Radical‐medicated end‐group transformation of amphiphilic methacrylate random copolymers for modulation of antimicrobial and hemolytic activities

This work describes synthesis of antimicrobial methacrylate copolymers by reversible addition‐fragmentation chain transfer (RAFT) polymerization and examines the versatility of this approach for improving chemical optimization to create potent, non‐toxic antimicrobial polymers. Specifically, this study focuses on the radical‐mediated transformation of end group of antimicrobial peptide‐mimetic polymer. RAFT polymerization using 2‐cyano‐2‐yl‐dithiobenzoate provided a statistical methacrylate copolymer consisting of aminobutyl and ethyl groups in the side chains. The following radical‐mediated modification using free radical initiators successfully transformed the ω‐end group of parent copolymer from dithiobenzoate to a cyanoisobutyl or aminoethyl cyanopentanoate group without any significant changes to the polymer molecular weight. In general, the parent polymer and variants showed a broad spectrum of activity against a panel of bacteria, but low hemolytic activity against human red blood cells. The parent copolymer with the dithiobenzoate end‐group showed highest antimicrobial and hemolytic activities as compared with other copolymers. The copolymers caused membrane depolarization in Staphylococcus aureus, while the ability of copolymers for membrane disruption is not dependent on the end‐group structures. The synthetic route reported in this study will be useful for further study of the role of polymer end‐groups in the antimicrobial activity of copolymers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 304–312Cationic amphiphilic methacrylate copolymers with antimicrobial activity were prepared by RAFT polymerization. The radical‐mediated modification method transformed the ω‐end groups from the RAFT agent to different functional groups, which modulate their antibacterial and hemolytic activities. The radical‐medicated approach would be a viable option to optimize the structures of methacrylate copolymers for their antimicrobial activity and selectivity to bacteria through pinpoint end‐group transformation as well as to functionalize polymers for potential applications such as surface modifications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135523/1/pola28384.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135523/2/pola28384-sup-0001-suppinfo1.pd

Unexpected Enhancement of Antimicrobial Polymer Activity against Staphylococcus aureus in the Presence of Fetal Bovine Serum

Cationic and amphiphilic polymers are known to exert broad-spectrum antibacterial activity by a putative mechanism of membrane disruption. Typically, nonspecific binding to hydrophobic components of the complex biological milieu, such as globular proteins, is considered a deterrent to the successful application of such polymers. To evaluate the extent to which serum deactivates antibacterial polymethacrylates, we compared their minimum inhibitory concentrations in the presence and absence of fetal bovine serum. Surprisingly, we discovered that the addition of fetal bovine serum (FBS) to the assay media in fact enhances the antimicrobial activity of polymers against Gram-positive bacteria S. aureus, whereas the opposite is the case for Gram-negative E. coli. Here, we present these unexpected trends and develop a hypothesis to potentially explain this unusual phenomenon

Token Economy–Based Hospital Bed Allocation to Mitigate Information Asymmetry: Proof-of-Concept Study Through Simulation Implementation

[Background:] Hospital bed management is an important resource allocation task in hospital management, but currently, it is a challenging task. However, acquiring an optimal solution is also difficult because intraorganizational information asymmetry exists. Signaling, as defined in the fields of economics, can be used to mitigate this problem. [Objective:] We aimed to develop an assignment process that is based on a token economy as signaling intermediary. [Methods:] We implemented a game-like simulation, representing token economy–based bed assignments, in which 3 players act as ward managers of 3 inpatient wards (1 each). As a preliminary evaluation, we recruited 9 nurse managers to play and then participate in a survey about qualitative perceptions for current and proposed methods (7-point Likert scale). We also asked them about preferred rewards for collected tokens. In addition, we quantitatively recorded participant pricing behavior. [Results:] Participants scored the token economy–method positively in staff satisfaction (3.89 points vs 2.67 points) and patient safety (4.38 points vs 3.50 points) compared to the current method, but they scored the proposed method negatively for managerial rivalry, staff employee development, and benefit for patients. The majority of participants (7 out of 9) listed human resources as the preferred reward for tokens. There were slight associations between workload information and pricing. [Conclusions:] Survey results indicate that the proposed method can improve staff satisfaction and patient safety by increasing the decision-making autonomy of staff but may also increase managerial rivalry, as expected from existing criticism for decentralized decision-making. Participant behavior indicated that token-based pricing can act as a signaling intermediary. Given responses related to rewards, a token system that is designed to incorporate human resource allocation is a promising method. Based on aforementioned discussion, we concluded that a token economy–based bed allocation system has the potential to be an optimal method by mitigating information asymmetry

Branched Poly(ethylene imine)s as Anti‐algal and Anti‐cyanobacterial Agents with Selective Flocculation Behavior to Cyanobacteria over Algae

Poly(ethylene imine)s (PEIs) have been widely studied for biomedical applications, including antimicrobial agents against potential human pathogens. The interactions of branched PEIs (B‐PEIs) with environmentally relevant microorganisms whose uncontrolled growth in natural or engineered environments causes health, economic, and technical issues in many sectors of water management are studied. B‐PEIs are shown to be potent antimicrobials effective in controlling the growth of environmentally relevant algae and cyanobacteria with dual‐functionality and selectivity. Not only did they effectively inhibit growth of both algae and cyanobacteria, mostly without causing cell death (static activity), but they also selectively flocculated cyanobacteria over algae. Thus, unmodified B‐PEIs provide a cost‐effective and chemically facile framework for the further development of effective and selective antimicrobial agents useful for control of growth and separation of algae and cyanobacteria in natural or engineered environments.Poly(ethylene imine)s (B‐PEIs) are shown as effective antimicrobial agents against environmentally relevant microorganisms (algae CR – Chlamydomonas reinhardtii, cyanobacterium SE – Synechococcus elongatus). B‐PEIs have dual‐functionalities and can 1) inhibit growth of both algae and cyanobacteria and 2) selectively flocculate cyanobacteria over algae. These molecules provide a cost‐effective and chemically facile framework for the further development of selective anti‐algal and anti‐cyanobacterial agents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146449/1/mabi201800187_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146449/2/mabi201800187.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146449/3/mabi201800187-sup-0001-SupMat.pd

