In 2017 Leïla Slimani simultaneously published two books that catalogue interviews about sexual life in Morocco, Sexe et mensonges: La vie sexuelle au Maroc and Paroles d'honneur. This article examines these works through the framework of expanded conceptions of the archive, analyzing how these (non)fiction works archive stories and the powers behind their collection and dissemination. Sexe et mensonges is an essai and Paroles d'honneur is a bande dessinée, and the first section of this article compares how the two different formats of these works affect the archived testimonies. The second section deconstructs the choice of publishing these stories with a French publisher for a European audience, and how this choice does and does not align with Slimani's goals for these works. The third section focuses on Slimani's role in the works. In the essai, Slimani serves as narrator and commentator, sharing her own stories and interpreting the interviews for the reader. In the bande dessinée, Slimani is a character in the story, participating in conversations with her interviewees. Looking at the accessibility, power structures, and political intentions, while also taking into account Slimani's positionality, authorial posture, and privilege in the assemblage of these stories allows greater insight into their construction.

Atopic dermatitis (AD) represents a complex intersection between skin barrier dysfunction, host immunologic response, and external factors such as allergenic triggers and the skin microbiome. However, the relative contributions of these factors are not clear. There is a surge in Staphylococcus aureus on the skin during flares of AD (Kong et al., 2012Kong H.H. Oh J. Deming C. Conlan S. Grice E.A. Beatson M.A. et al.Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis.Genome Res. 2012; 22: 850-859Crossref PubMed Scopus (998) Google Scholar). S. aureus strains seen in AD flares are unique to the host and capable of eliciting varied immune responses (Byrd et al., 2017Byrd A.L. Deming C. Cassidy S.K.B. Harrison O.J. Ng W.I. Conlan S. et al.Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis.Sci Transl Med. 2017; 9eaal4651Crossref PubMed Scopus (244) Google Scholar). No direct relationship between severity and in vitro toxin genotype has been established (Kim et al., 2009Kim D.W. Park J.Y. Park K.D. Kim T.H. Lee W.J. Lee S.J. et al.Are there predominant strains and toxins of Staphylococcus aureus in atopic dermatitis patients? Genotypic characterization and toxin determination of S. aureus isolated in adolescent and adult patients with atopic dermatitis.J Dermatol. 2009; 36: 75-81Crossref PubMed Scopus (36) Google Scholar). S. epidermidis may similarly contribute to the propagation of AD through the elucidation of toxins (Martínez-García et al., 2018Martínez-García S. Rodríguez-Martínez S. Cancino-Diaz M.E. Cancino-Diaz J.C. Extracellular proteases of Staphylococcus epidermidis: roles as virulence factors and their participation in biofilm.APMIS. 2018; 126: 177-185Crossref PubMed Scopus (27) Google Scholar). Further information on strains of staphylococci found on patients with AD may aid in developing therapeutic targets. δ-Toxin (also known as δ-hemolysin) is produced by 97% of S. aureus strains as well as many coagulase-negative staphylococci (Dinges et al., 2000Dinges M.M. Orwin P.M. Schlievert P.M. Exotoxins of Staphylococcus aureus.Clin Microbiol Rev. 2000; 13: 16-34Crossref PubMed Scopus (1260) Google Scholar). Staphylococcal δ-toxin lyses mammalian erythrocytes and is particularly potent against rabbit erythrocytes (Kreger et al., 1971Kreger A.S. Kim K.S. Zaboretzky F. Bernheimer A.W. Purification and properties of staphylococcal delta hemolysin.Infect Immun. 1971; 3: 449-465Crossref PubMed Google Scholar); it also induces mast cell degranulation in vitro and is capable of inducing inflammatory skin disease in mouse models (Nakamura et al., 2013Nakamura Y. Oscherwitz J. Cease K.B. Chan S.M. Muñoz-Planillo R. Hasegawa M. et al.Staphylococcus δ-toxin induces allergic skin disease by activating mast cells.Nature. 2013; 503: 397-401Crossref PubMed Scopus (310) Google Scholar). Variability in δ-toxin production by S. aureus strains is influenced by complex interactions between a number of genes, with the carA gene playing a critical role in its production (Su et al., 2020Su M. Lyles J.T. Petit Iii Iii R.A. Peterson J. Hargita M. Tang H. et al.Genomic analysis of variability in delta-toxin levels between Staphylococcus aureus strains.PeerJ. 