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Background Vaginal rejuvenation is a topic of interest to multiple specialties, including dermatologists, plastic and reconstructive surgeons, urologists, and gynecologists. Evidence suggests that minimally invasive, energy-based devices-radiofrequency and laser therapy-are effective at vaginal tightening and decreasing symptoms of genitourinary syndrome of menopause (GSM) and/or vulvovaginal atrophy (VVA). Materials and methods A systematic review was completed using PubMed in November 2018 with search terms "vaginal" or "vagina" and "rejuvenation" or "tightening" or "laxity" or "radiofrequency" or "laser," as well as "genitourinary syndrome of menopause," "pelvic prolapse," "atrophic vaginitis," "vulvovaginal atrophy," "sexual function," "urinary incontinence," and "radiofrequency" or "laser." Inclusion criteria were articles written in English and clinical trials or case reports/series dealing with human subjects. Results We identified 59 studies (3,609 women) treated for vaginal rejuvenation using either radiofrequency or fractional ablative laser therapy. Studies report improvement in symptoms of GSM/VVA and sexual function, high patient satisfaction, and minor adverse events, including treatment-associated pain, swelling, or vaginal discharge. Conclusion This review demonstrates radiofrequency and laser are efficacious for the treatment of vaginal laxity and/or atrophy. Further research needs to be completed to determine which specific pathologies can be treated, if maintenance treatment is necessary, and long-term safety concerns.

To assess the clinical presentation, treatment modalities, and outcome of primary melanomas arising in ovarian cystic teratomas (OCT). A systematic review on PubMed/MEDLINE was performed on June 5, 2017, to gather data on patients with primary melanomas arising in OCTs. No systematic reviews were identified. Consequently, only case reports and case series of individuals were analyzed. A total of 37 articles met our inclusion criteria, totaling 41 unique patients. The average age of diagnosis was 51.5 years. In total, 24% of patients were found to have metastatic disease. In total, 56.7% of patients eventually died of their disease, with an average time from diagnosis to death of 9.3 months. Disease recurrence was common, occurring in 65% of patients. The mainstay of treatment was surgical in 100% of the cases. Adjuvant chemotherapy, immunotherapy, and radiation were also used with varying degrees of efficacy. Malignant melanoma arising in OCT is a rare disease with poor prognosis. The current mainstay treatment is surgical. Potential benefits of targeted therapy, immunotherapy, and chemotherapy remain to be determined. A limitation of this study is that these melanomas have only been published in case reports.

Background Primary male genital melanomas are rare. Of these, scrotal melanoma is the least common, and is unfortunately often detected late in the disease course. Objective To assess the clinical presentation, treatment modalities, and outcome of scrotal melanoma to aid clinician management. Methods Systematic literature review of PubMed, yielding 23 cases, of which 20 met the inclusion criteria. Results Although previously thought to have the best outcome of genitourinary melanomas, scrotal melanomas are associated with high mortality and late presentation. Scrotal melanoma presented as Stage I/II disease 18.75% of the time, Stage III 56.3% of the time, and Stage IV 25% of the time, whereas typical cutaneous melanoma presents as Stage I/II disease 84% of the time, Stage III 8% of the time, and Stage IV 4% of the time. Half of patients experienced recurrence of their disease. All patients who presented with metastases to distant organs died. Limitations Small sample size. Few cases described a Breslow's depth making it difficult to draw conclusions on tumor thickness and survival outcome. Conclusion Scrotal melanoma is rare, aggressive, and is often caught late in the disease course. The authors encourage dermatologists to educate patients and destigmatize genital lesions to increase the likelihood of earlier detection and better patient outcomes.

