An Intriguing Case of Back Pain in an Elderly Male.

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Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study.

BACKGROUND: Atopic dermatitis (AD), a chronic, highly pruritic skin disorder, impairs quality of life (QoL). Janus kinase inhibitors suppress inflammatory and pruritus-associated cytokine signaling in AD. OBJECTIVE: To report the effects of ruxolitinib (RUX) cream on itch and QoL in AD. METHODS: A total of 307 adult patients with an Investigator's Global Assessment (score of 2 or 3) and 3% to 20% affected body surface area were randomly assigned for 8 weeks to receive double-blind treatment with RUX (1.5% twice daily, 1.5% once daily, 0.5% once daily, or 0.15% once daily), vehicle twice daily, or triamcinolone cream (0.1% twice daily for 4 weeks then vehicle for 4 weeks). Itch was measured by using the numerical rating scale, and patient QoL was assessed with Skindex-16. RESULTS: Improvements in itch numerical rating scale and Skindex-16 were observed with RUX cream. Overall, 42.5% of patients who applied 1.5% RUX twice daily experienced minimal clinically important difference in itch within 36 hours of treatment (vehicle, 13.6%; P < .01); near-maximal improvement was observed by week 4. Itch reduction was associated with improved QoL burden (Pearson correlation, 0.67; P < .001). Significant improvements in Skindex-16 overall scores were noted at week 2. LIMITATIONS: Facial AD lesions were not treated. CONCLUSION: RUX cream provides a clinically meaningful reduction in itch and QoL burden.

Evaluation of microleakage in class-II bulk-fill composite restorations.

BACKGROUND/PURPOSE: Despite the clinical appeal of restoring deep class II cavities in single increment using bulk-fill resin composite, sealing of bulk-filled composite restorations is a concern. This study evaluated interfacial adaptation of bulk-fill composite restoration to axial wall and gingival floor of class II cavities using cross-polarization optical coherence tomography (CP-OCT). MATERIALS AND METHODS: Box-shaped class II cavities were prepared in extracted molars and divided into three groups (n = 7) according to adhesive used; Clearfil SE Bond 2 (SE2), Tetric-N Bond Self-Etch (TSE) or Tetric-N Bond Universal (TNU). All adhesives were applied in self-etch mode and according to manufacturers' recommendation. Then, preparations were bulk-filled with Filtek Bulk Fill Posterior Restorative resin composite and immersed in a contrast agent. Tomographic images of axial wall and gingival floor of each restoration were obtained by CP-OCT (IVS-300, Santec) with a central wavelength of 1330 nm and were imported to an image analysis software to quantify microleakage. RESULTS: Mann-Whitney U test showed statistically significant difference in microleakage percentage between the groups at both axial wall and gingival floor (p < 0.05). SE2 group had the lowest percentage of microleakage (p < 0.05), as only few cross-sections showed areas of reflections from contrast agent penetrating into axial wall (8.23 ±â€¯6.8) and gingival floor (7.07 ±â€¯4.1), followed by TNU group (18.13 ±â€¯12.9 axially and 30.61 ±â€¯11.9 gingivally). Microleakage was frequently observed at the axial wall and gingival floor of TSE group, showing the highest percentages of 25.50 ±â€¯12.5 and 36.97 ±â€¯10.2, respectively (p < 0.05). CONCLUSION: All tested groups exhibited different extent of interfacial microleakage, however, two-step self-etch adhesive yielded superior adaptation in comparison to one-step self-etch adhesive and universal adhesive.

Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream.

BACKGROUND: Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase 1 and Janus kinase 2, potently suppresses cytokine signaling involved in AD pathogenesis. OBJECTIVE: We sought to evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD. METHODS: In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment score of 2 or 3 (mild or moderate), and 3% to 20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], 0.5% QD, 0.15% QD), vehicle, or triamcinolone cream (0.1% BID for 4 weeks, then vehicle for 4 weeks). Subsequently, patients could apply 1.5% RUX BID for 4 additional weeks of open-label treatment. The primary end point was the comparison between 1.5% RUX cream BID and vehicle in mean percentage change from baseline in Eczema Area and Severity Index at week 4. RESULTS: All RUX regimens demonstrated therapeutic benefit at week 4; 1.5% BID provided the greatest improvement in Eczema Area and Severity Index (71.6% vs 15.5%; P < .0001) and Investigator's Global Assessment responses (38.0% vs 7.7%; P < .001) versus vehicle. Rapid reductions in the itch numerical rating scale score occurred within 36 hours (1.5% BID vs vehicle, ‒1.8 vs ‒0.2; P < .0001) and were sustained through 12 weeks. Patients who transitioned to 1.5% RUX BID improved in all measures. RUX was not associated with clinically significant application-site reactions. CONCLUSIONS: RUX cream provided rapid and sustained improvements in AD symptoms and was well tolerated.

