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Biofilms present a great challenge in antimicrobial therapy due to their inherent tolerance to conventional antibiotics, promoting the need for advanced drug delivery strategies that improve therapy. While various nanoparticles (NPs) have been reported for this purpose, DNA-based NPs remain a largely unexploited resource against biofilm-associated infections. To fill this gap and to lay the groundwork for their potential therapeutic exploitation, we investigated the diffusion, penetration, and retention behaviors of three DNA-based nanocarriers -plain or modified-within P. aeruginosa biofilms. Watson-Crick base pairing or hydrophobic interactions mediated the formation of the plain NPs whilst electrostatic interaction enabled optimization of coated NPs via microfluidic mixing. We assessed the interactions of the nanocarriers with biofilm structures via Single Plane Illumination Microscopy - Fluorescence Correlation Spectroscopy (SPIM-FCS) and Confocal Laser Scanning Microscopy (CLSM). We demonstrate the impact of microfluidic parameters on the physicochemical properties of the modified DNA NPs and their subsequent distinct behaviors in the biofilm. Our results show that single stranded DNA micelles (ssDNA micelle) and tetrahedral DNA nanostructures (TDN) had similar diffusion and penetration profiles, whereas chitosan-coated TDN (TDN-Chit) showed reduced diffusion and increased biofilm retention. This is attributable to the relatively larger size and positive surface charge of the TDN-Chit NPs. The study shows first and foremost that DNA can be used as building block in drug delivery for antibiofilm therapeutics. Moreover, the overall behavioral findings are pivotal for the strategic selection of therapeutic agents to be encapsulated within these structures, possibly affecting the treatment efficacy. This research not only highlights the underexplored potential of DNA-based NPs in antibiofilm therapy but also advocates for further studies using different optimization strategies to refine these nanocarrier systems for targeted treatments in biofilm-related infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

In spite of multipurpose technologies offering broad-spectrum prevention for sexually transmitted infections (STIs) and contraception, the STIs incidences rise worldwide. The situation is even more alarming considering continuous rise in antimicrobial resistance (AMR) that limits therapy options. In this review we address the specific challenges of efficiently treating vaginal infections locally, at the infection site, by understanding the underlying barriers to efficient treatment such as vaginal biofilms. Knowledge on vaginal biofilms remains, up to now, rather scarce and requires more attention. We therefore propose a 'back to basics' insight that seeks to probe the complexity and role of the vaginal microbiota, its relationship with vaginal biofilms and implications to future therapeutic modalities utilizing advanced nano delivery systems. Our key objective is to highlight the interplay between biofilm, (nano)formulation and therapy outcome rather than provide an overview of all nanoformulations that were challenged against biofilms. We focused on the anatomy of the female reproductive organ and its physiological changes from birth, the unique vaginal microenvironment in premenopausal and postmenopausal women, vaginal biofilm infections and current nanomedicine-based approaches to treat infections in the vaginal site. Finally, we offer our perspectives on the current challenges associated with vaginal delivery and key considerations that can aid in the design and development of safer and potent products against persisting vaginal infections., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Nucleic acid-based materials showcase an increasing potential for antimicrobial drug delivery. Although numerous reports on drug-loaded DNA nanoparticles outline their pivotal antibacterial activities, their potential as drug delivery systems against bacterial biofilms awaits further studies. Among different oligonucleotide structures, micellar nanocarriers derived from amphiphilic DNA strands are of particular interest due to their spontaneous self-assembly and high biocompatibility. However, their clinical use is hampered by structural instability upon cation depletion. In this work, we used a cationic amphiphilic antibiotic (polymyxin B) to stabilize DNA micelles destined to penetrate P. aeruginosa biofilms and exhibit antibacterial/antibiofilm properties. Our study highlights how the strong affinity of this antibiotic enhances the stability of the micelles and confirms that antibacterial activity of the novel micelles remains intact. Additionally, we show that PMB micelles can penetrate P. aeruginosa biofilms and impact their metabolic activity. Finally, PMB micelles were highly safe and biocompatible, highlighting their possible application against P. aeruginosa biofilm-colonized skin wounds.

Racial microaggressions, racially based remarks, or actions that negatively impact marginalized physicians of color (Black, Latino/a/x, and American Indian/Alaskan Natives) often go unaddressed. This article provides four strategies for how individuals and institutions can engage in anti-racism allyship: (1) be an upstander during microaggressions, (2) be a sponsor and advocate for physicians of color, (3) acknowledge academic titles and accomplishments, and (4) challenge the idea of a "standard fit" for academic faculty and research. Skills in academic allyship should be taught to all physicians throughout the educational continuum to mitigate feelings of isolation that racialized minority physicians frequently experience., Competing Interests: No competing financial interests exist., (© Cassandra D.L. Fritz et al., 2023; Published by Mary Ann Liebert, Inc.)

