•MAL-PDT corrects abnormally expressed cancer-associated genes in actinic keratosis.•MAL-PDT normalizes cell cycle-related genes in actinic keratosis.•MAL-PDT at gene expression level indicates a ...remodeling effect on photodamaged skin.
Actinic keratoses (AK) are proliferations of neoplastic keratinocytes in the epidermis resulting from cumulative exposure to ultraviolet radiation (UVR), which are liable to transform into squamous cell carcinoma (SCC). Organ Transplant Recipients (OTR) have an increased risk of developing SCC as a consequence of long-term immunosuppressive therapy. The aim of this study was to determine the molecular signature of AKs from OTR prior to treatment with methyl aminolevulinate-photodynamic therapy (MAL-PDT), and to assess what impact the treatment has on promoting remodeling of the photo-damaged skin.
Seven patients were enrolled on a clinical trial to assess the effect of MAL-PDT with biopsies taken at screening prior to the first treatment session (week 1), and six weeks after completion of final treatment (week 18). Whole-genome gene expression analysis was carried out on skin biopsies isolated from an AK lesion, an area surrounding the lesion, and a non-sun exposed region of the body. Quantitative PCR was utilized to confirm the differential expression of key genes.
MAL-PDT treatment corrected abnormal proliferation-related gene profiles, corrected aberrantly expressed cancer-associated genes and induced expression of dermal extracellular matrix genes in photo-exposed skin.
The efficacy of the MAL-PDT on AK lesions was confirmed at whole-genome gene expression level. A transcriptional signature of remodeling, identified through assessing the effect of MAL-PDT on photodamaged skin, supports the use of MAL-PDT for treating photodamaged skin and field cancerized areas.
Introduction. Despite increasing application of molecular diagnostic methods for the detection of sexually transmitted infections, the cytological findings in pap smears of patients with pathogens ...that can be identified only by PCR are not yet well described. The aim of this study was to describe the most common cytological features in cervical pap smears of patients with Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum detected by multiplex PCR. Methods. Cervical samples for conventional and liquid-based cytology and for multiplex PCR were collected from women ranging from 23 to 54 years old, who underwent routine screening at a gynecological Unit. Results. Multiplex PCR was positive in 36.2% of the samples: Ureaplasma parvum 14.9%, Chlamydia trachomatis 10.6%, Trichomonas vaginalis 10.6%, Mycoplasma hominis 8.5%, Ureaplasma urealyticum 4.2%, Neisseria gonorrhoeae 2.1%, and Mycoplasma genitalium (0). Multiple pathogens were observed in 12.8% of samples. Microscopic cervicitis (≥10 polymorphonuclear leukocytes/epithelial cell) and normal (predominantly lactobacillary) microbiota were the most frequent findings in the samples in which the pathogens were detected alone or in multiple infections, except for samples with Trichomonas vaginalis in which the coccobacillary microbiota was the most common. In samples with microscopic cervicitis and normal microbiota, those with at least one pathogen identified by multiplex PCR were significantly more frequent than those with no pathogen, 66.6% versus 33.3%. Conclusion. Failure to identify an inflammatory agent in pap smear with intense neutrophil exudate may suggest the presence of Ureaplasma parvum, Ureaplasma urealyticum, Chlamydia trachomatis, or Trichomonas vaginalis. A remark on the intensity of inflammation should be made in the reports of cervical pap smears so that this cytological finding can be correlated with clinical and PCR results.
This letter presents a 26/38-GHz dual-band filtering balanced power amplifier (PA) using 100-nm GaAs process. Dual-band branch-line couplers are proposed for the balanced PA, which also engage into ...the dual-band input-output impedance matching and provide out-of-band rejection simultaneously. The proposed PA achieves the saturation output power (<inline-formula> <tex-math notation="LaTeX">P_{\text {sat}} </tex-math></inline-formula>) of 27.7/26.9 dBm, output 1-dB compression point (OP<inline-formula> <tex-math notation="LaTeX">_{\mathrm {1\,dB}} </tex-math></inline-formula>) of 27.1/25.6 dBm, peak power-added efficiency (PAE) of 31.5%/22.8%, and small signal gain of 22.4/15.8 dB at 26/38 GHz. At frequencies of 12, 34, and 45 GHz, the small signal suppressions are 45, 54, and 40 dBc, respectively. In virtue of the high output power in 5G band n258/n260 and good out-of-band rejection, the proposed PA can be a potential candidate for 5G applications.