2020; 8: e8717Crossref PubMed Scopus (7) Google Scholar). In this study, we report data from a pilot study to begin to define the relationship between hemolytic toxin production and AD severity in pediatric patients and young adults. The Emory University (Atlanta, GA) Institutional Review Board approved this study (Institutional Review Board #0087896 and 00093739). Written informed consent and/or assent was obtained from parents or patients aged 2–20 years with AD. The diagnosis of AD was confirmed by a board-certified pediatric dermatologist after initial screening on the basis of the criteria outlined by Hanifin and Rajka, 1980Hanifin J.M. Rajka G. Diagnostic features of atopic dermatitis.Acta Derm Venereol. 1980; : 44-47Google Scholar. Patients were recruited from the Emory University pediatric dermatology clinics from May 2016 to May 2018 and were not asked to modify their topical or oral medications before this study to collect preliminary data on this subject. We assessed disease severity at the time of sample collection on the basis of the SCORing Atopic Dermatitis Index and grouped it into mild, moderate, or severe (Chopra et al., 2017Chopra R. Vakharia P.P. Sacotte R. Patel N. Immaneni S. White T. et al.Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring Atopic Dermatitis (SCORAD), objective SCORAD, Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis.Br J Dermatol. 2017; 177: 1316-1321Crossref PubMed Scopus (99) Google Scholar). Patients taking oral antibiotics at the time of the visit were excluded. Swabs were collected from the three most significantly flared body sites from areas of active dermatitis (affected), unaffected volar forearm without active dermatitis, and anterior nares. Swabs from the antecubital fossa, volar forearm, and nares were collected from nine healthy controls. Details of sample collection and processing are available in Supplementary Material and Methods S1. A total of 30 patients and/or parents provided written consent for participation in this study. Most patients had a moderate (n = 12) SCORing Atopic Dermatitis Index score, with fewer mild (n = 5) and severe (n = 4) scores (Chopra et al., 2017Chopra R. Vakharia P.P. Sacotte R. Patel N. Immaneni S. White T. et al.Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring Atopic Dermatitis (SCORAD), objective SCORAD, Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis.Br J Dermatol. 2017; 177: 1316-1321Crossref PubMed Scopus (99) Google Scholar) (Supplementary Table S1). Samples were collected from nine patients without AD. The skin of severely affected patients had the highest staphylococcal density in all pooled samples (Supplementary Table S2) as well as relative to the affected skin in patients with mild or moderate AD (Figure 1). Density was not significantly different in nares or unaffected skin between mild, moderate, and severe patients (Figure 1). Hemolytic potential of 1,054 isolates was assessed in a rabbit blood lysis model (Supplementary Figure S1). There was a significant increase in average hemolytic activity of staphylococcal isolates pooled from all collected sites from mild patients relative to those from moderate patients and those from moderate patients relative to those from severe patients (Figure 2a and Supplementary Table S3), whereas hemolysis in control isolates was not significantly different from that in mild patients. A similar stepwise increase in average hemolytic activity was demonstrated in isolates from unaffected skin of patients with AD, as well as from nares, and affected skin when analyzed independently (Figure 2b‒d). Body site and patient-level data are provided in Supplementary Figures S2 and S3. Although severe patients were most heavily colonized with staphylococci in affected skin (Supplementary Table S2), our study aligns with previous studies showing that staphylococcal load alone does not consistently correlate with the severity of AD (Byrd et al., 2017Byrd A.L. Deming C. Cassidy S.K.B. Harrison O.J. Ng W.I. Conlan S. et al.Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis.Sci Transl Med. 2017; 9eaal4651Crossref PubMed Scopus (244) Google Scholar; Totté et al., 2019Totté J.E.E. Pardo L.M. Fieten K.B. Vos M.C. van den Broek T.J. Schuren F.H.J. et al.Nasal and skin microbiome are associated with disease severity in pediatric atopic dermatitis.Br J Dermatol. 