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Background Insecticide resistance remains a major public health problem. Resistance surveillance is critical for effective vector control and resistance management planning. Commonly used insecticide susceptibility bioassays for mosquitoes are the CDC bottle bioassay and the WHO tube test. Less commonly used in the field but considered the gold standard for assessing insecticide susceptibility in the development of novel insecticides is the topical application bioassay. Each of these bioassays has critical differences in how they assess insecticide susceptibility that impacts their ability to differentiate between resistant and susceptible populations or determine different levels of resistance intensity. Methods We compared the CDC bottle bioassay, the WHO tube test, and the topical application bioassay in establishing the dose–response against deltamethrin (DM) using the DM-resistant Aedes aegypti strain MC1. Mosquitoes were exposed to a range of insecticide concentrations to establish a dose–response curve and assess variation around model predictions. In addition, 10 replicates of 20–25 mosquitoes were exposed to a fixed dose with intermediate mortality to assess the degree of variation in mortality. Results The topical application bioassay exhibited the lowest amount of variation in the dose–response data, followed by the WHO tube test. The CDC bottle bioassay had the highest level of variation. In the fixed-dose experiment, a higher variance was similarly found for the CDC bottle bioassay compared with the WHO tube test and topical application bioassay. Conclusion These data suggest that the CDC bottle bioassay has the lowest power and the topical application bioassay the highest power to differentiate between resistant and susceptible populations and assess changes over time and between populations. This observation has significant implications for the interpretation of surveillance results from different assays. Ultimately, it will be important to discuss optimal insecticide resistance surveillance tools in terms of the surveillance objective, practicality in the field, and accuracy of the tool to reach that objective. Graphical Abstract

Abstract The objective of the study was to evaluate the efficacy of combining 1565-nm non-ablative fractional laser with low-dose compound betamethasone topical application in the treatment of immature early red hypertrophic scar. We enrolled 38 cases of patients who had immature red hypertrophic scar due to surgery or trauma which are all less than 6 months old. About 28 patients were assigned to the treatment group, and 10 patients were assigned to the control group. The patients in the treatment group were all treated with 1565-nm non-ablative fractional laser with the following parameters: spot size 10–16 mm, round or square-shaped according to lesional morphology, fluence 20–35 mJ/cm2, and density 150–200 microspot/cm2. The treated area was then applied immediately with low-dose compound betamethasone through topical application. Treatment cycles were repeated every month for a total 5 months. Photos were taken before the start of the treatment, and then monthly after. Vancouver Scar Scale score was used to evaluate the scar changes; all the patients were followed up for 3 more months after the last treatment. All side effects were documented. The patients in the control group received no treatment at all. All the parameters were recorded as the same as the treatment group. The total VSS score after the combination therapy is 0.96 ± 1.53, which in comparison with prior treatment VSS score 8.86 ± 1.43, showed a significant reduction following the treatments (P < 0.001). The control group without any treatment shows VSS score 7.10 ± 0.99 at the end of the study vs VSS score 7.70 ± 0.82 at the start of the study (P > 0.05). The patient satisfaction rate reaches 89.2% after treatment, The major side effects reported include 3 patients with post-inflammatory hyperpigmentation (10.7% of patients in the treatment group), and other minor discomfort such as transient warmth, erythema, and swelling of treatment sites. The combination approach using 1565-nm non-ablative laser and low dose of local application of compound betamethasone can effectively improve the immature red hypertrophic scar with no significant side effects; this should provide our practitioners with a new weapon in fighting those hard-to-manage early scar formations.

Cellulose acetate (CA) electrospun fibers have been used in different medical applications such as drug delivery systems to release various drugs. CA, usually available with a typical degree of substitution (DS) of 2.4–2.5, shows little control over the release rate of the incorporated substances, due to the lack of active functional groups. In this work, click chemistry was used to activate CA and produce crosslinked electrospun mats to provide sustained release for topical administration. CA was activated by introducing azide functional groups on the residual hydroxyl groups of the polymer chains with a DS Azido of 0.24 by a coupling reaction. Azido-CA was then electrospun to produce nanofibers, in which capsaicin and sodium diclofenac, as pain-relieving drugs were encapsulated. Propargylated maltose was synthesized as a crosslinker to the Azido-CA via triazole chemistry. Spectral analysis was used to confirm the chemical structure of the new derivatives and the click-matrices. SEM morphological analysis of the Azido-CA electrospun fibers showed a range of diameters from 140 to 270 nm, with clear, smooth surfaces. Samples of the matrices were assessed for cytotoxicity and showed an acceptable cell viability. In a rat model, sodium diclofenac and capsaicin-loaded electrospun mats of Azido-CA showed superior closure rates over the untreated rats and those treated with a commercial cream. Rats treated with electrospun mat of CA, Azido-CA loaded with drugs showed normal intact histological structure of the epidermis and dermis.

