JGI Plant Gene Atlas: an updateable transcriptome resource to improve functional gene descriptions across the plant kingdom.

Gene functional descriptions offer a crucial line of evidence for candidate genes underlying trait variation. Conversely, plant responses to environmental cues represent important resources to decipher gene function and subsequently provide molecular targets for plant improvement through gene editing. However, biological roles of large proportions of genes across the plant phylogeny are poorly annotated. Here we describe the Joint Genome Institute (JGI) Plant Gene Atlas, an updateable data resource consisting of transcript abundance assays spanning 18 diverse species. To integrate across these diverse genotypes, we analyzed expression profiles, built gene clusters that exhibited tissue/condition specific expression, and tested for transcriptional response to environmental queues. We discovered extensive phylogenetically constrained and condition-specific expression profiles for genes without any previously documented functional annotation. Such conserved expression patterns and tightly co-expressed gene clusters let us assign expression derived additional biological information to 64 495 genes with otherwise unknown functions. The ever-expanding Gene Atlas resource is available at JGI Plant Gene Atlas (https://plantgeneatlas.jgi.doe.gov) and Phytozome (https://phytozome.jgi.doe.gov/), providing bulk access to data and user-specified queries of gene sets. Combined, these web interfaces let users access differentially expressed genes, track orthologs across the Gene Atlas plants, graphically represent co-expressed genes, and visualize gene ontology and pathway enrichments.

A comprehensive review of nondermatophyte mould onychomycosis: Epidemiology, diagnosis and management.

Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the role of NDMs in the pathogenesis of onychomycosis (i.e. causative vs. contaminant). In studies where the ongoing invasive presence of NDMs is confirmed through repeat cultures, the global prevalence of NDMs in onychomycosis patients is estimated at 6.9% with the 3 most common genus being: Aspergillus, Scopulariopsis and Fusarium. NDM onychomycosis can, in many cases, appear clinically indistinguishable from dermatophyte onychomycosis. Clinical features suggestive of NDMs include proximal subungual onychomycosis with paronychia associated with Aspergillus spp., Fusarium spp. and Scopulariopsis brevicaulis, as well as superficial white onychomycosis in a deep and diffused pattern associated with Aspergillus and Fusarium. Longitudinal streaks seen in patients with distal and lateral onychomycosis may serve as an additional indicator. For diagnosis, light microscopic examination should demonstrate fungal filaments consistent with an NDM with at least two independent isolations in the absence of a dermatophyte; the advent of molecular testing combined with histological assessment may serve as an alternative with improved sensitivity and turnover time. In most instances, antifungal susceptibility testing has limited value. Information on effective treatments for NDM onychomycosis is relatively scarce, unlike the situation in the study of dermatophyte onychomycosis. Terbinafine and itraconazole therapy (continuous and pulsed) appear effective to varying extents for treating onychomycosis caused by Aspergillus, Fusarium or Scopulariopsis. There is scant literature on oral treatments for Neoscytalidium.

RepBox: a toolbox for the identification of repetitive elements.

BACKGROUND: Transposable elements (TEs) are short, mobile DNA elements that are known to play important roles in the genomes of many eukaryotic species. The identification and categorization of these elements is a critical task for many genomic studies, and the continued increase in the number of de novo assembled genomes demands new tools to improve the efficiency of this process. For this reason, we developed RepBox, a suite of Python scripts that combine several pre-existing family-specific TE detection methods into a single user-friendly pipeline. RESULTS: Based on comparisons of RepBox with the standard TE detection software RepeatModeler, we find that RepBox consistently classifies more elements and is also able to identify a more diverse array of TE families than the existing methods in plant genomes. CONCLUSIONS: The performance of RepBox on two different plant genomes indicates that our toolbox represents a significant improvement over existing TE detection methods, and should facilitate future TE annotation efforts in additional species.

Factors Associated With Musculoskeletal Pain Among Hair Transplant Surgeons: Analyses of Survey Data and Review of the Literature.

