Antibiotic resistance in dermatology: The scope of the problem and strategies to address it.

Antibiotic resistance is a growing health concern that has attracted increasing attention from clinicians and scientists in recent years. Although resistance is an inevitable consequence of bacterial evolution and natural selection, misuse and overuse of antibiotics play a significant role in its acceleration. Antibiotics are the mainstay of therapy for common dermatoses, including acne and rosacea, as well as for skin and soft tissue infections. Therefore, it is critical for dermatologists and physicians across all disciplines to identify, appropriately manage, and prevent cases of antibiotic resistance. This review explores dermatologic conditions in which the development of antibiotic resistance is a risk and discusses mechanisms underlying the development of resistance. We discuss disease-specific strategies for overcoming resistant strains and improving antimicrobial stewardship along with recent advances in the development of novel approaches to counter antibiotic resistance.

Management of Ichthyosis: A Brief Review

The ichthyoses, also termed the disorders of keratinization, are a heterogenous group of skin diseases in which a distinctive horny layer arises secondary to excessive transepidermal water loss. Although occasionally acquired, the majority of ichthyoses are inherited and can be pinpointed to characteristic genetic mutations. Management depends on disease severity and includes topical agents and lifestyle modifications with or without oral retinoids. Genetic counseling is also an important consideration. This review aims to highlight advances in our understanding of disease pathogenesis as well as the holistic approach necessary to adequately manage ichthyosis patients.

Tildrakizumab for Moderate-to-Severe Plaque Psoriasis

Psoriasis is an immune-mediated inflammatory skin condition associated with many comorbidities and poor quality of life. The pathogenesis of psoriasis is complex and involves numerous proinflammatory cytokines. Many biologic therapies have been developed to block the action of these proinflammatory molecules, including inhibitors of tumor necrosis factor (TNF), interleukin (IL)-17, IL-12, and IL-23. IL-23 is composed of two subunits, p19 and p40. The p40 subunit is shared with IL-12, and inhibitors of the p40 subunit can block both IL-12 and IL-23 signaling. Recent advances in the understanding of psoriasis, however, have shown IL-23 to be more important than IL-12 in the pathogenesis of psoriasis. This has led to the development of IL-23p19 antagonists, the newest class of biologics for psoriasis. Here, we will discuss the safety and efficacy of tildrakizumab, a monoclonal antibody targeting IL-23p19.

Brief Update on Dermatologic Uses of Methotrexate

Methotrexate (MTX), an agent originally intended for anti-neoplastic use, has been successfully employed in the treatment of a variety of dermatologic conditions. In addition to its multiple clinical indications, variable dosing and modes of administration make it a viable option for patients of all ages and most comorbidities. MTX is a folate analog that antagonizes dihydrofolate reductase, thus inhibiting thymidylate synthesis and, ultimately, the production of pyrimidine. Depending on dosage, MTX can function as an anti-inflammatory agent, immunomodulator, or antimetabolite. Patients suffering from psoriasis have benefited from MTX in addition to those with atopic dermatitis, chronic urticaria, pemphigus vulgaris, bullous pemphigoid, cutaneous lupus erythematosus, cutaneous sarcoidosis, and mycosis fungoides. Although patients with these conditions can benefit from MTX treatment, the drug can cause adverse sequelae, including hematologic, pulmonary, gastrointestinal, and hepatic side effects. Therefore, the drug should be administered under careful physician supervision.