Background Facial port-wine stains (PWS) are considered by some an aesthetic skin problem, yet impact on quality of life (QoL) has not been objectively documented. Objective We sought to (1) characterize the effect of PWS on QoL in adults, (2) to identify the clinical and demographic factors that affect QoL, and (3) to compare our results with QoL studies in other skin conditions. Methods In total, 244 adults with facial PWS completed an online QoL survey, which included the Skindex-29 instrument. Results QoL in adults with facial PWS was diminished, especially from an emotional perspective. Variables associated with reduced QoL in all Skindex-29 subdomains included comorbid depression, limited facial mobility, and presence of other skin conditions. Persons with hypertrophy had more emotional and symptomatic impairment. The composite dermatologic-specific QoL scores were similar to those of cutaneous T-cell lymphoma, rosacea, alopecia, and vitiligo. Limitations Selection bias was a potential limitation, as participants were primarily recruited from patient support groups. Conclusion Our analysis demonstrates that the presence of a facial PWS has a significant negative impact on QoL. Dermatologists caring for patients with PWS should inquire about QoL, provide appropriate support and resources, and consider QoL when discussing treatment options and obtaining authorization for these procedures.

Author(s): Balu, Mihaela; Lentsch, Griffin; Korta, Dorota Z; Konig, Karsten; Kelly, Kristen M; Tromberg, Bruce J; Zachary, Christopher B | Abstract: ImportanceImprovements in skin appearance resulting from treatment with fractionated picosecond-lasers have been noted, but optimizing the treatment efficacy depends on a thorough understanding of the specific skin response. The development of non-invasive laser imaging techniques in conjunction with laser therapy can potentially provide feedback for guidance and optimizing clinical outcome.ObjectiveThe purpose of this study was to demonstrate the capability of multiphoton microscopy (MPM), a high-resolution, label-free imaging technique, to characterize in vivo the skin response to a fractionated non-ablative picosecond-laser treatment.Design, setting, and participantsTwo areas on the arm of a volunteer were treated with a fractionated picosecond laser at the Dermatology Clinic, UC Irvine. The skin response to treatment was imaged in vivo with a clinical MPM-based tomograph at 3 hours and 24 hours after treatment and seven additional time points over a 4-week period.Main outcomes and measuresMPM revealed micro-injuries present in the epidermis. Pigmented cells were particularly damaged in the process, suggesting that melanin is likely the main absorber for laser induced optical breakdown.ResultsDamaged individual cells were distinguished as early as 3 hours post pico-laser treatment with the 532 nm wavelength, and 24 hours post-treatment with both 532 and 1064 nm wavelengths. At later time points, clusters of cellular necrotic debris were imaged across the treated epidermis. After 24 hours of treatment, inflammatory cells were imaged in the proximity of epidermal micro-injuries. The epidermal injuries were exfoliated over a 4-week period.Conclusions and relevanceThis observational and descriptive pilot study demonstrates that in vivo MPM imaging can be used non-invasively to provide label-free contrast for describing changes in human skin following a fractionated non-ablative laser treatment. The results presented in this study represent the groundwork for future longitudinal investigations on an expanded number of subjects to understand the response to treatment in different skin types with different laser parameters, critical factors in optimizing treatment outcome. Lasers Surg. Med. 49:555-562, 2017. © 2017 Wiley Periodicals, Inc.