Background Iatrogenic Cushing’s syndrome induced by oral and parenteral glucocorticoid administration is a well-known complication. Immediate withdrawal from exogenous steroids can lead to life-threatening adrenal insufficiency. However, Cushing’s syndrome caused by topical treatment with glucocorticoids, such as dexamethasone eye drops or dermal application, is rarely recognized. Young infants in particular are at high risk of suffering from iatrogenic Cushing’s syndrome when treated with highly potent topical glucocorticoids. Case presentation We present a 6-month-old Syrian boy with cushingoid face after dermal clobetasol cream treatment and a 2-year-old Iranian girl with severe growth retardation after application of dexamethasone eye drops. Both families have a migration background and language barriers. In both cases no endogenous cortisol secretion was initially detected in serum and in 24-hour collected urine. After dose reduction of glucocorticoids, severity of symptoms was reversible and serum cortisol was detectable. Discussion and conclusion Young infants are at high risk of developing Cushing’s syndrome from topically applied highly potent glucocorticoids. Precise recommendations of treatment dosage, duration, and frequency must be given to the parents, and if necessary, with the help of an interpreter. Monitoring of height and weight as well as regular pediatric follow-ups should be scheduled. Physicians should be aware of potential adrenal insufficiency following withdrawal from long-term topical glucocorticoid treatment, and hydrocortisone treatment should be considered.

This study was carried out to determine the insecticidal activities of Nepeta italica L. (Lamiaceae) extracts against Sitophilus granarius (Linnaeus, 1758) (Coleoptera: Curculionidae) and Tribolium confusum Jacquelin du Val, 1863 (Coleoptera: Tenebrionidae) pests along with chemical composition of the active extract. Topical and contact activity of three different extracts (hexane, n-butanol, water) of N. italica were evaluated against adults of the two pests. Chemical constituents of the active (hexane) extract were identified by gas chromatography-mass spectrometry (GC/MS) apparatus. The major compounds were determined as 2-tert-Butyl-6-methyl-phenol (4.94%), nonadecane (4.78%), 1,9-diepipresilphiperfolane-9,15-epoxide (4.47%), neophytadiene (3.49%) and palmitic acid (3.36%). It was found out that the concentration required to kill S. granarius adults (LC50: 758.343 ppm) after 96 h in topical application using hexane extracts was higher than the concentration required to kill T. confusum adults (LC50: 509.988 ppm). Likewise, when mortality times at the highest concentration were compared, the time required to kill S. granarius adults (LT50: 34.07 h) was found to be longer than the time required to kill T. confusum adults (LT50: 26.15 h). The results showed that N. italica hexane extract was highly effective in both application methods and it could be suggested to use as an alternative natural bioinsecticide in the management of these pests.

Staphylococcus aureus colonizes patients with atopic dermatitis (AD) and exacerbates disease by promoting inflammation. The present study investigated the safety and mechanisms of action of Staphylococcus hominis A9 ( Sh A9), a bacterium isolated from healthy human skin, as a topical therapy for AD. Sh A9 killed S. aureus on the skin of mice and inhibited expression of a toxin from S. aureus ( psm α) that promotes inflammation. A first-in-human, phase 1, double-blinded, randomized 1-week trial of topical Sh A9 or vehicle on the forearm skin of 54 adults with S. aureus -positive AD (NCT03151148) met its primary endpoint of safety, and participants receiving Sh A9 had fewer adverse events associated with AD. Eczema severity was not significantly different when evaluated in all participants treated with Sh A9 but a significant decrease in S. aureus and increased Sh A9 DNA were seen and met secondary endpoints. Some S. aureus strains on participants were not directly killed by Sh A9, but expression of mRNA for psm α was inhibited in all strains. Improvement in local eczema severity was suggested by post-hoc analysis of participants with S. aureus directly killed by Sh A9. These observations demonstrate the safety and potential benefits of bacteriotherapy for AD. First-in-human test of topical application of a commensal bacterium on skin of individuals with atopic dermatitis reduces colonization by proinflammatory Staphylococcus aureus .