2019; 181: 796-804Crossref PubMed Scopus (17) Google Scholar). Mild and moderate patients in our study did not have significantly higher staphylococcal colonization load than control patients (Supplementary Table S2) but did show a stepwise increase in hemolytic activity of staphylococcal isolates (Supplementary Table S3). Our results build on previous studies to suggest that a more precise understanding of staphylococcal strains is necessary to understand this interaction. In this study, we provide strong preliminary data that individual isolate level differences in staphylococcal hemolytic potential may influence the severity of AD in a predominantly pediatric population. A major driver in staphylococcal virulence is the agr system, and research aimed at the identification of small molecule inhibitors of this system in efforts to diminish S. aureus virulence has emerged over the past decade (Salam and Quave, 2018Salam A.M. Quave C.L. Targeting virulence in Staphylococcus aureus by chemical inhibition of the accessory gene regulator system in vivo.mSphere. 2018; 3: e00500-e00517Crossref PubMed Scopus (44) Google Scholar). In some cases, these studies have progressed toward acute and inflammatory models of skin disease. For example, solanamide B was recently reported to suppress δ-toxin‒induced disease in a modified epicutaneous murine disease model of AD (Baldry et al., 2018Baldry M. Nakamura Y. Nakagawa S. Frees D. Matsue H. Núñez G. et al.Application of an agr-specific antivirulence compound as therapy for Staphylococcus aureus-induced inflammatory skin disease.J Infect Dis. 2018; 218: 1009-1013Crossref PubMed Scopus (18) Google Scholar). Future studies on the association demonstrated in this study may provide insight into potential therapeutics targeting staphylococcal virulence. Although our study design was selective for staphylococci, our methods did not differentiate between hemolysis caused by distinct coagulase-negative species (Supplementary Figure S4). S. epidermidis strains may be important drivers of the association noted in this study. In vivo interactions between S. epidermidis and S. aureus are complex and warrant future investigation (Fredheim et al., 2015Fredheim E.G.A. Flægstad T. Askarian F. Klingenberg C. Colonisation and interaction between S. epidermidis and S. aureus in the nose and throat of healthy adolescents.Eur J Clin Microbiol Infect Dis. 2015; 34: 123-129Crossref PubMed Scopus (15) Google Scholar; Iwase et al., 2010Iwase T. Uehara Y. Shinji H. Tajima A. Seo H. Takada K. et al.Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization.Nature. 2010; 465: 346-349Crossref PubMed Scopus (587) Google Scholar). Although we noted a correlation between AD severity and staphylococcal hemolysis in this study, this study does not address the causation of this effect. Our study design did not control for all potential confounders such as immunosuppression, topical product use, or bathing practices, but we plan to address these factors in future studies. Topical steroid use may reduce the level of colonization with S. aureus on atopic skin (Nilsson et al., 1992Nilsson E.J. Henning C.G. Magnusson J. Topical corticosteroids and Staphylococcus aureus in atopic dermatitis.J Am Acad Dermatol. 1992; 27: 29-34Abstract Full Text PDF PubMed Scopus (171) Google Scholar), which may have influenced the density of colonization in some of our patients because we did not control for this factor. Clearly, the relationship between these factors is complex and warrants dedicated study. This was a single-site pilot study, and further research is required to define the generalizability of these results. We plan to explore the relative contribution of individual staphylococcal isolates in the severity of AD in future studies. Data are available within the article or its supplementary materials. Emily A. Gurnee: http://orcid.org/0000-0002-6450-7826 Mengqing Xu: http://orcid.org/0000-0002-0599-7888 Caitlin J. Risener: http://orcid.org/0000-0002-4824-6064 Kelly Lehman: http://orcid.org/0000-0001-8946-0342 Kate Nelson: http://orcid.org/0000-0001-8783-2157 Robert A. Swerlick: http://orcid.org/0000-0002-9802-4144 Cassandra L. Quave: http://orcid.org/0000-0001-9615-7886 The authors state no conflict of interest. We acknowledge the Department of Dermatology Emory University (Atlanta, GA) development funds for financial support. This work has been performed in Atlanta, Georgia. Conceptualization: CLQ, RAS; Data Curation: EAG, CLQ; Formal Analysis: CLQ; Investigation: EAG, MX, CJR, KL, KN; Methodology: CLQ, EAG, RAS; Project Administration: CLQ; Resources: CLQ, EAG; Supervision: CLQ, EAG; Validation: CLQ, EAG; Visualization: CLQ, EAG; Writing - Original Draft Preparation: EAG; Writing - Review and Editing: EAG, MX, CJR, KL, KN, RAS, CLQ Download .pdf (1.94 MB) Help with pdf files Supplementary Data