BACKGROUND: The prevalence of work-related musculoskeletal disorders (WRMD) is increasing among all surgical specialties. OBJECTIVE: Results of a cross-sectional survey of hair transplant surgeons were analyzed, with the aims to (1) determine the prevalence of WRMD, (2) assess risk factors associated with musculoskeletal (MSK) symptoms, and (3) identify mitigation measures. MATERIALS AND METHODS: A survey pertaining to demographics, MSK-related symptoms and its impacts, and pain mitigation measures taken, if any, were distributed to 834 hair transplant surgeons. Risk factors associated with pain severity were assessed using linear regression. RESULTS: Overall, 78.5% (73 of 93) respondents had experienced pain when performing surgery. Musculoskeletal symptoms were most severe in the neck, followed by upper/lower back, and extremities. Number of grafts performed per session of follicular unit extraction positively correlated with pain severity; female surgeons and surgeons aged >71 years were at higher risk. A majority expressed concern that WRMD may limit their career and agreed to a need for improved workplace education. Strength training and ergonomic improvements of surgical procedure were not commonly adopted. CONCLUSION: In sum, WRMD can be debilitating in health care professionals. Workplace ergonomic adjustments and physical exercise programs may be warranted to better mitigate MSK symptoms.

Combatting antifungal resistance: Paradigm shift in the diagnosis and management of onychomycosis and dermatomycosis.

Antifungal resistance has become prevalent worldwide. Understanding the factors involved in spread of resistance allows the formulation of strategies to slow resistance development and likewise identify solutions for the treatment of highly recalcitrant fungal infections. To investigate the recent explosion of resistant strains, a literature review was performed focusing on four main areas: mechanisms of resistance to antifungal agents, diagnosis of superficial fungal infections, management, and stewardship. The use of traditional diagnostic tools such as culture, KOH analysis and minimum inhibitory concentration values on treatment were investigated and compared to the newer techniques such as molecular methods including whole genome sequencing, and polymerase chain reaction. The management of terbinafine-resistant strains is discussed. We have emphasized the need for antifungal stewardship including increasing surveillance for resistant infection.

Strategies for the enhancement of nail plate permeation of drugs to treat onychomycosis.

Onychomycosis is caused by dermatophytes, non-dermatophytes and yeasts. It has a global prevalence of 5.5%, requires long treatment periods, and has high relapse rates following therapy. Oral antifungals are generally the most common treatment. While effective, they have limitations such as drug-drug interactions, hepatotoxicity and adverse side effects; thus, they cannot be used in several populations. Topical antifungals do not have the safety limitations but are typically not as effective. The primary challenge of topical treatment is the permeation of drug molecules across the nail plate barrier, which is a highly cross-linked keratin network. The use of drugs and formulations with favourable characteristics such as small size, absence of lipophilicity, hydrophilic nature, hydrating properties and appropriate pH can greatly improve permeation. Here, we review physical, nanoparticle-based, formulation-based, mechanical and chemical drug delivery strategies to improve the permeation of drugs across the nail plate.

Long-term Efficacy and Safety of Once-daily Efinaconazole 10% Topical Solution (Jublia) for Dermatophyte Toenail Onychomycosis: An Interim Analysis.

Onychomycosis, a difficult-to-treat fungal nail infection, is more prevalent in the elderly. Efinaconazole 10% topical solution is a firstline therapy for onychomycosis, based on phase III trials of 12-month treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. This is the first efficacy and safety data for a 24-month duration of efinaconazole 10% topical solution treatment for onychomycosis. Enrolled patients (N = 101) with mild to moderate distal lateral subungual onychomycosis applied efinaconazole to all affected toenails once daily for 18-24 months. Efficacy and safety were evaluated at months 6, 12, 18, and 24 (M6, M12, M18, and M24). The study is ongoing; to date, 47 patients have completed to M24. Mycological cure (MC) was 60.0% at M12, increasing to 74.2% at M24; effective cure (MC and ≤10% clinical involvement of the target toenail) was 17.8% at M12, rising to 19.4% at M24. Mild to moderate application site reactions were the only efinaconazole-related adverse events in 8 patients (7.9%). Increased age, increased severity of onychomycosis, and the presence of mixed infections (dermatophyte plus non-dermatophyte moulds) may drive a need for longer treatment durations. Although the data are interim, there is a trend of increasing efficacy beyond M12 use, without increased safety risk, even in patients >70 years of age.

