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The current study's objective was to formulate and evaluate a liposomal cream containing tolnaftate in order to improve the drug's bioavailability. Tolnaftate is a drug having low permeability which results in decreased drug absorption and so is the bioavailability. To overcome these problems tolnaftate is incorporated in liposomes. Liposome vesicular drug delivery system was preferred due to its greater solubility, permeability and bioavailability. It carries a substantial amount of drug which increased the drug's penetration. The liposomes were prepared using a variety of phospholipids, specifically soy lecithin and egg phosphatidylcholine in varying ratios. Liposomes were prepared by ethanol injection method and evaluated for morphology, percentage practical yield, percentage entrapment efficiency, drug content and invitro drug release study. The formulation with the best result according to the evaluation parameters was F2 with greater percentage drug entrapment, drug content and in-vitro drug release was considered to be optimized formulation and this F2 formulation was further evaluated by SEM, DSC and XRD. Liposomal cream was formulated using the optimized formulation. Spreadability, Viscocity, pH measurement and in-vitro drug release were evaluated for liposomal cream. Formulation F2 and optimized liposomal cream formulation showed in-vitro drug release of 92.44% and 77.48% respectively at the end of 8th hour. [ABSTRACT FROM AUTHOR]

Introduction: Topical antifungals for toenail onychomycosis must penetrate the nail to deliver an inhibitory concentration of free drug to the site of infection. In two ex vivo experiments, we tested the ability of topical antifungals to inhibit growth of Trichophyton rubrum and Trichophyton mentagrophytes, the most common causative fungi in toenail onychomycosis. Methods: Seven topical antifungals were tested: three U.S. Food and Drug Administration-approved products indicated for onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and four over-the-counter (OTC) products for fungal infections (tolnaftate 1% and/or undecylenic acid 25% solutions). The ability to inhibit fungal growth was tested in the presence and absence of keratin. Products were applied either to human cadaverous nails or keratin-free cellulose disks prior to placement on an agar plate (radius: 85 mm) seeded with a clinical isolate of T. rubrum or T. mentagrophytes. After incubation, the zone of inhibition (ZI), defined as the radius of the area of no fungal growth, was recorded. Results: In the nail penetration assay, average ZIs for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm) were significantly greater than those for tavaborole (63.5 mm; 39.1 mm), ciclopirox (7.4 mm; 3.6 mm) and all OTC products (range: 10.5–34.2 mm against both species; all P < 0.001). In the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal antifungal activity against both species (ZIs = 85 mm); average ZIs against T. rubrum and T. mentagrophytes were smaller for ciclopirox (59.0 and 55.7 mm, respectively) and OTC products (range: 31.2–57.8 mm and 25.7–47.7 mm, respectively). Conclusions: Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail. [ABSTRACT FROM AUTHOR]

Liquid chromatography-mass spectrometry (LC-MS) is a very sensitive technique for determining small concentrations of drugs in fixed dose combinations or even those deposited in skin layers. Therefore, an LC-MS method was applied for determining the drugs under investigation, namely, clioquinol (CLIO), tolnaftate (TOL), and betamethasone (BETA) in Quadriderm® cream and mixed lipid nanostructures (MLNs) prepared in laboratory in the presence of potential interferents, and was applied as a dermato-kinetic study in rat’s skin. The separation was achieved within 4.5 min by using C18 column as a stationary phase and the mobile phase used were 20% phase A composed of 0.1% formic acid (v/v) and 80% phase B composed of 0.1% formic acid in acetonitrile (v/v), coupled with triple quadrupole mass spectrometer. MLNs were prepared and characterized to be compared with the conventional commercially available Quadriderm® cream. The proposed method was accurate and precise with a linearity range of 0.2–20.0 µg·mL−1 for BETA, and 0.5–400.0 µg·mL−1 for CLIO and TOL and a better bioavailability of the new formulation was obtained ensuring the capability of the nanoparticles to accumulate the drugs within the skin layers. In conclusion, the LC-MS method was accurate and precise for the determination of the three drugs under investigation in cream dosage form and skin tissues.

