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1.
Annu Rev Neurosci ; 44: 153-172, 2021 07 08.
Article in English | MEDLINE | ID: mdl-33556251

ABSTRACT

During the approximately 5 days of Drosophila neurogenesis (late embryogenesis to the beginning of pupation), a limited number of neural stem cells produce approximately 200,000 neurons comprising hundreds of cell types. To build a functional nervous system, neuronal types need to be produced in the proper places, appropriate numbers, and correct times. We discuss how neural stem cells (neuroblasts) obtain so-called area codes for their positions in the nervous system (spatial patterning) and how they keep time to sequentially produce neurons with unique fates (temporal patterning). We focus on specific examples that demonstrate how a relatively simple patterning system (Notch) can be used reiteratively to generate different neuronal types. We also speculate on how different modes of temporal patterning that operate over short versus long time periods might be linked. We end by discussing how specification programs are integrated and lead to the terminal features of different neuronal types.


Subject(s)
Drosophila Proteins , Neural Stem Cells , Animals , Drosophila , Drosophila Proteins/genetics , Neurogenesis , Neurons
2.
Nature ; 604(7905): 316-322, 2022 04.
Article in English | MEDLINE | ID: mdl-35388222

ABSTRACT

The brain consists of thousands of neuronal types that are generated by stem cells producing different neuronal types as they age. In Drosophila, this temporal patterning is driven by the successive expression of temporal transcription factors (tTFs)1-6. Here we used single-cell mRNA sequencing to identify the complete series of tTFs that specify most Drosophila optic lobe neurons. We verify that tTFs regulate the progression of the series by activating the next tTF(s) and repressing the previous one(s), and also identify more complex mechanisms of regulation. Moreover, we establish the temporal window of origin and birth order of each neuronal type in the medulla and provide evidence that these tTFs are sufficient to explain the generation of all of the neuronal diversity in this brain region. Finally, we describe the first steps of neuronal differentiation and show that these steps are conserved in humans. We find that terminal differentiation genes, such as neurotransmitter-related genes, are present as transcripts, but not as proteins, in immature larval neurons. This comprehensive analysis of a temporal series of tTFs in the optic lobe offers mechanistic insights into how tTF series are regulated, and how they can lead to the generation of a complete set of neurons.


Subject(s)
Drosophila Proteins , Drosophila melanogaster , Gene Expression Regulation, Developmental , Optic Lobe, Nonmammalian , Transcription Factors , Vision, Ocular , Visual Perception , Animals , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/cytology , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Neurons/cytology , Neurons/metabolism , Optic Lobe, Nonmammalian/cytology , RNA-Seq , Single-Cell Analysis , Transcription Factors/metabolism
3.
J Urol ; 211(1): 90-100, 2024 01.
Article in English | MEDLINE | ID: mdl-37788015

ABSTRACT

PURPOSE: Penile cancer is rare, with significant morbidity and limited literature assessing utility of peripheral and deep en face margin assessment (PDEMA) vs traditional margin assessment (vertical sections) on treatment outcomes. MATERIALS AND METHODS: This was a 32-year retrospective multicenter cohort study at 3 academic tertiary care centers. The cohort consisted of 189 patients with histologic diagnosis of in situ or T1a cutaneous squamous cell carcinoma of the penis at Brigham and Women's, Massachusetts General Hospital (1988-2020), and Memorial Sloan Kettering Cancer Center (1995-2020) treated with PDEMA surgical excision, excision/circumcision, or penectomy/glansectomy. Local recurrence, metastasis, and disease-specific death were assessed via multivariable Cox proportional hazard models. RESULTS: The cohort consisted of 189 patients. Median age at diagnosis was 62 years. Median tumor diameter was 1.3 cm. The following outcomes of interest occurred: 30 local recurrences, 13 metastases, and 5 disease-specific deaths. Primary tumors were excised with PDEMA (N = 30), excision/circumcision (N = 110), or penectomy/glansectomy (N = 49). Of patients treated with traditional margin assessment (non-PDEMA), 12% had narrow or positive margins. Five-year proportions were as follows with respect to local recurrence-free survival, metastasis-free survival, and disease-specific survival/progression-free survival, respectively: 100%, 100%, and 100% following PDEMA; 82%, 96%, and 99% following excision/circumcision; 83%, 91%, and 95% following penectomy/glansectomy. A limitation is that this multi-institutional cohort study was not externally validated. CONCLUSIONS: Initial results are encouraging that PDEMA surgical management effectively controls early-stage penile squamous cell carcinoma.