Facial lipoatrophy (FLA), characterized by a decrease in facial volume, has a high prevalence in patients with human immunodeficiency virus (HIV) infection treated with long-term highly active antiretroviral therapy (HAART). The social stigmatization that results from such changes in facial appearance has led some HIV patients to discontinue HAART. The use of fillers is one method of restoring facial volume. A critical outcome of treatment concerns the patient's quality of life (QoL). Although many studies have assessed patient satisfaction, as well as the social and psychological outcomes associated with the correction of HIV FLA, fewer studies have assessed QoL. We reviewed treatment options for HIV FLA with a specific focus on QoL outcomes. Our analysis revealed that the following treatments were associated with improvements in QoL: poly-l-lactic acid; calcium hydroxylapatite; hyaluronic acid; polyacrylamide gel; polyalkylamide gel; polymethylmethacrylate; silicone oil; and autologous fat transfer. The treatment of HIV FLA with these agents appears to improve QoL as assessed by various QoL instruments. Additional studies are required to identify a unifying QoL instrument to effectively assess longitudinal QoL outcomes and to compare treatment modalities.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. The association of bullous pemphigoid with melanoma remains controversial and poorly understood. Recent studies report the presence of the bullous pemphigoid antigen, BP180, in melanoma cells, yet not normal melanocytes, suggesting an underlying mechanism for cases of melanoma-associated bullous pemphigoid. We report on an 88-year-old woman who showed a temporal relationship between the development of bullous pemphigoid and melanoma. The patient did not receive programmed death ligand 1 inhibitor therapy and improved rapidly following complete excision of her melanoma, with clobetasol, doxycycline, and niacinamide. We review the literature on the relationship between bullous pemphigoid and melanoma, and propose a mechanism underlying a melanoma-associated bullous pemphigoid.

Ultrasound (US) technology uses acoustic waves to heat tissue, resulting in thermal damage and coagulative necrosis leading to the renewal of skin elasticity, body contouring, and destruction of cellulite.This review will discuss the use of US for skin tightening, body contouring/sculpting, and cellulite reduction.A literature search identified studies using US for skin tightening, body contouring/sculpting, and cellulite reduction.Two hundred thirty-one studies were identified using US technology. Twenty studies each were identified addressing body contouring/sculpting and skin tightening, and 2 studies for cellulite reduction. Ultrasound is efficacious for skin rejuvenation, body contouring, and reduction of cellulite of the face, décolletage, abdomen, and thighs. Ultrasound lipolysis results in a 2- to 4.6-cm decrease in abdominal circumference. Ultrasound is safe and can be used in all skin types with minimal concern for postinflammatory hyperpigmentation.Ultrasound seems to be an efficacious, effective, and safe modality for correction of skin laxity, lipolysis, and decrease the appearance of cellulite. Adverse effects are minimal including procedural pain, postprocedure erythema, and swelling. Clinicians and patients are both satisfied with results after treatment. In this review, the authors will provide an update on the use of US in the dermatologic field.

Gel manicures have become a popular beauty trend in recent years. The specially formulated nail polish must undergo curing under light-based units. The majority of these curing lamps emit high-intensity ultraviolet A, which can cause skin damage and increase the risk for skin cancers. Incorporating relevant information in patient education endeavors can help them practice avoidance, apply broad-spectrum sunscreen prior, or use nitrile exam gloves in order to prevent photoaging and skin cancer resulting from these procedures.

Breast implantation is an increasingly common procedure for both cosmesis and reconstruction. Risk of cutaneous reactions to breast implants is low and typically described in postsurgical settings. Adverse skin hypersensitivity-like reactions to implants have also been reported but are not well described.To review the scientific literature on cutaneous hypersensitivity-like reactions to breast implants.A systematic literature review was conducted using PubMed. Articles pertaining to breast implants and cutaneous hypersensitivity-like reactions in humans were included.In total, 10 studies on hypersensitivity-like reactions from breast implants were included in the review. Potential allergenic compounds in breast implants include silicone, polyurethane texturing, and acellular dermal matrix. Perivascular lymphocytic infiltrate was a common finding on histopathology. Patch testing and preoperative silicone cube implantation were used to determine sensitivity. Attempted treatments included topical and oral corticosteroids, montelukast and antibiotics. Most cases required implant removal for resolution of symptoms.Cutaneous hypersensitivity-like reactions to breast implants seem to be rare complications, sometimes necessitating implant removal. Future studies are needed to establish their incidence and etiology, and the diagnostic role of patch testing and preoperative screening.

Steatocystoma multiplex is a well-recognized condition in which subjects develop dermal cysts generally inherited in an autosomal dominant fashion, though these can occur sporadically. This case report describes the successful treatment of a 51-year-old woman with steatocystomata limited to the face, who after two treatments with a fractionated ablative carbon dioxide laser remained free of cysts for three years. We conclude that this treatment should be considered as an efficient and effective treatment option for patients with steatocystoma multiplex.