The objective of the study was to determine the acaricidal properties of Bobgunnia madagascariensis (Desv.) J.H. Kirkbr. and Wiersema (Leguminosae) against adult Amblyomma variegatum (Fabricius) ticks, using Tephrosia vogelii Hook.f. (Leguminosae) as a positive control. Plant extracts of both were prepared using methanol, acetone and chloroform as extraction solvents. Methanol leaf extracts of T. vogelii (0.014 g) and methanol fruit extracts of B. madagascariensis (0.0062 g) gave the highest mean extraction weights among the plant parts and solvents used. In free contact bioassays, only methanol extracts of the bark and leaf material of T. vogelii and methanol fruit extracts of B. madagascariensis produced 100 % mortality of A. variegatum ticks in 24 h. The acaricidal activity of methanol leaf extracts of T. vogelii persisted for up to 8 days while that of fruit extracts of B. madagascariensis persisted for only 6 days. In topical application bioassays, the toxicity of T. vogelii and B. madagascariensis extracts was found to be significantly different at 95 % confidence level, with B. madagascariensis extracts (LD₅₀ 0.030 w/v) being more toxic than T. vogelii extracts (LD₅₀ 0.555 w/v). This study has shown that plant extracts of B. madagascariensis and T. vogelii extracts have significant in vitro acaricidal activity against A. variegatum ticks and can thus be considered as alternatives for tick control. Further research is however required on persistence, safety and the required application rates.

Reconstructing functional skin after a wound remains a challenge due to the complexity of healing. In this regard, biocompatible nanoparticles (NPs) carrying and releasing bioactive drugs in a controlled and sustained manner may significantly improve the efficacy of wound therapies compared with current treatments. Topical administration of drug-loaded NPs allows optimal delivery to the dermis and improves product efficacy. Furthermore, associating NPs with scaffolds represents a new concept of ‘dressing’. Experimental in vivo, ex vivo, and in vitro models have been developed in preclinical assays to evaluate the beneficial effects of nanoparticulate dressings. Drug-loaded NPs are promising tools for innovative wound healing treatment, especially with regard to their multifunctional properties. Nanoparticles (NPs) loaded with drugs such as growth factors or nucleic acids are promising tools for skin regeneration and represent a strategy for wound repair. Their incorporation into an ‘intelligent’ matrix to design a nanocomposite (NCP) gives rise to innovative dressings. Significant efforts are made to develop ‘green processes’ aimed at producing biocompatible composites. A successful outcome of these NCPs would result in a sequential release of loaded drugs following the healing process stages. Recent advances in alternative models to animal experimentation focus on in vitro human reconstructed skin cultured in static conditions. In vitro organ-on-a-chip techniques will allow the integration of microfluidic networks with 3D tissue-engineered models. This research field opens new windows for preclinical NP screening.

The primary function of the skin is to act as a barrier against insults from the environment, and its unique structure reflects this. The skin is composed of two layers: the epidermal outer layer is highly cellular and provides the barrier function, and the inner dermal layer ensures strength and elasticity and gives nutritional support to the epidermis. Normal skin contains high concentrations of vitamin C, which supports important and well-known functions, stimulating collagen synthesis and assisting in antioxidant protection against UV-induced photodamage. This knowledge is often used as a rationale for the addition of vitamin C to topical applications, but the efficacy of such treatment, as opposed to optimising dietary vitamin C intake, is poorly understood. This review discusses the potential roles for vitamin C in skin health and summarises the in vitro and in vivo research to date. We compare the efficacy of nutritional intake of vitamin C versus topical application, identify the areas where lack of evidence limits our understanding of the potential benefits of vitamin C on skin health, and suggest which skin properties are most likely to benefit from improved nutritional vitamin C intake.

Sustainable agriculture relies on practices and technologies that combine effectiveness with a minimal environmental footprint. RNA interference (RNAi), a eukaryotic process in which transcript expression is reduced in a sequence-specific manner, can be co-opted for the control of plant pests and pathogens in a topical application system. Double-stranded RNA (dsRNA), the key trigger molecule of RNAi, has been shown to provide protection without the need for integration of dsRNA-expressing constructs as transgenes. Consequently, development of RNA-based biopesticides is gaining momentum as a narrow-spectrum alternative to chemical-based control measures, with pests and pathogens targeted with accuracy and specificity. Limitations for a commercially viable product to overcome include stable delivery of the topically applied dsRNA and extension of the duration of protection. In addition to the research focus on delivery of dsRNA, development of regulatory frameworks, risk identification, and establishing avoidance and mitigation strategies is key to widespread deployment of topical RNAi technologies. Once in place, these measures will provide the crop protection industry with the certainty necessary to expend resources on the development of innovative dsRNA-based products. Readily evident risks to human health appear minimal, with multiple barriers to uptake and a long history of consumption of dsRNA from plant material. Unintended impacts to the environment are expected to be most apparent in species closely related to the target. Holistic design practices, which incorporate bioinformatics-based dsRNA selection along with experimental testing, represent important techniques for elimination of adverse impacts.