Subject(s)
Carcinoma, Squamous Cell , Penile Neoplasms , Skin Neoplasms , Male , Humans , Female , Middle Aged , Penile Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Cohort Studies , Organ Sparing Treatments/methods , Neoplasm Recurrence, Local/pathology , Retrospective Studies
4.
J Am Acad Dermatol ; 90(1): 52-57, 2024 01.
Article in English | MEDLINE | ID: mdl-37634737

ABSTRACT

BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.


Subject(s)
Hutchinson's Melanotic Freckle , Melanoma , Skin Neoplasms , Humans , Hutchinson's Melanotic Freckle/diagnostic imaging , Hutchinson's Melanotic Freckle/pathology , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathology , Retrospective Studies , Diagnosis, Differential , Melanoma/pathology , Microscopy, Confocal/methods , Dermoscopy/methods
5.
Article in English | MEDLINE | ID: mdl-38842227

ABSTRACT

BACKGROUND: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis. OBJECTIVES: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy. METHODS: Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed. RESULTS: Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22). CONCLUSIONS: History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.

6.
J Nutr ; 153(1): 301-311, 2023 01.
Article in English | MEDLINE | ID: mdl-36913466

ABSTRACT

BACKGROUND: Vitamins, minerals, and natural product (NP)-derived dietary supplements are commonly used among women with breast cancer, where interactions with treatments and the disease are possible, emphasizing the importance for health care providers to be aware of supplement use. OBJECTIVES: The study aimed to investigate current vitamin/mineral (VM) and NP supplement use among those diagnosed with breast cancer, including usage based on tumor type or concurrent breast cancer treatments and primary information sources for specific supplements. METHODS: Social media recruiting to complete an online questionnaire self-reporting current VM and NP use and breast cancer diagnosis and treatment information primarily attracted US participants. Analyses, including multivariate logistic regression, were performed on 1271 women who self-reported breast cancer diagnosis and completed the survey. RESULTS: Most participants reported current VM (89.5%) and NP (67.7%) use, with 46.5% (VM) and 26.7% (NP) using at least 3 products concurrently. Top-reported (>15% prevalence) products were vitamin D, calcium, multivitamin, and vitamin C for VM and probiotics, turmeric, fish oil/omega-3 fatty acids, melatonin, and cannabis for NP. Overall, VM or NP use was higher among those with hormone receptor-positive tumors. Although overall NP use did not differ according to current breast cancer treatments, VM use was significantly less common among those currently undergoing chemotherapy or radiation, but higher with current endocrine therapy. Among current chemotherapy users, specific VM and NP supplements with possible adverse effects were still used by 23% of respondents. Medical providers were the primary information source for VM, whereas NP information sources were more varied. CONCLUSIONS: Because women diagnosed with breast cancer commonly reported concurrent use of multiple VM and NP supplements, including those with known or underexplored risks (or benefits) in breast cancer, it is important for health care providers to inquire about and facilitate discussions regarding supplement use in this population.


Subject(s)
Dietary Supplements , Neoplasms , Dietary Supplements/adverse effects , Vitamins/therapeutic use , Minerals , Surveys and Questionnaires , Logistic Models
7.
J Am Acad Dermatol ; 88(5): e203-e209, 2023 05.
Article in English | MEDLINE | ID: mdl-30227192