A new reference genome for Sorghum bicolor reveals high levels of sequence similarity between sweet and grain genotypes: implications for the genetics of sugar metabolism.

BACKGROUND: The process of crop domestication often consists of two stages: initial domestication, where the wild species is first cultivated by humans, followed by diversification, when the domesticated species are subsequently adapted to more environments and specialized uses. Selective pressure to increase sugar accumulation in certain varieties of the cereal crop Sorghum bicolor is an excellent example of the latter; this has resulted in pronounced phenotypic divergence between sweet and grain-type sorghums, but the genetic mechanisms underlying these differences remain poorly understood. RESULTS: Here we present a new reference genome based on an archetypal sweet sorghum line and compare it to the current grain sorghum reference, revealing a high rate of nonsynonymous and potential loss of function mutations, but few changes in gene content or overall genome structure. We also use comparative transcriptomics to highlight changes in gene expression correlated with high stalk sugar content and show that changes in the activity and possibly localization of transporters, along with the timing of sugar metabolism play a critical role in the sweet phenotype. CONCLUSIONS: The high level of genomic similarity between sweet and grain sorghum reflects their historical relatedness, rather than their current phenotypic differences, but we find key changes in signaling molecules and transcriptional regulators that represent new candidates for understanding and improving sugar metabolism in this important crop.

Genomic evidence for convergent evolution of a key trait underlying divergence in island birds.

Reproductive isolation can be initiated by changes in one or a few key traits that prevent random mating among individuals in a population. During the early stages of speciation, when isolation is often incomplete, there will be a heterogeneous pattern of differentiation across regions of the genome between diverging populations, with loci controlling these key traits appearing the most distinct as a result of strong diversifying selection. In this study, we used Illumina-sequenced ddRAD tags to identify genomewide patterns of differentiation in three recently diverged island populations of the Monarcha castaneiventris flycatcher of the Solomon Islands. Populations of this species have diverged in plumage colour, and these differences in plumage colour, in turn, are used in conspecific recognition and likely important in reproductive isolation. Previous candidate gene sequencing identified point mutations in MC1R and ASIP, both known pigmentation genes, to be associated with the difference in plumage colour between islands. Here, we show that background levels of genomic differentiation based on over 70,000 SNPs are extremely low between populations of distinct plumage colour, with no loci reaching the level of differentiation found in either candidate gene. Further, we found that a phylogenetic analysis based on these SNPs produced a taxonomy wherein the two melanic populations appear to have evolved convergently, rather than from a single common ancestor, in contrast to their original classification as a single subspecies. Finally, we found evidence that the pattern of low genomic differentiation is the result of both incomplete lineage sorting and gene flow between populations.

Genetic dissection of sorghum grain quality traits using diverse and segregating populations.

