Dermatology Commons^™

The Effects Of Vitamin D On Chronic Wounds, Mufqi Handaru Priyanto, Eliza Miranda, Shannaz Nadia Yusharyahya, Lili Legiawati, Endi Novianto, Kusmarinah Bramono, Roro Inge Ade Krisanti

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Wounds that fail to proceed through the normal healing process are referred to as chronic wounds, also known as ulcers. Chronic wounds have immeasurable biological, psychological, social, and economic effects, bringing tremendous challenges for patients, doctors, healthcare providers, and healthcare systems.

Discussion: This condition is associated with a variety of comorbidities and complex etiologies. The global incidence of chronic wounds is expected to increase with longer life expectancy. Thus, a holistic approach is necessary, such as proper wound management, proper control of comorbidities, and provision of adequate nutrition, including vitamin D supplementation. Vitamin D is an essential pro-hormone for …

Low Plasma Melatonin Levels Negatively Correlate With Melasma Severity, I Gusti Ayu Agung Praharsini, Corry Khathreen, Nyoman Suryawati, I Gusti Ayu Agung Elis Indira, I Gusti Ayu Sattwika Pramita

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Chronic exposure to ultraviolet light plays a role in the pathogenesis of melasma. Exposure to excessive sunlight leads to the formation of free radicals. As a result, the body responds by forming antioxidants such as melatonin, which is activated through the melatoninergic antioxidative system to fight oxidative stress. The relationship between melatonin and melasma is yet to be elucidated. This study aims to determine the correlation between melatonin and the severity of melasma.

Methods: This analytical cross-sectional study involved 50 melasma subjects and 10 non-melasma subjects who met the inclusion criteria and were aged between 21-50 years at Prof. …

Empowering Nonmedical Personnel To Detect Scabies In Endemic Area Using Deskab Instrument: A Diagnostic Study, Sandra Widaty, Aria Kekalih, Dewi Friska, Kusmarinah Bramono, Siti Maulidya Sari, Irene Darmawan, Yufanti Sujudi, David Dwiadiputra Hartanto, Emiliana Kartika, Nikken Rima Oktavia

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Scabies has been added to World Health Organization (WHO) list of neglected tropical disease in 2017. Various methods have been developed to control scabies in highly prevalent communities. In this study we conducted a diagnostic study to evaluate the performance of scabies detection by trained nonmedical personnel (NMP) using Deteksi Skabies (Deskab) instrument which has been validated for NMP.
Methods: Eight NMPs in a boarding school were trained to detect scabies using DeSkab instrument. The NMPs diagnosis were compared to diagnosis of 10 medical doctors. The study was conducted in a religion-affiliated boarding school in West Java, Indonesia. Both …

Administration Of Vitamin D3 Topical In Increasing Serum Vitamin D Level: A Literature Review, He Yeon Asva Nafaisa, Fajar Waskito, Ronny Martien, Retno Danarti

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Vitamin D is an essential fat-soluble vitamin that is required daily by the body. Deficiency in vitamin D is experienced by most of the world's population. Vitamin D plays a role in maintaining the skin barrier by regulating keratinocyte proliferation and differentiation, promoting filaggrin formation, and intraepidermal lipids.

Discussion: The vital role of vitamin D, non-compliance with supplement consumption, and poor nutritional status of adult patients and the elderly with deficiency and insufficiency of vitamin D encourage studies regarding vitamin D delivery via the transdermal route. The lipophilicity of vitamin D allows it to penetrate through the skin barrier. …

Inter-Institutional Analysis Of Skin Of Color Representation In Dermatological Lecture Content At Md And Do Medical Schools, Oluwafunke Ogunremi

Sanford School of Medicine Posters and Presentations

The purpose of this study was to analyze the lecture materials provided in medical schools through a diversity lens. Skin pathologies manifest distinctively on various shades of skin and physicians must be equipped with the proper knowledge to identify and diagnose these conditions accurately and promptly. For most medical students, images in prominent textbooks and lecture slides are their first encounter with disease presentations. Therefore, it is important to analyze the diversity of skin tones in the content that is being delivered. Specifically, the use of images featuring darker skin tones compared to those depicting lighter skin tones. This study …

