Tailor‐Made Antimicrobial/Antiviral Star Polymer via ATRP of Cyclodextrin and Guanidine‐Based Macromonomer

Novel star‐like polymers are prepared via atom transfer radical polymerization (ATRP) of polyhexamethylene guanidine hydrochloride (PHMG) macromonomer and acrylamide (AM) using β‐cyclodextrin (CD) with 8‐active and 5‐active sites as a macroinitiator. The resulting star‐like polymers are characterized by gel permeation chromatography (GPC) and ¹H NMR and are used for deactivating bacteria and viruses. It is found that star polymers with comparable amounts of PHMG possess excellent antimicrobial activity, which, however, strongly depends on the topological structure (i.e., the arm number and the monomer ratio) of the composing copolymers. The in vitro antibacterial activities of the synthesized polymers are investigated against Escherichia coli in terms of the minimum inhibitory concentration (MIC), whereas the antiviral activity of star copolymers is assessed via a plaque assay against non‐enveloped adenovirus (ADV). The results show that the highest antimicrobial activity is achieved by the star‐like copolymer with the monomer ratio of 20:3 (AM:PHGM, mol/mol), while the number of functional arms is fixed at 8. The incorporation of PHMG also renders the star copolymer highly antiviral, thus permitting it to be used as an effective antibacterial/antiviral agent for various applications.

     

Membrane adaptation limitations in Enterococcus faecalis underlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes

The growing problem of antibiotic resistant bacteria, along with a dearth of new antibiotics, has redirected attention to the search for alternative antimicrobial agents. Conjugated oligoelectrolytes (COEs) are an emerging class of antimicrobial agents which insert into bacterial cell membranes and are inhibitory against a range of Gram-positive and Gram-negative bacteria. In this study, the extent of COE resistance that Enterococcus faecalis could achieve was studied. Enterococci are able to grow in hostile environments and develop resistance to membrane targeting antibiotics such as daptomycin in clinical settings. Herein we expand our knowledge of the antimicrobial mechanism of action of COEs by developing COE-resistant strains of E. faecalis OG1RF. Evolution studies yielded strains with a moderate 4–16 fold increase in antimicrobial resistance relative to the wild type. The resistant isolates accumulated agent-specific mutations associated with the liaFSR operon, which is a cell envelope-associated stress-response sensing and regulating system. The COE resistant isolates displayed significantly altered membrane fatty acid composition. Subsequent, exogenous supplementation with single fatty acids, which were chosen based on those dominating the fatty acid profiles of the mutants, increased resistance of the wild-type E. faecalis to COEs. In combination, genetic, fatty acid, and uptake studies support the hypothesis that COEs function through insertion into and disruption of membranes and that the mechanism by which this occurs is specific to the disrupting agent. These results were validated by a series of biophysical experiments showing the tendency of COEs to accumulate in and perturb adapted membrane extracts. Collectively, the data support that COEs are promising antimicrobial agents for targeting E. faecalis, and that there is a high barrier to the emergence of severely resistant strains constrained by biological limits of membrane remodeling that can occur in E. faecalis.

COEs are emerging antimicrobials to combat drug resistant infections and to which bacteria develop only limited resistance.     

Effects of high intensity interval training on exercise capacity in people with cystic fibrosis: study protocol for a randomised controlled trial

Background

In people with cystic fibrosis (CF), higher exercise capacity is associated with better health-related quality of life (HRQoL), reduced risk of hospitalisation for a respiratory infection and survival. Therefore, optimisation of exercise capacity is an important treatment goal. The Australian and New Zealand clinical practice guidelines recommend that people with CF complete 30 to 60 min of moderate intensity aerobic exercise on most days of the week. This recommendation can be difficult to achieve by people with CF because of time constraints, and intolerable breathlessness and muscle fatigue during continuous exercise. In contrast, a low-volume, high intensity interval training (HIIT) program may be a more achievable and efficient training method to improve exercise capacity in people with CF.

Methods

A randomised controlled trial will be undertaken. Forty people with CF (aged ≥15 years) will be randomly allocated, on a 1:1 ratio, to either the experimental or control group. Regardless of their group allocation, all participants will be asked to continue with their usual daily treatment for the study duration. Those in the experimental group will complete 8 weeks of thrice weekly HIIT on a cycle ergometer. Those in the control group will receive weekly contact with the investigators. The primary outcome of this study is exercise capacity. Secondary outcomes are HRQoL, exercise self-efficacy, feelings of anxiety, depression and enjoyment. These outcomes will be recorded at baseline (i.e. prior to randomisation) and following the 8-week intervention period. The study will also report other outcomes of the HIIT program (cardiovascular responses, symptom response, post-exercise muscle soreness and tolerance) and behaviour change techniques such as reinforcement, feedback and goal setting, used during the HIIT program.

Discussion

This study will determine the effects of 8-weeks of supervised, low-volume HIIT, completed on a cycle ergometer on measures of exercise capacity, HRQoL, exercise self-efficacy, feelings of anxiety, depression and enjoyment. If effective, this type of training could be an attractive alternative to traditional continuous training because it may be more achievable and time efficient.

Trial registration

Australian and New Zealand Clinical Trials Registry (ANZCTR):12617001271392 (04/09/2017).