ABSTRACT

BACKGROUND: Nonphysician practitioners (NPPS), including nurse practitioners (NPs) and physician assistants (PAs) are expanding their scope of practice outside of primary care and performing more procedures in dermatology. OBJECTIVE: To understand the scope and geographic pattern of practice by NPs and PAs in dermatology in the United States. METHODS: Cross-sectional retrospective cohort analysis of dermatology practices in the 2014 Medicare Physician/Supplier Procedure Summary master file, which reflects Part B carrier and durable medical equipment fee-for-service claims in the United States. RESULTS: Over 4 million procedures were billed independently by NPs and PAs, which accounted for 11.51% of all procedures. Injection, simple repair, and biopsy were the most commonly billed by the nonphysician practitioners, but complex procedures were also increasingly billed independently by NPs and PAs. Proportions of their claims are higher on the East Coast, Midwest, and Mountain states. LIMITATIONS: Data were collected at the state level and limited to Medicare beneficiaries, and did not include billing incident to physicians. CONCLUSIONS: This study demonstrated the increasing scope of practice of NPs and PAs in dermatology; this increase is alarming because of their limited training and the lack of uniform regulations guiding their practices. To ensure quality and safety of care, it is prudent to set benchmarks for proper supervision and utilization of procedures in dermatology.


Subject(s)
Nurse Practitioners , Physician Assistants , Physicians , Aged , Humans , United States , Medicare , Retrospective Studies , Cross-Sectional Studies , Fee-for-Service Plans
8.
J Am Acad Dermatol ; 88(2): 371-379, 2023 02.
Article in English | MEDLINE | ID: mdl-31812621

ABSTRACT

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins. OBJECTIVE: To evaluate the correlation of LM/LMM subclinical extension defined by RCM compared with the gold standard histopathology. METHODS: Prospective study of LM/LMM patients referred for dermatologic surgery. RCM was performed at the clinically defined initial surgical margin followed by margin-controlled staged excision with paraffin-embedded tissue, and histopathology was correlated with RCM results. RESULTS: Seventy-two patients were included. Mean age was 66.8 years (standard deviation, 11.1; range, 38-89); 69.4% were men. Seventy of 72 lesions (97.2%) were located on the head and neck with mean largest clinical diameter of 1.3 cm (range, 0.3-5). Diagnostic accuracy for detection of residual melanoma in the tumor debulk (after biopsy) had a sensitivity of 96.7% and a specificity of 66.7% when compared with histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (κ = 0.71; P < .001). LIMITATIONS: No RCM imaging beyond initial planned margins was performed. CONCLUSION: RCM showed moderate to excellent overall agreement between RCM imaging of LM/LMM and histopathology of staged excision margins.


Subject(s)
Hutchinson's Melanotic Freckle , Melanoma , Skin Neoplasms , Male , Humans , Aged , Female , Hutchinson's Melanotic Freckle/diagnostic imaging , Hutchinson's Melanotic Freckle/surgery , Hutchinson's Melanotic Freckle/pathology , Prospective Studies , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/surgery , Skin Neoplasms/pathology , Melanoma/diagnostic imaging , Melanoma/surgery , Melanoma/pathology , Margins of Excision , Microscopy, Confocal/methods
9.
Clin Exp Dermatol ; 48(6): 674-675, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-36805631

ABSTRACT

Mohs micrographic surgery (MMS) is the treatment of choice for high-risk basal cell carcinoma (BCC). However, there are no evidence-based recommendations regarding which biopsy type is more appropriate to obtain tumour samples prior to MMS. Shave or punch biopsies are performed depending on the clinical characteristics of the tumour, surgeon experience and local protocols. However, biopsy type might result in difficult histopathological interpretation and influence the practical implementation of MMS. We performed a retrospective study on 208 consecutive BCCs treated with MMS. Of the 208 BCC biopsies, 42 (20.2%) were obtained by the shave method and 166 (79.8%) via punch. Those obtained with the shave technique had a mean of 1.64 stages vs. 1.69 stages with the punch technique (P = 0.130). These findings suggest biopsy type does not affect Mohs surgery performance. The biopsy type of choice is the one deemed adequate for each specific case to obtain a diagnosis and tumour subtyping.