Effect of self-etch adhesives on the internal adaptation of composite restoration: a CP-OCT Study.

Despite improvements in dental adhesive materials, internal adaptation remains a challenge in bonded restorations. The aim of this study was to compare microgaps and internal floor adaptation between two different self-etch adhesives in class-V cavities using cross-polarization optical coherence tomography (CP-OCT). In this in vitro study, standardized round class-V cavities were prepared in 20 non-carious human upper central incisor teeth. They were randomly divided into two groups, TN and SE, with each group receiving a different dental adhesive. In TN group, the adhesive used was all-in-one Tetric N-Bond Self-Etch (TN; Ivoclar/Vivadent, Liechtenstein), while SE group was bonded with two-step self-etch Clearfil SE Bond 2 adhesive (SE; Kuraray Noritake Dental Inc, Japan). The prepared cavities were restored with flowable composite and then stored in distilled water for 24 h. Next, they were immersed in silver nitrate, followed by immersion in a photo-developing solution. Optical comparison was carried out by CP-OCT to assess microgaps and composite adaptation at the cavity floor. A Mann-Whitney test was applied to the data, which showed a statistically significant difference in composite adaptation among the two groups (p < 0.001) with the SE group showing superior adaptation. CP-OCT is a reliable tool for non-invasive imaging that gives an insight into composite performance. Better adaptation was found with the two-step self-adhesive for the composite used in this study.

Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials.

BACKGROUND: Side effects may limit the use of current tetracycline-class antibiotics for acne. OBJECTIVE: Evaluate the efficacy and safety of once-daily sarecycline, a novel, narrow-spectrum tetracycline-class antibiotic, in moderate to severe acne. METHODS: Patients 9-45 years with moderate to severe facial acne (Investigator's Global Assessment [IGA] score ≥ 3, 20-50 inflammatory and ≤ 100 noninflammatory lesions, and ≤ 2 nodules) were randomized 1:1 to sarecycline 1.5 mg/kg/day or placebo for 12 weeks in identically designed phase 3 studies (SC1401 and SC1402). RESULTS: In SC1401 (sarecycline n=483, placebo n=485) and SC1402 (sarecycline n=519, placebo n=515), at week 12, IGA success (≥ 2-grade improvement and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6% (sarecycline), respectively, versus 10.5% and 15.3% (placebo; P less than 0.0001 and P equals 0.0038). Onset of efficacy in inflammatory lesions occurred by the first visit (week 3), with mean percentage reduction in inflammatory lesions at week 12 in SC1401 and SC1402 of -51.8% and -49.9% (sarecycline), respectively, versus -35.1% and -35.4% (placebo; P less than 0.0001). Onset of efficacy for absolute reduction of noninflammatory lesion count occurred at week 6 in SC1401 (P less than 0.05) and week 9 in SC1402 (P less than 0.01). In SC1401, the most common TEAEs (in ≥ 2% of either sarecycline or placebo group) were nausea (4.6% [sarecycline]; 2.5% [placebo]), nasopharyngitis (3.1%; 1.7%), headache (2.7%; 2.7%), and vomiting (2.1%; 1.4%) and, in SC1402, nasopharyngitis (2.5%; 2.9%) and headache (2.9%; 4.9%). Most were not considered treatment-related. Vestibular (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs both occurred in ≤ 1% of sarecycline patients. Gastrointestinal TEAE rates for sarecycline were low. Among females, vulvovaginal candidiasis (SC1401: 1.1% [sarecycline] and 0 [placebo]; SC1402: 0.3% and 0) and mycotic infection (0.7% and 0; 1.0% and 0) rates were low. CONCLUSION: The narrow-spectrum antibiotic sarecycline was safe, well tolerated, and effective for moderate to severe acne, with low rates of side effects common with tetracycline antibiotics. J Drugs Dermatol. 2018;17(9):987-996.

Optical Evaluation of Enamel Microleakage with One-Step Self-Etch Adhesives.

