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1.
Annu Rev Neurosci ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33556251

RESUMO

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. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

3.
Dermatol Surg ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33625139

RESUMO

BACKGROUND: Extramammary Paget disease (EMPD) poses treatment challenges. Invasive and noninvasive treatment modalities exist with variable success reported. Reflectance confocal microscopy (RCM) is emerging as an adjuvant diagnostic tool. OBJECTIVE: To evaluate the treatment of EMPD patients and the role of RCM. METHODS: Prospective study. Demographic and tumor characteristics were recorded. Handheld-RCM was performed and correlated with histology. Treatment, clearance, pathology, and follow-up were all recorded. RESULTS: Thirty-six EMPD lesions in 33 patients were included. Mean age was 71.7 years, and 23 were men. Mean number of surgical stages needed to clear margins was 1.9 (SD, 0.9; 1.0-3.0 stages), and mean margin needed to clear was 1.8 cm. Reflectance confocal microscopy correlated well with scouting punch biopsies (kappa, 0.93; p < .001). Disruption of the dermoepidermal junction was associated with invasive EMPD versus in situ (83.3% vs 25.9%) on histology (p = .01). LIMITATIONS: Relatively small sample size. CONCLUSION: Extramammary Paget disease is challenging, and lesion demarcation is of the utmost importance. Using a staged surgical excision approach, the mean margins needed were 1.8 cm, less than previously reported. Nonsurgical modalities, including radiation therapy, imiquimod, or photodynamic therapy can be considered if surgery is not pursued. Reflectance confocal microscopy is a valuable noninvasive imaging modality for the management of EMPD.

5.
J Am Acad Dermatol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33096134

RESUMO

BACKGROUND: There are no well-defined clinical factors to predict the risk of occult invasion in melanoma of the lentigo maligna type (LM) prior to 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. 'LM clinical area' was calculated in square millimeters (length x width). All patients were treated with staged excision. RESULTS: We included 600 patients. Mean age was 65.9 years (SD 12.3; range 27 - 95 years); 62.8% (n=377) were males. The mean LM clinical area was 128.32 mm2 for in situ lesions vs 200.14 mm for invasive lesions (p=0.1). Based on quantile regression, the median margin required for complete removal increased with LM clinical area. LIMITATIONS: study 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.

6.
J Cell Sci ; 133(18)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32878942

RESUMO

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.

7.
Arch Dermatol Res ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32886149

RESUMO

Squamous cell carcinoma in situ (SCCIS) of the nail unit is a complex malignancy; with little understanding of rate of upstaging or occult invasion in these patients. We sought to evaluate the rate of upstaging in nail unit SCCIS after Mohs micrographic surgery (MMS). Retrospective review of 346 patients who referred for and underwent MMS for biopsy proven SCCIS on the hands and feet between January 1, 2000 and December 30, 2019. Only cases in the nail unit were included. Clinical, surgical details, histopathological features, HPV status, and rate of upstaging were recorded. Thirty-one cases met the inclusion criteria and were analyzed. Twenty-four patients were males (77.4%). The mean age was 55 years (SD 17.26, range 27-84). The mean clinical size was 9.9 mm; 19 cases tested for HPV, 15/19 were positive (78.9%), and 8/19 (42.1%) were associated with high-risk HPV. Three patients (9.7%) were upstaged to invasive on either MMS margins or tumor debulking. Limitations included a relatively small sample size and retrospective in nature. The rate of upstaging of SCCIS in the nail unit is not frequent, and when upstaging occurred it was focal, superficial, and with no PNI or bone invasion.

8.
J Am Acad Dermatol ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32827607

RESUMO

BACKGROUND: Radiation therapy (RT) is a treatment option for selected 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 non-invasive imaging modalities that may help characterize RT response. OBJECTIVES: To describe changes in the tumor and surrounding skin of basal cell carcinoma (BCC) patients treated with RT. METHODS: The study was conducted between 2014-2018. Patients with biopsy-proven BCCs were treated with 42 Gy in 6 fractions using a commercially available brachytherapy device. Dermoscopy, HFUS, RCM were performed before treatment, 6 weeks, 3 months and 12 months after RT. RESULTS: 137 imaging assessments (RCM + dermoscopy + HFUS) were performed in 12 patients. Presence of BCC-specific features were present in 81.8%, 91% and 17% of patients imaged with dermoscopy, RCM and HFUS at baseline, prior to treatment. After treatment, 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 31.7 months mean follow-up. LIMITATIONS: Small sample size and no histopathological correlation. CONCLUSION: Dermoscopy and HFUS were not as reliable as RCM at characterizing BCCs RT response.