KEY MESSAGE: Coordinated association and linkage mapping identified 25 grain quality QTLs in multiple environments, and fine mapping of the Wx locus supports the use of high-density genetic markers in linkage mapping. There is a wide range of end-use products made from cereal grains, and these products often demand different grain characteristics. Fortunately, cereal crop species including sorghum [Sorghum bicolor (L.) Moench] contain high phenotypic variation for traits influencing grain quality. Identifying genetic variants underlying this phenotypic variation allows plant breeders to develop genotypes with grain attributes optimized for their intended usage. Multiple sorghum mapping populations were rigorously phenotyped across two environments (SC Coastal Plain and Central TX) in 2 years for five major grain quality traits: amylose, starch, crude protein, crude fat, and gross energy. Coordinated association and linkage mapping revealed several robust QTLs that make prime targets to improve grain quality for food, feed, and fuel products. Although the amylose QTL interval spanned many megabases, the marker with greatest significance was located just 12 kb from waxy (Wx), the primary gene regulating amylose production in cereal grains. This suggests higher resolution mapping in recombinant inbred line (RIL) populations can be obtained when genotyped at a high marker density. The major QTL for crude fat content, identified in both a RIL population and grain sorghum diversity panel, encompassed the DGAT1 locus, a critical gene involved in maize lipid biosynthesis. Another QTL on chromosome 1 was consistently mapped in both RIL populations for multiple grain quality traits including starch, crude protein, and gross energy. Collectively, these genetic regions offer excellent opportunities to manipulate grain composition and set up future studies for gene validation.

Mutations in different pigmentation genes are associated with parallel melanism in island flycatchers.

The independent evolution of similar traits across multiple taxa provides some of the most compelling evidence of natural selection. Little is known, however, about the genetic basis of these convergent or parallel traits: are they mediated by identical or different mutations in the same genes, or unique mutations in different genes? Using a combination of candidate gene and reduced representation genomic sequencing approaches, we explore the genetic basis of and the evolutionary processes that mediate similar plumage colour shared by isolated populations of the Monarcha castaneiventris flycatcher of the Solomon Islands. A genome-wide association study (GWAS) that explicitly controlled for population structure revealed that mutations in known pigmentation genes are the best predictors of parallel plumage colour. That is, entirely black or melanic birds from one small island share an amino acid substitution in the melanocortin-1 receptor (MC1R), whereas similarly melanic birds from another small island over 100 km away share an amino acid substitution in a predicted binding site of agouti signalling protein (ASIP). A third larger island, which separates the two melanic populations, is inhabited by birds with chestnut bellies that lack the melanic MC1R and ASIP allelic variants. Formal FST outlier tests corroborated the results of the GWAS and suggested that strong, directional selection drives the near fixation of the MC1R and ASIP variants across islands. Our results, therefore, suggest that selection acting on different mutations with large phenotypic effects can drive the evolution of parallel melanism, despite the relatively small population size on islands.

Genomic variation at the tips of the adaptive radiation of Darwin's finches.

Adaptive radiation unfolds as selection acts on the genetic variation underlying functional traits. The nature of this variation can be revealed by studying the tips of an ongoing adaptive radiation. We studied genomic variation at the tips of the Darwin's finch radiation; specifically focusing on polymorphism within, and variation among, three sympatric species of the genus Geospiza. Using restriction site-associated DNA (RAD-seq), we characterized 32 569 single-nucleotide polymorphisms (SNPs), from which 11 outlier SNPs for beak and body size were uncovered by a genomewide association study (GWAS). Principal component analysis revealed that these 11 SNPs formed four statistically linked groups. Stepwise regression then revealed that the first PC score, which included 6 of the 11 top SNPs, explained over 80% of the variation in beak size, suggesting that selection on these traits influences multiple correlated loci. The two SNPs most strongly associated with beak size were near genes associated with beak morphology across deeper branches of the radiation: delta-like 1 homologue (DLK1) and high-mobility group AT-hook 2 (HMGA2). Our results suggest that (i) key adaptive traits are associated with a small fraction of the genome (11 of 32 569 SNPs), (ii) SNPs linked to the candidate genes are dispersed throughout the genome (on several chromosomes), and (iii) micro- and macro-evolutionary variation (roots and tips of the radiation) involve some shared and some unique genomic regions.

Clinical Diagnosis and Laboratory Testing of Abnormal Appearing Toenails: A Retrospective Assessment of Confirmatory Testing for Onychomycosis in the United States, 2022-2023.