This commentary addresses the increasingly competitive nature of applying to dermatology residency programs and how both interest groups in medical schools and their dermatology departments can help to better prepare applicants. As previous literature argued that dermatology has been underemphasized in medical school curricula, we propose five fundamental options that interest groups can implement in order to offer increased exposure to our field in medical training. Furthermore, with therecent trend of many schools conferring certificates in various specialized concentrations, we also discuss interest groups pioneering certificate-grantingprograms in dermatology competency. The pros and cons of having a recognized certificate program in dermatology are presented.

This manuscript addresses the significant considerations concerning the development and use of medical devices in dermatology. With the rapidly growing demand and booming market for medical devices, especially lasers, it is crucial that dermatologists become familiar with the nuances associated with supporting clinical studies, consumer-driven marketing strategies, and the complex relationships that exist between physicians, industry, and consumers. An examination of these relationships includes an overview of the potential biases pertaining to advisory panels and treating clinicians. The aim of this paper is to serve as an introduction to the background of medical devices and to offer dermatologists important information on what should be considered before recommending treatment.

BACKGROUND Dermatologists are at potential risk of acquiring infections from contamination of the mucous membranes by blood and body fluids. However, there are little data on splash safety during procedural dermatology. OBJECTIVE To determine dermatology resident perceptions about splash risk during dermatologic procedures and to quantify the rate of protective equipment use. METHODS An anonymous on-line survey was sent to 108 United States ACGME-approved dermatology residency programs assessing frequency of facial protection during dermatologic procedures, personal history of splash injury, and, if applicable, reasons for not always wearing facial protection. RESULTS A total of 153 dermatology residents responded. Rates of facial protection varied by procedure, with the highest rates during surgery and the lowest during local anesthetic injection. Over 54% of respondents reported suffering facial splash while not wearing facial protection during a procedure. In contrast, 88.9% of respondents correctly answered that there is a small risk of acquiring infection from mucosal splash. Residency program recommendations for facial protection seem to vary by procedure. CONCLUSION The authors' results demonstrate that although facial splash is a common injury, facial protection rates and protective recommendations vary significantly by procedure. These data support the recommendation for enhanced facial protection guidelines during procedural dermatology.

Full-body skin exams (FBSE) play an integral role inearly detection and treatment of skin cancer. Promptdetection of melanoma is especially importantas survival outcomes decrease significantly withpresentation of advanced disease. Given thatmelanoma may grow in areas of skin with little to nosun exposure, genital melanomas are a recognizedentity in cutaneous oncology.

This study assessed clinician awareness of surgical smoke risks and current safety practices during active electrosurgery among dermatology residents.

This commentary addresses the increasingly competitive nature of applying to dermatology residency programs and how both interest groups in medical schools and their dermatology departments can help to better prepare applicants. As previous literature argued that dermatology has been underemphasized in medical school curricula, we propose five fundamental options that interest groups can implement in order to offer increased exposure to our field in medical training. Furthermore, with therecent trend of many schools conferring certificates in various specialized concentrations, we also discuss interest groups pioneering certificate-grantingprograms in dermatology competency. The pros and cons of having a recognized certificate program in dermatology are presented.

This manuscript addresses the significant considerations concerning the development and use of medical devices in dermatology. With the rapidly growing demand and booming market for medical devices, especially lasers, it is crucial that dermatologists become familiar with the nuances associated with supporting clinical studies, consumer-driven marketing strategies, and the complex relationships that exist between physicians, industry, and consumers. An examination of these relationships includes an overview of the potential biases pertaining to advisory panels and treating clinicians. The aim of this paper is to serve as an introduction to the background of medical devices and to offer dermatologists important information on what should be considered before recommending treatment.

