Renal injury in scleromyxoedema due to monoclonal gammopathy associated C3 glomerulonephritis.

Scleromyxoedema is a rare mucinosis that primarily affects the skin. It is associated with monoclonal gammopathy and has many extracutaneous manifestations, however, renal involvement is rare. We report the case of a woman with monoclonal gammopathy and scleromyxoedema presenting with progressive exertional dyspnoea and acute renal failure. Workup of her renal failure revealed monoclonal gammopathy associated C3 glomerulonephritis. She was treated with intravenous steroids and discharged with plans to pursue annual monoclonal gammopathy laboratory monitoring. Given the rarity of renal scleromyxoedema, careful investigation of extracutaneous manifestations and comorbidities is critical to discern the primary pathological process in patients with scleromyxoedema who develop renal insufficiency.

A Survey-Based Comparison of Sun Safety Practices in a Representative Cohort of the General Public Versus Attendees of a Skin Cancer Screening

A large proportion of data on photoprotective practices is yielded from free skin cancer screenings. However, the sun safety practices of populations who seek these skin cancer screenings may differ from the general public. To examine differences in skin cancer prevention practices and risk factors, we surveyed pedestrians at six locations in Washington, DC (public group, n=285) and attendees of a free skin cancer screening (screening group, n=144) using an IRB-approved survey. The screening group was older and included more individuals with fair skin than the public group. Respondents from the screening group were significantly more likely to always wear sunscreen, always seeks shade, and always or sometimes wear sun-protective clothing than the public group (P<0.05). To examine whether younger and non-white participants, who were less likely to attend our free screening, have different practices and risk factors than older and white participants, respectively, we compared survey answers for all participants by age and race. White participants were more likely to always or sometimes wear sunscreen and sun-protective clothing than non-white participants (P<0.05). Patients over 61 years were more likely to always seek shade and wear sun-protective clothing than those younger than 31 years (P<0.05). Therefore, free skin cancer screenings need to be better popularized among non-white and younger populations or more effective educational vehicles are needed. J Drugs Dermatol. 2019;18(7):649-653.

A Survey-Based Comparison of Sun Safety Practices in a Representative Cohort of the General Public Versus Attendees of a Skin Cancer Screening

A large proportion of data on photoprotective practices is yielded from free skin cancer screenings. However, the sun safety practices of populations who seek these skin cancer screenings may differ from the general public. To examine differences in skin cancer prevention practices and risk factors, we surveyed pedestrians at six locations in Washington, DC (public group, n=285) and attendees of a free skin cancer screening (screening group, n=144) using an IRB-approved survey. The screening group was older and included more individuals with fair skin than the public group. Respondents from the screening group were significantly more likely to always wear sunscreen, always seeks shade, and always or sometimes wear sun-protective clothing than the public group (P<0.05). To examine whether younger and non-white participants, who were less likely to attend our free screening, have different practices and risk factors than older and white participants, respectively, we compared survey answers for all participants by age and race. White participants were more likely to always or sometimes wear sunscreen and sun-protective clothing than non-white participants (P<0.05). Patients over 61 years were more likely to always seek shade and wear sun-protective clothing than those younger than 31 years (P<0.05). Therefore, free skin cancer screenings need to be better popularized among non-white and younger populations or more effective educational vehicles are needed. J Drugs Dermatol. 2019;18(7):649-653.

Managing Seborrheic Keratosis: Evolving Strategies and Optimal Therapeutic Outcomes.

Seborrheic keratosis (SK) is the most common skin tumor seen by dermatologists in everyday practice. Although the lesions are mostly benign, many patients still elect to have asymptomatic SK removed. The historical standards of treatment are cryosurgery and electrocautery, two surgical options that are effective at lesion removal but have high rates of postoperative adverse events such as treatment-site scarring and pigmentary alterations. The cosmetic outcomes of SK treatment modalities are of keen interest to dermatologists, as the American population becomes increasingly more diverse. In this article, the inclusion of darker Fitzpatrick skin types into clinical studies investigating post-treatment side effects of SK therapy is reviewed. The recent approval of a 40% hydrogen peroxide topical formulation is discussed in light of these issues, and several non-invasive topical treatments that optimize cosmetic outcomes of SK lesion removal are highlighted. Finally, treatment strategies aimed at reducing cost and minimizing the burden of adverse sequelae are provided. J Drugs Dermatol. 2018;17(9):933-940.

