no / Quality of life in patients with vitiligo is impaired. This study explored the immediate effect of 20 days of climato­therapy at the Dead Sea on quality of life, coping with the disease, general well-being and individual stress levels in a group of 71 patients with vitiligo and 42 matched controls. The long-term effect was assessed after 12 months in 33/71 patients and 12/42 controls. Study instruments were Dermatology Life Quality Index, Beck Depression Inventory and the Adjustment to Chronic Skin Disorders Questionnaire. Stress measurements were based on cortisol and β-endorphin concentrations in saliva samples. Quality of life was significantly improved at day 20 at the Dead Sea compared with day 1, and this was still significant after 12 months. Moreover, social anxiety/avoidance, anxious-depressive mood and helplessness as measured by the Adjustment to Chronic Skin Disorders Questionnaire were significantly reduced. There was no difference in levels of cortisol and β-endorphin between patients and controls, indicating that stress per se is not a significant contributor in vitiligo. In conclusion, therapy in patient groups offers an effective tool for long-lasting improvement in quality of life and patients’ well-being.

no / Pterin-4a-carbinolamine dehydratase (PCD) is an essential component of the phenylalanine hydroxylase (PAH) system, catalyzing the regeneration of the essential cofactor 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin [6(R)BH4]. Mutations in PCD or its deactivation by hydrogen peroxide result in the generation of 7(R,S)BH4, which is a potent inhibitor of PAH that has been implicated in primapterinuria, a variant form of phenylketonuria, and in the skin depigmentation disorder vitiligo. We have synthesized and separated the 7(R) and 7(S) diastereomers confirming their structure by NMR. Both 7(R)- and 7(S)BH4 function as poor cofactors for PAH, whereas only 7(S)BH4 acts as a potent competitive inhibitor vs. 6(R)BH4 (Ki=2.3–4.9 μM). Kinetic and binding studies, as well as characterization of the pterin-enzyme complexes by fluorescence spectroscopy, revealed that the inhibitory effects of 7(R,S)BH4 on PAH are in fact specifically based on 7(S)BH4 binding. The molecular dynamics simulated structures of the pterin-PAH complexes indicate that 7(S)BH4 inhibition is due to its interaction with the polar region at the pterin binding site close to Ser-251, whereas its low efficiency as cofactor is related to a suboptimal positioning toward the catalytic iron. 7(S)BH4 is not an inhibitor for tyrosine hydroxylase (TH) in the physiological range, presumably due to the replacement of Ser-251 by the corresponding Ala297. Taken together, our results identified structural determinants for the specific regulation of PAH and TH by 7(S)BH4, which in turn aid in the understanding of primapterinuria and acute vitiligo. —Pey, A. L., Martinez, A., Charubala, R., Maitland, D. J., Teigen, K., Calvo, A., Pfleiderer, W., Wood, J. M., Schallreuter, K. U. Specific interaction of the diastereomers 7(R)- and 7(S)-tetrahydrobiopterin with phenylalanine hydroxylase: implications for understanding primapterinuria and vitiligo

This study explores processes of identity construction among women who have skin conditions and body modifications. Analyzing seven semi-structured qualitative interviews, the author examines how individuals affected by skin conditions employ body modification practices to organize their identities and promote feelings of agency across both personal and social domains. Engaging a Bakhtinian dialogic lens, the author argues that body modification may operate as a de-stigmatization strategy that supports individuals with skin conditions in cultivating a sense of self-determination and bodily sovereignty. Shaped by grounded theory, this study’s findings trace relationships between body modification and the development of agentic identities among women with skin conditions. Confronted by medical, physical, and social disenfranchisement, women affected by skin conditions may implement body modification practices to navigate treatment, incorporate their conditions, and negotiate their relationships. The author additionally suggests implications for the application of body modification practices as somatic therapeutic modalities.