9.
J Am Acad Dermatol ; 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32781177

RESUMO

Long-term survival of cancer patients 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 towards 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. Herein, we outline dermatologic sequelae of cancer therapies with a review of medical and procedural treatment strategies to restore dermatologic health in the survivorship population.

10.
Elife ; 92020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32628110

RESUMO

Temporal patterning of neural progenitors leads to the sequential production of diverse neurons. To understand how extrinsic cues influence intrinsic temporal programs, we studied Drosophila mushroom body progenitors (neuroblasts) that sequentially produce only three neuronal types: γ, then α'ß', followed by αß. Opposing gradients of two RNA-binding proteins Imp and Syp comprise the intrinsic temporal program. Extrinsic activin signaling regulates the production of α'ß' neurons but whether it affects the intrinsic temporal program was not known. We show that the activin ligand Myoglianin from glia regulates the temporal factor Imp in mushroom body neuroblasts. Neuroblasts missing the activin receptor Baboon have a delayed intrinsic program as Imp is higher than normal during the α'ß' temporal window, causing the loss of α'ß' neurons, a decrease in αß neurons, and a likely increase in γ neurons, without affecting the overall number of neurons produced. Our results illustrate that an extrinsic cue modifies an intrinsic temporal program to increase neuronal diversity.

11.
Dermatol Online J ; 26(3)2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32609441

RESUMO

The expanding role of social media in medical care has resulted in dermatology patients seeking support online regarding personal experience with diagnosis and treatment of skin cancer. Owing to increased privacy settings in closed Facebook groups, the current study analyzed themes of keratinocyte carcinoma patients' posts within a relatively private social media network. Although the majority of messages included sharing personal experience and provided psychosocial support (50%), there were a significant number of posts offering medical advice (35%), with the majority of such replies being unsupported by evidence-based medicine (87%). The level of medical misinformation and potential harm to patients seeking advice online is important for medical practitioners treating skin cancer and provides impetus for possible further research into online support and education groups that are moderated for misinformation.


Assuntos
Informação de Saúde ao Consumidor , Disseminação de Informação/métodos , Educação de Pacientes como Assunto/métodos , Grupos de Autoajuda , Neoplasias Cutâneas , Mídias Sociais , Comunicação , Medicina Baseada em Evidências , Humanos , Apoio Social
12.
Sci Adv ; 6(21): eaba6913, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32494751

RESUMO

To increase fitness, animals use both internal and external states to coordinate reproductive behaviors. The molecular mechanisms underlying this coordination remain unknown. Here, we focused on pheromone-sensing Drosophila Or47b neurons, which exhibit age- and social experience-dependent increase in pheromone responses and courtship advantage in males. FruitlessM (FruM), a master regulator of male courtship behaviors, drives the effects of social experience and age on Or47b neuron responses and function. We show that simultaneous exposure to social experience and age-specific juvenile hormone (JH) induces chromatin-based reprogramming of fruM expression in Or47b neurons. Group housing and JH signaling increase fruM expression in Or47b neurons and active chromatin marks at fruM promoter. Conversely, social isolation or loss of JH signaling decreases fruM expression and increases repressive marks around fruM promoter. Our results suggest that fruM promoter integrates coincident hormone and pheromone signals driving chromatin-based changes in expression and ultimately neuronal and behavioral plasticity.

13.
J Am Acad Dermatol ; 83(2): 463-468, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32320764

RESUMO

BACKGROUND: Functional status assessment may help estimate which patients ≥85 years of age will benefit from surgical treatment for keratinocyte carcinoma (KC), but predictive value for short-term survival in this population has not been determined. OBJECTIVE: We sought to assess the predictive value of functional status for short-term survival in patients ≥85 years of age who have KC. METHODS: This was a retrospective cohort review of 238 patients ≥85 years of age who presented for the management of KC between 2010 and 2015. Functional status was assessed with the Karnofsky Performance Scale (KPS) and Katz Activities of Daily Living (ADL) index. Overall survival was determined. RESULTS: Lower functional status scores of KPS ≤40 and Katz ADL ≤4 were associated with 37% and 53% survival at 2 years, respectively. LIMITATIONS: Retrospective design and single-center study. CONCLUSION: In this study, KPS and Katz ADL predicted short-term survival. Patients with low functional status scores had significantly decreased survival at 2 years, with double the death rate of patients with high functional status. Functional status should be considered during shared decision-making for elderly individuals who are seeking treatment for KC.