Subject(s)
Carcinoma, Basal Cell , Skin Neoplasms , Humans , Skin Neoplasms/surgery , Skin Neoplasms/pathology , Mohs Surgery/methods , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Carcinoma, Basal Cell/surgery , Carcinoma, Basal Cell/pathology , Biopsy
10.
Dermatol Surg ; 49(10): 914-920, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37643240

ABSTRACT

BACKGROUND: Perianal malignancies are rare tumors with unique presentations and treatment options. OBJECTIVE: To review published literature about primary malignancies that present on perianal skin and published guidelines and treatment options. MATERIALS AND METHODS: A PubMed search was conducted for original articles about perianal malignancies. RESULTS: Squamous cell carcinoma, basal cell carcinoma, melanoma, and extramammary Paget disease are the most common tumors to present on perianal skin. Anal squamous cell carcinoma incidence is increasing and certain populations may benefit from screening. Surgical management is often recommended for localized perianal tumors. CONCLUSION: Dermatologic surgeons should be familiar with the presentation and treatment options available for perianal malignancies.

11.
Dermatol Surg ; 49(2): 124-129, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36728061

ABSTRACT

BACKGROUND: Although there are evidence-based guidelines for actinic keratosis management, selecting a cost-effective field therapy is challenging because of limited studies comparing cost, efficacy, and adherence among treatments. OBJECTIVE: To review the literature on field-directed therapies for actinic keratosis, comparing efficacy, cost, and adherence data for topical and in-office treatments. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Google Scholar databases were searched from October 2020 to March 2021 for articles on field therapy for actinic keratosis. Total cost per regimen was estimated using wholesale acquisition cost package prices and Medicare coverage rates for May 2021. Effective cost was approximated by dividing total cost by complete response rate. RESULTS: Efficacy data for various field therapies range widely, and long-term follow-up is limited. Cross-study comparisons are challenging because of heterogeneity of studies. Field-directed therapy with topical 5-fluorouracil and photodynamic therapy have similar effective cost. Adherence may significantly affect real-world efficacy and long-term clearance; this would favor shorter duration topical regimens or in-office procedures. CONCLUSION: Standardization of future studies examining efficacy of field treatments for actinic keratosis will allow comparison across treatments. In-office treatments such as photodynamic therapy represent a cost-effective alternative to topical therapies with comparable efficacy.


Subject(s)
Keratosis, Actinic , Photochemotherapy , Aged , Humans , United States , Keratosis, Actinic/drug therapy , Medicare , Photochemotherapy/methods , Fluorouracil/therapeutic use , Treatment Outcome
12.
Dermatol Surg ; 49(12): 1165-1169, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37883805

ABSTRACT

BACKGROUND: With a rise in demand for cosmetic dermatologic procedures comes an increase in nonphysician providers performing such procedures. However, little is known about the practice of cosmetic procedures performed by nonphysicians. OBJECTIVE: To assess the differences in the practice of cosmetic procedures provided by physicians and nonphysicians. MATERIALS AND METHODS: A cross-sectional analysis was performed using participant ( n = 4,062) responses to an 18-point, web-based survey about previous cosmetic procedures. RESULTS: In total, 1,328 participants reported having previous cosmetic procedures done by a physician ( n = 828), a nonphysician ( n = 413), or an unknown provider ( n = 87). Respondents of all age ranges and male respondents ( p < .001) tended to choose physicians over nonphysician providers when choosing a practice. Moderate adverse events were more frequently seen when nonphysician providers completed cosmetic procedures ( p < .001). Despite a higher frequency (73.3% vs 51.8%) of more moderate complications seen in procedures done by nonphysician providers, over 70% of respondents believe that nonphysician providers are qualified enough to continue performing cosmetic procedures. CONCLUSION: People should be encouraged to make an informed decision when choosing a provider because cosmetic procedures are still considered medical procedures.