A Phase 3b, Open-Label, Single-Arm, Multicenter, Expanded-Access Study Of The Safety And Clinical Outcomes Of Stratagraft® Treatment In Adults With Deep Partial-Thickness Thermal Burns, James H. Holmes Iv, Angela L.F. Gibson, Tracee Short, Victor C. Joe, Jeffrey Litt, Joshua Carson, Jeffrey E. Carter, Lucy Wibbenmeyer, Helen Hahn, Janice M. Smiell, Randi Rutan, Richard Wu, Jeffrey W. Shupp

School of Medicine Faculty Publications

Background: A phase 3b, open-label, multicenter, expanded-access study (NCT04123548) evaluated safety and clinical outcomes of StrataGraft treatment in adults with deep partial-thickness thermal burns with intact dermal elements. Methods: Adult patients with 3 % to < 50 % total body surface area burns were treated with a single application of ≤ 1:1 meshed StrataGraft and followed for 24 weeks. Primary endpoint was count and percentage of patients with treatment-emergent adverse events (TEAEs). Secondary endpoints included confirmed wound closure (WC) at Week 12, durable WC at Week 24, time to WC, scar evaluation, and wound infection-related events. Results: Fifty-two patients with 96 treatment sites were enrolled. Pruritus was the most common TEAE (22 patients [42.3 %]). Twenty serious TEAEs occurred in 10 patients (19.2 %); none were related to StrataGraft. There were 4 (7.7 %) deaths (aspiration, myocardial infarction, self-injury, Gram-negative rod sepsis); none were related to StrataGraft. Confirmed WC was achieved by Week 12 in 33 patients (63.5 %; 95 % CI: 50.4–76.5 %) and 69 treatment sites (71.9 %; 95 % CI: 62.9–80.9 %). Durable WC was achieved by Week 24 in 29 patients (55.8 %; 95 % CI: 42.3–69.3 %) and 58 treatment sites (60.4 %; 95 % CI: 50.6–70.2 %). Conclusions: StrataGraft demonstrated clinical benefit. Safety data were consistent with previously reported findings.

Hairy Tongue Associated With The Use Of Baricitinib Therapy For Ophiasis Pattern Alopecia Areata, Anthony Gaspari

Department of Dermatology and Cutaneous Biology Faculty Papers

We report a case of hairy tongue that developed in a young Caucasian
/="/">woman during systemic baricitinib therapy for severe alopecia areata.
/="/">Because she experienced good clinical regrowth of her hair during
/="/">treatment, she did not want to interrupt therapy. We recommended she
/="/">use a toothbrush to debride her tongue on a daily basis, which was
/="/">successful. Hairy tongue most commonly occurs in elderly, debilitated
/="/">males with poor oral hygiene. It is thought to occur because of overgrowth
/="/">of chromogenic bacteria and/or yeast on the tongue. This unusual side
/="/">effect during baricitinib …

Fibroblast Subpopulations In Systemic Sclerosis: Functional Implications Of Individual Subpopulations And Correlations With Clinical Features, Honglin Zhu, Hui Luo, Brian Skaug, Tracy Tabib, Yi-Nan Li, Yongguang Tao, Alexandru-Emil Matei, Marka A Lyons, Georg Schett, Robert Lafyatis, Shervin Assassi, Jörg H W Distler

Faculty, Staff and Student Publications

Fibroblasts constitute a heterogeneous population of cells. In this study, we integrated single-cell RNA-sequencing and bulk RNA-sequencing data as well as clinical information to study the role of individual fibroblast populations in systemic sclerosis (SSc). SSc skin demonstrated an increased abundance of COMP+, COL11A1+, MYOC+, CCL19+, SFRP4/SFRP2+, and PRSS23/SFRP2+ fibroblasts signatures and decreased proportions of CXCL12+ and PI16+ fibroblast signatures in the Prospective Registry of Early Systemic Sclerosis and Genetics versus Environment in Scleroderma Outcome Study cohorts. Numerical differences were confirmed by multicolor immunofluorescence for selected fibroblast populations. COMP+, COL11A1+, SFRP4/SFRP2+, PRSS23/SFRP2+, and PI16+ fibroblasts were similarly altered between normal …

Characterization Of Disease Burden, Treatment And Comorbidities In A Large, Real-World Cohort Of Patients With Atopic Dermatitis: The Corevitas Atopic Dermatitis Registry, Jonathan I Silverberg, Angel Cronin, Eric A Jones, Swapna S Dave, Robert R Mclean, Jeffrey Greenberg, Bruce Strober, Thomas Bieber, Melinda Gooderham, Amy S Paller, Eric L Simpson

Faculty, Staff and Student Publications

No abstract provided.