Um eine verbesserte Therapieoption mit weniger Schmerzen und Nebenwirkun-gen für Patienten mit Depigmentierungsstörungen wie Vitiligo zu entwickeln, wurde eine Methode zur nichtinvasiven Gewinnung von autologen Melanozyten aus der Haarwurzel genutzt. Die Haarwurzel als einfach zugängliches Stammzell-reservoir bietet die Möglichkeit, Vorläufermelanozyten aus der äußeren Haar-wurzelscheide zu isolieren, differenzieren und zu proliferieren. Für zukünftige autologe Transplantationsversuche wurden in dieser Arbeit die kultivierten hu-manen Melanozyten aus der äußeren Haarwurzelscheide (Human Melanocytes from the Outer Root Sheath, HUMORS) auf drei unterschiedlichen Scaffolds getes-tet. Hinsichtlich mitochondrialer Aktivität (Marker für Zellproliferation), mela-nozytenspezifischer Markerexpression und ihrer Funktionalität (Tyrosinase-Enzymaktivität und Melaningehalt) wurden die Zellen auf Collagen Cell Carrier® (CCC), Poly-ε-Caprolacton-Scaffolds (PCL) und kollagen basierten Hydrogelen (cGEL) kultiviert und charakterisiert. Alle Scaffolds waren biokompatibel, immu-nologisch nur gering aktiv und wiesen eine dreidimensionale Struktur auf, die der extrazellulären Matrix nachempfunden war. Einen positiven Effekt auf die Prolife-ration wiesen die HUMORS auf den Collagen Cell Carrier® auf. Bei Untersuchun-gen der melanotischen Aktivität überzeugten die HUMORS auf dem cGEL Typ4 durch einen signifikant höheren Melaningehalt. Da Melanin das entscheidende Produkt der Repigmentierung bei Vitiligoläsionen ist, stellte sich damit das cGEL Typ4 als vielversprechender Zellträger für die Kultivierung und vorgesehene Transplantation der Melanozyten heraus.

Vitiligo is an acquired, depigmenting disorder. The etiology is unknown, but mostly autoimmune, associated with high levels of pro-inflammatory cytokines. These cytokines would stimulate atherosclerosis and develop metabolic syndrome. The aim of this study was to evaluate the relationship between vitiligo and metabolic syndrome. This is a transversal study, with 96 patients (47 with and 49 without vitiligo) treated at Hospital Universitário de Santa Maria RS, from March 2013 to January 2014. The vitiligo patients were selected by clinical diagnosis and the criteria of extension and time of disease were evaluated. The diagnostic criteria for metabolic syndrome were assessed, following IDF: total cholesterol, high-density lipoprotein-cholesterol (HDL-c), triglycerides, waist circumference and blood pressure. We evaluated the insulin resistance through the homeostasis model assessment-insulin resistance (HOMA-IR). The MS prevalence between the groups does not show significant difference (36,2% vs. 38,3%, p=1,000). Waist circumference was different between groups (95,5 vs. 90,5 cm). Vitiligo group showed smaller levels of HDL-c (48,2 mg/dL vs 57,7 mg/dL, p<0,001), and this difference was sustained in the sub-analysis of female patients. HOMA-IR did not show difference between groups. Metabolic syndrome was not associated with extension and evolution time of vitiligo. This study did not reveal relation between vitiligo and MS. HDL-c was smaller in vitiligo patients, and there was inverse correlation (r = -0,30, p = 0,045) between HDL-c and insulin only in vitiligo group. / O vitiligo é uma desordem adquirida da pigmentação. Sua etiologia é desconhecida, principalmente autoimune, associada com a elevação de citocinas pró-inflamatórias. As citocinas estimulariam a aterogênese, criando um estado de síndrome metabólica. O objetivo deste estudo é analisar a relação entre vitiligo e síndrome metabólica. Estudo transversal que avaliou 96 pacientes (47 com vitiligo e 49 sem vitiligo), atendidos no Hospital Universitário de Santa Maria RS, no período de março/2013 a janeiro/2014. Os pacientes com vitiligo foram selecionados por diagnóstico clínico, avaliados pela extensão da doença na pele e pelo tempo de evolução. Foram avaliados os critérios diagnósticos de síndrome metabólica (SM): dosagem sérica de colesterol total, HDL-colesterol, triglicerídeos, aferição de circunferência abdominal (CA) e da pressão arterial. A resistência insulínica (RI) foi avaliada