Dorota Z. Korta

Insulin signaling promotes germline proliferation in C. elegans

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.

S6K links cell fate, cell cycle and nutrient response in C. elegans germline stem/progenitor cells

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.

Soma-germline interactions that influence germline proliferation in Caenorhabditis elegans.

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. Developmental Dynamics 239:1449–1459, 2010.

Racial differences in skin cancer awareness and surveillance practices at a public hospital dermatology clinic.

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.

In vivo multiphoton-microscopy of picosecond-laser-induced optical breakdown in human skin

Improvements 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.

Quality of life in adults with facial port-wine stains

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.

Review of treatment for alopecia totalis and alopecia universalis

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.

Laser treatment of nongenital verrucae a systematic review

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.

Vesiculobullous eruption in a patient receiving psoralen ultraviolet A (PUVA) treatment for prurigo nodules: a case of PUVA‐aggravated pemphigoid nodularis

Pemphigoid nodularis (PN) is a rare variant of bullous pemphigoid (BP), manifesting with clinical features of prurigo nodularis with an autoantibody profile of BP. Psoralen ultraviolet A (PUVA) can induce blister formation acrally and in areas with friction or trauma. While this is generally distinct from BP, these blisters represent the initial manifestation of BP in some patients, and are thus considered PUVA-induced BP. A 73-year-old East Asian man presented with a vesiculobullous eruption following four treatments of oral PUVA for recalcitrant pruritus with prurigo nodules. Other than prurigo nodules and excoriations, the patient originally lacked other cutaneous manifestations. The initial cause of the patient’s pruritus was unclear. He had previously been prophylactically treated with permethrin, topical corticosteroids, pramoxine and gabapentin with little improvement. The patient’s other medications included amlodipine, aspirin, atorvastatin, apixaban, escitalopram and metoprolol. He had not had a biopsy taken prior to the start of his PUVA treatment and basic laboratory investigations at the time were unremarkable. On physical examination, the patient was found to have prurigo nodules and excoriations (Fig. 1), along with numerous coalescing vesicles and tense bullae on his hands, trunk and thighs. Histological examination of a biopsy taken from an intact vesicle demonstrated vesicular spongiotic dermatitis with numerous eosinophils (Fig. 2). Indirect immunofluorescence demonstrated linear staining for IgG along the basement membrane zone (BMZ) at a titre of 1 : 40 960 on monkey oesophagus, and an epidermal staining pattern on salt-split skin at a dilution of 1 : 5120. ELISA results for IgG to BP180 and BP230 were 114 and 59 ELISA units/mL, respectively, with a reference range of 9 ELISA units/mL for both tests. Therefore, a diagnosis of PN was made. The patient was successfully treated with a combination of a slow prednisone taper, intravenous IgG 2 g/kg/month, minocycline 100 mg twice daily, niacinamide 500 mg three times daily, and mycophenolate mofetil 1 g twice daily, as is standard in our immunobullous clinic to achieve durable remissions. The patient was successfully weaned off prednisone, and his other medications were continued. PN is a rare variant of BP. Although patients demonstrate an immunological phenotype of BP, some do not develop blisters. Similar nonbullous phenomena occur in patients with significant levels of BP antibodies in other pruritic disorders of the elderly, and PN is

Awareness of Surgical Smoke Risks and Assessment of Safety Practices During Electrosurgery Among US Dermatology Residents

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