Onychomycosis is an under-recognized healthcare burden. Despite the risk of misdiagnosis, confirmatory laboratory testing is under-utilized. Histopathologic examination with polymerase chain reaction (PCR) is currently the most effective diagnostic method; it offers direct detection and identification of a fungal invasion. In this retrospective cohort study, we assessed confirmatory testing results, with matching clinical diagnoses, in 96,293 nail specimens submitted during a 9-month period from 2022 to 2023. Toenail specimens were examined using fungal culture, histopathology and/or PCR. Clinical diagnoses were identified using the International Classification of Diseases 10th Revision codes. For clinically diagnosed onychomycosis patients, the overall positivity rate was 59.4%; a similar positivity rate (59.5%) was found in patients with clinically diagnosed non-fungal nail dystrophy. Performing a histopathologic examination with PCR was more likely to provide pathogen identification results than using fungal culture. Male patients had a higher rate of onychomycosis overall; however, female patients had more non-dermatophyte mold onychomycosis caused by Aspergillus. Clinically diagnosed onychomycosis patients with a co-diagnosis of tinea pedis were more likely to test positive for onychomycosis by PCR (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 2.7-6.4), histopathology (OR: 2.5; 95% CI: 2.0-3.1) and fungal culture (OR: 3.2; 95% CI: 1.5-6.6). Our results support the use of confirmatory laboratory testing when there is a clinical diagnosis of onychomycosis.

The emergence of Trichophyton indotineae: Implications for clinical practice.

Emergence and increase of terbinafine-resistant dermatophytosis led to the identification of Trichophyton mentagrophytes internal transcriber space (ITS) genotype VIII in 2017, later renamed as Trichophyton indotineae and classified as a separate species in 2020. With its suspected origin in South Asia, this novel strain has emerged in Bahrain, Canada, Denmark, Finland, France, Germany, India, Iran, Japan, Russia, and Switzerland, with its spread attributed primarily to travel and migration. Diagnosis using routine mycology laboratory techniques is unable to distinguish T. indotineae from T. mentagrophytes and T. interdigitale; specific identification requires genomic sequencing to identify unique, specific markers. One speculated reason for this recent outbreak is the unrestricted use of topical steroid creams and antifungal agents. Patients with extensive tinea corporis and cruris due to T. indotineae present with inflammatory red plaques in multiple body sites. The majority of these infections prove to be resistant to conventional antifungals, including allylamines and azoles (itraconazole and fluconazole), thus emphasizing the need for antifungal susceptibility testing before treatment initiation and for reassessing in nonresponsive patients. Molecular studies have identified several point mutations in the ERG1 (terbinafine resistance) and ERG11 (azole resistance) genes, which need to be analyzed further. Use of relatively new agents, such as voriconazole and luliconazole, as well as device modalities and combination therapy, could be investigated for recalcitrant T. indotineae infections.

The treatment of plantar warts using microwave-A review of 85 consecutive cases in the United States.

BACKGROUND: Plantar warts (verrucae plantaris) are a common source of pain for patients and are often refractory to treatment. Previous work has shown a high clearance rate of verrucae using a surface-based microwave device (Swift®). AIMS: To assess the efficacy, defined as the complete visible clearance of warts, in patients with verrucae plantaris receiving microwave treatment. PATIENTS: We undertook a retrospective review and identified records of 85 patients who underwent a course of microwave treatment at a single US-based podiatry centre. Efficacy was analyzed on the basis on intention-to-treat. RESULTS: In patients who received ≥1 session there was a complete clearance rate of 60.0% (51/85) (intention-to-treat; 59 patients completed treatment, 26 lost to follow-up) and 86.4% (51/59) per treatment completion; no significant differences in clearance rates of children and adults were observed (61.0% [25/41] vs. 59.1% [26/44]). There were 31 patients who received three sessions of microwave therapy with a clearance rate of 71.0% (22/31) as per intention-to-treat (27 patients completed treatment, 4 lost to follow-up). An average of 2.3 sessions (SD: 1.1; range: 1-6) was required for the complete clearance of plantar warts. Complete clearance was also observed in some patients with recalcitrant warts following additional treatment sessions (42.9% [3/7]). A significant reduction in wart related pain was reported for all patients undergoing treatment. Some patients continued to report a reduced amount of pain post-therapy compared with pretherapy. CONCLUSIONS: Microwave treatment of verrucae plantaris appears to be a safe and effective procedure.