Full-body skin exams (FBSE) play an integral role inearly detection and treatment of skin cancer. Promptdetection of melanoma is especially importantas survival outcomes decrease significantly withpresentation of advanced disease. Given thatmelanoma may grow in areas of skin with little to nosun exposure, genital melanomas are a recognizedentity in cutaneous oncology.

In dermatology, a particularly common ethical dilemma can arise when the skin lesions of bystanders are inadvertently viewed in public settings. Dermatology is a unique field, where a person’s organ of interest is readily visible to others. When lesions are suspicious for skin disease, unsolicited medical opinions may or may not be given depending on several factors. This study examined the actions and attitudes of dermatologists with different levels of experience through the use of case scenarios with various settings and skin lesions.

Background Patients from ethnoracial minority groups have lower incidence rates of melanoma compared with whites, but are more likely to have advanced melanomas at diagnosis and lower survival. Infrequent skin cancer screening and poor melanoma awareness may contribute to these disparities. Objective The purpose of this survey study was to evaluate skin cancer surveillance behaviors and awareness among patients attending a dermatology clinic at a public hospital in New York City. Methods Surveys were administered to 152 patients from April to June 2012. Results In all, 16% of patients previously had a total body skin examination for cancer, 11% were taught by a health care practitioner how to perform skin self-examinations, and 15% perform skin self-examinations. More whites had a total body skin examination compared with minorities (49% vs 5%). Only 33% of patients previously given a diagnosis of skin cancer performed skin self-examinations. Patients possessed a poor ability to recognize features suspicious for melanoma, with minorities (especially Hispanics) performing worse than whites. Limitations Small sample size is a limitation. Conclusions Few patients engage in skin cancer screening behaviors and their knowledge about melanoma is poor, with minorities demonstrating lower understanding than whites. Our findings emphasize the need for improved patient education about characteristics of melanoma, regardless of race.

Alopecia areata (AA) is an autoimmune disease directed at the hair follicle. Although usually limited to patchy hair loss over the scalp (focalis), AA can present as total loss of scalp hair (totalis; AT) or as total loss of both scalp and body hair (universalis; AU). Management of AT and AU can be challenging, and although multiple treatment modalities have been explored, no therapy is currently FDA-approved. This review focuses on the evidence for current treatment options for AT and AU. The PubMed database was searched from January 1, 2000, to September 1, 2016, for clinical trials, retrospective studies, and case reports of treatments for AT and AU. A total of 40 studies were retrieved and analyzed. Therapies studied for AT/AU included: topical immunotherapy, steroids, photodynamic therapy, immunosuppressive agents, TNFα inhibitors, and other therapies, such as sulfasalazine, bexarotene, JAK inhibitors, and simvastatin/ezetimibe. Although certain treatments showed significant hair regrowth, no treatment was completely effective. The most promising therapies with the highest quality data include diphenylcyclopropenone, squaric acid dibutylester, photodynamic therapy, steroids, and cyclosporine in combination with methylprednisolone. High-quality randomized-controlled trials with large sample sizes are lacking. Unified outcome guidelines are encouraged to facilitate the comparison of future studies.

Coupling of stem/progenitor cell proliferation and differentiation to organismal physiological demands ensures the proper growth and homeostasis of tissues. However, in vivo mechanisms underlying this control are poorly characterized. We investigated the role of ribosomal protein S6 kinase (S6K) at the intersection of nutrition and the establishment of a stem/progenitor cell population using the C. elegans germ line as a model. We find that rsks-1 (which encodes the worm homolog of mammalian p70S6K) is required germline-autonomously for proper establishment of the germline progenitor pool. In the germ line, rsks-1 promotes cell cycle progression and inhibits larval progenitor differentiation, promotes growth of adult tumors and requires a conserved TOR phosphorylation site. Loss of rsks-1 and ife-1 (eIF4E) together reduces the germline progenitor pool more severely than either single mutant and similarly to reducing the activity of let-363 (TOR) or daf-15 (RAPTOR). Moreover, rsks-1 acts in parallel with the glp-1 (Notch) and daf-2 (insulin-IGF receptor) pathways, and does not share the same genetic dependencies with its role in lifespan control. We show that overall dietary restriction and amino acid deprivation cause germline defects similar to a subset of rsks-1 mutant phenotypes. Consistent with a link between diet and germline proliferation via rsks-1, loss of rsks-1 renders the germ line largely insensitive to the effects of dietary restriction. Our studies establish the C. elegans germ line as an in vivo model to understand TOR-S6K signaling in proliferation and differentiation and suggest that this pathway is a key nutrient-responsive regulator of germline progenitors.