Subject(s)
Physicians , Humans , Male , Cross-Sectional Studies , Surveys and Questionnaires
13.
Dermatol Surg ; 49(8): 747-754, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37235869

ABSTRACT

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) of the ear is associated with poor outcomes. No studies have evaluated current staging system performance in this specific location. OBJECTIVE: Describe clinicopathologic characteristics and outcomes of ear cSCC and evaluate the performance of current staging systems. METHODS: Retrospective study including cases diagnosed and treated at a cancer center from January 2000 to December 2014. Demographic, clinical, and pathologic data were collected from clinical records. Biopsy slides were rereviewed and patients were staged according to the American Joint Committee on Cancer (AJCC) seventh, eighth, and Brigham Women's Hospital (BWH) staging. RESULTS: Of 125 patients, the mean age at diagnosis was 71.9 years (SD 12.5), with most men (89.6%, n = 112). Median follow-up was 22.3 months. Local recurrence and survival risk factors were similar to cSCC outside the ear. The Akaike's Information Criterion (AIC) estimates showed that the BWH system better predicted outcomes than the AJCC seventh, and the AJCC eighth, with AIC values of 189.9, 270.5, and 274.1, respectively. Limitations of the study include retrospective design, single center study, and no control group. CONCLUSION: Current staging systems perform well at stratifying risk in ear cSCC.


Subject(s)
Carcinoma, Squamous Cell , Ear Neoplasms , Skin Neoplasms , Male , Humans , Female , Aged , Carcinoma, Squamous Cell/pathology , Retrospective Studies , Skin Neoplasms/pathology , Neoplasm Staging , Risk Factors , Ear Neoplasms/pathology , Prognosis
14.
Int J Mol Sci ; 24(5)2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36901908

ABSTRACT

Medicinal properties of turmeric (Curcuma longa L.), a plant used for centuries as an anti-inflammatory, are attributed to its polyphenolic curcuminoids, where curcumin predominates. Although "curcumin" supplements are a top-selling botanical with promising pre-clinical effects, questions remain regarding biological activity in humans. To address this, a scoping review was conducted to assess human clinical trials reporting oral curcumin effects on disease outcomes. Eight databases were searched using established guidelines, yielding 389 citations (from 9528 initial) that met inclusion criteria. Half focused on obesity-associated metabolic disorders (29%) or musculoskeletal disorders (17%), where inflammation is a key driver, and beneficial effects on clinical outcomes and/or biomarkers were reported for most citations (75%) in studies that were primarily double-blind, randomized, and placebo-controlled trials (77%, D-RCT). Citations for the next most studied disease categories (neurocognitive [11%] or gastrointestinal disorders [10%], or cancer [9%]), were far fewer in number and yielded mixed results depending on study quality and condition studied. Although additional research is needed, including systematic evaluation of diverse curcumin formulations and doses in larger D-RCT studies, the preponderance of current evidence for several highly studied diseases (e.g., metabolic syndrome, osteoarthritis), which are also clinically common, are suggestive of clinical benefits.


Subject(s)
Curcumin , Osteoarthritis , Humans , Anti-Inflammatory Agents/therapeutic use , Curcuma , Curcumin/therapeutic use , Dietary Supplements , Inflammation/drug therapy , Osteoarthritis/drug therapy , Randomized Controlled Trials as Topic , Clinical Trials as Topic
15.
Medicina (Kaunas) ; 59(6)2023 May 28.
Article in English | MEDLINE | ID: mdl-37374244

ABSTRACT

Laser treatments have become popular in Dermatology. In parallel to technologic development enabling the availability of different laser wavelengths, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to explore morphologic and qualitative skin characteristics. Specifically, RCM can be applied to cosmetically sensitive skin areas such as the face, without the need for skin biopsies. For these reasons, apart from its current use in skin cancer diagnosis, our systematic review reveals how RCM can be employed in the field of laser treatment monitoring, being particularly suitable for the evaluation of variations in epidermis and dermis, and pigmentary and vascular characteristics of the skin. This systematic review article aims to provide an overview on current applications of RCM laser treatment monitoring, while describing RCM features identified for different applications. Studies on human subjects treated with laser treatments, monitored with RCM, were included in the current systematic review. Five groups of treatments were identified and described: skin rejuvenation, scar tissue, pigmentary disorders, vascular disorders and other. Interestingly, RCM can assist treatments with lasers targeting all chromophores in the skin and exploiting laser induced optical breakdown. Treatment monitoring encompasses assessment at baseline and examination of changes after treatment, therefore revealing details in morphologic alterations underlying different skin conditions and mechanisms of actions of laser therapy, as well as objectify results after treatment.