To avert the poor bioavailability of antibiotics during S. aureus biofilm infections, a series of zwitterionic nanoparticles containing nucleic acid nanostructures were fabricated for the delivery of vancomycin. The nanoparticles were prepared with three main lipids: (i) neutral (soy phosphatidylcholine; P), (ii) positively charged ionizable (1,2-dioleyloxy-3-dimethylaminopropane; D), and (iii) anionic (1,2-dipalmitoyl- sn -glycero-3-phospho((ethyl-1',2',3'-triazole) triethylene glycolmannose; M) or (cholesteryl hemisuccinate; C) lipids. The ratio of the anionic lipid was tuned between 0 and 10 mol %, and its impact on surface charge, size, stability, toxicity, and biofilm sensitivity was evaluated. Under biofilm mimicking conditions, the enzyme degradability (via dynamic light scattering (DLS)), antitoxin (via DLS and spectrophotometry), and antibiotic release profile was assessed. Additionally, biofilm penetration, prevention ( in vitro ), and eradication ( ex vivo ) of the vancomycin loaded formulation was investigated. Compared with the unmodified nanoparticles which exhibited the smallest size (188 nm), all three surface modified formulations showed significantly larger sizes (i.e., 222-277 nm). Under simulations of biofilm pH conditions, the mannose modified nanoparticle (PDM 90/5/5) displayed ideal charge reversal from a neutral (+1.69 ± 1.83 mV) to a cationic surface potential (+17.18 ± 2.16 mV) to improve bacteria binding and biofilm penetration. In the presence of relevant bacterial enzymes, the carrier rapidly released the DNA nanoparticles to function as an antitoxin against α-hemolysin. Controlled release of vancomycin prevented biofilm attachment and significantly reduced early stage biofilm formations within 24 h. Enhanced biocompatibility and significant ex vivo potency of the PDM 90/5/5 formulation was also observed. Taken together, these results emphasize the benefit of these nanocarriers as potential therapies against biofilm infections and fills the gap for multifunctional nanocarriers that prevent biofilm infections.

This review summarizes racial and ethnic disparities in the quality of cardiovascular care-a challenge given the fragmented nature of the health care delivery system and measurement. Health equity for all racial and ethnic groups will not be achieved without a substantially different approach to quality measurement and improvement. The authors adapt a tool frequently used in quality improvement work-the driver diagram-to chart likely areas for diagnosing root causes of disparities and developing and testing interventions. This approach prioritizes equity in quality improvement. The authors demonstrate how this approach can be used to create interventions that reduce systemic racism within the institutions and professions that deliver health care; attends more aggressively to social factors related to race and ethnicity that affect health outcomes; and examines how hospitals, health systems, and insurers can generate effective partnerships with the communities they serve to achieve equitable cardiovascular outcomes., Competing Interests: Funding Support and Author Disclosures Dr Schneider has received salary support from the Commonwealth Fund. Dr Chin was supported in part by the Robert Wood Johnson Foundation Advancing Health Equity: Leading Care, Payment, and Systems Transformation Program Office, the Merck Foundation Bridging the Gap: Reducing Disparities in Diabetes Care National Program Office, and the Chicago Center for Diabetes Translation Research (NIDDK P30 DK092949); and is a member of the Bristol Myers Squibb Company Health Equity Advisory Board and the Blue Cross Blue Shield Health Equity Advisory Panel. Dr Graham has received salary support from Google; and is a member of the National Heart, Lung, and Blood Institute Advisory Council. Dr Lopez has received salary support from the San Francisco VA Medical Center. Dr Obuobi has received salary support from University of Chicago Medicine. Dr Sequist was supported in part by a grant from the Agency for Healthcare Research and Quality R01HS023812; and was supported in part by a grant from the Agency for Healthcare Research and Quality R01HS023812. Dr McGlynn has received salary support from Kaiser Permanente., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Monitoring surgical wounds post-operatively is necessary to prevent infection, dehiscence and other complications. However, the monitoring of deep surgical sites is typically limited to indirect observations or to costly radiological investigations that often fail to detect complications before they become severe. Bioelectronic sensors could provide accurate and continuous monitoring from within the body, but the form factors of existing devices are not amenable to integration with sensitive wound tissues and to wireless data transmission. Here we show that multifilament surgical sutures functionalized with a conductive polymer and incorporating pledgets with capacitive sensors operated via radiofrequency identification can be used to monitor physicochemical states of deep surgical sites. We show in live pigs that the sutures can monitor wound integrity, gastric leakage and tissue micromotions, and in rodents that the healing outcomes are equivalent to those of medical-grade