ABSTRACT
Dermoscopy is a noninvasive, efficient and inexpensive tool used to aid diagnosis of skin conditions such as vitiligo. Furthermore, it aids in tracking patient progress, treatment response and disease activity. Vitiligo can be diagnosed on dermoscopy by the presence of white structureless areas signifying hypopigmentation with a typical glowing appearance. Other typical features are perilesional and perifollicular hyperpigmentation, pigmentation networks and leucotrichia. In total, 15 studies were reviewed to determine the dermoscopic signs of the three main stages of disease activity: active, stable and repigmenting vitiligo. Features that differentiate active, stable and repigmenting vitiligo are reviewed and discussed in this article. Notably, there is a conflict in the literature between various dermoscopic features and which type of vitiligo they are truly indicative of. However, dermoscopy can be coupled with other clinical, biological and physiological markers to strengthen diagnostic accuracy.
Subject(s)
Dermoscopy , Vitiligo , Dermoscopy/methods , Humans , Vitiligo/diagnostic imaging , Vitiligo/pathology , Vitiligo/diagnosis , Biomarkers/analysisABSTRACT
BACKGROUND: The prevalence of social media as a source of medical information has grown substantially in recent years, especially for skin conditions disproportionately affecting individuals with skin of color, such as melasma, keloids, and vitiligo. OBJECTIVE: This study aims to evaluate the nature of content related to these conditions on social media platforms, Instagram and TikTok. METHODS: In March 2023, the top five hashtags for melasma, keloid, and vitiligo were identified on both platforms. For each hashtag, the 10 most popular posts were selected, based on Instagram and TikTok algorithms. A content analysis was conducted, categorizing posts as Educational, Promotional, or Inspirational. Posts were further classified by content creator type. RESULTS: For the top 50 posts related to melasma on Instagram, the majority were promotional (58%), with the most common source being non-dermatologist social media influencers (50%). Dermatologists were the primary content creators for specific hashtags, such as #Melasma on TikTok, where the content was predominantly educational. CONCLUSION: Considering the high prevalence of dermatologist-creator content on TikTok, it is crucial to continue this shift toward dermatologist-driven educational content, as social media platforms continue to grow. These platforms are valuable channels for dermatologists to educate a broader audience, facilitating the dissemination of accurate medical information.J Drugs Dermatol. 2024;23(7):510-514. doi:10.36849/JDD.7716.
Subject(s)
Keloid , Melanosis , Skin Pigmentation , Social Media , Vitiligo , Social Media/statistics & numerical data , Humans , Vitiligo/therapy , Vitiligo/diagnosis , Vitiligo/psychology , Keloid/epidemiology , Melanosis/diagnosis , Dermatologists/statistics & numerical dataSubject(s)
Vitiligo , Humans , Vitiligo/psychology , Vitiligo/diagnosis , Vitiligo/therapy , Female , Male , Severity of Illness Index , Adult , Quality of Life , Treatment Outcome , Middle AgedSubject(s)
Dermatology , Hypopigmentation , Vitiligo , Humans , Vitiligo/diagnosis , Vitiligo/therapySubject(s)
Age of Onset , Vitiligo , Humans , Vitiligo/epidemiology , Vitiligo/diagnosis , Retrospective Studies , Female , Child , Male , Adolescent , Child, PreschoolSubject(s)
Vitiligo , Vulvar Lichen Sclerosus , Humans , Vitiligo/diagnosis , Vulvar Lichen Sclerosus/diagnosis , Vulvar Lichen Sclerosus/pathology , Vulvar Lichen Sclerosus/complications , Female , Diagnosis, Differential , Lichen Sclerosus et Atrophicus/diagnosis , Lichen Sclerosus et Atrophicus/pathologySubject(s)
Vitiligo , Vulvar Lichen Sclerosus , Humans , Vitiligo/diagnosis , Vitiligo/complications , Vulvar Lichen Sclerosus/complications , Vulvar Lichen Sclerosus/diagnosis , Vulvar Lichen Sclerosus/pathology , Female , Lichen Sclerosus et Atrophicus/complications , Lichen Sclerosus et Atrophicus/diagnosis , Lichen Sclerosus et Atrophicus/pathologySubject(s)
Hyperpigmentation , Hypopigmentation , Vitiligo , Humans , Vitiligo/complications , Vitiligo/diagnosis , Hyperpigmentation/diagnosisSubject(s)
Hypopigmentation , Vitiligo , Humans , Vitiligo/diagnosis , Reproducibility of Results , Hypopigmentation/diagnosis , FaceABSTRACT