Blastomycosis-like Pyoderma Arising in Lichen Planus.

Blastomycosis-like pyoderma (BLP) is a rare reactive skin disease that is most commonly caused by bacterial infection. Herein we present a case of BLP arising in lichen planus, a chronic inflammatory disease. We propose Wolf's isotopic response, or the appearance of a new skin disease at the site of an existing and unrelated disease, as the underlying molecular mechanism responsible for this unusual physical presentation. It is important that clinicians recognize atypical morphologies such as BLP, which mimics squamous cell carcinoma both clinically and pathologically. These similarities highlight the need for a tissue diagnosis to identify infectious etiologies and rule out malignancy when BLP is suspected. J Drugs Dermatol. 2018;17(2):233-235.

Phenotype and Antimicrobial Activity of Th17 Cells Induced by Propionibacterium acnes Strains Associated with Healthy and Acne Skin.

Studies of the human skin microbiome suggest that Propionibacterium acnes strains may contribute differently to skin health and disease. However, the immune phenotype and functions of T helper type 17 (Th17) cells induced by healthy (PH) versus acne (PA) skin-associated P. acnes strains are currently unknown. We stimulated peripheral blood mononuclear cells from healthy donors and observed that PA strains induce higher IL-17 levels than PH strains. We next generated PH and PA strain-specific Th17 clones and show that P. acnes strains induce Th17 cells of varied phenotype and function that are stable in the presence of IL-2 and IL-23. Although PH- and PA-specific clones expressed similar levels of LL-37 and DEFB4, only PH-specific clones secreted molecules sufficient to kill P. acnes. Furthermore, electron microscopic studies showed that supernatants derived from activated PH and not PA-specific clones exhibited robust bactericidal activity against P. acnes, and complete breaches in the bacterial cell envelope were observed. This antimicrobial activity was independent of IL-26, because both natural IL-26 released by Th17 clones and rhIL-26 lacked antimicrobial potency against P. acnes. Overall, our data suggest that P. acnes strains may differentially modulate the CD4+ T-cell responses, leading to the generation of Th17 cells that may contribute to either homeostasis or acne pathogenesis.

G2A Attenuates Propionibacterium acnes Induction of Inflammatory Cytokines in Human Monocytes.

BACKGROUND: Acne vulgaris is a disease of the pilosebaceous unit characterized by increased sebum production, hyperkeratinization, and immune responses to Propionibacterium acnes (PA). Here, we explore a possible mechanism by which a lipid receptor, G2A, regulates immune responses to a commensal bacterium. OBJECTIVE: To elucidate the inflammatory properties of G2A in monocytes in response to PA stimulation. Furthermore, our study sought to investigate pathways by which lipids modulate immune responses in response to PA. METHODS: Our studies focused on monocytes collected from human peripheral blood mononuclear cells, the monocytic cell line THP-1, and a lab strain of PA. Our studies involved the use of enzyme-linked immunosorbent, Western blot, reverse transcription polymerase chain reaction, small interfering RNA (siRNA), and microarray analysis of human acne lesions in the measurements of inflammatory markers. RESULTS: G2A gene expression is higher in acne lesions compared to normal skin and is inducible by the acne therapeutic, 13-cis-retinoic acid. In vitro, PA induces both the Toll-like receptor 2-dependent expression of G2A as well as the production of the G2A ligand, 9-hydroxyoctadecadienoic acid, from human monocytes. G2A gene knockdown through siRNA enhances PA stimulation of interleukin (IL)-6, IL-8, and IL-1ß possibly through increased activation of the ERK1/2 MAP kinase and nuclear factor kappa B p65 pathways. CONCLUSION: G2A may play a role in quelling inflammatory cytokine response to PA, revealing G2A as a potential attenuator of inflammatory response in a disease associated with a commensal bacterium.

Different Propionibacterium acnes Phylotypes Induce Distinct Immune Responses and Express Unique Surface and Secreted Proteomes.