Fungal keratitis (FK) is a devastating ocular disease that can cause corneal opacity and blindness if not treated effectively. Tolnaftate (TOL) is a selective fungicidal drug against Aspergillus spp. which are among the most common causes of mycotic keratitis. TOL is lipophilic drug with low water solubility and permeation which act as obstacles for its clinical ocular efficacy. Hence, this study aimed to statistically optimize a novel polymeric pseudorotaxanes (PSRs) containing TOL for enhancing its ocular permeability and antifungal effect. For achieving this goal, a full 31.22 factorial design was fashioned for preparing and optimizing TOL-PSRs using film hydration technique. Three formulation variables were studied: drug amount (X1), weight ratio of Pluronics to HPβCD (X2) and Pluronic system (X3). Entrapment efficiency percent (EE%) (Y1), particle size (PS) (Y2) and zeta potential (ZP) (Y3) were set as dependent variables. The selected optimal TOL-PSRs (PSR1) showed EE% of 71.55 ± 2.90%, PS of 237.05 ± 12.80 nm and ZP of −32.65 ± 0.92 mV. In addition, PSR1 was compared to conventional polymeric mixed micelles (PMMs) and both carriers significantly increased the drug flux and resulted in higher amount permeated per unit area in 8 h compared to drug suspension. The histopathological studies assured the safety of PSR1 for ocular use. The in vivo susceptibility testing using Aspergillus niger confirmed that PSR1 displayed sustained antifungal activity up to 24 h. The obtained results revealed the admirable potential of PSR1 to be used as novel nanocarriers for promoting TOL ocular delivery.

Simple and rapid stability indicating High Performance Liquid Chromatography-Photo Diode Array (HPLC-PDA) method was developed and validated for the estimation of tolnaftate in the presence of its forced degradation products. The method employed SunQSil C18 column (250 mm × 4.6 mm, 5 μm) as stationary phase and acetonitrile:water (85:15, v/v) as mobile phase. Retention time of tolnaftate was 6.9 min. Acid and alkali hydrolysis, oxidation, photo degradation and thermal degradation studies were carried out to evaluate the degradation behavior of tolnaftate. The developed and optimized method was validated as per International Conferences on Harmonization (ICH) guidelines. Limit of detection and limit of quantitation were found to be 0.092 and 0.276 μg/mL, respectively. Linearity was observed in a concentration range of 0.276–6 μg/mL with R2 = 0.9936. %Recovery was found to be between 98.28% and 100.71%. The developed and validated Reversed Phase-High Performance Liquid Chromatography (RP-HPLC) method was successfully applied for quantification of tolnaftate in in-house topical solution. Major base and oxidative degradation products were identified and characterized by liquid chromatography–electrospray ionization mass spectrometry. The probable mechanisms for the formation of degradation products were predicted based on the fragmentation pattern of degradation products. The in silico dermal penetration predictions and carcinogenicity of degradation products were evaluated by using QikProp and CarcinoPred-EL functionality. [ABSTRACT FROM AUTHOR]

Fungal keratitis (FK) is a devastating ocular disease that can cause corneal opacity and blindness if not treated effectively. Tolnaftate (TOL) is a selective fungicidal drug against Aspergillus spp. which are among the most common causes of mycotic keratitis. TOL is lipophilic drug with low water solubility and permeation which act as obstacles for its clinical ocular efficacy. Hence, this study aimed to statistically optimize a novel polymeric pseudorotaxanes (PSRs) containing TOL for enhancing its ocular permeability and antifungal effect. For achieving this goal, a full 31.22 factorial design was fashioned for preparing and optimizing TOL-PSRs using film hydration technique. Three formulation variables were studied: drug amount (X1), weight ratio of Pluronics to HPßCD (X2) and Pluronic system (X3). Entrapment efficiency percent (EE%) (Y1), particle size (PS) (Y2) and zeta potential (ZP) (Y3) were set as dependent variables. The selected optimal TOL-PSRs (PSR1) showed EE% of 71.55 ± 2.90%, PS of 237.05 ± 12.80 nm and ZP of -32.65 ± 0.92 mV. In addition, PSR1 was compared to conventional polymeric mixed micelles (PMMs) and both carriers significantly increased the drug flux and resulted in higher amount permeated per unit area in 8 h compared to drug suspension. The histopathological studies assured the safety of PSR1 for ocular use. The in vivo susceptibility testing using Aspergillus niger confirmed that PSR1 displayed sustained antifungal activity up to 24 h. The obtained results revealed the admirable potential of PSR1 to be used as novel nanocarriers for promoting TOL ocular delivery. [ABSTRACT FROM AUTHOR]

Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at developing novel modified spanlastics by modulating spanlastics composition using different glycols for enhancing TOL ocular delivery. To achieve this goal, TOL basic spanlastics were prepared by ethanol injection method using a full 32 factorial design. By applying the desirability function, the optimal formula (BS6) was selected and used as a nucleus for preparing and optimizing TOL-cosolvent spanlastics according to the full 31.21 factorial design. The optimal formula (MS6) was prepared using 30% propylene glycol and showed entrapment efficiency percent (EE%) of 66.10 ± 0.57%, particle size (PS) of 231.20 ± 0.141 nm, and zeta potential (ZP) of −32.15 ± 0.07 mV. MS6 was compared to BS6 and both nanovesicles significantly increased the corneal permeation potential of TOL than drug suspension. Additionally, in vivo histopathological experiment was accomplished and confirmed the tolerability of MS6 for ocular use. The fungal susceptibility testing using Aspergillus niger confirmed that MS6 displayed more durable growth inhibition than drug suspension. Therefore, MS6 can be a promising option for enhanced TOL ocular delivery. [ABSTRACT FROM AUTHOR]

The aim was to formulate and evaluate glycerosomes as novel carrier for dermal (trans) drug delivery systems (tDDDS). Tolnaftate Loaded Glycerosomes were prepared by thin film hydration technique. The thin-film was hydrated using aqueous solution of glycerol (30 %v/v) against liposomes as control and were characterized. Glycerosome formulations were sphere-shaped with a mean diameter of 165.5 nm and narrow size distribution (P.I: 0.744). Zeta potential was –22.8mv indicating good stability. Tolnaftate loading capacity was found to be between 17.5±0.56 % and 91.32±0.57%. In-vitro permeation experiments showed an improved skin deposition and permeation of tolnaftate (5mg) when 30% glycerol, DSPC (100mg), cholesterol (25mg) content were used. Ex-vivo skin penetration studies showed an improved drug release than conventional liposomes and drug suspension. Skin irritancy studies on guinea pig showed no signs of toxicity. Glycerosomes must be an ideal novel transdermal drug delivery system for the effective delivery of tolnaftate. [ABSTRACT FROM AUTHOR]

Rosmarinus, tolnaftate, christianity, no-observed-effect level, superfund amendments and reauthorization act. [Extracted from the article]

Nanoemulsion has been identified as a promising delivery system for various drugs including Biopharmaceuticals. Nanoemulsion is heterogeneous system composed of one immiscible liquid dispersed as droplets within another liquid. Aim of the present study was to investigate the nanoemulgel as transdermal delivery system for poorly water soluble drug, Tolnaftate in order to overcome the troubles associated with its oral delivery. Different nanoemulsion components (Oil, Surfactant and Cosurfactant) were selected on the basis of solubility and emulsification ability. High pressure Homogenization techninique were used for the preparation of Nanoemulsion. Carbopol 934 was added as gel matrix to convert nanoemulsion into nanoemulgel. Drug loaded Nanoemulgels were characterized for particle size, SEM, Viscosity, Spreadability, Diffusion study using egg membrane, Nanoemulgel containing 3% Almond oil, 5.25% Tween 80, Proplene glycol as Cosurfactant, 1% drug, Water upto Quantity sufficient was concluded as optimized formulation (F1). [ABSTRACT FROM AUTHOR]

