Interventions Designed to Increase the Uptake of Lung Cancer Screening: An Equity-Oriented Scoping Review.

Introduction: Participation in lung cancer screening (LCS) is lower in populations with the highest burden of lung cancer risk (through the social patterning of smoking behavior) and lowest levels of health care utilization (through structurally inaccessible care) leading to a widening of health inequities. Methods: We conducted a scoping review using the Arksey and O'Malley methodological framework to inform equitable access to LCS by illuminating knowledge and implementation gaps in interventions designed to increase the uptake of LCS. We comprehensively searched for LCS interventions (Ovid Medline, Excerpta Medica database, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and Scopus from 2000 to June 22, 2021) and included peer-reviewed articles and gray literature published in the English language that describe an intervention designed to increase the uptake of LCS, charted data using our previously published tool and conduced a health equity analysis to determine the intended-unintended and positive-negative outcomes of the interventions for populations experiencing the greatest inequities. Results: Our search yielded 3572 peer-reviewed articles and 54,292 pieces of gray literature. Ultimately, we included 35 peer-reviewed articles and one gray literature. The interventions occurred in the United States, United Kingdom, Japan, and Italy, focusing on shared decision-making, the use of electronic health records as reminders, patient navigation, community-based campaigns, and mobile computed tomography scanners. We developed an equity-oriented LCS framework and mapped the dimensions and outcomes of the interventions on access to LCS on the basis of approachability, acceptability, availability, affordability, and appropriateness of the intervention. No intervention was mapped across all five dimensions. Most notably, knowledge and implementation gaps were identified in dimensions of acceptability, availability, and affordability. Conclusions: Interventions that were most effective in improving access to LCS targeted priority populations, raised community-level awareness, tailored materials for sociocultural acceptability, did not depend on prior patient engagement/registration with the health care system, proactively considered costs related to participation, and enhanced utilization through informed decision-making.

Encapsulation of SAAP-148 in Octenyl Succinic Anhydride-Modified Hyaluronic Acid Nanogels for Treatment of Skin Wound Infections.

Chronic wound infections colonized by bacteria are becoming more difficult to treat with current antibiotics due to the development of antimicrobial resistance (AMR) as well as biofilm and persister cell formation. Synthetic antibacterial and antibiofilm peptide (SAAP)-148 is an excellent alternative for treatment of such infections but suffers from limitations related to its cationic peptidic nature and thus instability and possible cytotoxicity, resulting in a narrow therapeutic window. Here, we evaluated SAAP-148 encapsulation in nanogels composed of octenyl succinic anhydride (OSA)-modified hyaluronic acid (HA) to circumvent these limitations. SAAP-148 was efficiently (>98%) encapsulated with high drug loading (23%), resulting in monodispersed anionic OSA-HA nanogels with sizes ranging 204-253 nm. Nanogel lyophilization in presence of polyvinyl alcohol maintained their sizes and morphology. SAAP-148 was sustainedly released from lyophilized nanogels (37-41% in 72 h) upon reconstitution. Lyophilized SAAP-148-loaded nanogels showed similar antimicrobial activity as SAAP-148 against planktonic and biofilm-residing AMR Staphylococcus aureus and Acinetobacter baumannii. Importantly, formulated SAAP-148 showed reduced cytotoxicity against human erythrocytes, primary human skin fibroblasts and human keratinocytes. Additionally, lyophilized SAAP-148-loaded nanogels eradicated AMR S. aureus and A. baumannii colonizing a 3D human epidermal model, without inducing any cytotoxicity in contrast to SAAP-148. These findings indicate that OSA-HA nanogels increase SAAP-148's therapeutic potential for treatment of skin wound infections.

Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148.

Synthetic antimicrobial and antibiofilm peptide (SAAP-148) commits significant antimicrobial activities against antimicrobial resistant (AMR) planktonic bacteria and biofilms. However, SAAP-148 is limited by its low selectivity index, i.e., ratio between cytotoxicity and antimicrobial activity, as well as its bioavailability at infection sites. We hypothesized that formulation of SAAP-148 in PLGA nanoparticles (SAAP-148 NPs) improves the selectivity index due to the sustained local release of the peptide. The aim of this study was to investigate the physical and functional characteristics of SAAP-148 NPs and to compare the selectivity index of the formulated peptide with that of the peptide in solution. SAAP-148 NPs displayed favorable physiochemical properties [size = 94.1 ± 23 nm, polydispersity index (PDI) = 0.08 ± 0.1, surface charge = 1.65 ± 0.1 mV, and encapsulation efficiency (EE) = 86.7 ± 0.3%] and sustained release of peptide for up to 21 days in PBS at 37 °C. The antibacterial and cytotoxicity studies showed that the selectivity index for SAAP-148 NPs was drastically increased, by 10-fold, regarding AMR Staphylococcus aureus and 20-fold regarding AMR Acinetobacter baumannii after 4 h. Interestingly, the antibiofilm activity of SAAP-148 NPs against AMR S. aureus and A. baumannii gradually increased overtime, suggesting a dose-effect relationship based on the peptide's in vitro release profile. Using 3D human skin equivalents (HSEs), dual drug SAAP-148 NPs and the novel antibiotic halicin NPs provided a stronger antibacterial response against planktonic and cell-associated bacteria than SAAP-148 NPs but not halicin NPs after 24 h. Confocal laser scanning microscopy revealed the presence of SAAP-148 NPs on the top layers of the skin models in close proximity to AMR S. aureus at 24 h. Overall, SAAP-148 NPs present a promising yet challenging approach for further development as treatment against bacterial infections.