sutures. Battery-free wirelessly operated bioelectronic sutures may facilitate post-surgical monitoring in a wide range of interventions., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Electrocardiographic abnormalities, such as PR interval prolongation, have been anecdotally reported in patients with aortic root abscess (ARA). An electrocardiographic marker may be useful in identifying those patients with aortic valve endocarditis who may progress to ARA. The objective of this study is to evaluate the change in the PR interval in patients with surgically confirmed ARA and compare it to age- and gender-matched controls with echocardiographically or surgically confirmed aortic valve endocarditis but without aortic root abscess and those hospitalized with diagnoses other than endocarditis., Methods: Patients were eligible for enrollment if they were 18 years or older and were hospitalized for either ARA, aortic valve endocarditis, or for unrelated reasons and had at least one 12-lead electrocardiogram (ECG) prior to or on the day of hospitalization and at least one ECG after hospitalization but prior to any cardiac surgical procedure. Delta PR interval, defined as the difference between the pre- and post-admission PR interval, was the primary outcome of interest. The patients in the ARA group were age- and gender-matched to patients with aortic valve endocarditis and to those without endocarditis. Comparisons of demographic variables and study outcomes were performed., Results: Eighteen patients with surgically confirmed ARA were enrolled. These patients were age- and gender-matched to 19 patients with aortic valve endocarditis and 18 patients with no past history or evidence of endocarditis during hospitalization. No difference was noted in the baseline PR interval between the groups. However, the PR interval following admission in the aortic root abscess group (201 ± 66 ms) was significantly longer than the PR interval in both the aortic valve endocarditis (162 ± 27 ms) (24%, p = .009) and no endocarditis (143 ± 24 ms) (40%, p < .001) groups. The primary outcome measure, delta PR interval, was significantly longer in the ARA group (35 ± 51 ms) than no endocarditis (-5 ± 17 ms) (p = .001) and aortic valve endocarditis groups (0.2 ± 18) (p = .003)., Conclusions: The findings of our study support the notion that the PR interval is more likely to be prolonged in patients with ARA. Since ARA is associated with a high morbidity and mortality, PR interval prolongation in a patient with aortic valve endocarditis should prompt a thorough evaluation for aortic root involvement., (© 2021 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: The HOSPITAL Risk Score (HRS) predicts 30-day hospital readmissions and is internationally validated. Social determinants of health (SDOH) such as low socioeconomic status (SES) affect health outcomes and have been postulated to affect readmission rates. We hypothesized that adding SDOH to the HRS could improve its predictive accuracy., Methods: Records of 37,105 inpatient admissions at the University of Chicago Medical Center were reviewed. HRS was calculated for each patient. Census tract-level SDOH then were combined with the HRS and the performance of the resultant "Social HRS" was compared against the HRS. Patients then were assigned to 1 of 7 typologies defined by their SDOH and a balanced dataset of 14,235 admissions was sampled from the larger dataset to avoid over-representation by any 1 sociodemographic group. Principal component analysis and multivariable linear regression then were performed to determine the effect of SDOH on the HRS., Results: The c-statistic for the HRS predicting 30-day readmission was 0.74, consistent with published values. However, the addition of SDOH to the HRS did not improve the c-statistic (0.71). Patients with unfavorable SDOH (no high-school, limited English, crowded housing, disabilities, and age > 65 yrs) had significantly higher HRS (p < 0.05 for all). Overall, SDOH explained 0.2% of the HRS., Conclusion: At an urban tertiary care center, the addition of census tract-level SDOH to the HRS did not improve its predictive power. Rather, the effects of SDOH are already reflected in the HRS.

Cage-shaped nucleic acid nanocarriers are promising molecular scaffolds for the organization of polypeptides. However, there is an unmet need for facile loading strategies that truly emulate nature's host-guest systems to drive encapsulation of antimicrobial peptides (AMPs) without loss of biological activity. Herein, we develop DNA nanogels with rapid in situ loading of L12 peptide during the thermal annealing process. By leveraging the binding affinity of L12 to the polyanionic core, we successfully confine the AMPs within the DNA nanogel. We report that the thermostability of L12 in parallel with the high encapsulation efficiency, low toxicity and sustained drug release of the pre-loaded L12 nanogels can be translated into significant antimicrobial activity. Using an S. aureus model of infectious bacterial keratitis, we observe fast resolution of clinical symptoms and significant reduction of bacterial bioburden. Collectively, this study paves the way for the development of DNA nanocarriers for caging AMPs with immense significance to address the rise of resistance.