Recovery of physiological traits in saplings of invasive Bischofia tree compared with three species native to the Bonin Islands under successive drought and irrigation cycles

Partial leaf shedding induced by hydraulic failure under prolonged drought can prevent excess water consumption, resulting in delayed recovery of carbon productivity following rainfall. To understand the manner of water use of invasive species in oceanic island forests under a fluctuating water regime, leaf shedding, multiple physiological traits, and the progress of embolism in the stem xylem under repeated drought-irrigation cycles were examined in the potted saplings of an invasive species, Bischofia javanica Blume, and three endemic native species, Schima mertensiana (Sieb. Et Zucc, ) Koitz., Hibiscus glaber Matsum, and Distylium lepidotum Nakai, from the Bonin Islands, Japan. The progress of xylem embolism was observed by cryo-scanning electron microscopy. The samples exhibited different processes of water saving and drought tolerance based on the different combinations of partial leaf shedding involved in embolized conduits following repeated de-rehydration. Predawn leaf water potential largely decreased with each successive drought-irrigation cycle for all tree species, except for B. javanica. B. javanica shed leaves conspicuously under drought and showed responsive stomatal conductance to VPD, which contributed to recover leaf gas exchange in the remaining leaves, following a restored water supply. In contrast, native tree species did not completely recover photosynthetic rates during the repeated droughtirrigation cycles. H. glaber and D. lepidotum preserved water in vessels and adjusted leaf osmotic rates but did not actively shed leaves. S. mertensiana exhibited partial leaf shedding during the first cycle with an osmotic adjustment, but they showed less responsive stomatal conductance to VPD. Our data indicate that invasive B. javanica saplings can effectively use water supplied suddenly under drought conditions. We predict that fluctuating precipitation in the future may change tree distributions even in mesic or moist sites in the Bonin Islands

A Cationic Amphiphilic Random Copolymer with pH-Responsive Activity against Methicillin-Resistant Staphylococcus aureus.

In this report, we demonstrate the pH-dependent, in vitro antimicrobial activity of a cationic, amphiphilic random copolymer against clinical isolates of drug-resistant Staphylococcus aureus. The polymer was developed toward a long-term goal of potential utility in the treatment of skin infections. The proposed mechanism of action of the polymer is through selectively binding to bacterial membranes and subsequent disruption of the membrane structure/integrity, ultimately resulting in bacterial cell death. The polymer showed bactericidal activity against clinical isolates of methicillin-resistant or vancomycin-intermediate S. aureus. The polymer was effective in killing S. aureus at neutral pH, but inactive under acidic conditions (pH 5.5). The polymer did not exhibit any significant hemolytic activity against human red blood cells or display cytotoxicity to human dermal fibroblasts over a range of pH values (5.5-7.4). These results indicate that the polymer activity was selective against bacteria over human cells. Using this polymer, we propose a new potential strategy for treatment of skin infections using the pH-sensitive antimicrobial polymer agent that would selectively target infections at pH-neutral wound sites, but not the acidic, healthy skin

Ultrasonic shears assistance can shorten the console time in robotic gastrectomy for early gastric cancer

markdownabstract__Abstract__ Why do legal arrangements for the institutions of government (legislative, executive, judicial branches) in Western liberal democracies develop faster, or in a different way, in one jurisdiction in comparison to another? In this article, it is argued that constitutional theory can help us understand the development of these legal institutional arrangements, for example in light of of the changing role of national highest courts in the the globalised legal context. For this purpose, the concept of constitutional (in-)flexibility is introduced, which can explain how national constitutional frameworks enable or constrain the integration of normative changes in national legal systems. Four elements encompassed by this concept are identified: the detail of constitutional norms, the modalities for revising the national Constitution, the approach to legal argumentation taken by interpreters of the Constitution, and the influence attributed to international law within the national legal system. This analytical framework is applied to the illustrative case of judicial globalisation - concerning, inter alia, the judicial use of non-binding foreign law - to explain similarities and differences concerning the way in which changes affecting the functioning of national highest courts are integrated within different legal systems. This analysis, in turn, yields some insight into the further development of constitutional theory in the era of globalisation

Natural History of Exophytic Type Gastrointestinal Stromal Tumor: A Case Report

Gastrointestinal stromal tumor (GIST) is the most common submucosal tumor of the stomach. GISTs are often detected by esophagogastroduodenal endoscopy. We have previously reported on endoscopically invisible medium-sized exophytic type GISTs. We present here a case of small exophytic GIST detected by transabdominal ultrasonography (TUS) in which the natural history of the tumor could be traced retrospectively through incidental findings obtained during follow-up for intraductal papillary mucinous neoplasm by magnetic resonance of imaging or computed tomography over about 10 years. The tumor appeared 7 years before its detection, and the doubling time was calculated as 6.9 years. In conclusion, low-risk exophytic GIST was estimated to have taken at least about 7 years to reach a size detectable by TUS