Achille Civatte (1877-1956) was one of the most highly regarded dermatologists of the 20th century. We provide a succinct account of Civatte's academic life and contributions to the field of dermatopathology, in addition to briefly discussing his son, Jean Civatte, who himself became a highly regarded dermatologist.

Skin metastases from visceral malignancies have been well documented in the literature, and may be the presenting sign of an occult internal malignancy. Lung cancer in particular is a relatively common cause of skin metastases, which are considered a poor prognostic sign. Rarely, patients with lung cancer develop a second primary lung cancer that may require a novel chemotherapeutic regimen. The frequency of second primary malignancies presenting with metastatic skin lesions is not documented in the literature. We present a case of a 50-year-old man with a history of metastatic lung adenocarcinoma who was referred for evaluation of a nodule overlying his right mandible, which had been progressively enlarging for two weeks. Biopsy demonstrated metastatic squamous cell carcinoma. Subsequent CT-guided biopsy of a left retroperitoneal lymph node was conducted and notable for squamous cell carcinoma. Therefore, this patient's skin lesion was the presenting sign of a second primary visceral tumor, likely originating in the lung. We present this case to raise clinical awareness of the rare phenomenon that cutaneous metastasis may be the first sign of a visceral cancer, even in the setting of a previous distinct primary malignancy.

Tumor necrosis factor (TNF) inhibitors are powerful biologic medications that have been used successfully in the treatment of a variety of inflammatory conditions, including psoriasis. Although TNF inhibitors are generally well tolerated, their use increases the risk of infections such as tuberculosis (TB), and paradoxically, they have been associated with development of sarcoidosis. We report the case of a 54-year old man with plaque psoriasis who developed a positive TB test and pulmonary sarcoidosis after 12 months of adalimumab treatment. After stopping adalimumab, his psoriasis worsened and he was started on ustekinumab and narrowband UVB, with improvement in symptoms. We provide a review of the literature and discuss treatment challenges.

Angiokeratomas can present therapeutic challenges, especially in cases of extensive lesions, where traditional surgical methods carry high risks of scarring and hemorrhage. Argon, pulsed dye (PDL), neodymium-doped yttrium aluminum garnet (Nd:YAG), copper vapor, potassium titanyl phosphate, carbon dioxide, and erbium-doped yttrium aluminum garnet (Er:YAG) lasers have emerged as alternative options. To review the use and efficacy of lasers in treating angiokeratomas. A PubMed search identified randomized clinical trials, cohort studies, case series, and case reports involving laser treatment of cutaneous angiokeratomas. Twenty-five studies were included. Quality ratings were assigned using the Oxford Centre for Evidence-Based Medicine scheme. Several laser modalities are effective in treating multiple variants of angiokeratomas. Vascular lasers like PDL, Nd:YAG, and argon are the most studied and of these, PDL offers the safest side effect profile. Nd:YAG may be more effective for hyperkeratotic angiokeratomas. Combination treatment with multiple laser modalities has also demonstrated some success. Lasers are a promising treatment option for angiokeratomas, but current use is limited by the lack of treatment guidelines. There are limited high quality studies comparing laser treatments to each other and to non-laser options. Additional studies are needed to establish guidelines and to optimize laser parameters.