Treatment Of Recalcitrant Hailey-Hailey Disease With Naltrexone And Dupilumab: A Report Of Two Cases., Breanna Santoso, Rachel Krevh, Alexa Israeli, Austin Cusick, Dawn Merritt, Michael Holsinger

Ambulatory and Primary Care Articles

This report presents two cases of patients with long-standing, treatment-resistant Hailey-Hailey disease (HHD) who experienced significant symptom relief through a combination therapy of oral naltrexone and dupilumab injections. The therapeutic potential of targeting the Th2 pathway and Ca

A Large Pilar Sheath Acanthoma Of The Cheek Successfully Treated With Surgical Excision, Yelena Dokic, Maria S Bloomquist, Hafeez Diwan, Omid Jalali, Jennifer S Ranario

Faculty, Staff and Students Publications

This case report describes an atypically large pilar sheath acanthoma (PSA) presenting on a patient's cheek. Due to the bothersome nature of the lesion, the patient underwent surgical excision, with subsequent histopathological analysis confirming the diagnosis of an unusually large PSA. In addition to a definitive diagnosis, surgical excision provided symptomatic relief for the patient.

Two Cases Of Pigmented Basal Cell Carcinoma In African American Patients, Angelique Ruml, Joan K Fernandez, Ibeth Caceres, Nisha Ramani, Ida Orengo, Theodore Rosen

Faculty, Staff and Students Publications

Basal cell carcinoma (BCC) is the most common cutaneous malignancy, comprising approximately 80% of non-melanoma skin cancers. There are numerous subtypes, including pigmented basal cell carcinoma (pBCC), a rare clinical and histological variant. Skin cancers in African American patients, although rare, still do occur. BCC is an uncommon neoplasm in this population, but when it does occur, pigmentation is present in more than 50% of tumors compared with only 5% to 6% of BCCs in Caucasians. This report presents two cases of histologically verified pBCC in African American patients from dermatology clinics at the Veterans Affairs Hospital located in the …

Bacillary Angiomatosis In A Patient With Hiv And Disseminated Mycobacterium Avium Complex Infection, Ibeth P Caceres, Angelique Ruml, Rubi Montejano, Omid Jalali, Theodore Rosen

Faculty, Staff and Students Publications

Bartonella is a genus of arthropod-borne bacterial pathogens that typically cause persistent infections of erythrocytes and endothelial cells in mammalian hosts. The species that primarily infect humans are Bartonella henselae and Bartonella quintana. Depending on immune status, the clinical presentation of B. henselae may differ, manifesting as cat-scratch disease in immunocompetent individuals or bacillary angiomatosis (BA) and peliosis in immunocompromised patients. The cutaneous manifestations of BA are typically characterized by occasionally painful, angiomatous papules and nodules, often with a chronic, persistent course. Herein, we present a case of biopsy-confirmed B. henselae infection in a 32-year-old HIV-positive female with acquired immunodeficiency …

Inter-Institutional Analysis Of Skin Of Color Representation In Dermatological Lecture Content At Md And Do Medical Schools, Oluwafunke Oluwatosin Ogunremi

Sanford School of Medicine Posters and Presentations

The purpose of this study was to analyze the lecture materials provided in medical schools through a diversity lens. Skin pathologies manifest distinctively on various shades of skin and physicians must be equipped with the proper knowledge to identify and diagnose these conditions accurately and promptly. For most medical students, images in prominent textbooks and lecture slides are their first encounter with disease presentations. Therefore, it is important to analyze the diversity of skin tones in the content that is being delivered. Specifically, the use of images featuring darker skin tones compared to those depicting lighter skin tones. This study …

Sdsma 2024: Inter-Institutional Analysis Of Skin Of Color Representation In Dermatological Lecture Content At Md And Do Medical Schools, Oluwafunke Oluwatosin Ogunremi