pelo cálculo do HOMA-IR. A prevalência da SM entre os pacientes com vitiligo e sem vitiligo não mostrou diferença significativa (36,2% vs. 38,3%, p = 1,00). A CA diferiu entre os grupos, sendo maior no grupo com vitiligo (95,5 cm vs. 90,5 cm, p = 0,046). Os níveis de HDL-c foram menores no grupo com vitiligo (48,2 mg/dL vs 57,7 mg/dL, p = 0,002) , mantendo-se significativos na subanálise dos pacientes do sexo feminino (p = 0,012). O HOMA-IR também não apresentou diferença entre os grupos (2,6±1,8 vs. 2,0±1,1, p=0,285). Não houve associação de SM com tempo de evolução e nem com a extensão de acometimento do vitiligo. Não foi encontrada relação entre vitiligo e SM, entretanto, o HDL-colesterol foi mais baixo e a CA maior nos pacientes com vitiligo, e houve correlação inversa (r = - 0,31 , p = 0,045) entre valores de HDL-colesterol e insulina apenas no grupo com vitiligo.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-11-27T10:31:50Z No. of bitstreams: 2 Dissertação - Rachel de Paula Santos Ribeiro - 2017.pdf: 12713551 bytes, checksum: c361c2531a99b684a3f4f3633f77b96c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-11-27T10:32:23Z (GMT) No. of bitstreams: 2 Dissertação - Rachel de Paula Santos Ribeiro - 2017.pdf: 12713551 bytes, checksum: c361c2531a99b684a3f4f3633f77b96c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-11-27T10:32:24Z (GMT). No. of bitstreams: 2 Dissertação - Rachel de Paula Santos Ribeiro - 2017.pdf: 12713551 bytes, checksum: c361c2531a99b684a3f4f3633f77b96c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-10-26 / Autoimmune diseases can be triggered by viruses, bacteria and parasites. However, the participation of these infectious agents in the etiology of vitiligo, it is a current research topic. In this study, the serum of 51 participants with vitiligo and 51 control subjects was analyzed for the presence of anti-Toxoplasma gondii (T.gondii) IgG, anti-herpes simplex (HSV) 1/2 IgG, anti-cytomegalovirus (CMV) IgG and anti-hepatitis C (HCV) IgG. / As doenças automimunes podem ser desencadeadas por vírus, bactérias ou parasitas. E o envolvimento destes agentes infecciosos na etiologia do vitiligo, é tema de intensa investigação atual. Neste estudo, o soro de 51 participantes com vitiligo e de 51 pessoas controle pareados por sexo e idade foi analisado para presença de imunoglobulinas IgG anti- Toxoplasma gondii (T.gondii), anti-herpes simples (HSV) 1/2, anti citomegalovírus (CMV) e anti-hepatite C (HCV).

Um eine verbesserte Therapieoption mit weniger Schmerzen und Nebenwirkun-gen für Patienten mit Depigmentierungsstörungen wie Vitiligo zu entwickeln, wurde eine Methode zur nichtinvasiven Gewinnung von autologen Melanozyten aus der Haarwurzel genutzt. Die Haarwurzel als einfach zugängliches Stammzell-reservoir bietet die Möglichkeit, Vorläufermelanozyten aus der äußeren Haar-wurzelscheide zu isolieren, differenzieren und zu proliferieren. Für zukünftige autologe Transplantationsversuche wurden in dieser Arbeit die kultivierten hu-manen Melanozyten aus der äußeren Haarwurzelscheide (Human Melanocytes from the Outer Root Sheath, HUMORS) auf drei unterschiedlichen Scaffolds getes-tet. Hinsichtlich mitochondrialer Aktivität (Marker für Zellproliferation), mela-nozytenspezifischer Markerexpression und ihrer Funktionalität (Tyrosinase-Enzymaktivität und Melaningehalt) wurden die Zellen auf Collagen Cell Carrier® (CCC), Poly-ε-Caprolacton-Scaffolds (PCL) und kollagen basierten Hydrogelen (cGEL) kultiviert und charakterisiert. Alle Scaffolds waren biokompatibel, immu-nologisch nur gering aktiv und wiesen eine dreidimensionale Struktur auf, die der extrazellulären Matrix nachempfunden war. Einen positiven Effekt auf die Prolife-ration wiesen die HUMORS auf den Collagen Cell Carrier® auf. Bei Untersuchun-gen der melanotischen Aktivität überzeugten die HUMORS auf dem cGEL Typ4 durch einen signifikant höheren Melaningehalt. Da Melanin das entscheidende Produkt der Repigmentierung bei Vitiligoläsionen ist, stellte sich damit das cGEL Typ4 als vielversprechender Zellträger für die Kultivierung und vorgesehene Transplantation der Melanozyten heraus.