A shortage of conventional medicine during the American Civil War (1861–1865) spurred Confederate physicians to use preparations of native plants as medicines. In 1863, botanist Francis Porcher compiled a book of medicinal plants native to the southern United States, including plants used in Native American traditional medicine. In this study, we consulted Porcher’s book and collected samples from three species that were indicated for the formulation of antiseptics: Liriodendron tulipifera, Aralia spinosa, and Quercus alba. Extracts of these species were tested for the ability to inhibit growth in three species of multidrug-resistant pathogenic bacteria associated with wound infections: Staphylococcus aureus, Klebsiella pneumoniae, and Acinetobacter baumannii. Extracts were also tested for biofilm and quorum sensing inhibition against S. aureus. Q. alba extracts inhibited growth in all three species of bacteria (IC50 64, 32, and 32 µg/mL, respectively), and inhibited biofilm formation (IC50 1 µg/mL) in S. aureus. L. tulipifera extracts inhibited biofilm formation (IC50 32 µg/mL) in S. aureus. A. spinosa extracts inhibited biofilm formation (IC50 2 µg/mL) and quorum sensing (IC50 8 µg/mL) in S. aureus. These results support that this selection of plants exhibited some antiseptic properties in the prevention and management of wound infections during the conflict.

Atopic dermatitis (AD) is one of the most prevalent diseases of childhood and impacts quality of life for patients and their families. AD is characterized by pruritus and eczematous skin changes and is known to result from various environmental and genetic factors. During AD flares, microbial diversity declines as the population of Staphylococcus aureusincreases. The contribution of S. aureus to the pathogenesis of AD is well established but, the mechanism of this contribution is poorly understood. The hemolytic exotoxin, δ-hemolysin, is known to damage the skin barrier and promote pruritus through stimulation of mast cell degranulation and histamine release. However, exotoxins are produced differentially in diverse S. aureus strains. We aimed to determine if differential hemolytic exotoxin expression in S. aureus isolates from AD patients correlates to disease severity. We collected skin swabs from the three most significantly flared sites from each patient (aged 2-17), as well as ventral forearm. Clinical severity was graded based on a global assessment of disease severity in our initial pilot study on 5 patients and SCORAD for 14. Assessment included severity of lesions, body surface area involvement, and patient reported itch. Samples were grown on selective media and multiple colonies picked based on differences in colony morphology. Hemolytic activity of >700 isolates was determined based on zone of lysis (mm) on rabbit blood agar. We found a significant difference in hemolysis between healthy controls (0.52 ± 0.89 mm) and moderate (0.66 ± 1.79, p<0.05), control and severe (3.68 ± 3.69, p<0.0001), mild and severe (p<0.0001), and moderate and severe (p<0.0001) AD patients. The data indicate that disease severity is linked to the exotoxin producing potential of S. aureus, with moderate and severe AD flares being colonized by high toxin producers. Better understanding the role of S. aureus in AD pathogenesis is key to future drug development initiatives.