Single-Point Nail Sampling to Diagnose Onychomycosis Caused by Non-Dermatophyte Molds: Utility of Polymerase Chain Reaction (PCR) and Histopathology.

The three most commonly used methods for diagnosing non-dermatophyte mold (NDM) onychomycosis are culture, polymerase chain reaction (PCR), and histopathology. Toenail samples from 512 patients (1 sample/patient) with suspected onychomycosis were examined using all three diagnostic tests. A statistically significant association was found between PCR and histopathology results, as well as between fungal culture and histopathology results. All PCR-positive and culture-positive dermatophyte samples were confirmed by histopathology. However, 15/116 (12.9%) of culture-positive NDM samples had negative histopathology results, while all PCR-positive NDM samples were confirmed by histopathology. The overall rate of dermatophyte detection was higher using PCR compared to culture (38.9% vs. 11.7%); the lower rate of NDM detection by PCR (11.7% vs. 38.9%) could be attributed to the restriction of the assay design to seven pre-selected targets. When repeat sampling in the clinic is not possible, a combination of NDM detection by PCR and positive histopathology of hyphae may be a proxy for NDM infection, particularly where the NDM occurs without a concomitant dermatophyte. There was a high degree of correlation between negative PCR and negative histopathology. A negative PCR result with negative histopathology findings may be a reliable proxy for the diagnosis of non-fungal dystrophy.

Utility of devices for onychomycosis: a review.

Onychomycosis is difficult to treat due to long treatment durations, poor efficacy rates of treatments, high relapse rates, and safety issues when using systemic antifungal agents. Device-based treatments are targeted to specific regions of the nail, have favorable safely profiles, and do not interfere with systemic agents. They may be an effective alternative therapy for onychomycosis especially with increasing reports of squalene epoxidase gene mutations and potential resistance to terbinafine therapy. In this review, we discuss four devices used as antifungal treatments and three devices used as penetration enhancers for topical agents. Lasers, photodynamic therapy, microwaves, and non-thermal plasma have the capacity to inactivate fungal pathogens demonstrated through in vivo studies. Efficacy rates for these devices, however, remain relatively low pointing toward the need to further optimize device or usage parameters. Ultrasound, nail drilling, and iontophoresis aid in improving the permeability of topical agents through the nail and have been investigated as adjunctive therapies. Due to the paucity in clinical data, their efficacy in treating onychomycosis has not yet been established. While the results of clinical studies point toward the potential utility of devices for onychomycosis, further large-scale randomized clinical trials following regulatory guidelines are required to confirm current results.

Antifungal Resistance, Susceptibility Testing and Treatment of Recalcitrant Dermatophytosis Caused by Trichophyton indotineae: A North American Perspective on Management.