OBJECTIVE: In this in vitro study, cross-polarization optical coherence tomography (CP-OCT) was used to evaluate microleakage in dental composite restorations bonded to enamel with two types of one-step self-etching (SE) adhesives. BACKGROUND DATA: One-step SE adhesives were proposed to simplify bonding of composite restorations. However, bonding of these simplified adhesive to dental enamel is still questionable. OCT is a promising diagnostic tool that allows micron-scale imaging of biological tissues and structures. METHODS: Class-V cavities (4-mm diameter × 1-mm depth) were prepared on the labial surfaces of extracted human anterior teeth with margins and floor located in enamel. The cavities were then divided into two groups (n = 5) and restored with either Tetric N-Bond Universal (Ivoclar Vivadent, Liechtenstein) or Palfique Bond (Tokuyama Dental Corporation, Japan), followed by Estelite Flow Quick flowable composite (Tokuyama Dental Corporation). After storage in 100% humidity for 24 h, specimens were immersed in ammoniacal silver nitrate solution for another 24 h. Later, they were rinsed and immersed in photo-developing solution under fluorescent light for 8 h. CP-OCT at 1310 nm center wavelength was used to scan seven two-dimensional cross-sectional images from each specimen. Each cross-sectional image was analyzed using ImageJ software to quantify interfacial microleakage at the cavity floor. RESULTS: Student's t-test showed significant difference between the tested adhesives (p < 0.05). Palfique Bond adhesive presented inferior interfacial adaptation as it obtained higher values of floor microleakage compared to Tetric N-Bond Universal adhesive group. CONCLUSIONS: CP-OCT enabled nondestructive quantitative assessment of microleakage in enamel dental restorations.

Polyglycolic acid microneedles modified with inkjet-deposited antifungal coatings.

In this study, the authors examined use of piezoelectric inkjet printing to apply an antifungal agent, voriconazole, to the surfaces of biodegradable polyglycolic acid microneedles. Polyglycolic acid microneedles with sharp tips (average tip radius = 25 ± 3 µm) were prepared using a combination of injection molding and drawing lithography. The elastic modulus (9.9 ± 0.3 GPa) and hardness (588.2 ± 33.8 MPa) values of the polyglycolic acid material were determined using nanoindentation and were found to be suitable for use in transdermal drug delivery devices. Voriconazole was deposited onto the polyglycolic acid microneedles by means of piezoelectric inkjet printing. It should be noted that voriconazole has poor solubility in water; however, it is readily soluble in many organic solvents. Optical imaging, scanning electron microscopy, energy dispersive x-ray spectrometry, and Fourier transform infrared spectroscopy were utilized to examine the microneedle geometries and inkjet-deposited surface coatings. Furthermore, an in vitro agar plating study was performed on the unmodified, vehicle-modified, and voriconazole-modified microneedles. Unlike the unmodified and vehicle-modified microneedles, the voriconazole-modified microneedles showed antifungal activity against Candida albicans. The unmodified, vehicle-modified, and voriconazole-modified microneedles did not show activity against Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. The results indicate that piezoelectric inkjet printing may be useful for loading transdermal drug delivery devices such as polyglycolic acid microneedles with antifungal pharmacologic agents and other pharmacologic agents with poor solubility in aqueous solutions.

Energy efficient cooperation in underlay RFID cognitive networks for a water smart home.

Shrinking water resources all over the world and increasing costs of water consumption have prompted water users and distribution companies to come up with water conserving strategies. We have proposed an energy-efficient smart water monitoring application in [1], using low power RFIDs. In the home environment, there exist many primary interferences within a room, such as cell-phones, Bluetooth devices, TV signals, cordless phones and WiFi devices. In order to reduce the interference from our proposed RFID network for these primary devices, we have proposed a cooperating underlay RFID cognitive network for our smart application on water. These underlay RFIDs should strictly adhere to the interference thresholds to work in parallel with the primary wireless devices [2]. This work is an extension of our previous ventures proposed in [2,3], and we enhanced the previous efforts by introducing a new system model and RFIDs. Our proposed scheme is mutually energy efficient and maximizes the signal-to-noise ratio (SNR) for the RFID link, while keeping the interference levels for the primary network below a certain threshold. A closed form expression for the probability density function (pdf) of the SNR at the destination reader/writer and outage probability are derived. Analytical results are verified through simulations. It is also shown that in comparison to non-cognitive selective cooperation, this scheme performs better in the low SNR region for cognitive networks. Moreover, the hidden Markov model's (HMM) multi-level variant hierarchical hidden Markov model (HHMM) approach is used for pattern recognition and event detection for the data received for this system [4]. Using this model, a feedback and decision algorithm is also developed. This approach has been applied to simulated water pressure data from RFID motes, which were embedded in metallic water pipes.

