Značajke kože važne za pojavu kontaktnog dermatitisa u zdravstvenih djelatnika

The occurrence of skin lesions in healthcare workers is associated with a negative impact on important skin functions, including protection from mechanical injuries, sunlight, dehydration, and penetration of chemical substances or pathogenic microorganisms. In healthcare professionals, the most common occupational skin disease is contact dermatitis (CD), either irritant (ICD) or allergic (ACD), and typically on the hands. ICD accounts for about 80% of occupational CD, making it the most frequent cause. According to the literature, CD frequency is higher among healthcare professionals than other occupations, with critical occupational risk factors including contact with irritants and allergens at the workplace. Furthermore, ICD is a multifactorial disorder influenced by many constituent and environmental factors. Constituent factors include age, gender, body location, atopy, and genetic factors, while environmental factors include temperature, airflow, humidity, and occlusion. Commonly encountered irritants are water, detergents and surfactants, solvents, oxidizing agents, acids, and alkalis; however, use of protective gloves or equipment, hand-washing habits, use of cleansers and creams, active inflammatory skin diseases, and daily activities are also important for ICD onset. Additionally, ICD is known to predispose to ACD. Important risk factors for ACD development include occupation, age, history of atopic dermatitis, genetics, female gender, and fair skin phototype. In summary, numerous skin features and other occupation-related factors contribute to CD among healthcare practitioners. Given the high level of exposure to contact irritants/allergens in the healthcare setting, implementation of preventive measures is crucial for a safer work environment.Pojava kožnih promjena u zdravstvenih radnika povezana je s negativnim utjecajem rada na važne funkcije kože, uključujući zaštitu od mehaničkih ozljeda, sunčeve svjetlosti, dehidracije i prodora kemijskih tvari ili patogenih mikroorganizama. U zdravstvenih radnika najčešća profesionalna bolest kože je kontaktni dermatitis (CD), iritativni kontaktni dermatitis (ICD) i alergijski kontaktni dermatitis (ACD), koji se javljaju najčešće na šakama. Pritom ICD čini oko 80% profesionalnog CD-a, što ga čini njegovim najčešćim oblikom. Prema literaturi, učestalost CD-a veća je u zdravstvenih radnika nego kod ostalih zanimanja, gdje je kontakt s iritansima i alergenima na radnom mjestu ključni profesionalni čimbenik rizika. Nadalje, ICD je multifaktorski poremećaj na koji utječu mnogi konstitucijski i okolišni čimbenici. Konstitucijski čimbenici uključuju dob, spol, mjesto na tijelu, atopiju i genetske čimbenike, dok čimbenici okoliša uključuju temperaturu, protok zraka, vlažnost i okluziju. Iritansi koji se često susreću su voda, deterdženti i surfaktanti, otapala, oksidirajuće tvari, kiseline i lužine; međutim, upotreba zaštitnih rukavica ili opreme, navike pranja ruku, uporaba sredstava za čišćenje i kreme, aktivne upalne bolesti kože i svakodnevne aktivnosti također su važne za pojavu ICD-a. Uz to, poznato je da ICD predisponira osobu za pojavu ACD-a. Važni čimbenici rizika za razvoj ACD-a uključuju zanimanje, dob, anamnezu atopijskog dermatitisa, genetiku, ženski spol i fototip svijetle kože. Ukratko, brojne značajke kože i drugi čimbenici povezani sa zanimanjem doprinose nastanku CD-a u zdravstvenih djelatnika. S obzirom na visoku razinu izloženosti kontaktnim iritansima/alergenima u zdravstvu, provedba preventivnih mjera presudna je za sigurnije radno okruženje

Dynamic and Polarized Muscle Cell Behaviors Accompany Tail Morphogenesis in the Ascidian Ciona intestinalis

BACKGROUND: Axial elongation is a key morphogenetic process that serves to shape developing organisms. Tail extension in the ascidian larva represents a striking example of this process, wherein paraxially positioned muscle cells undergo elongation and differentiation independent of the segmentation process that characterizes the formation of paraxial mesoderm in vertebrates. Investigating the cell behaviors underlying the morphogenesis of muscle in ascidians may therefore reveal the evolutionarily conserved mechanisms operating during this process. METHODOLOGY/PRINCIPLE FINDINGS: A live cell imaging approach utilizing subcellularly-localized fluorescent proteins was employed to investigate muscle cell behaviors during tail extension in the ascidian Ciona intestinalis. Changes in the position and morphology of individual muscle cells were analyzed in vivo in wild type embryos undergoing tail extension and in embryos in which muscle development was perturbed. Muscle cells were observed to undergo elongation in the absence of positional reorganization. Furthermore, high-speed high-resolution live imaging revealed that the onset and progression of tail extension were characterized by the presence of dynamic and polarized actin-based protrusive activity at the plasma membrane of individual muscle cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that in the Ciona muscle, tissue elongation resulted from gradual and coordinated changes in cell geometry and not from changes in cell topology. Proper formation of muscle cells was found to be necessary not only for muscle tissue elongation, but also more generally for completion of tail extension. Based upon the characterized dynamic changes in cell morphology and plasma membrane protrusive activity, a three-phase model is proposed to describe the cell behavior operating during muscle morphogenesis in the ascidian embryo

