Polyglycerol-Shelled Reduction-Sensitive Polymersome for DM1 Delivery to HER-2-Positive Breast Cancer

Supramolecular delivery systems with the prolonged circulation, the potential for diverse functionalization, and few toxin-related limitations have been extensively studied. For the present study, we constructed a linear polyglycerol-shelled polymersome attached with the anti-HER-2-antibody trastuzumab. We then covalently loaded the anticancer drug DM1 in the polymersome via dynamic disulfide bonding. The resulted trastuzumab-polymersome-DM1 (Tra-PS-DM1) exhibits a mean size of 95.3 nm and remarkable drug loading efficiency % of 99.3%. In addition to its superior stability, we observed the rapid release of DM1 in a controlled manner under reductive conditions. Compared to the native polymersomes, Tra-PS-DM1 has shown greatly improved cellular uptake and significantly reduced IC50 up to 17-fold among HER-2-positive cancer cells. Moreover, Tra-PS-DM1 demonstrated superb growth inhibition of HER-2-positive tumoroids; specifically, BT474 tumoroids shrunk up to 62% after 12 h treatment. With exceptional stability and targetability, the PG-shelled Tra-PS-DM1 appears as an attractive approach for HER-2-positive tumor treatment

Endoscopic Ultrasound-Guided Biliary Drainage Using a Fully Covered Metallic Stent after Failed Endoscopic Retrograde Cholangiopancreatography

Background and Study Aims. Endoscopic ultrasound- (EUS-) guided biliary drainage (EUS-BD) is an alternative treatment for biliary obstruction after failed endoscopic retrograde cholangiopancreatography (ERCP). In this study, we present the outcomes of inpatients with obstructive jaundice treated with EUS-BD using a fully covered metallic stent after failed ERCP. Patients and Methods. A total of 21 patients with biliary obstruction due to malignant tumors and prior unsuccessful ERCP underwent EUS via an intra- or extrahepatic approach with fully covered metallic stent between March 2014 and October 2015. A single endoscopist performed all procedures. Results. Seven patients underwent hepatogastrostomy (HGS) and 14 underwent choledochoduodenostomy (CDS). The technical and clinical success rates were both 100%. There was no difference in efficacy between HGS and CDS. Adverse events occurred in three patients, including two in the HGS group (1 bile leakage and 1 sepsis) and one in the CDS group (sepsis). Four patients died as a result of their primary tumors during a median follow-up period of 13 months (range: 3–21 months). No patient presented with stent migration. Conclusion. EUS-BD using a fully covered metallic stent appears to be a safe and effective method for the treatment of obstructive jaundice

EUS assisted transmural cholecystogastrostomy fistula creation as a bridge for endoscopic internal gallbladder therapy using a novel fully covered metal stent

BACKGROUND: Laparoscopic cholecystectomy (LC) has become the “gold standard” for treating symptomatic gallstones. Innovative methods, such as a scarless therapeutic procedure through a natural orifice are being introduced, and include transgastric or transcolonic endoscopic cholecystectomy. However, before clinical implementation, instruments still need modification, and a more convenient treatment is still needed. The aim of this study was to evaluate the feasibility of endoscopic internal gallbladder therapy such as cholecystolithotomy in an animal survival model. METHODS: Four pigs underwent endoscopic-ultrasound (EUS)-guided cholecystogastrostomy and the placement of a novel covered mental stent. Four weeks later the stents were removed and an endoscope was advanced into the gallbladder via the fistula, and cholecystolithotomy was performed. Two weeks later the pigs were sacrificed, and the healing of the fistulas was assessed. RESULTS: EUS-guided cholecystogastrostomy with mental stent deployment was successfully performed in all the animals. Four weeks after the procedure, the fistulas had formed and all the stents were removed. Endoscopic cholecystolithotomy was performed through each fistula. All the animals survived until they were sacrificed 2 weeks later. The fistulas were found to be completely healed. CONCLUSIONS: This study reports the first endoscopic transmural cholecystolithotomy after placement of a novel mental stent in an animal survival model

