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Activation-induced cytidine deaminase (AID) is a genome-mutating enzyme that initiates class switch recombination and somatic hypermutation of antibodies in jawed vertebrates. We previously described the biochemical properties of human AID and found that it is an unusual enzyme in that it exhibits binding affinities for its substrate DNA and catalytic rates several orders of magnitude higher and lower, respectively, than a typical enzyme. Recently, we solved the functional structure of AID and demonstrated that these properties are due to nonspecific DNA binding on its surface, along with a catalytic pocket that predominantly assumes a closed conformation. Here we investigated the biochemical properties of AID from a sea lamprey, nurse shark, tetraodon, and coelacanth: representative species chosen because their lineages diverged at the earliest critical junctures in evolution of adaptive immunity. We found that these earliest-diverged AID orthologs are active cytidine deaminases that exhibit unique substrate specificities and thermosensitivities. Significant amino acid sequence divergence among these AID orthologs is predicted to manifest as notable structural differences. However, despite major differences in sequence specificities, thermosensitivities, and structural features, all orthologs share the unusually high DNA binding affinities and low catalytic rates. This absolute conservation is evidence for biological significance of these unique biochemical properties.

Nondermatophyte moulds (NDMs) onychomycosis is often difficult to diagnose as NDMs have been considered contaminants of nails. There are several diagnostic methods used to identify NDMs, however, repeated laboratory isolation is recommended to validate pathogenicity. With NDM and mixed infection (dermatophytes plus NDM) onychomycosis on the rise, accurate clinical diagnosis along with mycological tests is recommended. Systemic antifungal agents such as itraconazole and terbinafine (e.g. pulse regimen: 1 pulse = every day for one week, followed by no treatment for three weeks) have shown efficacy in treating onychomycosis caused by various NDMs such as Aspergillus spp., Fusarium spp., Scopulariopsis brevicaulis, and Onychocola canadensis. Studies investigating topical therapy and devices for NDM onychomycosis are limited. The emergence of antifungal resistance necessitates the incorporation of antifungal susceptibility testing into diagnosis when possible, for the management of recalcitrant infections. Case studies documented in the literature show newer azoles such as posaconazole and voriconazole as sometimes effective in treating resistant NDM onychomycosis. Treatment with broad-spectrum antifungal agents (e.g. itraconazole and efinaconazole) and other combination therapy (oral + oral and/or oral + topical) may be considerations in the management of NDM onychomycosis.

SignificanceCytidine deaminases of the AID/APOBEC family mutate the genetic material of pathogens or contribute to the generation and diversification of antibody repertoires in jawed vertebrates. In the extant jawless vertebrate, the lamprey, two members of the AID/APOBEC family are implicated in the somatic diversification of variable lymphocyte receptor (VLR) repertoires. We discovered an unexpected diversity of cytidine deaminase genes within and among lamprey species. The cytidine deaminases with features comparable to jawed vertebrate AID are always present, suggesting that they are involved in essential processes, such as VLR assembly. In contrast, other genes show a remarkable copy number variation, like the APOBEC3 genes in mammals. This suggests an unexpected similarity in functional deployment of AID/APOBEC cytidine deaminases across all vertebrates.

Background Hair loss affects most people at some point in their lifetime, causing anxiety and decreased self‐esteem. There are multiple surgical and nonsurgical treatments available, with the surgical options having greater and longer‐lasting effects. Such treatments have evolved over time with advances in technology and research, with numerous patients researching these treatments on Google. Many surgeons who provide these treatments belong to the International Society of Hair Restoration Surgeons (ISHRS). Aims To investigate trends in surgical hair restoration treatment from both the surgeon and patient perspectives. Methods Patient epidemiological and surgical data from the ISHRS were combined with search trend data from Google to analyze changing trends in surgical hair restoration treatment. Results Worldwide Internet searches for “hair transplant” have increased from 2004 to the present. Follicular unit excision (FUE) has supplanted follicular unit transplant (FUT) as the most popular hair transplant performed. Since 2004, there has been an increase in both nonsurgical and surgical female patients. Beard and eyebrow transplants have increased in popularity. Google searches follow this trend. Nonsurgical treatments such as platelet‐rich plasma (PRP) are being searched more frequently. Hair restoration clinics and Google searches were affected adversely by the COVID‐19 pandemic. Conclusion Technological advances in available therapies, improvement in delivery systems, changes in hair fashion, and global events have direct impact on hair restoration treatments offered by physicians and researched by patients. It is in the best interest of all hair restoration providers to keep abreast of changing technologies and treatment trends to stay at the forefront of their profession.

Patients suffering from hair loss and thinning may improve, stabilize, or minimize their condition if properly diagnosed and treated using nonsurgical therapies at early onset. 1 The various causes of hair loss are multifactorial and complex, including hormonal (eg, androgenetic alopecia (AGA), genetic, immune (eg, alopecia areata), scarring, and infectious (eg, tinea capitis). Prescription-based pharmaceuticals

Background: Microneedling is a relatively novel therapeutic modality introduced in the 1990s where small, fine needles are used to create micro punctures in the skin. It is a minimally invasive procedure used for various dermatological conditions, including androgenetic alopecia (AGA). Objective and Methods:We comprehensively summarize the literature regarding microneedling in dermatology. We performed linear multivariable regressions to synthesize evidence from the clinical trials that investigated the efficacy of microneedling for AGA. Studies eligible for quantitative analyses were assessed for evidence quality. Results:The exact mechanism of microneedling action is yet to be determined, with theories that include the wound-healing cascade. Microneedling monotherapy significantly increased total hair count more than topical minoxidil 5% (β = 12.29; p < 0.001).The combination treatment of microneedling with topical 5% minoxidil increased total hair count significantly compared to monotherapy with microneedling (β = 7.63, p < 0.05). Increasing the overall treatment duration of microneedling and reducing the frequency of microneedling sessions may positively influence an increase in total hair count. Conclusion:There are limited studies that investigate microneedling as a monotherapy for hair loss since majority of the trials combine it with other therapies such as topical minoxidil or platelet-rich plasma. While preliminary results look promising, further investigation of microneedling as a monotherapy in larger, randomized controlled trials will help determine its safety and efficacy, and place in treating AGA.

APOBEC3s (A3) are endogenous DNA-editing enzymes that are expressed in immune cells including T lymphocytes. A3s target and mutate the genomes of retroviruses that infect immune tissues such as the human immunodeficiency virus (HIV). Therefore, A3s were classically defined as host anti-viral innate immune factors. In contrast, we and others showed that A3s can also benefit the virus by mediating escape from adaptive immune recognition and drugs. Crucially, whether A3-mediated mutations help or hinder HIV, is not up to chance. Rather, the virus has evolved multiple mechanisms to actively and maximally subvert A3 activity. More recently, extensive A3 mutational footprints in tumor genomes have been observed in many different cancers. This suggests a role for A3s in cancer initiation and progression. On the other hand, multiple anti-tumor activities of A3s have also come to light, including impact on immune checkpoint molecules and possible generation of tumor neo-antigens. Here, we review the studies that reshaped the view of A3s from anti-viral innate immune agents to host factors exploited by HIV to escape from immune recognition. Viruses and tumors share many attributes, including rapid evolution and adeptness at exploiting mutations. Given this parallel, we then discuss the pro- and anti-tumor roles of A3s, and suggest that lessons learned from studying A3s in the context of anti-viral immunity can be applied to tumor immunotherapy.