A Case of Mistaken Identity: HSP Masquerading as Urticaria

An 8-year-old boy with an atopic history presented to the ED with back pain, cough, diarrhea and two weeks of bruising and arthralgias. He denied fevers, abdominal pain, or gross hematuria. Vital signs were normal. His elbows, knees and ankles were tender to palpation without restricted range of motion. Skin exam was notable for petechiae, palpable purpura, ecchymoses at various stages of healing, and evanescent urticarial plaques on the trunk, upper and lower extremities, buttocks, and genitalia. CBC, CMP, coagulation studies, ANA, RF, lyme serologies, and urinalysis were normal. C4 complement was low and ASO titers were elevated. Punch biopsies showed peri- and intravascular infiltrate of neutrophils and eosinophils involving the superficial and deep vascular plexuses. Direct immunofluorescence (DIF) demonstrated IgA vascular deposition. These findings are consistent with Henoch-Schonlein purpura (HSP). HSP is the most common small vessel vasculitis in children. Clinical presentation classically includes palpable purpura, arthritis, abdominal pain, and nephritis, though not necessarily concurrently. On skin biopsy, HSP demonstrates a neutrophilic infiltrate and IgA deposition in the superficial to mid-dermal vessels. HSP is a self-limited disorder, but 2% of patients will have permanent renal sequelae; thus, close follow-up is required. Our patient had atypical HSP, in which the cutaneous manifestation included urticaria. HSP typically follows an upper respiratory tract infection but can also follow exposure to other infectious agents. Mucosal IgA and microbial antigen complexes disseminate hematogenously and deposit in vessel walls, inducing complement activation, mast cell degranulation, and neutrophil chemotaxis. Proteolytic enzymes cause vessel wall damage, resulting in palpable purpura. Superficial vessel involvement leads to urticaria and purpura while deep vessel involvement leads to bullous or necrotic lesions. Similar to HSP, acute urticaria develops after exposure to an infectious agent, medication, or allergen. The binding of these substrates to mast cells causes histamine release and leakage of plasma into the dermis. This creates classic erythematous and evanescent wheals. Conditions associated with immune dysregulation are found in a significant number of HSP patients. Our patient’s history of atopy may have played a role in his unusual cutaneous features. We present this case to highlight an atypical presentation of HSP involving urticaria

The Impact of ATR Mutations in Melanoma on Genomic Stability, Tumor Invasion Potential, and Metastasis

Throughout the day, the skin is constantly exposed to harmful UV rays. The body has various defense mechanisms to protect the skin from detrimental DNA damage, such as melanin production by melanocytes in the epidermis, as well as intracellular DNA damage repair proteins. When these defense mechanism fail, cells can accumulate multiple DNA breaks which in turn leads to genomic instability and the potential for cancer development. This summer, I studied the impact of ATR, a kinase involved in the UV-induced ssDNA damage response, on melanoma development and progression. We propose that defects in the DNA damage response mechanism involving ATR leads to the ability to accumulate multiple mutations and speeds up melanoma progression. Dr. Ganesan’s lab has already discovered that loss of ATR activity increases melanoma tumor volume, number of tumors, and number of metastases. For my project, I sought to further validate this hypothesis by studying the downstream effects of loss of ATR activity. We used RT-PCR to confirm a mouse model with the kinase domain of ATR floxed out. Additionally, using western blot analysis, we studied the level of CHK1 phosphorylation, a downstream target of the ATR DNA damage response mechanism, in ATR mutant versus ATR wild-type human melanoma cultures. Lastly, we genotyped 100 mice using PCR to collect at least 5 mice each with a ATR wt/wt, ATR fl/wt, or ATR fl/fl genotype for use in future experiments on immune cell infiltration into the tumor microenvironment. A preliminary study of T cell, B cell, and macrophage infiltration into the tumors was performed using flow cytometry. While we were able to confirm that the ATR kinase domain had successfully by floxed out of the mouse models, we were unable to come to any further conclusions during my summer experience. More protocol troubleshooting was needed for the western blot analysis of CHK1 phosphorylation, as well as for the flow cytometry analysis of the immune cell infiltration. We successfully collected at least 5 mice in each ATR genotype category for later use in immune cell infiltration studies with flow cytometry, as well as gene expression investigation using a Nanostring immune profiling panel. While I was unable to complete the experiments for this project, positive results would suggest that ATR mutation plays a vital role in the progression of melanoma, and could be a potential therapeutic target to slow expansion of disease

Medication-Induced Repigmentation of Gray Hair: A Systematic Review

Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In this article we review the literature on medication-induced hair repigmentation, discuss the potential mechanisms of action, and review the quality of the literary data. To date, there have been 27 studies discussing medication-induced gray hair repigmentation, including 6 articles on gray hair repigmentation as a primary objective, notably with psoralen treatment or vitamin supplementation, and 21 reports on medication-induced gray hair repigmentation as an incidental finding. Medications noted in the literature include anti-inflammatory medications (thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, cyclosporin, cisplatinum, interferon-α, and psoralen), stimulators of melanogenesis (latanoprost, erlotinib, imatinib, tamoxifen, and levodopa), vitamins (calcium pantothenate and para-amino benzoic acid), a medication that accumulates in tissues (clofazimine), and a medication with an undetermined mechanism (captopril). Diffuse repigmentation of gray hair can be induced by certain medications that inhibit inflammation or stimulate melanogenesis. There is also low-quality evidence that some vitamin B complex supplementation can promote gray hair darkening. While these compounds are not currently indicated for the treatment of gray hair, their mechanisms shed light on targets for future medications for hair repigmentation