Summary
Background Onychomycosis is common, accounting for up to 50% of all nail disorders. Toenail onychomycosis can cause nail deformity, embarrassment, pain and walking difficulties. Some ...populations, such as individuals with diabetes, are at higher risk for developing secondary complications such as infections. Treatment takes many months and therapeutic choices can increase clinical effectiveness, lower toxicity and minimize healthcare costs.
Objectives Based on the results of a previous pilot study, the objective of the present study was to show, in a larger population, the enhanced efficacy of a combination of amorolfine nail lacquer and oral terbinafine in the treatment of onychomycosis with matrix involvement. In addition, a cost‐effectiveness analysis was performed.
Methods In this multicentre, randomized, open‐label, parallel group study, patients were randomized to receive either a combination of amorolfine hydrochloride 5% nail lacquer once weekly for 12 months plus terbinafine 250 mg once daily for 3 months (AT group) or terbinafine alone once daily for 3 months (T group). The study duration was 18 months including a 6‐month treatment‐free phase following the 12‐month active treatment phase for the AT group and a 15‐month treatment‐free phase following the 3‐month active treatment phase for the T group. The primary efficacy criterion was overall response, dichotomized into success or failure, success being the combination of clinical cure and negative mycology at month 18. This criterion was used as the effectiveness measure in the pharmacoeconomic analysis, conducted from a payer perspective.
Results In total, 249 patients were included into the study: 120 in the AT group and 129 in the T group. A significantly higher success rate was observed for patients in the AT group relative to those in the T group at 18 months (59·2% vs. 45·0%; P = 0·03). Both treatment regimens were safe and well tolerated. Treatment cost per cured patient was lower for the combination than for terbinafine alone in all countries.
Conclusions Study results confirmed that, in the treatment of dermatophytic toenail onychomycosis with matrix involvement, amorolfine nail lacquer in combination with oral terbinafine enhances clinical efficacy and is more cost‐effective than terbinafine alone.
In the realm of 5G-enabled Internet of Things (IoT), the smartphone plays a pivotal role in providing users access to various IoT scenarios. With the emergence of millimeter-wave (mmWave) technology ...in 5G mobile terminals, it is feasible to realize an ultra-broadband, ultra-high speed and ultra-low latency communication for advanced IoT applications. However, in a smartphone, the end-fire mmWave radiation is blocked by the metal frame. To solve this problem without altering the industrial design (ID) of the smartphone, we present a new mmWave beam-tilted phased array antenna with multiple hybrid modes operation. Our approach employs a physically oblique radiating aperture to achieve a tilted and frequency-insensitive radiation pattern, effectively addressing the interference from the smartphone platform while preserving the integrity of the ID. To expand the impedance bandwidth, monopole mode, magnetic dipole mode, and stepped patch mode are generated with an effective space utilization. For experimental validation, the proposed prototype is measured in a simplified mobile terminal. The 1×4 phased array achieves a -10 dB impedance bandwidth of 23.5-30.5 GHz, which covers the 5G n257 and n258 bands, with an in-band realized gain higher than 9.4 dBi. Furthermore, at 27.0 GHz, a wide 3-dB scanning range of 102.5∘/72.0∘ is obtained for vertical/horizontal polarization, along with a peak gain of 9.4/11.0 dBi. The experimental results validate the proposed beam-tilted antenna solution, indicating that it can effectively address impedance mismatching, radiation distortion, low robustness, and other practical issues in 5G smartphones.
Background Standard treatment for onychomycosis often results in less than half of subjects achieving disease‐free nails. Onychomycosis is even more challenging to treat as relapses and ...re‐infections are common.