The persistence of Staphylococcus aureus has been accredited to its ability to escape immune response via host cell invasion. Despite the efficacy of many antibiotics against S. aureus, the high extracellular concentrations of conventional antibiotics required for bactericidal activity is limited by their low cellular accumulation and poor intracellular retention. While nanocarriers have received tremendous attention for antibiotic delivery against persistent pathogens, they suffer daunting challenges such as low drug loading, poor retention and untimely release of hydrophilic cargos. Here, a hybrid system (Van&#95;DNL) is fabricated wherein nucleic acid nanogels are caged within a liposomal vesicle for antibiotic delivery. The central principle of this approach relies on exploiting non-covalent electrostatic interactions between cationic cargos and polyanionic DNA to immobilize antibiotics and enable precise temporal release against intracellular S. aureus. In vitro characterization of Van&#95;DNL revealed a stable homogenous formulation with circular morphology and enhanced vancomycin loading efficiency. The hybrid system significantly sustained the release of vancomycin over 24 h compared to liposomal or nanogel controls. Under enzymatic conditions relevant to S. aureus infections, lipase triggered release of vancomycin was observed from the hybrid. While using Van&#95;DNL to treat S. aureus infected macrophages, a dose dependent reduction in intracellular bacterial load was observed over 24 h and exposure to Van&#95;DNL for 48 h caused negligible cellular toxicity. Pre-treatment of macrophages with the antimicrobial hybrid resulted in a strong anti-inflammatory activity in synergy with vancomycin following endotoxin stimulation. Conceptually, these findings highlight these hybrids as a unique and universal platform for synergistic antimicrobial and anti-inflammatory therapy against persistent infections., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Hydrogels as artificial biomaterial scaffolds offer a much favoured 3D microenvironment for tissue engineering and regenerative medicine (TERM). Towards biomimicry of the native ECM, polysaccharides from Nature have been proposed as ideal surrogates given their biocompatibility. In particular, derivatives from microbial sources have emerged as economical and sustainable biomaterials due to their fast and high yielding production procedures. Despite these merits, microbial polysaccharides do not interact biologically with human tissues, a critical limitation hampering their translation into paradigmatic scaffolds for in vitro 3D cell culture. To overcome this, chemical and biological functionalization of polysaccharide scaffolds have been explored extensively. This review outlines the most recent strategies in the preparation of biofunctionalized gellan gum, xanthan gum and dextran hydrogels fabricated exclusively via material blending. Using inorganic or organic materials, we discuss the impact of these approaches on cell adhesion, proliferation and viability of anchorage-dependent cells for various TERM applications.', (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The rapid emergence of drug resistance continues to outpace the development of new antibiotics in the treatment of infectious diseases. Conventional therapy is currently limited by drug access issues such as low intracellular drug accumulations, drug efflux by efflux pumps and/or enzymatic degradation. To improve access, targeted delivery using nanocarriers could provide the quantum leap in intracellular drug transport and retention. Silica nanoparticles (SiNPs) with crucial advantages such as large surface area, ease-of-functionalization, and biocompatibility, are one of the most commonly used nanoparticles in drug delivery applications. A porous variant, called the mesoporous silica nanoparticles (MSN), also confers additional amenities such as tunable pore size and volume, leading to high drug loading capacity. In the context of bacterial infections, SiNPs and its variants can act as a powerful tool for the targeted delivery of antimicrobials, potentially reducing the impact of high drug dosage and its side effects. In this review, we will provide an overview of SiNPs synthesis, its structural proficiency which is critical in loading and conjugation of antimicrobials and its role in different antimicrobial applications with emphasis on intracellular drug targeting in anti-tuberculosis therapy, nitric oxide delivery, and metal nanocomposites. The role of SiNPs in antibiofilm coatings will also be covered in the context of nosocomial infections and surgical implants., (Copyright © 2020 Selvarajan, Obuobi and Ee.)