South Asian youth mental health in Peel Region, Canada: Service provider perspectives.

The Peel Region of Toronto, Canada is home to over a third of the province's South Asian population. Youth are at a vulnerable time period in terms of their mental health. South Asian youth populations may face additional challenges to their mental health such as acculturative stress, intergenerational conflict, and racism and discrimination. This qualitative study set out to understand the mental health concerns and service access barriers experienced by South Asian youth populations in the Peel Region of Toronto, Canada from the perspective of mental health service providers. In-depth semi-structured interviews were carried out with mental health service providers (n = 22) who work with South Asian youth living in Peel Region. Thematic analysis was used to elucidate themes related to mental health stressors and service access barriers experienced by youth. According to mental health service providers, South Asian youth navigate a number of unique stressors related to the domains of culture, religion, and family dynamics, experiences of discrimination, the impact of migration, beliefs around mental illness and help-seeking, help-seeking trajectories and therapy recommendations, and lastly, sex differences. Mental health service providers outlined steps needed to effectively address the unique mental health challenges, best practice guidelines, and recommendations for working with South Asian youth, families, and communities to provide a practical and nuanced overview on how a multi-level strategy for mental health care can effectively meet the needs of South Asian youth populations.

Current Advances in Lipid and Polymeric Antimicrobial Peptide Delivery Systems and Coatings for the Prevention and Treatment of Bacterial Infections.

Bacterial infections constitute a threat to public health as antibiotics are becoming less effective due to the emergence of antimicrobial resistant strains and biofilm and persister formation. Antimicrobial peptides (AMPs) are considered excellent alternatives to antibiotics; however, they suffer from limitations related to their peptidic nature and possible toxicity. The present review critically evaluates the chemical characteristics and antibacterial effects of lipid and polymeric AMP delivery systems and coatings that offer the promise of enhancing the efficacy of AMPs, reducing their limitations and prolonging their half-life. Unfortunately, the antibacterial activities of these systems and coatings have mainly been evaluated in vitro against planktonic bacteria in less biologically relevant conditions, with only some studies focusing on the antibiofilm activities of the formulated AMPs and on the antibacterial effects in animal models. Further improvements of lipid and polymeric AMP delivery systems and coatings may involve the functionalization of these systems to better target the infections and an analysis of the antibacterial activities in biologically relevant environments. Based on the available data we proposed which polymeric AMP delivery system or coatings could be profitable for the treatment of the different hard-to-treat infections, such as bloodstream infections and catheter- or implant-related infections.

Interventions designed to increase the uptake of lung cancer screening and implications for priority populations: a scoping review protocol.

BACKGROUND: When designing any health intervention, it is important to respond to the unequal determinants of health by prioritising the allocation of resources and tailoring interventions based on the disproportionate burden of illness. This approach, called the targeting of priority populations, can prevent a widening of health inequities, particularly those inequities which can be further widened by differences in the uptake of an intervention. The objective of this scoping review is to describe intervention(s) designed to increase the uptake of lung cancer screening, including the health impact on priority populations and to describe knowledge and implementation gaps to inform the design of equitable lung cancer screening. METHODS: We will conduct a scoping review following the methodological framework developed by Arksey and O'Malley. We will conduct comprehensive searches for lung cancer screening promotion interventions in Ovid Medline, Embase, the Cochrane Library, Cumulative Index to Nursing & Allied Health (CINAHL) and Scopus. We will include published English language peer-reviewed and grey literature published between January 2000 and 2020 that describe an intervention designed to increase the uptake of low-dose CT (LDCT) lung cancer screening in the Organization for Economic Cooperation and Development countries. Articles not in English or not describing LDCT will be excluded. Three authors will review retrieved literature in three steps: title, abstract and then full text. Three additional authors will review discrepancies. Authors will extract data from full-text papers into a chart adapted from the Template for Intervention Description and Republication checklist, the Consolidated Standards of Reporting Trials and a Health Equity Impact Assessment tool. Findings will be presented using a narrative synthesis. ETHICS AND DISSEMINATION: The knowledge synthesised will be used to inform the equitable design of lung cancer screening and disseminated through conferences, publications and shared with relevant partners. The study does not require research ethics approval as literature is available online.

Application of specialized pro-resolving mediators in periodontitis and peri-implantitis: a review.