Subject(s)
Pigmentation Disorders , Skin Diseases , Skin Neoplasms , Humans , Skin/diagnostic imaging , Skin/pathology , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/radiotherapy , Skin Neoplasms/surgery , Skin Diseases/pathology , Pigmentation Disorders/diagnosis , Microscopy, Confocal/methods
16.
J Cell Sci ; 133(18)2020 09 17.
Article in English | MEDLINE | ID: mdl-32878942

ABSTRACT

Cellular polarization underlies many facets of cell behavior, including cell growth. The rod-shaped fission yeast Schizosaccharomyces pombe is a well-established, genetically tractable system for studying growth polarity regulation. S. pombe cells elongate at their two cell tips in a cell cycle-controlled manner, transitioning from monopolar to bipolar growth in interphase when new ends established by the most recent cell division begin to extend. We previously identified cytokinesis as a critical regulator of new end growth and demonstrated that Fic1, a cytokinetic factor, is required for normal polarized growth at new ends. Here, we report that Fic1 is phosphorylated on two C-terminal residues, which are each targeted by multiple protein kinases. Endogenously expressed Fic1 phosphomutants cannot support proper bipolar growth, and the resultant defects facilitate the switch into an invasive pseudohyphal state. Thus, phosphoregulation of Fic1 links the completion of cytokinesis to the re-establishment of polarized growth in the next cell cycle. These findings broaden the scope of signaling events that contribute to regulating S. pombe growth polarity, underscoring that cytokinetic factors constitute relevant targets of kinases affecting new end growth.This article has an associated First Person interview with Anthony M. Rossi, joint first author of the paper.


Subject(s)
Schizosaccharomyces pombe Proteins , Schizosaccharomyces , Cell Division , Cell Polarity/genetics , Cytokinesis/genetics , Schizosaccharomyces/genetics , Schizosaccharomyces pombe Proteins/genetics
17.
Dermatol Surg ; 48(11): 1155-1158, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36342247

ABSTRACT

BACKGROUND: There are multiple modalities for patient education ranging from written to audiovisual formats. However, little is known regarding which modality is optimal. OBJECTIVE: To assess patient preference for educational materials about scar care following surgery for facial skin cancer using the FACE-Q Skin Cancer patient reported outcome measure. MATERIALS AND METHODS: On the day of Mohs surgery, patients were given a written handout or viewed a 3-minute animation video regarding best practices in scar improvement. Afterward, patients received the FACE-Q Skin Cancer-Satisfaction with Information: Appearance scale. Three months later, patients were called and given the same scale and additional questions regarding scar care. RESULTS: A total of 75 patients were enrolled. There was no difference between the 2 groups' preoperative information scores (p = .85) and the three-month postoperative scores (p = .37). The change in preoperative and postoperative score showed no significant difference between the 2 groups (p = .21); but there was a trend of higher satisfaction in the video group on the day of Mohs surgery. After the 3-month timepoint, there was a higher satisfaction trend observed with the written handout group. CONCLUSION: Patient preferences in information delivery and accessibility will contribute to greater information retention and satisfaction.


Subject(s)
Facial Neoplasms , Skin Neoplasms , Humans , Mohs Surgery/adverse effects , Cicatrix/etiology , Cicatrix/prevention & control , Cicatrix/surgery , Patient Preference , Patient Satisfaction , Patient Education as Topic , Skin Neoplasms/surgery , Facial Neoplasms/surgery
18.
J Am Acad Dermatol ; 85(3): 693-707, 2021 09.
Article in English | MEDLINE | ID: mdl-32781177

ABSTRACT

The long-term survival of patients with cancer has risen dramatically during the last few decades. Despite this remarkable success, the same treatments that have enabled cure or remission often secondarily affect the skin, hair, and nails. Conditions including scarring, striae distensae, persistent alopecia, pigmentary changes, nail alterations, chronic radiation dermatitis, and radiation fibrosis have been associated with anxiety, depression, decreased quality of life, and impaired function. These dermatologic changes are cosmetically disfiguring, may limit activities, and are a visual reminder of past illness. Interventions toward improving these untoward sequelae and restoring the appearance and function of skin and appendages are critical for normalization and may contribute to improved quality of life in cancer survivors. Here, we outline dermatologic sequelae of cancer therapies with a review of medical and procedural treatment strategies to restore dermatologic health in the survivorship population.