Sanford School of Medicine Posters and Presentations

The purpose of this study was to analyze the lecture materials provided in medical schools through a diversity lens. Skin pathologies manifest distinctively on various shades of skin and physicians must be equipped with the proper knowledge to identify and diagnose these conditions accurately and promptly. For most medical students, images in prominent textbooks and lecture slides are their first encounter with disease presentations. Therefore, it is important to analyze the diversity of skin tones in the content that is being delivered. Specifically, the use of images featuring darker skin tones compared to those depicting lighter skin tones. This study …

Pediatric Dermatologists Versus Ai Bots: Evaluating The Medical Knowledge And Diagnostic Capabilities Of Chatgpt, Charles Y. Huang, Esther Zhang, Marie-Chantal Caussade, Trinity Brown, Griffin Stockton Hogrogian, Albert C. Yan

Student Papers, Posters & Projects

This study evaluates the clinical accuracy of OpenAI's ChatGPT in pediatric dermatology by comparing its responses on multiple-choice and case-based questions to those of pediatric dermatologists. ChatGPT's versions 3.5 and 4.0 were tested against questions from the American Board of Dermatology and the "Photoquiz" section of Pediatric Dermatology. Results show that human pediatric dermatology clinicians generally outperformed both ChatGPT iterations, though ChatGPT-4.0 demonstrated comparable performance in some areas. The study highlights the potential of AI tools in aiding clinicians with medical knowledge and decision-making, while also emphasizing the need for continual advancements and clinician oversight in using such technologies.

The Efficacy Of Baricitinib As A Treatment Option For Alopecia, In Terms Of Promoting Hair Regrowth And Improving Patient Reported Outcomes, Bhaumik Patel, Abhiram Gollapudi, Samrat Gollapudi, Srinidhi Banala, Brian Joseph Mathew, Prince Patel

Rowan-Virtua Research Day

Background: Alopecia, an autoimmune condition characterized by hair loss, significantly impacts millions globally, often leading to psychological distress such as anxiety and depression. Current treatments are variably effective and frequently associated with adverse effects that restrict long-term use. This study evaluates the efficacy of Baricitinib, a Janus Kinase inhibitor, in treating severe alopecia, focusing on hair regrowth and patient-reported outcomes.

Methods: This research synthesized data from recent publications (2018-2023) including clinical trials, reviews, meta-analyses, and systematic reviews, sourced from databases such as PubMed, Springer, and Elsevier. The inclusion criteria focused on recent studies in English evaluating Baricitinib's effectiveness in severe …

Facial Skincare Routine Adherence In The General Population, Leah Cliatt, Joanna Petrides

Rowan-Virtua Research Day

Background: The COVID-19 pandemic sparked an interest in skincare with the closure of spas and salons. “Skincare”, one of the most popular dermatology related hashtags on TikTok in July 2020 received 378 million views. The American Academy of Dermatology (AAD) has shared facial cleansing recommendations; however, it is unclear how many people follow them. Studies have shown a good daily facial cleansing and moisturizing routine can increase microbiome diversity and skin hydration. This can be beneficial in conditions like psoriasis, eczema, and acne.

Purpose: The aim of the study is to assess how well people follow the AAD …

Janus Kinase (Jak) Inhibitors: A New Frontier In The Treatment Of Vitiligo, Catherine F. Alapatt, Amanda Greenspan, Mohammad Fardos

Rowan-Virtua Research Day

Up to 70 million people worldwide suffer from vitiligo, an autoimmune disease characterized by the destruction of melanin. Current treatment options vary in efficacy. The disease manifests clinically as white circular macules of depigmentation seen primarily on the face and appendages.1 The pathophysiology of vitiligo is multifactorial and still being studied. One proposed mechanism behind the pathophysiology of vitiligo involves the upregulation of interferon gamma (IFN-γ) with downstream effects on JAK/STAT pathways resulting in CXCL10 transcription.1,2 Here we discuss Ruxolitinib, a topical JAK inhibitor, that recently passed its clinical trial phase, and Ritlecitinib, an oral JAK inhibitor which is currently …

Updates To Acne Vulgaris Treatment: A Review Of A Topical Androgen Receptor Inhibitor, Catherine F. Alapatt, Klaudia Matanaj