Infantile haemangiomas ( IH s) with functional or cosmetic concerns necessitate systemic treatment for which propranolol is the preferred treatment. However, the mechanism of action is unknown. Mouse models suggest the angiopoietin‐2 (Ang2)/Tie‐2 system is implicated. Ang2 can promote endothelial growth or induce apoptosis depending on the presence of vascular endothelial growth factor. This pilot study investigates the saliva Ang2 levels in infants with IH treated with and without systemic propranolol. Patients with clinically confirmed IH s were recruited from an academic paediatric dermatology centre. Treatment was based on clinical evaluation. Saliva samples were collected over 6 months. An enzyme‐linked immunosorbent assay determined Ang2 levels. Ang2 levels were detectable in 45% of samples. However, by the late time point, only 28% had detectable levels. There were no changes of Ang2 over time, and there were no differences in Ang2 levels between groups. However, Ang2 levels were correlated with baseline size and changes in size from baseline. Ang2 is detectable in saliva of affected infants, but does not decrease with propranolol treatment. However, Ang2 levels are positively correlated with size and changes in size. Thus, Ang2 is not the primary factor in the mechanism of propranolol resulting in IH reduction.

and Missouri beyond the typical summary of the war’s earliest days. Throughout the military narrative, despite the notion of a separate war west of the river, Cutrer demonstrates that trans-Mississippi soldiers on both sides frequently fought with skill and determination equal to that of their comrades to the east. Moreover, Cutrer shows that soldiers in the eastern and western theaters varied in their perceptions of trans-Mississippi troops and their service. Those who served in more famous battles and campaigns did not necessarily dismiss the contributions of their comrades in the Far West. In recent years, scholars have embraced the importance of the transMississippi and western theaters and have begun to explore the immense research potential of those regions and to integrate their findings into the larger Civil War narrative. The University of North Carolina Press should be commended as a leader in the publication of such scholarship, including the December 2016 issue of the Journal of the Civil War Era, dedicated entirely to interpreting the war era west of the Mississippi River; William L. Shea’s Fields of Blood: The Prairie Grove Campaign (2009); and especially Earl J. Hess’s The Civil War in the West: Victory and Defeat from the Appalachians to the Mississippi (2012). For the most part, Theater of a Separate War is a work of synthesis that brings together four decades of scholarship produced since Kerby’s 1972 classic study of the trans-Mississippi theater. Cutrer has expertly written a compelling narrative that will become a standard source on the subject. Civil War scholars would do well to partner Cutrer’s Theater of a Separate War with Hess’s The Civil War in the West, both volumes in the prestigious Littlefield History of the Civil War Era series, for masterful coverage of the important developments west of the Appalachians. Bradley R. Clampitt