Background: Lack of trust in artificial intelligence (AI) models in medicine is still the key blockage for the use of AI in clinical decision support systems (CDSS). Although AI models are already performing excellently in systems medicine, their black-box nature entails that patient-specific decisions are incomprehensible for the physician. Explainable AI (XAI) algorithms aim to "explain" to a human domain expert, which input features influenced a specific recommendation. However, in the clinical domain, these explanations must lead to some degree of causal understanding by a clinician., Results: We developed the CLARUS platform, aiming to promote human understanding of graph neural network (GNN) predictions. CLARUS enables the visualisation of patient-specific networks, as well as, relevance values for genes and interactions, computed by XAI methods, such as GNNExplainer. This enables domain experts to gain deeper insights into the network and more importantly, the expert can interactively alter the patient-specific network based on the acquired understanding and initiate re-prediction or retraining. This interactivity allows us to ask manual counterfactual questions and analyse the effects on the GNN prediction., Conclusion: We present the first interactive XAI platform prototype, CLARUS, that allows not only the evaluation of specific human counterfactual questions based on user-defined alterations of patient networks and a re-prediction of the clinical outcome but also a retraining of the entire GNN after changing the underlying graph structures. The platform is currently hosted by the GWDG on https://rshiny.gwdg.de/apps/clarus/., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tolnaftate, a classic antifungal compound, has been found to crystallize from 1:1 (v/v) acetone-water as large flat colorless needles in the centrosymmetric monoclinic space group P21/c. These crystals contain a 50:50 mixture of the (+ap,-sp,+ac,-ac) and (-ap,+sp,-ac,+ac) conformers. The bond lengths in the central CNOS unit are 1.3444 (19), 1.3556 (18) and 1.6567 (15) A À for C--N, C--O and C--S, respectively, and the CNOS and C3N moieties are flat and nearly coplanar with each other, consistent with the C--N bond possessing partial double-bond character. Tolnaftate and the four most closely related N,N-disubstituted thiocarbamates in the Cambridge Structural Database (CSD) all exist as E-conformational isomers in the solid state. Among these five compounds, tolnaftate is the only one in which the N-tolyl moiety is positioned trans to the S atom, i.e. the N-aryl substituent in each of the other compounds is positioned cis to their respective S atom. Notably, and more importantly, our experimental X-ray structure is unlike all prior theoretical models available for tolnaftate. The implication, either directly or indirectly, is that some of those theoretical models used in earlier studies to explain the spectroscopic properties of tolnaftate and to suggest which protein-ligand interactions are responsible for the binding of tolnaftate to squalene epoxidase are either inappropriate or structurally unreasonable, i.e. the results and conclusions from those prior studies are in need of critical reassessment. [ABSTRACT FROM AUTHOR]

Graphene “The novel carbon nano-trope” tailors auspicious platform for designing antimicrobial regimen by virtue of its conspicuous molecular interaction with the microorganism. In this work, Tolnaftate (Tf), an antifungal drug, was mingled with Graphene nanoplatelets (Gn) to develop composite (Tf-Gn) via the wet chemical route, embedded in a biocompatible polymeric blend of Eudragit RL100/Eudragit RS100 (EuRL100/EuRS100) and subjected to electrospinning to obtain nonwoven nanoengineered scaffolds (nanofibers) for enhanced anti-dermatophytic virtue. Pursuing cluster of optimization experiments, 20% w/v EuRL100/EuRS 100 was found to be adequate for formation of smooth, defect-free, and regular fibers. Field emission electron microscopy (FESEM) acknowledged zestfully fabrication of smooth, shiny, nano-range, and mesh-like architecture, comprising distinct pockets within their structure. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC) conceded formation of the composite Tf-Gn, its physical compatibility with polymers, and improved thermal behavior. Exceptional swelling capacity, significant hydrophilicity, and immense drug entrapment efficiency were obtained of nanofibers fabricated from 3:1 ratio of EuRL100/EuRS100 polymers blend owing to relatively higher permeability which gratified essential benchmark for fabrication of nanofibrous scaffold to alleviate fungal infections caused by dermatophytes. In vitro drug release interpreted controlled liberation of Tf in dissolution media, following Korsmeyer-Peppas model kinetics, and suggested a diffusion-based mechanism. Microdilution broth method was performed for in vitro antifungal efficacy against extremely devastating dermatophytes, i.e., anthropophilic Trichophyton rubrum and zoophilic Microsporum canis, exhibited preeminent growth inhibition against T.rubrum and scanty for M.canis. Findings revealed the superior antifungal activity of Tf-Gn-loaded nanofibers as compared to Tf-loaded nanofibers and recommended potential dressing materials for an effective regimen of dermatomycosis. [ABSTRACT FROM AUTHOR]