Bakgrund: Människans försvar mot omvärlden och patogena mikrober består av ett väl utvecklat immunsystem innehållande det medfödda immunsystemet, innate, som inte förändras nämnbart över tid samt det adaptiva immunsystemet som skapar minnesceller efter immunrespons på peptidantigen. Det medfödda immunsystemets receptorer binder främmande strukturer och agerar snabbt genom att skapa inflammatorisk respons. Människans adaptiva immunsystem har celler som tar upp, bryter ned och via major histocompatibility complex (MHC) presenterar peptidantigen för T-celler. T-celler behöver flera stimuleringsvägar för att starta immunrespons. Immunsystemets celler kontrolleras så immunologisk tolerans upprätthålls. Autoimmunitet orsakas troligen av genetisk känslighet där den genetiska dispostitionen inte kan upprätthålla immunologisk tolerans vid trauma. Alopecia areata och vitiligo är de enda kända autoimmuna hudsjukdomarna som inte är antikroppsmedierade. Sjukdomarna drabbar 1 – 2 % av befolkningen. Hårfolliklar attackeras av autoreaktiva T-celler vid alopecia areata vilket ger håravfall. Vitiligo ger depigmenterade hudområden orsakat av autoreaktiva T-celler som förstört melanocyter. Sjukdomarna behandlas med immunsuppressiva läkemedel lokalt på huden eller systemiskt. Syfte: Examensarbetet syftade till att erhålla en djupare kunskap rörande likheter och skillnader i mekanism mellan de autoimmuna hudsjukdomarna alopecia areata och vitiligo samt undersöka och besvara frågeställningen vilken effekt olika typer av immunsuppressiv behandling har vid dessa sjukdomar.  Metod: Examensarbetet är en litteraturstudie som baseras på sex stycken vetenskapliga artiklar framsökta ur databasen PubMed genom flera sökningar. Sökningarna avgränsades genom användande av bl.a. sökorden alopecia areata, vitiligo, treatment, tacrolimus och janus kinase. Resultat: Studie 1 och 2 utvärderar systemisk puls-behandling med glukokortikoider. Patienterna i studie 1 hade alopecia areata med omfattande håravfall och behandlingsrespons sågs hos många patienter. Vitiligo-patienterna i studie 2 uppvisade minskad sjukdomsaktivitet vilket ses i färre nya lesioner samt repigmenterade lesioner, dock ses ingen repigmentering hos en del patienter. Studie 3 och 4 utvärderar lokal behandling med takrolimus-salva. Patienter med vitiligo i studie 3 fick viss repigmentering av lesionerna och patienterna med alopecia areata i studie 4 fick delvis håråterväxt. Effekten av oralt administrerade januskinas-hämmare utvärderas i studie 5 och 6. Studie 5 visar att många patienter med alopecia areata fått mycket håråterväxt vid behandlingens slut och studie 6 påvisar behandlingsrespons hos hälften av vitiligo-patienterna där repigmentering främst ses på hudområden exponerade för solljus. Slutsats: Litteraturstudien visar att olika typer av immunsuppressiv behandling kan lindra sjukdoms-utbrott samt förkorta sjukdomstid vid de autoimmuna hudsjukdomarna alopecia areata och vitiligo. Immunologiskt sett har sjukdomarna liknande sjukdomsmekanismer genom inflammatorisk respons som ger aktivering av autoreaktiva T-celler. Behandlingsresistensförekommer och därför behövs fortsatt forskning kring sjukdomsmekanismer och nya läkemedel. / Humans are depending on a functional immune system that provides defense against microbes and other things in our environment that can harm us. The skin is the largest and the heaviest of our organs. It’s important to have a barrier between the inner functions of the body and the world outside. The innate immune system specificities are recognition of microbes and damage. The adaptive immune system includes B and T cells which develops from stem cells in the bone marrow. The mature B and T cells are tested for self-tolerance before they are released. Having a functional immune system needs immunologic cells with immunologic tolerance. Immunologic tolerance demand B and T cells to know the difference between self antigens and pathogens.  Autoimmunity is probably caused by genetic susceptibility under influence of trauma such as local tissue injury and infection. The trauma cause imbalance in the immune system and gives an autoimmune response with activated T cells reacting on self antigens. Autoimmune diseases can be systemic or organ specific and different mechanisms cause the damage of tissue. Diseases caused by autoimmunity tend to be chronic, self-perpetuating and progressive. Alopecia areata and vitiligo are autoimmune skin diseases which gives hair loss and depigmentation. Hair loss in alopecia areata is caused by autoimmune T cells attacking hair follicles and depigmentation in vitiligo is caused by destruction of melanocytes by autoimmune T cells. The diseases can’t be cured but immunosuppressive therapy can reduce disease activity and give faster recovery.  