Hypericum perforatum L. (Hypericaceae), or St. John's Wort, is a well-known medicinal herb often associated with the treatment of anxiety and depression. Additionally, an oil macerate (Oleum Hyperici) of its flowering aerial parts is widely used in traditional medicine across the Balkans as a topical wound and ulcer salve. Other studies have shown that Oleum Hyperici reduces both wound size and healing time. Of its active constituents, the naphthodianthrone hypericin and phloroglucinol hyperforin are effective antibacterial compounds against various Gram-positive bacteria. However, hyperforin is unstable with light and heat, and thus should not be present in the light-aged oil macerate. Additionally, hypericin can cause phototoxic skin reactions if ingested or absorbed into the skin. Therefore, the established chemistry presents a paradox for this H. perforatum oil macerate: the hyperforin responsible for the antibacterial bioactivity should degrade in the sunlight as the traditional oil is prepared; alternately, if hypericin is present in established bioactive levels, then the oil macerate should cause photosensitivity, yet none is reported. In this research, various extracts of H. perforatum were compared to traditional oil macerates with regards to chemical composition and antibacterial activity (inhibition of growth, biofilm formation, and quorum sensing) vs. several strains of Staphylococcus aureus in order to better understand this traditional medicine. It was found that four Kosovar-crafted oil macerates were effective at inhibiting biofilm formation (MBIC50 active range of 0.004-0.016% v/v), exhibited moderate inhibition of quorum sensing (QSIC50 active range of 0.064-0.512% v/v), and contained detectable amounts of hyperforin, but not hypericin. Overall, levels of hypericin were much higher in the organic extracts, and these also exhibited more potent growth inhibitory activity. In conclusion, these data confirm that oil macerates employed in traditional treatments of skin infection lack the compound credited with phototoxic reactions in H. perforatum use and exhibit anti-biofilm and modest quorum quenching effects, rather than growth inhibitory properties against S. aureus.

Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract “430D-F5” against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC50 2–32 μg mL−1) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections.

Schisandra chinensis (Chinese starvine) is a popular dietary supplement with a rich history of use in traditional Chinese medicine. Schisandra glabra (bay starvine) is the only North American representative of the genus, and little is known about its history of traditional use, chemistry, and potential biological activity. In this study, we conducted comparative high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis on S. glabra and S. chinensis fruits. Additional characterization of S. glabra was performed by liquid chromatography-Fourier transform mass spectrometry (LC-FTMS). Quantitative analysis of four bioactive marker compounds revealed that S. glabra does not have statistically higher levels of schisandrin A or schisandrol B than S. chinensis. S. glabra has lower levels of schisandrol A and γ-schisandrin. Total phenolic contents of the two species' fruits were not statistically different. S. glabra had higher total tannin content than S. chinensis. We discuss the relevance of this analytical analysis to the study of S. glabra as a potential dietary supplement ingredient and give specific consideration to the conservation challenges involved in commercially developing a regionally threatened species, even in semicultivated conditions.

Staphylococcus aureus is a leading cause of hospital-acquired infections. It is listed among the top "serious threats" to human health in the USA, due in large part to rising rates of resistance. Many S. aureus infections are recalcitrant to antibiotic therapy due to their ability to form a biofilm, which acts not only as a physical barrier to antibiotics and the immune system, but results in differences in metabolism that further restricts antibiotic efficacy. Development of a modular strategy to synthesize a library of phenolic glycosides allowed for bioactivity testing and identification of anti-biofilm compounds within an extract of the elmleaf blackberry (Rubus ulmifolius). Two ellagic acid (EA) derivatives, EA xyloside and EA rhamnoside, have been identified as components of the Rubus extract. In addition, EA rhamnoside has been identified as an inhibitor of biofilm formation, with activity comparable to the complex extract 220D-F2 (composed of a mixture of EA glycosides), and confirmed by confocal laser scanning microscopy analyses.

Unique iodine-containing meroditerpenes iodocallophycoic acid A (1) and iodocallophycols A-D (2-5) were discovered from the Fijian red alga Callophycus sp. Because flexibility of the molecular skeleton impaired full characterization of relative stereochemistries by NMR spectroscopy, a DFT-based theoretical model was developed to derive relevant interproton distances which were compared to those calculated from NOE measurements, yielding the relative stereochemistries. The correct 2S,6S,7S,10S,14S enantiomers were then identified by comparison of theoretical and experimental ECD spectra. Biological activities of these iodinated and brominated meroditerpenes and additional new, related bromophycoic acid F (6) and bromophycoic acid A methyl ester (7), were evaluated for relevant human disease targets. Iodocallophycoic acid A (1) showed moderate antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) with MIC values of 1.4 and 2.2 μg mL-1, respectively. It also potentiated the anti-MRSA activity of oxacillin in a synergistic fashion, resulting in an 8-fold increase in oxacillin potency, for a MIC of 16 μg mL-1.