Subject(s)
Neoplasms , Quality of Life , Alopecia , Humans , Neoplasms/complications , Neoplasms/therapy , Radiation Fibrosis Syndrome , Skin
19.
J Am Acad Dermatol ; 84(5): 1295-1301, 2021 May.
Article in English | MEDLINE | ID: mdl-33096134

ABSTRACT

BACKGROUND: There are no well-defined clinical factors to predict the risk of occult invasion in melanoma of the lentigo maligna type (LM) before complete histopathologic analysis. OBJECTIVE: To evaluate whether clinical size was a predictor of invasion in LM and subclinical extension. METHODS: Consecutive cases of LM were recorded in a prospectively maintained database from 2006 to 2019. Patient and tumor data were recorded during initial evaluation. The LM clinical area was calculated in square millimeters (length × width). All patients were treated with staged excision. RESULTS: We included 600 patients. The mean age was 65.9 years (standard deviation, 12.3; range, 27-95 years); 62.8% (n = 377) were men. The mean LM clinical area was 128.32 mm2 for in situ lesions versus 200.14 mm for invasive lesions (P = .1). Based on quantile regression, the median margin required for complete removal increased with LM clinical area. LIMITATIONS: The study was performed in a tertiary cancer center with possible referral bias and more complex cases. CONCLUSIONS: LM can present with variable clinical size, which may correlate with subclinical extension; however, the presence of invasion is not well estimated by LM clinical area.


Subject(s)
Hutchinson's Melanotic Freckle/diagnosis , Mohs Surgery , Skin Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Biopsy , Female , Humans , Hutchinson's Melanotic Freckle/pathology , Hutchinson's Melanotic Freckle/surgery , Male , Margins of Excision , Middle Aged , Neoplasm Invasiveness/diagnosis , Prognosis , Prospective Studies , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Tumor Burden
20.
J Am Acad Dermatol ; 84(6): 1575-1584, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32827607

ABSTRACT

BACKGROUND: Radiation therapy (RT) is a treatment option for select skin cancers. The histologic effects of RT on normal skin or skin cancers are not well characterized. Dermoscopy, high-frequency ultrasonography (HFUS), and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that may help characterize RT response. OBJECTIVES: To describe changes in the tumor and surrounding skin of patients with basal cell carcinoma (BCC) treated with RT. METHODS: The study was conducted between 2014 and 2018. Patients with biopsy-proven BCCs were treated with 42 Gy in 6 fractions using a commercially available brachytherapy device. Dermoscopy, HFUS, and RCM were performed before treatment and at 6 weeks, 3 months, and 12 months after RT. RESULTS: A total of 137 imaging assessments (RCM + dermoscopy + HFUS) were performed in 12 patients. BCC-specific features were present in 81.8%, 91%, and 17% of patients imaged with dermoscopy, RCM, and HFUS at baseline, respectively, before treatment. After treatment, the resolution of these features was noted in 33.4%, 91.7%, and 100% of patients imaged with the respective modalities. No recurrences were seen after a mean of 31.7 months of follow-up. LIMITATIONS: Small sample size and no histopathologic correlation. CONCLUSION: Dermoscopy and HFUS were not as reliable as RCM at characterizing BCC RT response.


Subject(s)
Carcinoma, Basal Cell/radiotherapy , Dose Fractionation, Radiation , Neoplasm Recurrence, Local/diagnosis , Skin Neoplasms/radiotherapy , Skin/diagnostic imaging , Aged , Aged, 80 and over , Biopsy , Carcinoma, Basal Cell/diagnosis , Dermoscopy/statistics & numerical data , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Microscopy, Confocal/statistics & numerical data , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Prospective Studies , Reproducibility of Results , Skin/radiation effects , Skin Neoplasms/diagnostic imaging , Treatment Outcome , Ultrasonography/statistics & numerical data
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