Rowan-Virtua Research Day

Acne Vulgaris is an inflammatory skin disorder that is common among adolescents and young adults. Acne is defined as a chronic inflammatory dermatosis which consists of open comedones (blackheads), closed comedones (whiteheads) and inflammatory lesions.1 There are many ways to combat acne, one of which is to stop the effects of androgens on androgen receptors. Here we will review Clascoterone, a medication approved for the treatment of acne. Clascoterone is the first topical medication to target the hormonal pathogenesis of acne. It was approved by the FDA in 2020 and is effective in treatment of acne vulgaris in patients 12 …

Waiting For A Cure: Factors Influencing Melanoma Treatment Delays, Lisa Huang, David Rubin, Lothar Vidal, Jordan Riser, Christopher Jones, Samantha Hiester

Rowan-Virtua Research Day

Melanoma, with a five-year survival rate of 94% in early-stage diagnosis, drops significantly when diagnosed at later stages, making identifying barriers to timely treatment crucial. This literature review examines factors influencing melanoma treatment wait times and their impact on patient outcomes. Elderly, male, and Medicare patients, along with those with higher Breslow thickness and severe melanoma stages, experienced longer wait times. Patients receiving intervention within 30 days had better survival rates. Lack of knowledge and misconceptions about melanoma contribute to delayed care, particularly in communities with lower incidence rates. Black patients faced longer waits from diagnosis to surgery, indicating disparities. …

Trichotillomania Case Report, Kimberly Kluglein, David F. Lo, Don D. Shamilov

Rowan-Virtua Research Day

Trichotillomania is a psycho-dermatologic disorder involving self-inflicted hair loss through pulling. Often complicated by anxiety and depression. Multifactorial etiology and limited evidence-based treatment options makes management difficult. Treatment approaches include a combination of pharmacotherapy, CBT, HRT, and ACT. Case presentation involves a 24-year-old female, diagnosed with treatment-resistant trichotillomania who achieved remission and hair regrowth through mindset reframing, physical barriers, and community support. Novel approaches focusing on mindset and community support can yield positive outcomes.

Sunscreen Cost And Its Effect On Skin Cancer In Low-Income Communities: A Systemic Review, John Sauer

Rowan-Virtua Research Day

This research examines the pivotal connection between sunscreen affordability and its impact on skin cancer prevalence, especially in low-income communities. Despite universal dermatological recommendations for daily sunscreen use, stringent criteria contribute to elevated prices, averaging around $10 for a 6 oz unit. This financial strain is compounded for families adhering to recommended application rates, leading to significant economic burdens. Outdoor laborers, less likely to follow guidelines, face heightened risks. Government programs' excluding sunscreen costs further exacerbate challenges for low-income communities, contributing to increased skin cancer incidence. This review aims to establish a correlation between sunscreen cost and skin cancer rates, …

Rosarugosides A And D From Osa Rugosa Flower Buds: Their Potential Anti-Skin-Aging Effects Intnf-Α-Induced Human Dermal Fibroblasts, Kang Sub Kim, So-Ri Son, Yea Jung Choi, Yejin Kim, Si-Young Ahn, Dae Sik Jang, Sullim Lee

Faculty, Staff and Student Publications

This present study investigated the anti-skin-aging properties of Rosa rugosa. Initially, phenolic compounds were isolated from a hot water extract of Rosa rugosa's flower buds. Through repeated chromatography (column chromatography, MPLC, and prep HPLC), we identified nine phenolic compounds (1-9), including a previously undescribed depside, rosarugoside D (1). The chemical structure of 1 was elucidated via NMR, HR-MS, UV, and hydrolysis. Next, in order to identify bioactive compounds that are effective against TNF-α-induced NHDF cells, we measured intracellular ROS production in samples treated with each of the isolated compounds (1- …

Metastatic Osteosarcoma Involving The Skin: A Systematic Review Of Patient Demographics, Clinical Characteristics, And Treatment Outcomes, Sarah Fried, Ameen Suhrawardy, Rafey Rehman, Malik Al-Jamal, Drew Moore, Darius Mehregan

Posters

Skeletal osteosarcomas - most common primary malignant bone tumor1 and commonly metastasize to:

• Lungs (95%)2 •

Other bones (50%)2 •

Kidneys (12%)2 •

Rarely to the skin3

Extraskeletal osteosarcomas (ESOS) – soft tissue tumors that may also metastasize to the skin4,5,6

Value in gathering data on this rare phenomenon:

• Informs biology and dermatologic care of patients suffering from this cancer.