Acne vulgaris is a common skin disorder that affects >85% of teenagers. Propionibacterium acnes is implicated in its pathogenesis, and like many other bacteria, is subject to emerging trends in antibiotic resistance. Novel therapies are in high demand. The aim of this study was to identify new leads for future pre-clinical development from herbal skin remedies used in Italy. We screened a unique natural product library composed of extracts from medicinal and randomly collected plants and fungi from the Mediterranean for growth-inhibitory and anti-biofilm activity in P. acnes. Evaluation of 157 extracts from 10 fungi and 58 plants led to the identification of crude extracts from seven species exhibiting growth inhibitory activity (MICs from 64-256 μg mL-1) and one with biofilm eradication activity (MBEC of 256 μg mL-1). None of these species, with the exception of Sweet Chestnut, have ever been reported for activity against P. acnes. All active extracts were examined for cytotoxicity against an immortalized line of human keratinocytes (HaCaT), and while most were non-toxic, one fungal species was toxic at the same concentration required for its anti-acne activity (IC50=256 μg mL-1). Comparison of these extracts to natural product standards by HPLC revealed the presence of chlorogenic acid, p-coumaric acid, ellagic acid, gallic acid and tannic acid. The compound responsible for toxicity in the bioactive fungal sample was determined by LC-FTMS to be polyporic acid. Species used in the traditional medicine for skin infections and inflammations exhibited significantly greater (p<0.05) growth inhibitory activity than those with no reported topical application, suggesting that herbal remedies remain an untapped source for discovery efforts aimed at development of new therapeutics and cosmeceuticals for acne.

Propionibacterium acnes is implicated in the pathogenesis of acne vulgaris, which impacts >85% of teenagers. Novel therapies are in high demand and an ethnopharmacological approach to discovering new plant sources of anti-acne therapeutics could contribute to filling this void in effective therapies. The aims of our study were two-fold: (1) To determine if species identified in ethnopharmacological field studies as having traditional uses for skin and soft tissue infection (SSTI) exhibit significantly more activity against P. acnes than species with no such reported use; and (2) Chemically characterize active extracts and assess their suitability for future investigation. Extracts of Italian medicinal (for acne and other skin infection) and randomly collected plants and fungi were screened for growth-inhibitory and anti-biofilm activity in P. acnes using broth microdilution methods. Bioactive extracts were chemically characterized by HPLC and examined for cytotoxicity against human keratinocytes (HaCaTs). Following evaluation of 157 extracts from 10 fungi and 58 plants, we identified crude extracts from seven species exhibiting growth inhibitory activity (MICs 64-256 μg mL-1). All active extracts were examined for cytotoxicity against HaCaTs; extracts from one fungal and one plant species were toxic (IC50 256 μg mL-1). HPLC analysis with chemical standards revealed many of these extracts contained chlorogenic acid, p-coumaric acid, ellagic acid, gallic acid, and tannic acid. In conclusion, species used in traditional medicine for the skin exhibited significantly greater (p < 0.05) growth inhibitory and biofilm eradication activity than random species, supporting the validity of an ethnobotanical approach to identifying new therapeutics. The anti-acne activity of three extracts is reported for the first time: Vitis vinifera leaves, Asphodelus microcarpus leaves, and Vicia sativa aerial parts.