Dermatophytosis, topical fungal infection is the most common cause of skin bug in the world, generally underestimated and ignored. It is commonly caused by immensely mortifying and keratinophilic fungal eukaryotes which invade keratinized tissues and generate different tinea diseases in Mediterranean countries. We herein fabricated nanofibers/scaffolds embedded with thiocarbamate derivative topical antifungal tolnaftatefor the first time to target the complete elimination of dermatophyte at the site of infection. In this regard, variable combinations of biocompatible Eudragit grades (ERL100 and ERS100) were selected to provide better adhesion on the site of dermatophytosis, ample absorption of exudates during treatment, and customized controlled drug release. Surface topography analysis indicated that the fabricated nanofibers were regular and defect-free, comprising distinct pockets with nanoscaled diameters. Characterization and compatibility studies of tolnaftate, polymers, and their nanofibers were performed through ATR-FTIR, TGA, and PXRD. Remarkable hydrophilicity and an excellent swelling index were obtained from a 3:1 ratio of ERL100/ERS100 electrospun D3 nanofibers, which is an essential benchmark for the fabrication of nanofibrous scaffolds for alleviating dermatophytosis. In vitro drug release investigation revealed that a nonwoven nanomesh of nanofibers could control the rate of drug release for 8 h. A microdilution assay exhibited inhibition of more than 95% viable cells of Trichophyton rubrum for 96 h. However, Microsporum species rigidly restricted the effect of bioactive antifungal nanofibers and hence showed resistance. In vivo activity on Trichophyton rubrum infected Swiss albino mice revealed complete inhibition of fungal pathogens on successive applications of D3 nanofibers for 7 days. This investigation suggests potential uses of tolnaftate loaded polyacrylate nanofibers as dressing materials/scaffolds for effective management of dermatophytosis. [ABSTRACT FROM AUTHOR]

We describe a rare case of fungal peritoneal dialysis (PD) peritonitis caused by the ascomycete fungus Neurospora sitophila ( N. sitophila ). The patient had little response to initial antibiotics and PD catheter removal was necessary for source control. The fungal biomarker β-d-glucan (BDG) was positive prior to N. sitophila being cultured and remained positive for 6 months after discharge. Use of BDG early in the assessment of PD peritonitis may reduce time to definitive therapy in fungal peritonitis.