Vitiligo is a hypopigmented skin disease characterized by the loss of melanin. The progressive nature and widespread incidence of vitiligo necessitate timely and accurate detection. Usually, a single diagnostic test often falls short of providing definitive confirmation of the condition, necessitating the assessment by dermatologists who specialize in vitiligo. However, the current scarcity of such specialized medical professionals presents a significant challenge. To mitigate this issue and enhance diagnostic accuracy, it is essential to build deep learning models that can support and expedite the detection process. This study endeavors to establish a deep learning framework to enhance the diagnostic accuracy of vitiligo. To this end, a comparative analysis of five models including ResNet (ResNet34, ResNet50, and ResNet101 models) and Swin Transformer series (Swin Transformer Base, and Swin Transformer Large models), were conducted under the uniform condition to identify the model with superior classification capabilities. Moreover, the study sought to augment the interpretability of these models by selecting one that not only provides accurate diagnostic outcomes but also offers visual cues highlighting the regions pertinent to vitiligo. The empirical findings reveal that the Swin Transformer Large model achieved the best performance in classification, whose AUC, accuracy, sensitivity, and specificity are 0.94, 93.82%, 94.02%, and 93.5%, respectively. In terms of interpretability, the highlighted regions in the class activation map correspond to the lesion regions of the vitiligo images, which shows that it effectively indicates the specific category regions associated with the decision-making of dermatological diagnosis. Additionally, the visualization of feature maps generated in the middle layer of the deep learning model provides insights into the internal mechanisms of the model, which is valuable for improving the interpretability of the model, tuning performance, and enhancing clinical applicability. The outcomes of this study underscore the significant potential of deep learning models to revolutionize medical diagnosis by improving diagnostic accuracy and operational efficiency. The research highlights the necessity for ongoing exploration in this domain to fully leverage the capabilities of deep learning technologies in medical diagnostics.
Subject(s)
Deep Learning , Vitiligo , Vitiligo/diagnosis , HumansABSTRACT
Importance: Evidence-based recommendations for the treatment of vitiligo in pediatric, adolescent, and young adult patients in the US are needed. Objective: To develop evidence- and consensus-based expert recommendations on the diagnosis and treatment of vitiligo in young patients. Evidence Review: A process was developed to produce consensus recommendations addressing questions regarding pediatric vitiligo. A librarian-conducted literature review was performed using articles that met the inclusion criteria: published in English, containing primary data (including meta-analysis) and pediatric-specific data, and analysis of 6 or more patients. Included articles were graded by the Strength of Recommendation Taxonomy criteria and Oxford Centre for Evidence-based Medicine's Levels of Evidence and Grades of Recommendation. Research questions were reviewed on May 9, 2022, through a video conference. One month after the conference, participants participated in an online survey documenting their level of agreement with the generated statements, using a 5-point Likert scale. Findings: Articles on topical corticosteroids and/or topical calcineurin inhibitors (n = 50), topical Janus kinase inhibitors (n = 5), pseudocatalase (n = 2), and microdermabrasion (n = 2) met inclusion criteria. Forty-two recommendations were made on the diagnosis of vitiligo and optimal topical therapeutics, with 33 recommendations obtaining a 70% or greater composite agreement and strong agreement. Topical calcineurin inhibitors twice daily, topical corticosteroids with time limitation due to atrophy risk, and topical ruxolitinib, 1.5%, cream-used off-label for patients younger than 12 years and limited to nonsegmental vitiligo-were identified as evidence-based first-line therapies in the management of pediatric and adolescent patients, with specific guidance on age-based data, minimum therapeutic trial of 6 months or greater, prolonged therapy to prevent recurrence, and the positive benefit of coordinated use of UV therapeutic sources. Conclusions and Relevance: Evidence supports the use of topical calcineurin inhibitors, topical corticosteroids, and topical Janus kinase inhibitors as effective therapeutics for vitiligo in pediatric, adolescent, and young adult patients, with specific decisions on choice of agent based on factors such as site location, body surface area, and age.