The Civil War from Apache Pass Megan Kate Nelson (bio) You are standing in an old wagon rut in Apache Pass, Arizona. The blue grama grasses undulate in the breeze and the grasshoppers whir around your feet. You are somewhat out of breath, as it is more than five thousand feet above sea level in the pass. The air is dry and the sky is a clear, vivid blue. You look around the broad valley, broken by gulches and ravines and surrounded by steep hillsides dotted with Arizona white oaks, mesquite trees, and chaparral. You are pretty sure you’re the only person out here. The wagon rut is one of the last traces of the old Butterfield Overland Mail Route, a vital link between Arizona mines and ranches, and markets both east and west. Beside it are the ruins of the mail station, a 1858 stone structure that housed a stationmaster and a cook, and stored food and forage for the stage teams that came up and over the Pass twice a week. A short distance away, more ruins: Old Fort Bowie, built in 1862 by Union soldiers, and abandoned six years later for a more suitable site higher in the pass. Down the hill from the rut, headstones push out of the grama like teeth. Into one of them are carved these words: “In Memory of Col. Stone. Supposed to be.” In the midst of all of these vestiges of the past is Apache Spring. It is the reason that the ruts, the station, the fort, and the cemetery are here. The spring bubbles up out of a small cavern in the hillside, the only water source in a sixty-mile radius. From where you are standing, beside a small trickle of a stream in the midst of the Chiricahua Mountains, the American Civil War seems very far away. These are not the verdant fields of Gettysburg, the dense and humid swamps of the Virginia Peninsula, the sandy beaches of the Sea Islands. There were no huge army camps here or massed charges at the enemy through the thick smoke of artillery fire. And therefore very few Civil War historians have examined this theater of the war, or even considered it part of the war’s master narrative, as Stacey Smith points out in her review essay for this special issue. But the West—an area of the continent stretching from the Pacific Coast to the 100th meridian—was a region [End Page 510] that provoked the sectional conflicts that brought on the American Civil War. And it is central to the military, political, and social histories of the war itself. Apache Pass sits at the center of the Southwest (West Texas, New Mexico, Arizona, southern Colorado, and southern Utah), the region in which most of the Civil War battles in the West were fought. The Spanish called the summit Puerto del Dado: Pass of the Die, suggesting that people moving through here rolled the dice and gambled with their lives. It was both a barrier and a bridge, a crossroads of war. Union and Confederate troops moved through Apache Pass many times over the course of the war, attempting to establish some measure of control and authority over the West, to make their dreams of empire manifest. Chiricahua Apaches—especially bands led by Cochise and Mangas Coloradas—clashed with American soldiers and civilians here, asserting their own territorial claims and disrupting both Union and Confederate plans for the future. When you stand in Apache Pass and see the war from here, you reorient your vision. You see the Civil War as a central part of the complex history of American expansion and empire building, and resistance to it—not a lull in that history.1 You see clearly, perhaps more clearly than any other theater of the war, the important role of natural resources in provoking struggles for power and in shaping the nature of warfare. You see the Civil War as not only a fight between white men over the right to own slaves, but also a series of conflicts between American Indians and Anglo Americans over the right to self-determination.2 These battles left...

Alarming trends in the spread of antibiotic resistance among pathogens, including Staphylococcus aureus, have pushed mankind toward what has been coined as the “post-antibiotic era.” Therefore, an indirect therapy is proposed, quorum quenching. Investigation of botanical folk medicines used in the Mediterranean for the treatment of skin and soft tissue infections identified Castanea sativa (European Chestnut) for its potential antibacterial activity. This work demonstrates the quorum sensing inhibitory activity of a methanolic C. sativa leaf extract against all S. aureus accessory gene regulator (agr) alleles (IC50 1.56 – 25 µg mL-1). The extract is nontoxic to human keratinocytes and does not inhibit the growth of S. aureus or skin commensal bacteria. The bioactivity guided fractionation identified several compounds with ursene (1) and oleanene (2) backbones as the active compounds. The isolation and complete structure elucidation was performed using LC FT-MS and a suite of 1D and 2D NMR experiments.

[This corrects the article DOI: 10.1371/journal.pone.0136486.].

Plant material from different organs of Pistacia terebinthus L., (Anacardiaceae) were collected in Kosovo with aim to analyze the chemical variability of the essential oils among native populations and to test them for potential antibacterial activity against Staphylococcus aureus.