Background: Otomycosis is the superficial mycotic infection of the external ear canal which occurs as acute, subacute and chronic infection. It is the cause of 6.5% to 12.5% of external otitis. More than 62 species and 28 genera of fungi have been identified in patients with otomycosis among which the most common organisms are Aspergillus Niger and Candida Albicans. Recommended topical medications include steroids, anti-septic, acidic solutions, antifungal, and drying agents. The commonly recommended antifungal drugs are clotrimazole, amphotericin B, otosporin, and tolnaftate. This study aimed to identify two genera of fungus, and compare the efficacy of the treatment of clotrimazole and tolnaftate and the recurrence rate after the treatment. Methods: This was a clinical trial study conducted on 54 patients diagnosed with otomycosis (based on culture and smear with identification of the fungus genus and species). We compared the effect of clotrimazole and tolnaftate on the treatment and its recurrence on different types of fungus. Findings: After finishing the treatment course, 22 patients were improved in clotrimazole (81.5%); however, in the tolnaftate group, there were 21 improved patients (77.8%). Besides, Chi-square test showed no significant difference between the two groups (P = 0.99). Furthermore, out of 43 patients who have improved after the treatment, recurrence was seen in 15 of them (34.9%). Disease recurrence cases in the group treated with clotrimazole and tolnaftate were 8 and 7 patients respectively (36.4% vs. 33.3%). Although, the frequency distribution of disease recurrence was lower in the tolnaftate group, according to chi-square test, there was no significant difference between the two groups (P = 0.99). Conclusion: According to the results of this study and its comparison with other studies, both clotrimazole and tolnaftate had an appropriate impact on treating fungal infections of the ear. Given the non-improvement and recurrence cases, we should attempt to detect other therapeutic methods of otomycosis, and currently aspects such as financial and economic issues should be taken into account in choosing to use either of the drugs.

Introduction: Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. Climate change and host migration emphasize the need to optimize this infection diagnosis., Objective: To evaluate the implementation of Paracoccidioides spp. DNA detection in the mycological diagnosis of patients with suspected paracoccidioidomycosis., Materials and Methods: It is a retrospective study with laboratory data from patients with clinical suspicion of paracoccidioidomycosis, who consulted a university hospital from a non-endemic area., Results: We analyzed the laboratory results of samples from 19 patients with suspected paracoccidioidomycosis. Seventeen out of 19 patients were born in or had visited an endemic area in Latin America. Fourteen adult male patients were confirmed to have paracoccidioidomycosis by conventional diagnosis: the direct examination was positive in 12 samples while fungal growth was found only in 4. Anti-Paracoccidioides spp. antibodies were detected in 10 patients, 8 of them with proven paracoccidioidomycosis. Nested PCR for Paracoccidioides spp. detection was performed on clinical samples from 14 patients, and positive results were obtained for 9 out of 10 patients with the conventional diagnosis of paracoccidioidomycosis., Conclusions: The incorporation of molecular techniques to detect Paracoccidioides spp. DNA complements the conventional diagnosis of paracoccidioidomycosis. This tool allows the prescription of antifungal treatment in those cases where the fungus is not observed in the clinical samples.

Introduction: Sporotrichosis is an implantation mycosis caused by Sporothrix spp. It is distributed worldwide and can be found in vegetation and soil. The most frequent route of infection is by trauma with elements contaminated with fungal propagules. Since domestic cats are the most affected animals and can transmit this infection to humans, sporotrichosis is considered a zoonosis. Clinical presentations include nodular lymphangitis, fixed cutaneous, pulmonary (rare), and disseminated (exceptional)., Objectives: To analyze the epidemiology of sporotrichosis in Argentina during 2010 and 2022. To describe the clinical presentation, diagnostic methods, and treatment of cases diagnosed during this period. To know the circulating genotypes and to observe possible associations with the geographic location where the infection was acquired., Materials and Methods: Analytical, retrospective, and observational study. We analyzed the medical records of patients with sporotrichosis from 12 health institutions in Argentina, between 2010 and 2022., Results: We present 54 cases in which the most frequent clinical form was nodular lymphangitis, and the treatment of choice was itraconazole. Conventional diagnosis was made in all cases. Culture of clinical samples was more sensitive than direct examination because it allowed the isolation of Sporothrix spp. in all 54 cases. Molecular identification was performed in 22 cases, with Sporothrix schenkii sensu stricto being the most frequently isolated species., Conclusions: This study allowed to know the epidemiology of this mycosis in Argentina, as well as the availability of diagnostic methods and the treatment of choice.