Scaling and root planning is a key element in the mechanical therapy used for the eradication of biofilm, which is the major etiological factor for periodontitis and peri-implantitis. However, periodontitis is also a host mediated disease, therefore, removal of the biofilm without adjunctive therapy may not achieve the desired clinical outcome due to persistent activation of the innate and adaptive immune cells. Most recently, even the resident cells of the periodontium, including periodontal ligament fibroblasts, have been shown to produce several inflammatory factors in response to bacterial challenge. With increased understanding of the pathophysiology of periodontitis, more research is focusing on opposing excessive inflammation with specialized pro-resolving mediators (SPMs). This review article covers the major limitations of current standards of care for periodontitis and peri-implantitis, and it highlights recent advances and prospects of SPMs in the context of tissue reconstruction and regeneration. Here, we focus primarily on the role of SPMs in restoring tissue homeostasis after periodontal infection.

The effect of lipoxin A4 on E. coli LPS-induced osteoclastogenesis.

OBJECTIVES: The objective of the present study was to investigate the effect of lipoxin-type A4 (LXA4) on bacterial-induced osteoclastogenesis. MATERIAL AND METHODS: Human periodontal ligament cells (PDLCs) in coculture with osteoclast precursors (RAW264.7 cells) were exposed to bacterial stimulation with lipopolysaccharide (LPS) to induce inflammation. After 24 h, cells were treated to 100 ng/ml of LXA4 and 50 ng/ml of forymul peptide receptor 2 (FPR2/ALX) receptor antagonist (Boc-2). After 5 days, osteoclastic resorptive activity was assessed on calcium phosphate (CaP) synthetic bone substitute. Additionally, osteoclastic differentiation was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, TRAP enzymatic activity assay, and on the expression of osteoclast-specific genes. RESULTS: We found that stimulation of in the osteoclasts with LPS-stimulated PDLCs induced a significant increase in tartrate-resistant acid phosphatase (TRAP) positive cells, higher resorptive activity, and enhanced expression of specific genes. Meanwhile, LXA4-treatment exhibited strong anti-inflammatory activity, and was able to reverse these inflammatory effects. CONCLUSIONS: We conclude that (1) PDLCs are a potential target for treating bacterial-induced bone resorption in patients with periodontal disease, and (2) LXA4 is a suitable candidate for such therapy. CLINICAL RELEVANCE: The results prove that lipoxins have a protective role in bacterial-induced periodontal inflammation and alveolar bone resorption, which can be translated into a clinical beneficial alterative treatment.

A comparison of acyl-moieties for noncovalent functionalization of PLGA and PEG-PLGA nanoparticles with a cell-penetrating peptide.

Efficient intracellular drug delivery in nanomedicine strongly depends on ways to induce cellular uptake. Conjugation of nanoparticles (NPs) with cell-penetrating peptides (CPPs) is a known means to induce uptake via endocytosis. Here, we functionalized NPs consisting of either poly(d,l-lactide-co-glycolide) (PLGA) or polyethene glycol (PEG)-PLGA block-copolymer with a lactoferrin-derived cell-penetrating peptide (hLF). To enhance the association between the peptide and the polymer NPs, we tested a range of acyl moieties for N-terminal acylation of the peptide as a means to promote noncovalent interactions. Acyl moieties differed in chain length and number of acyl chains. Peptide-functionalized NPs were characterized for nanoparticle size, overall net charge, storage stability, and intracellular uptake. Coating particles with a palmitoylated hLF resulted in minimal precipitation after storage at -20C and homogeneous particle size (<200 nm). Palmitoyl-hLF coated NPs showed enhanced delivery in different cells in comparison to NPs lacking functionalization. Moreover, in comparison to acetyl-hLF, palmitoyl-hLF was also suited for coating and enhancing the cellular uptake of PEG-PLGA NPs.

Lipoxin suppresses inflammation via the TLR4/MyD88/NF-κB pathway in periodontal ligament cells.

OBJECTIVE: The objective of the present study was to evaluate the anti-inflammatory effects of lipoxin A4 (LXA4) for the treatment of periodontitis in an in vitro model. METHODS: Human PDLCs were challenged with Escherichia coli (E. coli) lipopolysaccharide (LPS) to evoke an inflammatory response. This was done either in monoculture or in coculture with THP-1, a monocytic cell line. Thereafter, cytokine expression was measured by ELISA, with or without LXA4. In addition, the effects of LXA4 were analyzed on the TLR-MyD88-NF-κB (TMN)-mediated intracellular signal pathway using immunocytochemistry. RESULTS: In response to LPS, the level of the pro-inflammatory cytokine tumor necrosis factor alpha increased, whereas the anti-inflammatory cytokine interleukin-4 decreased significantly (p < .05). These effects were consistently reversed when LPS-challenged PDLCs were also treated with LXA4. The results in the coculture system were comparable to the monoculture. Immunohistochemistry and quantitative assessment confirmed the importance of the TMN signal pathway in these processes. CONCLUSION: These results corroborate earlier findings that PDLCs play an important role in inflammation. Moreover, LXA4 might offer new approaches for the therapeutic treatment of periodontal disease.