Resveratrol Demonstrates Antimicrobial Effects Against Propionibacterium acnes In Vitro

IntroductionResveratrol (3,5,4'-trihydroxystilbene) is an antioxidant that has multiple biologic effects including antimicrobial properties. Acne vulgaris is a disease of the pilosebaceous unit, characterized by an inflammatory host immune response to the bacteria Propionibacterium acnes (P. acnes). This study sought to determine whether resveratrol may be a potential treatment for acne vulgaris.MethodsColony-forming unit (CFU) assays together with transmission electron microscopy using P. acnes treated with resveratrol or benzoyl peroxide were used to assess antibacterial effects. Blood was drawn from healthy human volunteers, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays were used to assess cytotoxicity in monocytes and keratinocytes.ResultsResveratrol demonstrated sustained antibacterial activity against P. acnes, whereas benzoyl peroxide, a commonly used antibacterial treatment for acne, demonstrated a short-term bactericidal response. A combination of resveratrol and benzoyl peroxide showed high initial antibacterial activity and sustained bacterial growth inhibition. Electron microscopy of P. acnes treated with resveratrol revealed altered bacterial morphology, with loss of membrane definition and loss of well-defined extracellular fimbrial structures. Resveratrol was less cytotoxic than benzoyl peroxide.ConclusionThe sustained antibacterial activity and reduced cytotoxicity versus benzoyl peroxide demonstrated by resveratrol in this study highlight its potential as a novel therapeutic option or adjuvant therapy in the treatment of acne vulgaris

Antimicrobial and anti-inflammatory activity of chitosan-alginate nanoparticles: a targeted therapy for cutaneous pathogens.

Advances in nanotechnology have demonstrated potential application of nanoparticles (NPs) for effective and targeted drug delivery. Here we investigated the antimicrobial and immunological properties and the feasibility of using NPs to deliver antimicrobial agents to treat a cutaneous pathogen. NPs synthesized with chitosan and alginate demonstrated a direct antimicrobial activity in vitro against Propionibacterium acnes, the bacterium linked to the pathogenesis of acne. By electron microscopy (EM) imaging, chitosan-alginate NPs were found to induce the disruption of the P. acnes cell membrane, providing a mechanism for the bactericidal effect. The chitosan-alginate NPs also exhibited anti-inflammatory properties as they inhibited P. acnes-induced inflammatory cytokine production in human monocytes and keratinocytes. Furthermore, benzoyl peroxide (BP), a commonly used antiacne drug, was effectively encapsulated in the chitosan-alginate NPs and demonstrated superior antimicrobial activity against P. acnes compared with BP alone while demonstrating less toxicity to eukaryotic cells. Together, these data suggest the potential utility of topical delivery of chitosan-alginate NP-encapsulated drug therapy for the treatment of dermatologic conditions with infectious and inflammatory components

Reduced SPAG17 Expression in Systemic Sclerosis Triggers Myofibroblast Transition and Drives Fibrosis

Systemic sclerosis (SSc) is a clinically heterogeneous fibrotic disease with no effective treatment. Myofibroblasts are responsible for unresolving synchronous skin and internal organ fibrosis in SSc, but the drivers of sustained myofibroblast activation remain poorly understood. Using unbiased transcriptome analysis of skin biopsies, we identified the downregulation of SPAG17 in multiple independent cohorts of patients with SSc, and by orthogonal approaches, we observed a significant negative correlation between SPAG17 and fibrotic gene expression. Fibroblasts and endothelial cells explanted from SSc skin biopsies showed reduced chromatin accessibility at the SPAG17 locus. Remarkably, mice lacking Spag17 showed spontaneous skin fibrosis with increased dermal thickness, collagen deposition and stiffness, and altered collagen fiber alignment. Knockdown of SPAG17 in human and mouse fibroblasts and microvascular endothelial cells was accompanied by spontaneous myofibroblast transformation and markedly heightened sensitivity to profibrotic stimuli. These responses were accompanied by constitutive TGF-β pathway activation. Thus, we discovered impaired expression of SPAG17 in SSc and identified, to our knowledge, a previously unreported cell-intrinsic role for SPAG17 in the negative regulation of fibrotic responses. These findings shed fresh light on the pathogenesis of SSc and may inform the search for innovative therapies for SSc and other fibrotic conditions through SPAG17 signaling