Shingrix for Herpes Zoster: A Review

Herpes zoster (HZ), also known as shingles, results from reactivation of the latent varicella-zoster virus (VZV), which commonly causes chickenpox in childhood. Greater than 90% of adults are infected with this virus, putting them at risk for reactivation. HZ presents as a painful, vesicular rash distributed in a unilateral and dermatomal pattern along dorsal root or cranial nerve ganglia. The rash often presents with prodromal symptoms and progresses to include clear vesicular clusters, evolving through stages of pustulation, ulceration, and crusting. HZ therapy currently involves the use of antiviral agents and pain management; however, HZ prophylaxis has been strongly recommended in older adults through vaccination with a live attenuated vaccine, Zostavax®. A new recombinant subunit vaccine, HZ/su (Shingrix®), is the subject of this review. In clinical trials, HZ/su demonstrated an overall vaccine efficacy of 97.2% among participants 50 years of age or older, indicating a significantly reduced risk of HZ in these individuals. Shingrix® was approved by the US FDA in October 2017 as HZ prophylaxis.

Glycopyrronium Tosylate (Qbrexza) for Hyperhidrosis

Hyperhidrosis is a condition characterized by excessive sweat production beyond which is physiologically necessary for thermal regulation. Affecting over 4.8% of the United States population, studies have shown that severe primary hyperhidrosis interferes with daily activities and can be considered intolerable, negatively impacting a patient's quality of life. Glycopyrronium tosylate is a topical anticholinergic agent that reduces sweat production by blocking the activation of acetylcholine receptors in peripheral sweat glands. In clinical trials, topical glycopyrronium tosylate, a pre-moistened cloth containing 2.4% glycopyrronium solution, was shown to be an effective, safe and non-invasive treatment for patients suffering from primary hyperhidrosis. This review examines the clinical trials of topical glycopyrronium tosylate and its role in primary hyperhidrosis. Glycopyrronium tosylate was recently US FDA-approved (as of June 2018) to manage patients with primary axillary hyperhidrosis.

Topical Diacerein Ointment for Epidermolysis Bullosa Simplex: A Review

Epidermolysis bullosa (EB) is a group of rare mucocutaneous fragility disorders often presenting in infancy and early childhood with painful blistering of the skin and mucous membranes. The severity of EB blister burden varies by disease subtype. Studies have shown that patients with generalized severe epidermolysis bullosa simplex (EBS), a variant characterized by extreme fragility, develop blisters in the setting of overproduced, mutated K14 protein, a component of the intermediate filament integral in keratinocyte stability, and constitutive activation of interleukin (IL)-1 , a pro-inflammatory cytokine that promotes the hyperproliferation of keratinocytes. Diacerein, a rhein prodrug and anthraquinone, has been shown to reduce expression of K14 and inhibit IL-1 converting enzyme. In clinical trials, topical 1% diacerein was shown to be an effective and safe, non-invasive treatment for patients suffering from EBS. This review examines the clinical trials of topical diacerein and its role in EBS. Diacerein ointment was granted US FDA Rare Pediatric Disease designation in May 2018 and Fast Track development designation in August 2018.

An assessment of social media usage by dermatology residency programs.

Despite the increasing popularity of social media, the activity of dermatology residency programs on top social media platforms has never been investigated to our knowledge. We investigated a total of 126 dermatology residency programs to assess their presence and popularity on social media. Searches were conducted to identify dermatology residency departments' accounts on Facebook, Twitter, and Instagram. The number of Facebook likes, Twitter followers, and Instagram followers were recorded. Of the 126 dermatology residency programs, 29 (23%) were active on Facebook, 14 (11%) on Twitter, and 9 (7%) on Instagram. There was a wide range in the number of Facebook likes, Twitter followers, and Instagram followers. The top ten dermatology residency programs with the highest Facebook likes, Twitter followers, and Instagram followers were charted. Our results demonstrate the sparse usage of social media by dermatology residency programs. Although social media continues to increase in prevalence, dermatology residency programs are underutilizing these valuable resources.

Evaluation and Prediction of Human Lumbar Vertebrae Endplate Mechanical Properties Using Indentation and Computed Tomography.