Subject(s)
Dermatologic Agents , Janus Kinase Inhibitors , Vitiligo , Adolescent , Child , Humans , Young Adult , Administration, Topical , Calcineurin Inhibitors/therapeutic use , Dermatologic Agents/therapeutic use , Glucocorticoids/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Vitiligo/diagnosis , Vitiligo/drug therapyABSTRACT
Vitiligo is an autoimmune disorder characterized by epidermal melanocyte damage, with the typical clinical manifestation of white patches of skin. Keratinocytes, which work in concert with melanocytes to maintain the structural and functional integrity of the skin, are implicated in the progression of vitiligo. Recent studies have reported abnormal keratinocyte proliferation and epidermal thickening in some patients with vitiligo; however, the relationship between these changes and the clinical characteristics of vitiligo remains unclear. We assessed the changes in epidermal thickness in patients with vitiligo and their correlation with clinical characteristics. Compared to the non-lesional skins, the stratum corneum, viable epidermis, and full epidermis in the lesional skins were all significantly thicker. The thickness of the stratum corneum in the head, neck, and trunk was greatly lower than that in the extremities. The thickness of the stratum corneum in the sun-exposed area was higher than that in the sun-protected area, whereas the thickness of the viable epidermis decreased. In conclusion, our study found that the epidermis in the lesional skins of patients with vitiligo was significantly thickened, especially in the sun-exposed areas and extremities.
Subject(s)
Epidermis , Vitiligo , Humans , Vitiligo/pathology , Vitiligo/diagnosis , Epidermis/pathology , Male , Adult , Female , Middle Aged , Young Adult , Adolescent , Melanocytes/pathology , Keratinocytes/pathology , Child , Sunlight/adverse effects , AgedABSTRACT
In recent years, adalimumab has been increasingly used in the chronic treatment of non-infectious uveitis. This case report aimed to describe a drug-induced adverse event in a 34-year-old man who presented with blurred vision and floaters in the right eye and was being treated for intermediate uveitis. The patient had started topical treatment with a diagnosis of uveitis at another center. Best corrected visual acuity at presentation was 0.8 (decimal) in the right eye and 1.0 in the left eye. On examination, the anterior chamber in the right eye was clear, with anterior vitreous cells and mild haze, and snow banking and vitreous opacities in the inferior periphery. Fluorescein angiography (FA) showed hyperfluorescence in the right disc and leakage in the inferior periphery. As the inflammation did not resolve with local treatment, systemic cyclosporine was administered, after which the patient exhibited vomiting and weakness. Cyclosporine was discontinued and adalimumab treatment was started. On examination 5 months later, bilateral vitreous cells and mild vitreous opacity were noted, and FA showed mild leakage in the inferior periphery bilaterally. In addition, a depigmented patchy vitiligo lesion was observed on the chin. Due to the persistence of intraocular inflammation and on the recommendation of the dermatology clinic, adalimumab treatment was continued and topical tacrolimus was started for the lesion. On examination 3 months later, the inflammatory findings had resolved and there was no progression of the vitiligo lesion. The patient's treatment was continued. Taken together with the previous literature findings, no pathology was found in the patient's systemic examination, suggesting that this lesion was a side effect of the treatment. Ophthalmologists should be alert for this side effect in patients receiving adalimumab.