Woman-Centered Design through Humanity, Activism, and Inclusion

Women account for over half of the global population, however, continue to be subject to systematic and systemic disadvantage, particularly in terms of access to health and education. At every intersection, where systemic inequality accounts for greater loss of life or limitations on full and healthy living, women are more greatly impacted by those inequalities. The design of technologies is no different, the very definition of technology is historically cast in terms of male activities, and advancements in the field are critical to improve women's quality of life. This article views HCI, a relatively new field, as well positioned to act critically in the ways that technology serve, refigure, and redefine women's bodies. Indeed, the female body remains a contested topic, a restriction to the development of women's health. On one hand, the field of women's health has attended to the medicalization of the body and therefore is to be understood through medical language and knowledge. On the other hand, the framing of issues associated with women's health and people's experiences of and within such system(s) remain problematic for many. This is visible today in, e.g., socio-cultural practices in disparate geographies or medical devices within a clinic or the home. Moreover, the biological body is part of a great unmentionable, i.e., the perils of essentialism. We contend that it is necessary, pragmatically and ethically, for HCI to turn its attention toward a woman-centered design approach. While previous research has argued for the dangers of gender-demarcated design work, we advance that designing for and with women should not be regarded as ghettoizing, but instead as critical to improving women's experiences in bodily transactions, choices, rights, and access to and in health and care. In this article, we consider how and why designing with and for woman matters. We use our design-led research as a way to speak to and illustrate alternatives to designing for and with women within HCI.QC 20200930</p

Evaluating Gene Drive Approaches for Public Benefit

Gene drive approaches—those which bias inheritance of a genetic element in a population of sexually reproducing organisms—have the potential to provide important public benefits. The spread of selected genetic elements in wild populations of organisms may help address certain challenges, such as transmission of vector-borne human and animal diseases and biodiversity loss due to invasive animals. Adapting various naturally occurring gene drive mechanisms to these aims is a long-standing research area, and recent advances in genetics have made engineering gene drive systems significantly more technically feasible. Gene drive approaches would act through changes in natural environments, thus robust methods to evaluate potential research and use are important. Despite the fact that gene drive approaches build on existing paradigms, such as genetic modification of organisms and conventional biological control, there are material challenges to their evaluation. One challenge is the inherent complexity of ecosystems, which makes precise prediction of changes to the environment difficult. For gene drive approaches that are expected to spread spatially and/or persist temporally, responding to this difficulty with the typical stepwise increases in the scale of studies may not be straightforward after studies begin in the natural environment. A related challenge is that study or use of a gene drive approach may have implications for communities beyond the location of introduction, depending on the spatial spread and persistence of the approach and the population biology of the target organism. This poses a particular governance challenge when spread across national borders is plausible. Finally, community engagement is an important element of responsible research and governance, but effective community engagement for gene drive approaches requires addressing complexity and uncertainty and supporting representative participation in decision making. These challenges are not confronted in a void. Existing frameworks, processes, and institutions provide a basis for effective evaluation of gene drive approaches for public benefit. Although engineered gene drive approaches are relatively new, the necessities of making decisions despite uncertainty and governing actions with potential implications for shared environments are well established. There are methodologies to identify potential harms and assess risks when there is limited experience to draw upon, and these methodologies have been applied in similar contexts. There are also laws, policies, treaties, agreements, and institutions in place across many jurisdictions that support national and international decision making regarding genetically modified organisms and the potential applications of gene drive approaches, such as public health and biodiversity conservation. Community engagement is an established component of many decision-making processes, and related experience and conceptual frameworks can inform engagement by researchers. The existence of frameworks, processes, and institutions provides an important foundation for evaluating gene drive approaches, but it is not sufficient by itself. They must be rigorously applied, which requires resources for risk assessment, research, and community engagement and diligent implementation by governance institutions. The continued evolution of the frameworks, processes, and institutions is important to adapt to the growing understanding of gene drive approaches. With appropriate resources and diligence, it will be possible to responsibly evaluate and make decisions on gene drive approaches for public benefit