This systematic review characterizes metastatic osteosarcomas involving the skin.

An Atypical Facial Eruption In Skin Of Color: A Rare Presentation Of Histiocytoid Sweet Syndrome., Brittany Ehlert, Lauren Shegos, Matthew Franklin, Kaila Buckley, Jaimie Rodger

Ambulatory and Primary Care Articles

No abstract provided.

The Role Of Radiotherapy In The Complex Treatment Of Mycosis Fungoides; A Case Report, Laura Florentina Rebegea, Claudia-Elena Pavel, Nadejda Corobcean, Ana Maria Ilie, Dorel Firescu, Madalin Guliciuc, Elena Niculet, Mihaela Dumitru, Daniela Mihalache, Flavius Bulgaru, Roxana-Andreea Rahnea-Nita

Journal of Mind and Medical Sciences

Introduction. Mycosis fungoides (MF) is the most common form of primary cutaneous T-cell lymphoma. Radiotherapy induces excellent response rates in the treatment of localized or extensive lesions of MF, both as monotherapy and as part of a multidisciplinary treatment. Total skin irradiation with electrons or protons is available in a limited number of medical centers and is mainly used in patients with extensive MF. Case presentation. It is presented the case of a 47-year-old patient who developed erythematous papules and plaques on the chest, upper limbs, face and scalp, initially diagnosed as chronic eczema and treated with systemic corticotherapy, antihistamines …

Actinic Granuloma Complicated By Secondary Syphilis: A Case Report, Kevin H. Nguyen, Christopher M. Wong, Ethan Q. Nguyen

HCA Healthcare Journal of Medicine

Introduction

Actinic granuloma (AG) is a rare skin eruption thought to result from a sun-induced inflammatory response attracting giant cells, which are large, multinucleated, and inflammatory, to form granulomas and degrade surrounding elastic material. Clinically, lesions begin on sun-exposed skin as pink papules and nodules that coalesce into demarcated annular plaques with a hypopigmented center. Histologically, actinic elastosis surrounds the outer annulus ring, with histiocytes and giant cells within the raised border, and the innermost central zone is filled with minimal to absent elastic fibers.

Case Presentation

We present a middle-aged female with a pruritic eruption of diffuse erythematous macules …

Management Of Keloid-Associated Pruritus With Topical Crisaborole 2% Ointment: A Case Report, Daniel A. Nguyen, Elizabeth Thai Ms, Stephen E. Weis

HCA Healthcare Journal of Medicine

Introduction

The pathophysiology of keloid formation is poorly understood, and current treatments, including intralesional corticosteroids, cryotherapy, and surgery, are often associated with high resistance to treatment and recurrence. The multifactorial pathogenesis of keloid formation suggests that aberrant inflammatory cytokine signaling associated with keratinocyte dysregulation may contribute to keloid-associated pruritus.

Case Presentation

In this paper, we report 2 cases of keloid-associated pruritus that were successfully treated with topical crisaborole 2% ointment, a phosphodiesterase 4 (PDE4) inhibitor. Both patients had previously undergone multiple unsuccessful treatments before being treated with crisaborole 2% ointment. In both cases, the patients experienced complete relief of pruritus …

Presentations Of Cutaneous Disease In Various Skin Pigmentations: Porokeratosis, Henry Lim, Christopher M. Wong, Christian J. Scheufele, Daniel A. Nguyen, Michael Carletti, Stephen E. Weis

HCA Healthcare Journal of Medicine

Porokeratosis was first described in 1893. It is a relatively rare disorder with over 9 subtypes. Lesions are clinically characterized as well-demarcated, erythematous papules (raised, <1 cm) or plaques (raised, >1 cm), with an atrophic center, and raised scaly border. Porokeratosis is an important diagnosis to identify because it may undergo malignant transformation and mimics many commonly encountered diagnoses. These commonly mimicked diagnoses include squamous cell carcinoma, tinea corporis, nummular dermatitis, and psoriasis vulgaris, to name a few. The clinical images in this review focus on identifying porokeratosis along the full spectrum of skin tones.