Subject(s)
Adalimumab , Anti-Inflammatory Agents , Fluorescein Angiography , Vitiligo , Humans , Adalimumab/adverse effects , Adalimumab/therapeutic use , Male , Adult , Fluorescein Angiography/methods , Vitiligo/diagnosis , Vitiligo/chemically induced , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/administration & dosage , Visual Acuity , Fundus OculiABSTRACT
BACKGROUND: Clinical data are limited in patients with vitiligo with or without autoimmune thyroid disease. OBJECTIVES: The objective of the study was to investigate the clinical features and basic data of patients with vitiligo, especially those with autoimmune thyroid disease. METHODS: The study was a single-center retrospective study. A total of 1305 patients with vitiligo from June 2018 to May 2023 were included, and the clinical characteristics and basic information of the patients were recorded in detail. RESULTS: We identified an association between sex (odds ratio [OR]: 2.380; 95% confidence interval [CI]: 1.772-1.198), vitiligo duration (OR: 1.449; 95% CI: 1.076-1.952), skin involvement exceeding 5% of the body surface area (OR: 3.764; 95% CI: 2.134-6.640), negative emotions (OR: 3.076; 95% CI: 2.292-4.127), vitiligo type (OR: 1.974; 95% CI: 1.096-3.555), family history of AITD (OR: 4.979; 95% CI: 2.687-9.225), and family history of AD (OR: 2.418; 95% CI: 1.410-4.146) and patients with vitiligo. CONCLUSIONS: For patients with statistically significant associated risk factors, differential diagnosis and early intervention should be performed.
Subject(s)
Autoimmune Diseases , Thyroid Diseases , Vitiligo , Humans , Vitiligo/complications , Vitiligo/epidemiology , Vitiligo/diagnosis , Retrospective Studies , Risk Factors , Body Surface Area , Thyroid Diseases/complications , Thyroid Diseases/epidemiology , Autoimmune Diseases/complications , Autoimmune Diseases/epidemiologyABSTRACT
BACKGROUND: Vitiligo is a multifactorial disease characterized by the progressive loss of melanocytes. The worldwide prevalence ranges from 0.5% to 2%, and in children from 0% to 2.16%. The objective of this study was to determine the variables associated with progression of vitiligo. METHODS: A retrospective cohort was carried out where a random sample of records of pediatric patients with vitiligo from January 2016 to December 2020 was analyzed. The variables were studied: age at onset, sex, hereditary family history, personal history of thyroid diseases, time of evolution, classification, Köebner phenomena, mucosal vitiligo, halo nevus, premature graying and the presence of other dermatoses. The final state was classified as progression, stability, partial remission and complete remission. RESULTS: 574 children with vitiligo; 290 (50.5%) women, 284 (49.5%) men. Non-segmental vitiligo in 324 (56.4%), segmental vitiligo in 250 (43.6%). Mean age of onset 8.7 years (SD: 4.54). Median evolution time 6 months (25th percentile of 3 months and 75th percentile of 24 months). Family history 27 (4.70%). Thyroid disease 7 (1.21%). Evolution remained stable in 44 (7.7%), 68 (11.8%) had progression, 32 (5.6%) complete remission, 222 (38.7%) partial remission and 208 (36.2%) one consultation. Non-segmental vitiligo was obtained p < 0.028, younger age of onset p < 0.000, and none skin comorbidities p < 0.009. CONCLUSIONS: The variables that were associated with a more progression were non-segmental vitiligo, early ages at the onset of the disease, and not presenting with other skin diseases.