Analisis Strategi Penerapan Sistem Manajemen Keamanan Pangan HACCP (Hazard Analysis and Critical Control Points) Di PT. Sierad Produce Tbk. Parung

Quality and safety food products problem was usually after thought in the food industry development issues, accordance with the consumer\u27s desirability that understand the importance of product quality and food safety. Hazard Analysis and Critical Control Points (HACCP) certification is one way for company to implementing food safety. Sierad Produce Corp. at this moment has obtained HACCP certificate to produce chicken carcasses.But the implementation need to be controlled, as the case of foodborne illness and foodborne disease can occur easily if not properly controlled. The main objective of this research is to develop the best strategy to implement HACCP and to maintain the food safety quality system at Sierad Produce Corp. The information and data that has been collected within this research were covering both the primary and secondary data based on the date of September 2012 to December 2012. The methods used in this research are descriptive analysis, Internal Factor Evaluation (IFE), External Factor Evaluation (EFE), Internal External (IE), Strength Weakness Opportunity Threat (SWOT) and Analysis Hierarchy Process (AHP). Based on this research, the best strategy for implementing HACCP and sustain the system on Sierad Produce are Critical Control Points (CCP) evaluation and improvement of production room

Interferon Induction by RNA Viruses and Antagonism by Viral Pathogens

Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR). Host PRR for RNA viruses include Toll-like receptors (TLR) and retinoic acid-inducible gene I (RIG-I) like receptors (RLR). Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses

Evaluation of A Better Approach for Open Reduction Of Severe Gartland Type III Supracondylar Humeral Fracture

Background An optimal surgical approach is required to treat Gartland type III supracondylar humerus fractures (SHFs) in children when open reduction is inevitable, especially in patients with neurovascular injuries. The purposes of this study were to find a better approach for open reduction of Gartland type III SHFs and to achieve anatomic reduction, stable fixation, and good functional and cosmetic outcomes with this approach. Methods: This retrospective study was performed in our hospital between January 2008 and June 2014. After the exclusion criteria were applied, 91 children were treated with the mini-anterior approach for severe Gartland type III SHFs. A 2–3-cm long anterior incision was made radially along the anterior transverse groove of the elbow, through which the nerve and vessel were probed, if necessary, and fracture reduction and Kirschner (K)-wire insertion were performed. Radiological evaluation included the Baumann angle and carrying angle. The functional and cosmetic evaluation was based on range-of-motion measurements and the criteria defined by Flynn. Chi-square and independent t tests were used for the statistical analyses. Results: Thirty-two patients were impossible to reduce, 1 patient had brachial artery injury, 37 patients had a sign with compartmental syndrome, 6 patients had open fractures, and 15 patients had multiple trauma. The interval between injury and hospitalization was 1 hour to 12 days. Overall, 91 patients were followed for 12 months to 4 years (average, 26.5 months). All incisions were healed by primary intervention. The fracture healing time was 3–5 weeks (average, 3.8 weeks). Elbow function recovered after 3 months, without obvious cubitus varus. Postoperative radial nerve paralysis occurred in 2 patients and healed within 2 months. Postoperative ulnar nerve paralysis occurred in 2 patients, and one of the K-wires was removed after 1 day. Nerve injuries were relieved within 3 months for both patients. The outcomes, according to the Flynn criteria, were excellent in 73 patients, good in 12 patients, and fair in 6 patients. The rate of excellent and good outcomes was 93.41%. Conclusions: The advantages of the mini-anterior approach include minimal trauma, simple and rapid exposure, easy tissue repair, and possibility of probing and repairing nerves, vessels, and muscles. It is an optimal surgical approach for the treatment of Gartland type III SHFs when open reduction is inevitable, especially in patients with neurovascular injuries