The aim of this literature study was to get a deeper knowledge about the autoimmune skin diseases alopecia areata and vitiligo, and evaluate the efficiency of different immunosuppressive therapies used against alopecia areata and vitiligo. Found six scientific articles from the database PubMed through several searches. The searches were delimited by use of the keywords alopecia areata, vitiligo, treatment, tacrolimus and janus kinase.  Studies 1 and 2 evaluate systemic pulse management with glucocorticoids. The patients in study 1 had alopecia areata with extensive hair loss and treatment reactions were seen in many patients. Vitiligo patients in study 2 show reduced disease activity as seen in fewer lesions as well as repigmented lesions, however, no repigmentation seen in some patients. Studies 3 and 4 evaluate local treatment with tacrolimus ointment. Patients with vitiligo in study 3 received some repigmentation of the lesions and the patients with alopecia areata in study 4 received partial hair regrowth. The effect of orally administered janus kinase inhibitors is evaluated in studies 5 and 6. Study 5 shows that many patients with alopecia have received a lot of hair regrowth at the end of treatment and study 6 shows treatment response in half of vitiligo patients where repigmentation is mainly seen in sunlight exposed areas.  The literature study shows that different types of immunosuppressive treatment can relieve disease outbreaks and shorten disease in autoimmune skin diseases alopecia areata and vitiligo. Immunologically the diseases have similar disease mechanisms through inflammatory responses that provide activation of autoreactive T cells. Conclusion of this smallscale literature study is the need for further research on mechanisms of the diseases and research on therapies because therapy resistance is seen in both diseases although many patients responded to the immunosuppressive therapies.

Introdução: A literatura tem demonstrado que a presença de distúrbios emocionais nos cuidadores de crianças com dermatoses crônicas influenciam no curso e tratamento da doença. A ansiedade e a depressão estão entre os diagnósticos psiquiátricos mais relacionados, porém a maioria das publicações afere esta relação de forma indireta, através de escalas de qualidade de vida e não de escalas diretas para ansiedade e depressão. Objetivo: Avaliar a presença de ansiedade e depressão nos cuidadores de pacientes pediátricos com dermatite atópica, vitiligo ou psoríase e correlacioná-las à qualidade de vida dos pacientes, à extensão corporal total da doença e à área acometida exposta à visualização. Materiais e Métodos: Amostra composta por 118 pacientes com dermatite atópica, vitiligo e psoríase acompanhados pelo principal responsável por seus cuidados diários. A avaliação da ansiedade nos cuidadores foi realizada através da Escala de Hamilton de Ansiedade e a depressão através do Inventário de Beck para Depressão. Foi aplicado o Índice de Qualidade de Vida na Dermatologia Infantil. Aferiu-se a superfície corporal total acometida pela doença em áreas expostas à visualização através do modelo humano para queimados. Resultados: Ansiedade foi verificada em 36% dos cuidadores do grupo de pacientes com dermatite atópica, em 36% do grupo com psoríase e 42% do grupo com vitiligo. Depressão ocorreu em 36% dos cuidadores de pacientes com dermatite atópica, 36% dos responsáveis pelos pacientes com psoríase, e em 26% dos cuidadores de pacientes com vitiligo. Observou-se uma correlação significativa entre a pior qualidade de vida dos pacientes com vitiligo e a presença de depressão e ansiedade nos seus cuidadores. Quanto maior a superfície corporal total comprometida pela psoríase maior o índice de depressão e ansiedade nos seus cuidadores, e quanto maior superfície corporal em áreas expostas à visualização nos pacientes com vitiligo, maior a presença de ansiedade nos seus cuidadores. Na análise comparativa da qualidade