Conventional antibiotic therapy is often challenged by poor drug penetration/accumulation at infection sites and poses a significant burden to public health. Effective strategies to enhance the therapeutic efficacy of our existing arsenal include the use of nanoparticulate delivery platforms to improve drug targeting and minimize adverse effects. However, these nanocarriers are often challenged by poor loading efficiency, rapid release and inefficient targeting. Nucleic acid hybrid nanocarriers are nucleic acid nanosystems complexed or functionalized with organic or inorganic materials. Despite their immense potential in antimicrobial therapy, they are seldom utilized against pathogenic bacteria. With the emergence of antimicrobial resistance and the associated complex interplay of factors involved in antibiotic resistance, nucleic acid hybrids represent a unique opportunity to deliver antimicrobials against resistant pathogens and to target specific genes that control virulence or resistance. This review provides an unbiased overview on fabricating strategies for nucleic acid hybrids and addresses the challenges of pristine oligonucleotide nanocarriers. We report recent applications to enhance pathogen targeting, binding and control drug release. As multifunctional next-generational antimicrobials, the challenges and prospect of these nanocarriers are included.

There is growing interest in the development of nucleic acid nanostructures as smart functional materials for applications in drug delivery. Inspired by the diverse physical interactions that exist in nature, crosslinked DNA nanostructures can serve as attractive affinity binding networks that interact with therapeutic cargos or living cells. Herein we report a strategy that addresses the challenges of topical oligopeptide therapy by exploiting high binding affinity between polyanionic DNA nanostructures and cationic antimicrobial peptides (AMPs) to fabricate hydrogels that release a model antimicrobial L12 peptide in response to pathogenic S. aureus infections. We further demonstrated controlled peptide release profiles via the DNA hydrogels that were biocompatible and delivered superior antimicrobial activity against nuclease-releasing susceptible and methicillin-resistant S. aureus infections. Single application of the L12-loaded DNA hydrogels on porcine explant S. aureus infections revealed potent efficacy after 24h. As a result of the capacity of the crosslinked DNA nanostructures to elicit a strong anti-inflammatory response, in vivo treatment of mice excision wounds translated into faster healing rates. Overall, the crosslinked DNA nanostructures reported in this study offer significant advantage as functional wound dressings and their future adaptation holds equally great promise for the delivery of cationic antimicrobials., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Protein-based polymeric polyelectrolytes are emerging as alternative synthetic nanoparticles owing to their biodegradability and biocompatibility. However, potential in vivo toxicity remains a significant challenge. Herein an array of protein polyelectrolytes generated from cationic human serum albumin (cHSA) and polyethylene glycol (PEG) are synthesized via synthetic customization as antimicrobials for the treatment of systemic infections. By varying PEG molecular weight and chain length, in vitro hemolytic activity can be fine-tuned without significantly affecting antimicrobial potency. The optimal hybrid material, PEG (2000) 18 -cHSA, with potent antimicrobial character, low hemolytic activity, and in vitro biofilm disruptive properties is identified. Surface plasmon resonance (SPR) evaluation demonstrates significantly higher binding activity of the protein nanoparticles to bacteria cell wall components and microfluidic live-cell imaging indicates that the nanoparticles act through a membranolytic mechanism. Given their low susceptibility to drug resistance and potent activity against resistant bacteria strains, these findings establish the PEGylated albumin nanoparticles as a potent weaponry against drug resistance and biofilm-related infection., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Pneumocephalus is a common finding following intracranial procedures, typically asymptomatic and resolves within several days. However, in some cases, pneumocephalus presents with headache, encephalopathy, or symptoms of elevated intracranial pressure. Here, we present a case of iatrogenic tension pneumocephalus following endoscopic sinus surgery, presenting as abnormal involuntary movements resembling a movement disorder with choreiform movements., Case Description: A 67-year-old previously healthy male presented with new onset chorea and dystonia associated with headache, encephalopathy, and postural instability 4 days after undergoing endoscopic sinus surgery for chronic sinusitis and nasal polyps. Computed tomography showed prominent intraventricular pneumocephalus causing enlargement of the anterior horns of both lateral ventricles with lateral displacement of the basal ganglia nuclei and a bony defect in the skull base. Neurosurgical correction of the cranial defect provided complete symptomatic resolution. Pneumocephalus as a result of an iatrogenic injury of the skull base manifesting as an acute movement disorder is a rare complication of a nasal sinus procedure. We speculate that compression of the caudate nucleus and striatum resulted in decreased pallidothalamic inhibition and thalamocortical disinhibition leading to the development of a hyperkinetic movement disorder., Conclusion: This unusual presentation of a common procedure illustrates a neurological emergency that requires prompt recognition and timely correction., Competing Interests: There are no conflicts of interest.