There is an ongoing epidemic of chronic, relapsing dermatophytoses caused by Trichophyton indotineae that are unresponsive to one or multiple antifungal agents. Although this new species may have originated from the Indian subcontinent, there has been a notable increase of its reporting in other countries. Based on current literature, antifungal susceptibility testing (AFST) showed a large variation of terbinafine minimum inhibitory concentrations (MICs) (0.04 to ≥ 32 µg/ml). Elevated terbinafine MICs can be attributed to mutations in the squalene epoxidase gene (single mutations: Leu393Phe, Leu393Ser, Phe397Leu, and double mutations: Leu393Phe/Ala448Thr, Phe397Leu/Ala448Thr). Itraconazole MICs had a lower range when compared with that of terbinafine (0.008-16 µg/ml, with most MICs falling between 0.008 µg/ml and < 1 µg/ml). The interpretation of AFST results remains challenging due to protocol variations and a lack of established breakpoints. Adoption of molecular methods for resistance detection, coupled with AFST, may provide a better evaluation of the in vitro resistance status of T. indotineae. There is limited information on treatment options for patients with confirmed T. indotineae infections by molecular diagnosis; preliminary evidence generated from case reports and case series points to itraconazole as an effective treatment modality, while terbinafine and griseofulvin are generally not effective. For physicians working outside of endemic regions, there is currently an unmet need for standardized clinical trials to establish treatment guidelines; in particular, combination therapy of oral and topical agents (e.g., itraconazole and ciclopirox), as well as with other azoles (i.e., fluconazole, voriconazole, ketoconazole), warrants further investigation as multidrug resistance is a possibility for T. indotineae.

Detection of Squalene Epoxidase Mutations in United States Patients with Onychomycosis: Implications for Management.

Resistance to oral terbinafine, the most commonly used antifungal to treat dermatophytosis and onychomycosis worldwide, is being increasingly reported. In this study, we aimed to investigate the species distribution and prevalence of squalene epoxidase mutations among toenail dermatophyte isolates. Samples from 15,683 patients suspected of onychomycosis visiting the offices of dermatologists and podiatrists in the United States were analyzed. Clinical information was reviewed, and dermatophyte species with or without squalene epoxidase mutations were detected using multiplex real-time PCRs. The frequency of dermatophytes was 37.6%; of isolates belonging to the Trichophyton genus, 88.3% were the T. rubrum complex, and 11.2% were the T. mentagrophytes complex. Individuals aged >70 years exhibited higher infection rates for the T. mentagrophytes complex. The overall mutation rate among Trichophyton spp. was 3.7%, with a higher mutation rate detected in the T. mentagrophytes complex (4.3 vs. 3.6%). Commonly detected mutations were T1189C/Phe397Leu (34.5%), T1306C/Phe415Ser (16.0%), and C1191A/Phe397Leu (11.0%). Squalene epoxidase gene mutations associated with decreased terbinafine susceptibility have been identified in United States patients with toenail onychomycosis. Physicians should be aware of the risk factors for resistance development and engage in antifungal stewardship practices such as directed diagnosis and treatment of dermatophytosis and onychomycosis.

Systematic review of nondermatophyte mold onychomycosis: diagnosis, clinical types, epidemiology, and treatment.

Nondermatophyte mold (NDM) onychomycosis is difficult to diagnose given that NDMs are common contaminants of the nails and of the mycology laboratory. Diagnostic criteria and definition of cure are inconsistent between studies, which may affect the quality of published data. We identified 6 major criteria used in the literature: identification of the NDM in the nail by microscopy (using potassium hydroxide preparation), isolation in culture, repeated isolation in culture, inoculum counting, failure to isolate a dermatophyte in culture, and histology. Most studies used 3 or more of these (range = 1-5). We recommend using at least 3 of the criteria to rule out contamination; these should include potassium hydroxide preparation for direct microscopy and isolation of the organism in culture. We review geographic distribution and clinical presentations associated with different NDMs. The treatment with the greatest quantity of data and highest reported cure rates is terbinafine, for the treatment of Scopulariopsis brevicaulis and Aspergillus species infections. Topicals such as ciclopirox nail lacquer may also be effective (data originating from Scopulariopsis brevicaulis and Acremonium species infections), especially when combined with chemical or surgical avulsion of the nail. We recommend that future studies use (and clearly indicate) at least 3 of the main criteria for diagnosis, and report the clinical type of onychomycosis and the isolated organism. When evaluating different treatments, we suggest that authors clearly define their efficacy outcomes.