     

Loose Cigarette Purchasing and Nondaily Smoking Among Young Adult Bar Patrons in New York City

Objectives. We examined loose cigarette (loosie) purchasing behavior among young adult (aged 18–26 years) smokers at bars in New York City and factors associated with purchase and use.Methods. Between June and December 2013, we conducted cross-sectional surveys (n = 1916) in randomly selected bars and nightclubs. Using multivariable logistic regression models, we examined associations of loose cigarette purchasing and use with smoking frequency, price, social norms, cessation behaviors, and demographics.Results. Forty-five percent (n = 621) of nondaily smokers and 57% (n = 133) of daily smokers had ever purchased a loosie; 15% of nondaily smokers and 4% of daily smokers reported that their last cigarette was a loosie. Nondaily smokers who never smoked daily were more likely than were daily smokers to have last smoked a loosie (odds ratio = 7.27; 95% confidence interval = 2.35, 22.48). Quitting behaviors and perceived approval of smoking were associated with ever purchasing and recently smoking loosies.Conclusions. Loosie purchase and use is common among young adults, especially nondaily smokers. Smoking patterns and attitudes should be considered to reduce loose cigarette purchasing among young adults in New York City.Widespread adoption of clean indoor air laws and cigarette tax increases denormalize smoking behavior1 and decrease smoking rates.2,3 Although increasing taxes is one of the most effective means of smoking prevention and reduction,3 the increased price of cigarettes can also lead to tax-avoidant behaviors, such as buying untaxed packs smuggled from states with lower cigarette taxes and purchasing loose cigarettes, or “loosies.”4–6 In New York City (NYC), where a cigarette pack costs about $11.50, it has become common for smokers to purchase discounted packs and individual cigarettes from street peddlers and friends.7,8Much of the research exploring loosie purchasing in the United States has focused on underage or low-income minority populations, often in urban areas.7,9,10 One study found that in early 1993, 70% of stores in central Harlem sold loosies to minors.7 Another study conducted with a 2005–2006 convenience sample in inner-city Baltimore found that 77% of African American smokers aged 18 to 24 years had purchased loosies in the past month.11 Similarly, loosie purchasing in Mexico was more common among younger smokers with lower incomes.12Availability and visibility of loosies can promote smoking and encourage relapse.13 We defined nondaily smokers as those who smoked on 1 to 29 of the past 30 days.14,15 Shiffman et al. found that nondaily smokers were more likely than daily smokers to report that social and environmental stimuli motivated their smoking behavior.16 More specifically, cues such as taste, smell, social goading to smoke, and specific situations (e.g., smoking after meals) are more likely to be reported as motivators to smoke by nondaily smokers than by daily smokers.16 Because social–environmental cues have substantial impact on nondaily smokers’ motivation to smoke, it is likely that the cue of seeing loosies in one’s environment also motivates nondaily smokers to smoke.16Previous research substantiates this claim, with 1 study showing that people who regularly saw loosies available for purchase were more likely to be current smokers.17 Therefore, the widespread availability of loosies may have a greater impact on nondaily smokers. Nondaily smokers make up a third of US smokers,18,19 and nondaily smoking is increasingly common among young adults.20 Many young adults who smoke on only some days do not self-identify as smokers,21 and nondaily smoking is frequently paired with alcohol consumption.22–24 Nondaily and light smoking carry a lower, but substantial, risk for lung cancer and a similar risk as does daily smoking for cardiovascular disease.25–27 Occasional smokers also have higher smoking-related morbidity and mortality than do people who have never smoked.26,28–30Nondaily smoking can be a long-term behavior pattern31,32 or a transition to or from daily smoking.31 Nondaily smokers include different subgroups that may have very different smoking patterns or motivations to quit.33,34 Nondaily smokers who previously smoked daily have been defined in previous research as converted nondaily smokers. Nondaily smokers who have never smoked daily are defined as native nondaily smokers.18,19 Important differences exist between these subgroups of smokers: converted nondaily smokers are more likely to quit smoking than are native nondaily smokers and daily smokers,18,19 although most converted and native nondaily smokers were unable to remain abstinent for more than 90 days.19Loosie purchasing and use may play an important role in promoting continued tobacco use among nondaily smokers. The 2010 NYC Community Health Survey35 found that more than one third (34%) of young adult nondaily smokers (aged 18–26 years) reported that their last cigarette smoked was a loosie, compared with 14% of young adult daily smokers. Another study of NYC adults demonstrated that nondaily smokers were more likely to purchase loose cigarettes than were light and heavy smokers.36 To the best of our knowledge, little is known about the factors associated with loosie purchasing among nondaily smokers in the United States.We sought to better understand the factors associated with loosie purchasing among NYC young adults, specifically to determine (1) loosie purchase and use rates among converted nondaily, native nondaily, and daily smokers; (2) whether loosie purchase or use are associated with perceived social norms of smoking behavior; and (3) whether loosie purchasing is associated with smoking cessation intention or behavior.     

Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center

Objective

To determine adverse event rates for adult cranial neuro-oncologic surgeries performed at a high-volume quaternary academic center and assess the impact of resident participation on perioperative complication rates.

An Impaled Potential Unexploded Device in the Civilian Trauma Setting: A Case Report and Review of the Literature

Background

The management of patients with impaled unexploded devices is rare in the civilian setting. However, as the lines of the traditional battlefield are blurred by modern warfare and terrorist activity, emergency providers should be familiar with facility protocols, plans, and contact information of their local resources for unexploded devices.