While physically crosslinked polycarbonate hydrogels are effective drug delivery platforms, their hydrophobic nature and lack of side chain functionality or affinity ligands for controlled release of hydrophilic drugs underscore the importance of their chemical compositions. This study evaluates an array of anionic hydrogel systems of phenylboronic acid functionalized triblock copolymers prepared via reversible physical interactions. Variation of key chemical functionalities while maintaining similar core structural features demonstrates the influence of the substitution position and protection of the boronic acid functionality on gel viscoelasticity and mechanical strength at physiological pH. The optimum gel systems obtained from the meta-substituted copolymers (m-PAP) are stable at physiological pH and nontoxic to mammalian dermal cells. The polymyxin B loaded m-PAP hydrogels demonstrate controlled in vitro drug release kinetics and in vitro antimicrobial activity against Pseudomonas aeruginosa over 48 h. In vivo antimicrobial efficacy of the drug loaded hydrogels further corroborates the in vitro results, demonstrating sustained antimicrobial activity against P. aeruginosa burn wound infections. The current strategy described in this study demonstrates a straightforward approach in designing physiologically relevant boronic acid hydrogel systems for controlled release of cationic antimicrobials for future clinical applications., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The escalating threat of antimicrobial resistance has increased pressure to develop novel therapeutic strategies to tackle drug-resistant infections. Antimicrobial peptides have emerged as a promising class of therapeutics for various systemic and topical clinical applications. In this study, the de novo design of α-helical peptides with idealized facial amphiphilicities, based on an understanding of the pertinent features of protein secondary structures, is presented. Synthetic amphiphiles composed of the backbone sequence (X 1 Y 1 Y 2 X 2 ) n , where X 1 and X 2 are hydrophobic residues (Leu or Ile or Trp), Y 1 and Y 2 are cationic residues (Lys), and n is the number repeat units (2 or 2.5 or 3), demonstrated potent broad-spectrum antimicrobial activities against clinical isolates of drug-susceptible and multi-drug resistant bacteria. Live-cell imaging revealed that the most selective peptide, (LKKL) 3 , promoted rapid permeabilization of bacterial membranes. Importantly, (LKKL) 3 not only suppressed biofilm growth, but effectively disrupted mature biofilms after only 2h of treatment. The peptides (LKKL) 3 and (WKKW) 3 suppressed the production of LPS-induced pro-inflammatory mediators to levels of unstimulated controls at low micromolar concentrations. Thus, the rational design strategies proposed herein can be implemented to develop potent, selective and multifunctional α-helical peptides to eradicate drug-resistant biofilm-associated infections., Statement of Significance: Antimicrobial peptides (AMPs) are increasingly explored as therapeutics for drug-resistant and biofilm-related infections to help expand the size and quality of the current antibiotic pipeline in the face of mounting antimicrobial resistance. Here, synthetic peptides rationally designed based upon principles governing the folding of natural α-helical AMPs, comprising the backbone sequence (X 1 Y 1 Y 2 X 2 ) n , and which assemble into α-helical structures with idealized facial amphiphilicity, is presented. These multifunctional peptide amphiphiles demonstrate high bacterial selectivity, promote the disruption of pre-formed drug-resistant biofilms, and effectively neutralize endotoxins at low micromolar concentrations. Overall, the design strategies presented here could provide a useful tool for developing therapeutic peptides with broad-ranging clinical applications from the treatment and prevention of drug-resistant biofilms to the neutralization of bacterial endotoxins., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Oxidative stress is a much-appreciated phenomenon associated with the progression of neurodegenerative diseases (NDDs) due to imbalances in redox homeostasis. The poor correlations between the in vitro benefits and clinical trials of direct radical scavengers have prompted research into indirect antioxidant enzymes such as Nrf2. Activation of Nrf2 leads to the upregulation of a myriad of cytoprotective and antioxidant enzymes/proteins. Traditionally, early Nrf2-activators were studied as chemoprotective agents. There is a consequential lack of clinical trials testing Nrf2 activation in NDDs. However, there is abundant evidence of their utility in pre-clinical studies. Herein, we review the endogenous Nrf2 regulatory pathway and avenues for targeting this pathway. Furthermore, we provide updated information on pre-clinical studies for natural and synthetic Nrf2 activators. On the basis of our findings, we posit that successful therapeutics for NDDs rely on the design of potent synthetic Nrf2 activators with a careful combination of other neuroprotective activities.