de vida entre os três grupos de pacientes portadores de dermatoses, verificou-se que os pacientes com dermatite atópica e psoríase têm qualidade de vida significativamente piores que os portadores de vitiligo. Conclusão: A presença de ansiedade e depressão nos cuidadores de pacientes com vitiligo foi significativamente relacionada a uma pior qualidade de vida dos pacientes e a uma maior extensão da doença exposta à visualização. Entre os cuidadores de pacientes com psoríase, observaram-se maiores índices de depressão e ansiedade diante da maior superfície corporal total comprometida pela doença. Porém, os piores escores de qualidade de vida foram identificados entre os pacientes atópicos. Assim, acreditamos que distúrbios emocionais tendem a estar presentes no nicho familiar de crianças portadoras das dermatoses crônicas estudadas. / Introduction: The literature has shown that the presence of emotional disturbances in caregivers of children with skin diseases affects the course and treatment of the disease. Anxiety and depression are among the most frequently reported psychiatric diagnoses related to this fact. However, most publications have attempted to gauge this relationship indirectly by using quality of life scales rather than direct scales developed for the evaluation of anxiety and depression. Objective: To evaluate the presence of anxiety and depression in caregivers of 118 pediatric patients with chronic skin disorders, exemplified by atopic dermatitis, psoriasis and vitiligo, and correlate them to the quality of life of the patients, total body area affected by the disease and the extent of that affected area exposed to view. Methods: The sample consisted of patients with atopic dermatitis, vitiligo and psoriasis accompanied by their main caregiver. The levels of anxiety and depression in the caregivers were assessed using the Hamilton Anxiety Scale and the Beck Depression Inventory, respectively. The validated for Portuguese Children's Dermatology Life Quality Index was applied. The total body surface affected by the disease and the area exposed to view were measured using the human model for burn patients. Results: Anxiety was observed in 36% of the caregivers of the patients with atopic dermatitis, 36% of those of children affected by psoriasis and 42% of those responsible for pediatric patients with vitiligo. Depression occurred in 36% of the caregivers of patients with atopic dermatitis, 36% of those of children affected by psoriasis and 26% of those responsible for pediatric patients with vitiligo affected. There was a significant correlation between poor quality of life scores in patients with vitiligo and the presence of depression and anxiety in their caregivers. The greater the total body surface affected by psoriasis the higher the rate of depression and anxiety in their caregivers. For vitiligo, extensive surface body area corresponded to more intense anxiety in their caregivers. In the comparative analysis of the quality of life between the three groups of dermatoses, the quality of life of patients with atopic dermatitis and psoriasis was significantly worse than for those affected by vitiligo. Conclusion: The presence of anxiety and depression in caregivers of patients with vitiligo was significantly related to the lower quality of life of the patients and the greater extent of disease exposed to view. Among caregivers of patients with psoriasis, the larger total body surface affected by the disease, the higher were the observed levels of depression and anxiety. However, the worst quality of life scores were identified among atopic patients. Thus, we believe that emotional disorders tend to be present in the close family of children with the studied chronic skin diseases.

Dissertação (mestrado) - Pontifícia Universidade Católica do Paraná, Curitiba, 2012 / Bibliografia: f. 66-68 / INTRODUÇÃO: Alterações de adesão nos melanócitos parecem estar envolvidas na etiopatogênese do vitiligo. Recentemente variações genéticas do gene DDR1 foram associadas com vitiligo, e até o presente momento não há relato de variações na expressão protei / etiopathogenesis of vitiligo. Genetic variants of DDR1 gene have been recently associated with vitiligo with rare reports of proteic expression variations. Other adhesion molecules related to this disease patogenesis have been studied. OBJECTIVE: This stu