficacy and safety of sofosbuvir plus RBV treatment were clearly demonstrated compared with those of peg-IFN plus RBV treatment. The decline in hemoglobin levels was not related to the discontinuation of the former treatment, irrespective of age or the effect of the ITPA gene.