15.
Arch Dermatol Res ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020324

RESUMO

INTRODUCTION: Recently, a combined reflectance confocal microscopy (RCM)-optical coherence tomography (OCT) has been tested for the diagnosis of basal cell carcinoma (BCC). Evaluating the role of RCM-OCT in management of complex BCCs has not been studied. The objective of the study was to investigate the utility of a new combined RCM-OCT device in the evaluation and management of complex BCCs in a descriptive study. METHODS: Prospective study of consecutive cases (July 2018-June 2019) of biopsy-proven 'complex' BCC defined as BCC in the head-and-neck area with multiple high-risk criteria such as large size in the mask area, multiple recurrences, and high-risk subtype. All cases were evaluated with a combined RCM-OCT device that provided simultaneous image viewing on a screen. Lesions were evaluated bedside with RCM-OCT according to previously described criteria. RESULTS: Ten patients with complex head-and-neck BCCs had mean age of 73.1 ± 13.0 years. Six (60%) patients were males. Mean BCC clinical size was 1.9 ± 1.2 cm (range 0.6-4.0 cm). RCM detected residual BCC in 8 out of 10 cases (80%) and OCT detected residual BCC in all 10 cases (100%). Six BCCs (60%) had a depth estimate of > 1000 µm under OCT. In five cases, (50%) RCM-OCT imaging results led to a change/modification in BCC management. CONCLUSION: The use of a combined RCM-OCT device may help in the evaluation of complex head-and-neck BCCs by guiding treatment selection and defining the extent of surgery.

16.
Adv Drug Deliv Rev ; 153: 185-194, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923431

RESUMO

Keratinocyte carcinomas (KC) are the most common malignant human neoplasms. Although surgery and destructive approaches are first-line treatments, topical therapies are commonly used. Due to limited uptake of topical agents across the skin barrier, clearance rates are often sub-optimal. In pre-clinical investigations, ablative fractional laser (AFL)-assisted drug delivery has demonstrated improved uptake of topical drugs commonly used to treat KC. In 22 clinical trials, the effect of AFL-assisted treatments has been investigated for actinic keratosis (AK; n = 14), Bowen's disease (BD; n = 5), squamous cell carcinoma (n = 1), and basal cell carcinoma (n = 7). The most substantial evidence currently exists for AFL-assisted photodynamic therapy for the treatment of AK and BD. AFL improved 12-months follow-up clearance rates of photodynamic therapy from 45.0-51.0% to 78.5-84.8% for AK and from 50.0-55.3% to 87.0-87.5% for BD. AFL-assisted pharmacological therapy is a promising tool for optimizing topical treatments of KC and its precursor lesions. Future developments include AFL-assisted immune activation, changing drug administration route of systemic therapies, and utilizing drug chemo-combinations.

19.
Dermatol Surg ; 46(4): 514-518, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31592922

RESUMO

BACKGROUND: Postoperative concerns after Mohs micrographic surgery (MMS) are not well characterized. OBJECTIVE: To better define patient concerns and contributing characteristics in the immediate postoperative period after MMS. MATERIALS AND METHODS: A standardized telephone encounter template was implemented to better assess patient concerns in the 24-hour postoperative period. A review was then performed of patients undergoing MMS from October 2016 to July 2017 to assess for the most common patient concerns and association with clinical characteristics. RESULTS: We included 307 patients. Overall, 60.6% of patients reported a concern. Fifty-four percent of patients reported pain. Most pain was characterized as "a little" (67.7%). On univariate analysis, flap repairs, location on the upper extremities, and swelling were associated with higher mean postoperative pain. Tumor type was not associated with increased pain. On multivariate analyses, patients with larger defects and associated edema were statistically significantly associated with higher degrees of pain. CONCLUSION: Over half of patients experience postoperative concerns after MMS, most commonly pain. The immediate postoperative period may be an optimal time to identify patient concerns allowing for reassurance or early intervention when necessary.


Assuntos
Assistência ao Convalescente/métodos , Cirurgia de Mohs/efeitos adversos , Dor Pós-Operatória/epidemiologia , Cuidados Pós-Operatórios/métodos , Neoplasias Cutâneas/cirurgia , Adulto , Assistência ao Convalescente/normas , Assistência ao Convalescente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Cuidados Pós-Operatórios/normas , Cuidados Pós-Operatórios/estatística & dados numéricos , Período Pós-Operatório , Estudos Retrospectivos , Inquéritos e Questionários/normas , Inquéritos e Questionários/estatística & dados numéricos , Telefone
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