Objective To determine if a prophylactic effect exists when a treatment with amorolfine nail lacquer (ANL), with half the frequency of the standard regimen, is instituted following successful treatment of dermatophytic toenail onychomycosis with matrix involvement.
Methods Efficacy and safety of a group treated with ANL (once every 2 weeks) were compared with that of an untreated group in a 36‐month (3 years), single‐centre, randomized, open‐label, comparison study. Subjects to be included in the study were required to be cured of confirmed onychomycosis with matrix involvement after an initial treatment with either ANL + oral terbinafine or oral terbinafine alone in a previous study. Prophylaxis of onychomycosis was assessed by global recurrence rate, confirmed onychomycosis, clinical recurrence and mycological recurrence.
Results A total of 52 subjects were enrolled (26 in each group) in the study. Throughout the study, recurrences occurred more quickly in the untreated group compared with that in the ANL group. Statistically significant differences were observed at month 12 (ANL, 8.3%; untreated, 31.8%; P = 0.047). At endpoint, 70.8% of the subjects treated with ANL remained cured compared to 50% in the untreated group (P = 0.153). Recurrence was delayed by nearly 200 days for the ANL group compared with that of the untreated group. Amorolfine was safe and well tolerated during the study, with no treatment‐related adverse events.
Conclusion These results suggest that amorolfine nail lacquer may be effective and is safe for use as a prophylactic treatment for the recurrence of onychomycosis.
Summary
As onychomycosis is unsightly, this study clinically evaluated whether the antifungal efficacy of amorolfine 5% nail lacquer (NL) was affected by a masking, natural‐coloured, cosmetic nail ...varnish applied 24 h later; in vitro investigations were also performed. Subjects with mild‐to‐moderate distal subungual toenail onychomycosis were randomised to receive amorolfine 5% NL once weekly with or without cosmetic nail varnish applied 24 h later. After 12‐week treatment, antifungal activity of affected toenail clippings was assessed by measurement of zones of inhibition (ZOIs) on Trichophyton mentagrophytes seeded agar plates. Mean diameters were 53.5 mm for the amorolfine 5% NL‐alone group (n = 23) and 53.6 mm for amorolfine 5% NL plus cosmetic nail varnish group (n = 25). Also, mycological cultures of subungual debris at week 12 were negative for all subjects in both groups. Most subjects (88%) reported that cosmetic nail varnish masked their infected toenails. Additionally, cadaver human nails coated in vitro with or without cosmetic nail varnish 10 min or 24 h post amorolfine NL application all gave ZOIs on Trichophyton rubrum agar plates representing potent antifungal activity. In conclusion, cosmetic nail varnish applied post amorolfine had no effect on the subungual antifungal activity of amorolfine 5% NL or its penetration through toenails.
BACKGROUNDVolume restoration is an essential part of facial rejuvenation.
OBJECTIVETo assess long-term full-facial volume restoration using HAEL Volume Lidocaine hyaluronic acid filler.
METHODSAn ...18-month open study in 60 subjects with at least Grade 2 on the 4-point volume loss scale (VLS) for full face and at least 2 indications affected among chin, temporal areas, jawline, cheeks, cheekbones, and nasolabial folds (NLF). Performance was assessed by VLS, Lemperle rating scale (LRS), investigator Global Aesthetic Improvement Scale (GAIS), and 3-dimensional (3D) imaging.
RESULTSMost subjects (71.6%) had 3 or 4 indications injected, most commonly cheekbones (96.7%) and NLF (93.3%). At 18 months, at least a 1-grade improvement in VLS was observed for full face (68.3% of subjects), chin (77.8%), temporal areas (73.7%), cheeks (66.6%), cheekbones (58.6%), jawline (43.1%), and NLF (71.4%; LRS). For all indications, more than 60% of the volume gained at 3 weeks was sustained at 18 months based on 3D digital imaging. At 18 months, 95.0% of subjects had improved full-face GAIS and all subjects were satisfied with their aesthetic outcome. One subject (1.6%) had treatment-related adverse events.
CONCLUSIONFull-facial volume restoration was well sustained over 18 months with high patient satisfaction and good tolerability.