Current implant materials and designs used in spinal fusion show high rates of subsidence. There is currently a need for a method to predict the mechanical properties of the endplate using clinically available tools. The purpose of this study was to develop a predictive model of the mechanical properties of the vertebral endplate at a scale relevant to the evaluation of current medical implant designs and materials. Twenty vertebrae (10 L1 and 10 L2) from 10 cadavers were studied using dual-energy X-ray absorptiometry to define bone status (normal, osteopenic, or osteoporotic) and computed tomography (CT) to study endplate thickness (µm), density (mg/mm3), and mineral density of underlying trabecular bone (mg/mm3) at discrete sites. Apparent Oliver-Pharr modulus, stiffness, maximum tolerable pressure (MTP), and Brinell hardness were measured at each site using a 3 mm spherical indenter. Predictive models were built for each measured property using various measures obtained from CT and demographic data. Stiffness showed a strong correlation between the predictive model and experimental values (r = 0.85), a polynomial model for Brinell hardness had a stronger predictive ability compared to the linear model (r = 0.82), and the modulus model showed weak predictive ability (r = 0.44), likely due the low indentation depth and the inability to image the endplate at that depth (≈0.15 mm). Osteoporosis and osteopenia were found to be the largest confounders of the measured properties, decreasing them by approximately 50%. It was confirmed that vertebral endplate mechanical properties could be predicted using CT and demographic indices.

Dermatology on Google.

Google+ sets itself apart from other social media platforms through a number of unique features, including search engine optimization services and high user satisfaction. The purpose of this study was to evaluate the presence of dermatological entities on Google+. Searches were conducted to locate any Google+ accounts associated with the most popular dermatology journals, dermatological patient-centered organizations, and professional dermatology-related organizations on social media. Additionally, "dermatology Google+" was searched via Google, and Google+ profiles retrieved in the first page of results were assessed. Four of the five active Google+ profiles identified in the first page of Google search results were run by private dermatology practices. Only one of the 13 searched journals was active on Google+. Twenty-six of the 34 patient-centered and professional organizations had Google+ accounts, but only seven of these accounts were active in the last year. Therefore, unlike some private practices, the majority of dermatology journals and organizations have yet to take advantage of the exclusive opportunities offered by Google+ to expand their audiences and bolster their overall online presence.

Dermatology on Flickr.

Flickr, which was launched in 2004, is one of the oldest photo-sharing services online. The company, which was once at the forefront of the internet social media explosion, lost users and received criticism as its repeated acquisitions by other companies forced users to adapt to new owners. Now facing another acquisition by the online photo-sharing service SmugMug, the future is uncertain again for the once popular internet and mobile application service. Flickr, with its rapid rise in popularity, sudden halt in growth, and its gradual loss of users and popularity, has been repeatedly looked to as a lesson for other internet startups on the necessity of adapting quickly in the current internet age. Given the rise of social media use in the healthcare field, and the long-standing presence of Flickr on the internet, this study investigated the presence of dermatology-related content on Flickr and how the photo-sharing platform has applied to the visual field of dermatology, its dermatologists, and its professional associations.

An updated assessment of social media usage by dermatology journals and organizations.

Despite the increasing prevalence of social media usage, the activity of dermatology journals and professional and patient-centered organizations on top social media platforms has not been investigated since 2012. We investigated a total of 124 dermatology journals, 242 professional organizations, and 78 patient-centered organizations to assess their presence and popularity on social media. Searches were conducted to identify journals and organizations on Facebook and Twitter. Similar searches were done for organizations on LinkedIn. The number of Facebook likes, Twitter followers, and LinkedIn followers of the dermatological entities were quantified. There were 22 (17.7%) dermatology journals active on Facebook and 21 (16.9%) on Twitter. Amongst the professional organizations, 114 (47.1%) were on Facebook, 69 (28.5%) on Twitter, and 50 (20.7%) on LinkedIn. In comparison, 68 (87.2%) patient-centered organizations were on Facebook, 56 (71.8%) on Twitter, and 56 (71.8%) on LinkedIn. Our results demonstrate that the popularity of dermatology journals and professional and patient-centered organizations on top social networking sites has grown markedly since 2012. Although the number of dermatology journals on social media has increased since 2012, their presence continues to trail behind professional and patient-centered dermatological organizations, suggesting underutilization of a valuable resource.