INTRODUCCIÓN: El vitiligo es una enfermedad multifactorial caracterizada por la pérdida de melanocitos. La prevalencia mundial oscila entre el 0.5% y el 2%, y en niños entre el 0% y el 2.16%. El objetivo de este estudio fue determinar las características clínicas asociadas a la progresión del vitiligo. MÉTODOS: En una cohorte retrospectiva se analizó una muestra aleatoria de expedientes de pacientes con vitiligo de 0-18 años de edad, de enero de 2016 a diciembre de 2020. Se estudiaron la edad de inicio, el sexo, los antecedentes heredofamiliares, el antecedente personal de enfermedades tiroideas, el tiempo de evolución, la clasificación, el fenómeno de Köebner, el vitiligo en mucosas, el halo nevo, el encanecimiento prematuro y la relación con otras dermatosis. El estado final se clasificó en progresión, estabilidad, remisión parcial y remisión completa. RESULTADOS: 574 niños con vitiligo; 290 (50.5%) mujeres y 284 (49.5%) varones. Vitiligo no segmentario en 324 (56.4%), vitiligo segmentario en 250 (43.6%). Edad promedio de aparición 8.7 años (DE: 4.54). Mediana de tiempo de evolución 6 meses (percentil 25 de 3 meses y percentil 75 de 24 meses). Se encontraron antecedentes familiares en 27 (4.70%). Enfermedad tiroidea en 7 (1.21%). En la evolución permanecieron estables 44 (7.7%), progresaron 68 (11.8%), remisión completa 32 (5.6%), remisión parcial 222 (38.7%) y una consulta 208 (36.2%). Se obtuvo p < 0.028 en vitiligo no segmentario, p < 0.000 en menor edad de aparición y p < 0.009 en comorbilidad cutánea. CONCLUSIONES: Las variables que se asociaron a progresión fueron vitiligo no segmentario, edad temprana de inicio y no cursar con otras enfermedades cutáneas.
Subject(s)
Age of Onset , Disease Progression , Vitiligo , Humans , Vitiligo/diagnosis , Vitiligo/pathology , Vitiligo/epidemiology , Male , Female , Retrospective Studies , Child , Prognosis , Child, Preschool , Adolescent , Cohort Studies , Infant , Thyroid Diseases/epidemiology , Thyroid Diseases/pathologyABSTRACT
BACKGROUND: Diagnosis of cutaneous hypopigmentation can sometimes be challenging. Dermoscopy may play a role in identifying hypo or-depigmented dermatoses. The aim was to investigate which dermoscopic criteria represent potent indicators for the diagnosis of vitiligo, nevus depigmentosus, pityriasis alba, hypopigmented pityriasis versicolor, idiopathic guttate hypomelanosis, hypopigmented mycosis fungoides (MF), lichen sclerosus et atrophicus and ash leaf hypopigmented macules of tuberous sclerosis, and evaluate their diagnostic accuracy. 168 individuals diagnosed with one of these hypopigmented disorders were evaluated for the presence or absence of predetermined dermoscopic criteria. Evaluation of dermatoscopic characteristics in each condition and analysis for sensitivity and specificity of dermatoscopic diagnosis in these hypopigmented lesions was performed. The starburst pattern, micro-koebnerization, and trichrome pattern were unique to vitiligo diagnosis. Vitiligo had higher comet-tail appearance, perifollicular pigmentation, and perilesional hyperpigmentation than other hypopigmented illnesses. Other hypopigmented lesions had greater incidence of amoeboid pattern, faint or diminished pigment network, islands of pigmentation, ill-defined boundaries, pseudopods, and widespread scaling than vitiligo. Finally, perifollicular scaling, comedo-like openings, blue-gray specks, and fibrotic regions excluded vitiligo. Dermoscopy can help identify common hypopigmented skin lesions and reduce the need for skin biopsy. Nevus depigmentosus, pityriasis alba and idiopathic guttate hypomelanosis were the top three hypopigmented dermatoses that could be diagnosed by dermoscopy with 100% sensitivity. Vitiligo was in the second rank (94.7%), followed by lichen sclerosis et atrophicus (93.3%) then hypopigmented MF at 81.2% sensitivity. Dermoscopy sensitivity was lowest in pityriasis versicolor and ash leaf macules of tuberous sclerosis (52.6% and 46.7%, respectively).