Introduction. Medical device colonization by pathogenic microorganisms is a risk factor for increasing infections associated with health care and, consequently, the morbidity and mortality of intubated patients. In Colombia, fungal colonization of endotracheal tubes has not been described, and this information could lead to new therapeutic options for the benefit of patients. Objective. To describe the colonizing fungi of the endotracheal tubes from patients in the intensive care unit, along with its antifungal sensitivity profile. Materials and methods. We conducted a descriptive, observational study in two health centers for 12 months. Endotracheal tubes were collected from patients in intensive care units. Samples were processed for culture, fungi identification, and antifungal sensitivity profile assessment. Results. A total of 121 endotracheal tubes, obtained from 113 patients, were analyzed: 41.32 % of the tubes were colonized by Candida albicans (64.62%), C. non‑albicans (30.77%), Cryptococcus spp. (3.08%) or molds (1.54%). All fungi evaluated showed a high sensitivity to antifungals, with a mean of 91%. Conclusion. Fungal colonization was found in the endotracheal tubes of patients under invasive mechanical ventilation. The antifungal sensitivity profile in these patients was favorable. A clinical study is required to find possible correlations between the colonizing microorganisms and infectivity.

We discuss Ye et al. 2022, which combines instrumental variables methods with difference in differences. First, we compare the paper to other works in the difference in differences literatures and argue that the main contribution lies in the multiply robust estimation approach. Then, we reformulate the causal assumptions in Ye et al. 2022 in the usual theoretical framework of the instrumental variables literature. This clarifies in which sense the difference in differences design can weaken the standard instrumental variable conditions., (© 2022 The International Biometric Society.)

We reinterpret the instrumented difference-in-differences (iDID) under a linear instrumental variables (IV) model. Under the linear IV model, we show why iDID is a clear improvement over two existing methods, difference-in-differences (DID) and a cross-sectional, IV analysis. We also re-express some of the assumptions of iDID using familiar, regression-based identification assumptions. We conclude with a method inspired by the linear IV model that can potentially remedy the weak identification problem in iDID., (© 2022 The Authors. Biometrics published by Wiley Periodicals LLC on behalf of International Biometric Society.)

Dermatophytosis, topical fungal infection is the most common cause of skin bug in the world, generally underestimated and ignored. It is commonly caused by immensely mortifying and keratinophilic fungal eukaryotes which invade keratinized tissues and generate different tinea diseases in Mediterranean countries. We herein fabricated nanofibers/scaffolds embedded with thiocarbamate derivative topical antifungal tolnaftatefor the first time to target the complete elimination of dermatophyte at the site of infection. In this regard, variable combinations of biocompatible Eudragit grades (ERL100 and ERS100) were selected to provide better adhesion on the site of dermatophytosis, ample absorption of exudates during treatment, and customized controlled drug release. Surface topography analysis indicated that the fabricated nanofibers were regular and defect-free, comprising distinct pockets with nanoscaled diameters. Characterization and compatibility studies of tolnaftate, polymers, and their nanofibers were performed through ATR-FTIR, TGA, and PXRD. Remarkable hydrophilicity and an excellent swelling index were obtained from a 3:1 ratio of ERL100/ERS100 electrospun D3 nanofibers, which is an essential benchmark for the fabrication of nanofibrous scaffolds for alleviating dermatophytosis. In vitro drug release investigation revealed that a nonwoven nanomesh of nanofibers could control the rate of drug release for 8 h. A microdilution assay exhibited inhibition of more than 95% viable cells of Trichophyton rubrum for 96 h. However, Microsporum species rigidly restricted the effect of bioactive antifungal nanofibers and hence showed resistance. In vivo activity on Trichophyton rubrum infected Swiss albino mice revealed complete inhibition of fungal pathogens on successive applications of D3 nanofibers for 7 days. This investigation suggests potential uses of tolnaftate loaded polyacrylate nanofibers as dressing materials/scaffolds for effective management of dermatophytosis.

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest form is provided with the online version of the article (http://links.lww.com/JBJS/H365).