Cannabinoids in dermatology: a scoping review.

The therapeutic applications of cannabis and cannabinoids are an increasingly conspicuous topic as de-criminalization and legalization of these products continues to expand. A limited number of cannabinoid compounds have been approved for a specific set of conditions. However, the current role of cannabinoids for the treatment of dermatologic conditions remains to be defined. We conducted a review of the current literature to determine the applications of cannabinoids for the therapy of various skin diseases. After conducting our analysis, we found that cannabinoid products have the potential to treat a variety of skin conditions, including acne vulgaris, allergic contact dermatitis, asteatotic dermatitis, atopic dermatitis, hidradenitis suppurativa, Kaposi sarcoma, pruritus, psoriasis, skin cancer, and the cutaneous manifestations of systemic sclerosis. However, the majority of available data on these compounds are pre-clinical and there is a corresponding lack of high-quality randomized, controlled trials that evaluate their effects. Cannabinoids have shown some initial promise as therapy for a variety of skin diseases. However, there is a requirement for thorough pre-clinical research and large-scale, randomized, controlled trials before cannabinoids can be considered safe and effective treatments for these conditions.

Dermatology on YouTube - an update and analysis of new trends.

Because YouTube is one of the most popular search engines, it is an instrumental tool to stay up to date on the most relevant dermatology trends and content in order to better direct patients and improve health outcomes. Twelve select terms (i.e. Dermatology, Sun protection, Skin cancer awareness, Skin cancer, Skin condition, Sun safety, Tanning, Melanoma, Basal cell carcinoma, Squamous cell carcinoma, Skin cancer treatment, Skin cancer prevention) were searched on YouTube. Overall, the results included 240 videos with over 160 million views. Educational content was most prevalent at 35% of the total search results. Of the total videos, 42% were uploaded by or featured a medical health professional (MD, DO, PhD, RN, ND), with 28% involving a board-certified dermatologist. Trends in content type have changed: educational and personal videos have increased, while advocacy and advertising have decreased. Most search terms are moving in a positive, informative direction, specifically the term "tanning." Other search terms such as "skin condition" and "skin cancer treatment" should be more closely monitored for misleading and perhaps harmful information. Therefore, dermatologists and other medical personnel should keep pace with relevant and popular dermatology content on YouTube in order to understand, advise, market, educate, and address patients' questions and concerns.

Atorvastatin calcium encapsulated eudragit nanoparticles with enhanced oral bioavailability, safety and efficacy profile.

Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.

Dermatology on Snapchat.

Launched in 2011, Snapchat is one of the newest social media platforms with over 158 million active daily users. This study investigated the presence of dermatology-related content on Snapchat. We searched for Snapchat accounts for the top ten most popular dermatology journals, professional dermatological organizations, and dermatology-related patient advocate groups on social media. None of the above-mentioned entities were found on Snapchat. Plastic surgeons were found to primarily utilize the application, although one prominent dermatologist was also found. It was theorized that the brevity of the "snaps" was a contributing factor for dermatological organizations to not use the application. However, Snapchat in the right practice setting may be useful for dermatologists, not only to educate followers, but also as a marketing tool to Millennials.

Simultaneous Detection and Quantification of Phytohormones by a Sensitive Method of Separation in Culture of Pseudomonas sp.