Subject(s)
Dermoscopy , Hypopigmentation , Sensitivity and Specificity , Vitiligo , Humans , Hypopigmentation/diagnosis , Hypopigmentation/diagnostic imaging , Hypopigmentation/pathology , Female , Male , Adolescent , Adult , Child , Vitiligo/diagnosis , Vitiligo/diagnostic imaging , Vitiligo/pathology , Young Adult , Middle Aged , Child, Preschool , Skin/pathology , Skin/diagnostic imaging , Diagnosis, Differential , AgedABSTRACT
Vitiligo is considered an autoimmune disease, and its treatment is challenging. We assessed and compared the effect of fractional erbium:yttrium-aluminum-garnet (Er:YAG) laser-assisted delivery of platelet-rich plasma versus microneedling (Mn) with platelet-rich plasma (PRP) in enhancing skin repigmentation in localized stable vitiligo patients. In total, 40 patients with localized stable vitiligo were selected in a random manner into two similar groups (20 each). Group (A) was subjected to fractional Er:YAG laser combined with platelet-rich plasma and Group (B) was subjected to microneedling combined with platelet-rich plasma. The procedure was repeated every 2 weeks for up to 6 months. Each individual was assessed clinically utilizing Vitiligo Area Scoring Index (VASI). Fractional Er:YAG + PRP group achieved better pigmentation100% (excellent 30%, very good 15%, good 30% and satisfactory 25%) which is comparable to Mn + PRP where 80% of cases demonstrate repigmentation (20% very good, 10% good and 50% mild). When comparing the VASI scores for both groups after therapy to the baseline VASI, there was a statistically significant decrease [p = 0.001 for group(A) and 0.003 for group(B)]. Regarding the treatment side effects, there was significantly (p = 0.048) side effects among cases treated with microneedling group(B) (25%) than those fractional Er:Yag laser therapy group(A) (5%). Both forms of therapy demonstrated induction of repigmentation of vitiligo, but fractional Er:YAG laser efficacy is greater when combined with platelet-rich plasma.Clinical trials.gov identifier: NCT05511493.
Subject(s)
Lasers, Solid-State , Needles , Platelet-Rich Plasma , Skin Pigmentation , Vitiligo , Humans , Vitiligo/therapy , Vitiligo/radiotherapy , Vitiligo/diagnosis , Lasers, Solid-State/therapeutic use , Female , Male , Adult , Treatment Outcome , Skin Pigmentation/radiation effects , Young Adult , Middle Aged , Adolescent , Dry Needling/methods , Dry Needling/instrumentation , Combined Modality Therapy/methods , Percutaneous Collagen InductionABSTRACT
The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.
Subject(s)
Janus Kinase 3 , Protein Kinase Inhibitors , Vitiligo , Humans , Vitiligo/drug therapy , Vitiligo/diagnosis , Vitiligo/immunology , Male , Female , Adult , Janus Kinase 3/antagonists & inhibitors , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Treatment Outcome , Chemokine CXCL9/blood , Chemokine CCL5/blood , Young Adult , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , B7-H1 Antigen/blood , Melanocytes/drug effects , Double-Blind Method , Skin Pigmentation/drug effects , Administration, Oral , Interferon-gammaABSTRACT
Loss and absence of melanocytes due to a number of factors is responsible for vitiligo; known to be the commonest disorder of pigmentation. The aim of the current work was to compare the efficacy and safety of excimer light with topical tacrolimus ointment 0.1% versus excimer light with topical bimatoprost gel 0.01% in treatment of facial vitiligo. The study was carried out on 48 patients presented with facial vitiligo. The patients were divided randomly using sealed envelope method into two groups (24 patients each). Group 1 were treated with excimer light plus topical tacrolimus ointment 0.1% and group 2 treated with excimer light plus topical bimatoprost gel 0.01%. Clinical improvement based on the quartile grading scale at the end of treatment did not show any statistically significant difference between groups. The majority of subjects in both groups experienced good to excellent improvement. Only 20.9% of patients in group 1 and 33.3% of subjects in group 2 achieved less than 50% repigmentation (p = 0.889). Our study demonstrated that 0.01% topical bimatoprost gel in combination with excimer light is considered safe and effective as treatment of nonsegmental facial vitiligo with comparable results to 0.1% tacrolimus.