Propionibacterium acnes is a skin commensal bacterium that contributes to the development of acne vulgaris and other infections. Recent work revealed that P. acnes clinical isolates can be classified into distinct phylotypes, several of which have associations with healthy skin or acne. We sought to determine if these phylotypes induce different immunological responses and express protein factors that may contribute to their disease associations. We found that acne-associated P. acnes phylotypes induced 2- to 3-fold higher levels of IFN-γ and IL-17 in peripheral blood mononuclear cells compared with healthy phylotypes. On the other hand, P. acnes phylotypes associated with healthy skin induced 2- to 4-fold higher levels of IL-10. Comparative proteomic analysis of P. acnes phylotypes revealed a differential expression of several proteins, including an adhesion protein that was expressed at least 10-fold higher in acne-associated phylotypes and a cell surface hydrolase expressed in all phylotypes except those associated with healthy skin. Taken together, our data provide insight into how specific P. acnes phylotypes influence immune responses and the pathogenesis of acne.

Nitric Oxide-Releasing Nanoparticles Prevent Propionibacterium acnes-Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response.

Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 (NLR, nucleotide oligomerization domain-like receptor) inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we used an established nanotechnology capable of generating/releasing NO over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, although human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1ß, tumor necrosis factor-α (TNF-α), IL-8, and IL-6 from human monocytes, and IL-8 and IL-6 from human keratinocytes, respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 ß secretion from monocytes, and neither TNF-α nor IL-6 secretion, nor inhibition by NO-np was found to be dependent on this pathway. The observed mechanism by which NO-np impacts IL-1ß secretion was through inhibition of caspase-1 and IL-1ß gene expression. Together, these data suggest that NO-np can effectively prevent P. acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response.

Fluorescence-based endoscopic imaging of Thomsen-Friedenreich antigen to improve early detection of colorectal cancer.

Thomsen-Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level.

Linking genes of unknown function with abiotic stress responses by high-throughput phenotype screening.

Over 13% of all genes in the Arabidopsis thaliana genome encode for proteins classified as having a completely unknown function, with the function of >30% of the Arabidopsis proteome poorly characterized. Although empirical data in the form of mRNA and proteome profiling experiments suggest that many of these proteins play an important role in different biological processes, their functional characterization remains one of the major challenges in modern biology. To expand the annotation of genes with unknown function involved in the response of Arabidopsis to different environmental stress conditions, we selected 1007 such genes and tested the response of their corresponding homozygous T-DNA insertional mutants to salinity, oxidative, osmotic, heat, cold and hypoxia stresses. Depending on the specific abiotic stresses tested, 12-31% of mutants had an altered stress-response phenotype. Interestingly, 832 out of 1007 mutants showed tolerance or sensitivity to more than one abiotic stress treatment, suggesting that genes of unknown function could play an important role in abiotic stress-response signaling, or general acclimation mechanisms. Further analysis of multiple stress-response phenotypes within different populations of mutants revealed interesting links between acclimation to heat, cold and oxidative stresses, as well as between sensitivity to ABA, osmotic, salinity, oxidative and hypoxia stresses. Our findings provide a significant contribution to the biological characterization of genes with unknown function in Arabidopsis and demonstrate that many of these genes play a key role in the response of plants to abiotic stresses.

Carpal tunnel syndrome as an occupational disease.

BACKGROUND: Symptoms related to carpal tunnel syndrome (CTS) represent common patient complaints for many primary care physicians. However, there is a surprising lack of guidelines on diagnosing occupational CTS readily accessible to primary care physicians. This article aims to fill part of that void by reviewing historical aspects of occupational CTS, leading up to more current epidemiologic studies of the association of CTS with occupational ergonomic risk factors. METHODS: The English medical literature was reviewed on the relationship between CTS and occupational ergonomic risk factors. Recent legislative initiatives are discussed. Guidelines of diagnosing and managing occupational CTS are outlined. RESULTS: Many studies are divided regarding whether CTS is associated with highly repetitive/forceful/vibration work. However, a subset of patients presenting with symptoms related to CTS probably has occupational CTS. These patients can be objectively diagnosed and successfully treated and are able to return to work. CONCLUSIONS: By being armed with knowledge regarding the background of CTS and by following simple diagnosis and treatment guidelines, the family practitioner should be able to manage many patients presenting with work-related CTS.