The skin is one of the target organs most commonly affected in lupus erythematosus (LE) and a wide range of cutaneous changes have been described in LE patients. Papulonodular mucinosis (PNM) in particular is an uncommon cutaneous manifestation of LE. We discuss the case of a 26-year-old Senegalese woman with systemic LE and antiphospholipid syndrome (APS) who presented with pruritic papules on her back and extremities that appeared when she was on vacation in Africa and non-compliant with medications. Histopathologic examination was consistent with PNM. The patient was treated with mycophenolate mofetil and hydroxychloroquine, with subjective relief in pruritis at 6-week follow-up. To our knowledge, this is the first case of PNM presenting in a patient with both SLE and APS. Whether APS contributes to the pathogenesis of PNM is currently unknown.

Coupling of stem/progenitor cell proliferation and differentiation to organismal physiological demands ensures the proper growth and homeostasis of tissues. However, in vivo mechanisms underlying this control are poorly characterized. We investigated the role of ribosomal protein S6 kinase (S6K) at the intersection of nutrition and the establishment of a stem/progenitor cell population using the C. elegans germ line as a model. We find that rsks-1 (which encodes the worm homolog of mammalian p70S6K) is required germline-autonomously for proper establishment of the germline progenitor pool. In the germ line, rsks-1 promotes cell cycle progression and inhibits larval progenitor differentiation, promotes growth of adult tumors and requires a conserved TOR phosphorylation site. Loss of rsks-1 and ife-1 (eIF4E) together reduces the germline progenitor pool more severely than either single mutant and similarly to reducing the activity of let-363 (TOR) or daf-15 (RAPTOR). Moreover, rsks-1 acts in parallel with the glp-1 (Notch) and daf-2 (insulin-IGF receptor) pathways, and does not share the same genetic dependencies with its role in lifespan control. We show that overall dietary restriction and amino acid deprivation cause germline defects similar to a subset of rsks-1 mutant phenotypes. Consistent with a link between diet and germline proliferation via rsks-1, loss of rsks-1 renders the germ line largely insensitive to the effects of dietary restriction. Our studies establish the C. elegans germ line as an in vivo model to understand TOR-S6K signaling in proliferation and differentiation and suggest that this pathway is a key nutrient-responsive regulator of germline progenitors.

Cell proliferation must be coordinated with cell fate specification during development, yet interactions among pathways that control these two critical aspects of development are not well understood. The coordination of cell fate specification and proliferation is particularly crucial during early germline development, when it impacts the establishment of stem/progenitor cell populations and ultimately the production of gametes. In C. elegans, insulin/IGF-like receptor (IIR) signaling has been implicated in fertility, but the basis for the fertility defect had not been previously characterized. We found that IIR signaling is required for robust larval germline proliferation, separate from its well-characterized role in preventing dauer entry. IIR signaling stimulates the larval germline cell cycle. This activity is distinct from Notch signaling, occurs in a predominantly germline-autonomous manner, and responds to somatic activity of ins-3 and ins-33, genes that encode putative insulin-like ligands. IIR signaling in this role acts through the canonical PI3K pathway, inhibiting DAF-16/FOXO. However, signaling from these ligands does not inhibit daf-16 in neurons nor in the intestine, two tissues previously implicated in other IIR roles. Our data are consistent with a model in which: (1) under replete reproductive conditions, the larval germline responds to insulin signaling to ensure robust germline proliferation that builds up the germline stem cell population; and (2) distinct insulin-like ligands contribute to different phenotypes by acting on IIR signaling in different tissues.