Fungal vaccines and immunotherapeutics: current concepts and future challenges

Purpose of review The remarkable advances in modern medicine have paradoxically resulted in a rapidly expanding population of immunocompromised patients displaying extreme susceptibility to life-threatening fungal infections. There are currently no licensed vaccines, and the prophylaxis and therapy of fungal infections in at-risk individuals remains challenging, contributing to undesirable mortality and morbidity rates. The design of successful antifungal preventive approaches has been hampered by an insufficient understanding of the dynamics of the host-fungus interaction and the mechanisms that underlie heterogenous immune responses to vaccines and immunotherapy. Recent findings Recent advances in proteomics and glycomics have contributed to the identification of candidate antigens for use in subunit vaccines, novel adjuvants, and delivery systems to boost the efficacy of protective vaccination responses that are becoming available, and several targets are being exploited in immunotherapeutic approaches. Summary We review some of the emerging concepts as well as the inherent challenges to the development of fungal vaccines and immunotherapies to protect at-risk individuals.ThisworkwassupportedbytheNorthernPortugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (contracts IF/00735/ 2014 to A.C., and SFRH/BPD/96176/2013 to C.C).info:eu-repo/semantics/publishedVersio

Core commitments for field trials of gene drive organisms

This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via the DOI in this record Gene drive organisms (GDOs), whose genomes have been genetically engineered to spread a desired allele through a population, have the potential to transform the way societies address a wide range of daunting public health and environmental challenges. The development, testing, and release of GDOs, however, are complex and often controversial. A key challenge is to clarify the appropriate roles of developers and others actively engaged in work with GDOs in decision-making processes, and, in particular, how to establish partnerships with relevant authorities and other stakeholders. Several members of the gene drive community previously proposed safeguards for laboratory experiments with GDOs (1) that, in the absence of national or international guidelines, were considered essential for responsible laboratory work to proceed. Now, with GDO development advancing in laboratories (2–5), we envision similar safeguards for the potential next step: ecologically and/or genetically confined field trials to further assess the performance of GDOs. A GDO's propensity to spread necessitates well-developed criteria for field trials to assess its potential impacts (6). We, as a multidisciplinary group of GDO developers, ecologists, conservation biologists, and experts in social science, ethics, and policy, outline commitments below that we deem critical for responsible conduct of a field trial and to ensure that these technologies, if they are introduced, serve the public interest.British AcademyBritish Academ

Monte Carlo studies of combined shielding and veto techniques for neutron background reduction in underground dark matter experiments based on liquid noble gas targets

We present results of a detailed simulation study of neutron background reduction in dark matter detectors based on observation of nuclear recoils below 100 keV. Background rates are estimated for neutrons from muons and from natural radioactivity, and with separate Monte Carlo simulations for the underground rock, shielding, and detector components. With optimum shielding combinations, further reduction of background can be achieved with muon and neutron vetos, simulations of the latter giving first estimates of the rejection efficiency as a function of veto geometry. Design options for neutron vetos are also discussed. A detailed tabulation of backgrounds is given, from which it is concluded that the total neutron background can be reduced below the level 10−4–10−3 kg−1 d−1 needed to detect dark matter particle-nucleon cross sections in the range 10−10–10−9 pb, with further reductions attainable in principle with lower-activity detector materials