A high-performance thin-layer chromatography (HPTLC)-based sensitive, rapid and stringent protocol is designed for detection and quantification of five phytohormones simultaneously. Culture filtrate of Pseudomonas bacteria was acidified with 7 M HCl and extracted with an equal volume of ethyl acetate to separate abscisic acid (ABA), jasmonic acid (JA), gibberellic acid (GA3), and indole-3-acetic acid (IAA). Kinetin was extracted from the remaining water fraction of the same extract. Various extracts were loaded on silica gel 60 F254 foil using Linomat 5 spray on applicator. Standard phytohormones were also loaded adjacent to the sample, and the foils were developed with isopropanol-ammonia-water [10:1:1 (v/v)] as the mobile phase. A quantitative estimation of the separated ABA, kinetin, JA, GA3, and IAA was performed by measuring the absorbance at 260, 275, 295, 265, and 280 nm, respectively. HPTLC method was found to be cost effective, robust technique that can be routinely used for simultaneous phytohormone detection in plant or bacterial samples. The present work is not only useful for detection and quantification of phytohormones but also for screening of phytohormone producing microorganisms.

Formulation, optimization and characterization of cationic polymeric nanoparticles of mast cell stabilizing agent using the Box-Behnken experimental design.

OBJECTIVE: The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. METHODS: The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. RESULTS: SCG-CSNPs exhibited particle size of 200.4 ± 4.06 nm and %EE of 62.68 ± 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in-vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. CONCLUSIONS: The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs.

Curcumin-polymeric nanoparticles against colon-26 tumor-bearing mice: cytotoxicity, pharmacokinetic and anticancer efficacy studies.

CONTEXT: Curcumin (CUR), can inhibit proliferation and induce apoptosis of tumor cells, its extreme insolubility and limited bioavailability restricted its clinical application. OBJECTIVE: An innovative polymeric nanoparticle of CUR has been developed to enhance the bioavailability and anti-cancer efficacy of CUR, in vitro and in vivo. MATERIALS AND METHODS: Cationic copolymer Eudragit E 100 was selected as carrier, which can enhance properties of poor bioavailable chemotherapeutic drugs (CUR). The CUR-loaded Eudragit E 100 nanoparticles (CENPs) were prepared by emulsification-diffusion-evaporation method. The in vitro cytotoxicity study of CENPs was carried out using sulphorhodamine B assay. Pharmacokinetic and anti-cancer efficacy of CENPs was investigated in Wister rats as well as colon-26 tumor-bearing mice after oral administration. RESULTS: CENPs showed acceptable particle size and percent entrapment efficiency. In vitro cytotoxicity studies in terms of 50% cell growth inhibition values demonstrated ∼19-fold reduction when treated with CENPs as compared to pure CUR. ∼91-fold increase in Cmax and ∼95-fold increase in AUC0-12h were observed indicating a significant enhancement in the oral bioavailability of CUR when orally administered as CENPs compared to pure CUR. The in vivo anti-cancer study performed with CENPs showed a significant increase in efficacy compared with pure CUR, as observed by tumor volume, body weight and survival rate. CONCLUSIONS: The results clearly indicate that the developed polymeric nanoparticles offer a great potential to improve bioavailability and anticancer efficacy of hydrophobic chemotherapeutic drug.

Highly water-soluble mast cell stabiliser-encapsulated solid lipid nanoparticles with enhanced oral bioavailability.

Cromolyn sodium (CS), a mast cell stabiliser, is widely employed for the prevention and treatment of allergic conditions. However, high hydrophilicity and poor oral permeability hinder its oral clinical translation. Here, solid lipid nanoparticles (SLNs) have been developed for the purpose of oral bioavailability enhancement. The CS-SLNs were engineered by double emulsification method (W1/O/W2) and optimised by using Box-Behnken experimental design. The surface and solid-state characterisations revealed the presence of CS in an amorphous form without any interactions inside the spherical-shaped SLNs. The in-vitro release study showed an extended release up to 24 hr by diffusion controlled process. Ex-vivo and in-vivo intestinal permeation study showed ∼2.96-fold increase in permeability of CS by presentation as SLNs (p < 0.05). Further, in-vivo pharmacokinetic study exhibited ∼2.86-fold enhancements in oral bioavailability of CS by encapsulating inside SLNs, which clearly indicate that SLNs can serve as the potential therapeutic carrier system for oral delivery of CS.