The intersection between developmental programs and environmental conditions that alter physiology is a growing area of research interest. The C. elegans germ line is emerging as a particularly sensitive and powerful model for these studies. The germ line is subject to environmentally regulated diapause points that allow worms to withstand harsh conditions both prior to and after reproduction commences. It also responds to more subtle changes in physiological conditions. Recent studies demonstrate that different aspects of germ line development are sensitive to environmental and physiological changes and that conserved signaling pathways such as the AMPK, Insulin/IGF, TGFβ, and TOR-S6K, and nuclear hormone receptor pathways mediate this sensitivity. Some of these pathways genetically interact with but appear distinct from previously characterized mechanisms of germline cell fate control such as Notch signaling. Here, we review several aspects of hermaphrodite germline development in the context of “feasting,” “food-limited,” and “fasting” conditions. We also consider connections between lifespan, metabolism and the germ line, and we comment on special considerations for examining germline development under altered environmental and physiological conditions. Finally, we summarize the major outstanding questions in the field.

© 2016 American Medical Association. IMPORTANCE Although cutaneous warts are common lesions, full remission is not always achieved with conventional therapies. Laser modalities including carbon dioxide (CO2), erbium:yttrium-aluminum-garnet (Er:YAG), pulsed dye (PDL), and Nd:YAG have been investigated as alternative treatments for warts. OBJECTIVE To review the use and efficacy of lasers for treating nongenital cutaneous warts. EVIDENCE REVIEW Published randomized clinical trials (RCTs), cohort studies, case series, and case reports involving laser treatment of nongenital warts were retrieved by searching PubMed with no date limits. Quality ratings of studies were based on a modified version of the Oxford Centre for Evidence-Based Medicine scheme for rating individual studies. A higher emphasis was placed on RCTs and prospective cohort studies with large sample sizes and detailed methodology. FINDINGS There were 35 studies published between 1989 and 2015 that comprised an aggregate of 2149 patients. Simple and recalcitrant nongenital warts treated with lasers show variable response rates (CO2 laser, 50%-100%; Er:YAG laser, 72%-100%; PDL, 47%-100%; and Nd:YAG laser, 46%-100%). Current RCTs suggest that PDL is equivalent to conventional therapies such as cryotherapy and cantharidin. Combination therapies with lasers and other agents including bleomycin, salicylic acid, and light-emitting diode have shown some success. CONCLUSIONS AND RELEVANCE Lasers can be an effective treatment option for both simple and recalcitrant warts. The lasers most studied for this purpose are CO2, PDL, and Nd:YAG, and of these, PDL has the fewest adverse effects. Currently, use of lasers for wart treatment is limited by lack of established treatment guidelines. Future studies are needed to compare laser modalities with each other and with nonlaser treatment options, and to establish optimal treatment protocols.

Caenorhabditis elegans boasts a short lifecycle and high fecundity, two features that make it an attractive and powerful genetic model organism. Several recent studies indicate that germline proliferation, a prerequisite to optimal fecundity, is tightly controlled over the course of development. Cell proliferation control includes regulation of competence to proliferate, a poorly understood aspect of cell fate specification, as well as cell-cycle control. Furthermore, dynamic regulation of cell proliferation occurs in response to multiple external signals. The C. elegans germ line is proving a valuable model for linking genetic, developmental, systemic, and environmental control of cell proliferation. Here, we consider recent studies that contribute to our understanding of germ cell proliferation in C. elegans. We focus primarily on somatic control of germline proliferation, how it differs at different life stages, and how it can be altered in the context of the life cycle and changes in environmental status.

The proper renewal and maintenance of tissues by stem cell populations is simultaneously influenced by anatomical constraints, cell proliferation dynamics and cell fate specification. However, their relative influence is difficult to examine in vivo. To address this difficulty we built, as a test case, a cell-centered state-based computational model of key behaviors that govern germline development in C. elegans, and used it to drive simulations of cell population dynamics under a variety of perturbations. Our analysis provided unexpected possible explanations for laboratory observations, including certain ‘all-or-none’ phenotypes and complex differentiation patterns. The simulations also offered insights into niche-association dynamics and the interplay between cell cycle and cell fate. Subsequent experiments validated several predictions generated by the simulations. Notably, we found that early cell cycle defects influence later maintenance of the progenitor cell population. This general modeling approach is potentially applicable to other stem cell systems.