Eruptive cherry hemangiomatosis associated with multicentric Castleman disease: a case report and diagnostic clue.

BACKGROUND: Eruptive cherry hemangiomatosis, which involves the sudden onset of multiple small vascular proliferations, has been rarely reported as a heralding sign of multicentric Castleman disease (MCD) and other lymphoproliferative diseases. We report a case wherein the rapid appearance of cherry hemangiomata is the presenting sign of MCD. OBSERVATIONS: A 25-year-old man with a 10-year history of benign vascular growths developed 23 cutaneous vascular proliferations and systemic symptoms 5 days prior to presentation. Biopsy of the cutaneous lesions revealed a polypoidal proliferation of vessels consistent with cherry hemangiomata. Laboratory studies disclosed systemic abnormalities, and the findings of a subsequent lymph node biopsy confirmed MCD. Combination chemotherapy was initiated, and the cutaneous proliferations improved in association with the systemic disease. CONCLUSIONS: There is a scarcity of literature describing the association between eruptive cherry hemangiomatosis and MCD. The likely underlying mechanism is hypersecretion of vascular endothelial growth factor secondary to an elevated interleukin 6 level. Failure to recognize this association may have led to diagnostic delays. The authors suggest careful evaluation and follow-up of all patients presenting with the sudden onset of cherry hemangiomata, particularly with systemic symptoms, lymphadenopathy, or other benign vascular endothelial growths, for the potential development of MCD and other lymphoproliferative diseases.

Nanotechnology and dermatology education in the United States: data from a pilot survey.

BACKGROUND: Nanotechnology is a rapidly growing discipline with important implications for consumers, patients, physicians and investigators. In an era when nanotechnology is being both incorporated into educational requirements for medical fields such as radiology and oncology and vigorously pursued and developed by cosmeceutical companies, dermatology is falling behind. A survey was conducted to ascertain knowledge, attitudes and perception of nanotechnology in dermatology teaching programs. METHODS: To ascertain baseline knowledge, attitudes and preceptions regarding nanotechnology among dermatology trainees, dermatology investigators and dermatology faculty in US academic medical centers, an online survey was sent out to random members of the dermatology community and data analyzed (100 participants, 23% response rate). Participants responded to a questionnaire on a five-point scale ranging from strongly disagree, disagree, uncertain, agree, to strongly agree. Due to the low response rate, strongly disagree/disagree and strongly agree/agree values were combined and compared to uncertain responses. RESULTS: Approximately equal numbers of faculty vs. chief residents responded to the survery (52% vs. 47.75%, respectively). The majority of respondents had not previously attended any educational activity on nanotechnology (69.57%). The majority of participants agreed that more education on nanotechnology for dermatologists is needed (78.26% agreed vs. 21.74% uncertain) and that it should be incorporated into the residency training curriculum (60.87% agree vs. 13.04% disagree). Participants mostly agreed that nanotechnology research can contribute to better fundamental understanding of skin disease (78.26%), to advances in the diagnosis of skin disease (73.91%) and to therapies (78.26%). Participants mostly agreed that more research is needed (82.60%) and that this research should be funded (78.26%). Not surprisingly, respondents were uncertain with respect to issues of nanotechnology safety both in the pharmaceutical realm (60.87%) and cosmeceutical realm (69.57%). Furthermore, the overwhelming majority responded that research is also needed to evaluate nanomaterial safety (86.96%). LIMITATIONS: Both the populations size and response rate were low, possibly affecting the power and significance of the results in this study. CONCLUSION: The survey results indicate a significant gap in dermatology training. Participants indicated a need for more training and education in the area of nanotechnology, and called for more research to evaluate the potential pitfalls associated with nanomaterials as well and to seek new advances in diagnostic and therapeutic modalities.

Clinical evaluation of safety and efficacy of a new topical treatment for onychomycosis.

OBJECTIVE: This clinical study assessed the safety and efficacy of an investigational topical product for the treatment of onychomycosis (nail fungus). METHOD: A prospective, multi-center, single-arm, self-controlled clinical investigation was done with adult subjects that met the inclusion criteria, primarily culture-confirmed dermatophyte infection of at least one great toe. Subjects self-treated in a weekly regimen of topical application for six months, with clinical assessment at one, three, and six months. Primary efficacy endpoint was clearance of fungal nail infection after six months of weekly treatment. Primary safety endpoint was freedom from product-related adverse events for the duration of the treatment term. RESULTS: Fifty males and 13 females, ages 24 to 65, infected with Trichophyton (n=62) or Epidermophyton (n=1) were enrolled; 53 completed six months of assessment. Sixty percent showed improvement in clinical parameters (nail color, nail plate involvement, onycholysis, thickness, and hyperkeratosis) at six months. Cumulative rates of dermatophyte-negative culture results (test of cure) were 28, 36, and 62 percent of subjects after one, three, and six months of treatment, respectively. Three minor adverse events were device-related, with no unanticipated or serious adverse events. LIMITATIONS: This study was single-arm and self-controlled; 53 of 63 enrolled subjects completed the study. CONCLUSION: This study describes a new topical medical device with safety and efficacy profiles that compare favorably to results reported for topically applied onychomycosis drug treatments.

The growing role of nanotechnology in combating infectious disease.

The treatment and prevention of infectious diseases is a major part of both clinical and investigative medicine. As the use of conventional antibiotics rises, antimicrobial resistance patterns develop, necessitating the continuous need for newer and more effective therapies. Nanotechnology, defined as the production and application of materials in the nanoscale range (1-100 nm), has been the focus of several investigations as a result of unique physical and chemical properties of nanomaterials. . Specifically, nanomaterials provide added benefits due to their small size; allowing for an increased ability to surpass most physiologic barriers and reach their intended targets, and high surface area-to-volume ratio, allowing for increased potential to interact with pathogen membranes and cell walls. This review focuses of the potential therapeutic and preventative applications of nanotechnology-based drug delivery systems in infectious disease.

Photonanodermatology: the interface of photobiology, dermatology and nanotechnology.

This review focuses on the optical properties of matter on the nanoscale and discusses some of their potential applications in dermatology. The applications will be divided into three main categories: those with consumer potential; those with diagnostic potential; and those with therapeutic potential.

Nanodermatology: a bright glimpse just beyond the horizon - part I.

Nanotechnology is a relatively new branch of engineering that is making rapid inroads in medicine and dermatology. Nanotechnology applies the unique properties of matter on the nanoscale (1000 nm and smaller) for the purposeful design of new materials. Dermatology is already one of the leading beneficiaries of nanotechnology. Among US patent holders in nanotechnology, the sixth largest is a cosmetics company. Nanotechnology applications have been realized in sunscreens and are being developed for the maintenance of skin health, as well as for the diagnosis and management of skin disease. This article summarizes some of the recent and anticipated advances in nanotechnology for dermatology. In part II, the author addresses the chief concerns of nanotechnology.

Nanotechnology and the Nanodermatology Society.

Nanotechnology is a rapidly developing discipline with enormous promise for consumers and patients. Currently, it is entering an inflection point in its growth phase--both in the number and diversity of products developed or soon to be available for society and medicine. It is no surprise that a vast number of patents have been issued for nanotechnology in the cosmetics arena as a means of enhancing topical delivery of a broad range of over-the-counter products. In fact, the skin is the first point of contact for a whole host of nanomaterials, ranging from topical preparations, articles of clothing and household products, to sporting goods and industrial manufactured goods. Very little is known about the safety aspects of the nano-engineered materials that are being released in the environment, as well as those in consumer and healthcare products.

Topical botulinum toxin.

Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indications have been for the management of axillary hyperhydrosis and facial rhytides. Traditional methods of botulinum toxin delivery have been needle-based. These have been associated with increased pain and cost. Newer methods of botulinum toxin formulation have yielded topical preparations that are bioactive in small pilot clinical studies. While there are some risks associated with topical delivery, the refinement and standardization of delivery systems and techniques for the topical administration of botulinum toxin using nanotechnology is anticipated in the near future.

Nanotechnology in vaccine development: a step forward.

The study of nanotechnology for epicutaneous delivery of pharmaceuticals and vaccines is burgeoning. Topically applied nanomaterials have been shown to enter tape-stripped skin and reach draining lymph nodes in an inbred strain of mice. Nanomaterials in the form of plasmid DNA, proteins, and virus particles accumulate in hair follicles, diffuse via dendritic cells to draining lymph nodes, and elicit antigen-specific humoral and cell-mediated immunity. Topically immunized mice have also demonstrated resistance to infection with live virus. Advantages of nanotechnology include uniformity, reproducibility, and precision in the synthesis and manufacture of candidate compounds. Combined with novel pharmacokinetics and the possibility of targeted therapy, nanotechnology-based vaccines may prove superior to existing vaccines and have the potential to open therapeutic avenues for treating infectious disease and malignancy.