Orientador: Paulo Eduardo Neves Ferreira Velho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T04:23:44Z (GMT). No. of bitstreams: 1 Castro_EneidaLazzarinide_M.pdf: 1114056 bytes, checksum: a5208169cfed868777391385bab148e2 (MD5) Previous issue date: 2013 / Resumo: Introdução: O ensino superior deve educar socialmente o cidadão, independente da sua área de conhecimento. As doenças sexualmente transmitidas (DST) são a principal causa global de doença aguda e morte e representam elevado custo socioeconômico. Os universitários são altamente expostos e ter outras infecções aumenta enormemente o risco de contrair o HIV. Objetivos: Avaliar o conhecimento de universitários sobre as DST, desenvolvendo um instrumento didático de autopercepção deste (des)conhecimento sobre o tema. Material e métodos: Um questionário foi enviado aos graduandos da Universidade Estadual de Campinas no final de 2011 e, em 2012, aos alunos recém-ingressos. Resultados e conclusões: Responderam o questionário 1.448 veteranos e 371 calouros. Metade era de cada sexo e houve representatividade de todas as áreas. Não tinham tido atividade sexual 20,0 e 38,0% dos veteranos e calouros, respectivamente. Dos alunos que já haviam tido, 26,9% não tinham parceria fixa e 28,2% mais que 2 parcerias/ano. A bissexualidade foi informada por 9,0% dos alunos, enquanto 5,8% dos homens e 1,1% das mulheres a homossexualidade. O preservativo foi usado por 99% dos alunos, mas menos de 20% deles fazia uso adequado do mesmo. Entre os alunos, 43% entenderam errado um slogan da campanha do governo. Cerca de 80% não sabiam que o preservativo não protege fora da área de barreira; não souberam identificar lesões de herpes simples e que não há cura para este vírus; quando apontadas lesões discretas da infecção pelo HPV, afirmaram que elas poderiam ser confundidas com "pintas"; pretendiam ler mais sobre DST e aprenderam algo sobre o assunto. Quase a metade dos alunos julgou que uma disciplina deveria ser oferecida a todos os graduandos. Vacinação pré-exposição poderia ter sido oferecida a mais de 43% dos calouros. Os dados encontrados serão úteis para definir estratégias de prevenção e o instrumento didático poderá ser utilizado em outros ambientes de ensino / Abstract: Higher education should educate students socially, regardless of their area of expertise. STDs are a global major cause of acute illness and death and represent high socioeconomic cost. Undergraduate students are highly exposed to them. Having other infection greatly increases the risk of contracting HIV. Our goals were to develop a teaching tool to generate perception of (un) knowledge about STDs and quantify that knowledge and the interest of the students in a course about this subject. A questionnaire was sent to students from State University of Campinas in late 2011 and, in 2012, to beginner students. The questionnaire was answered by 1,448 seniors and 371 freshmen. They were half of each gender and were representative of all areas. Twenty percent of seniors and 38,0% of freshmen had no sexual activity. Among the students that already had sexual activity, 26.9% had no regular partner and 28.2% had more than 2 partnerships a year. Bisexuality was reported by 9.0% of students, while 5.8% of men and 1.1% of female referred homosexuality. The condom was used by 99% of students, but less than 20% of them made proper use of it. Among the students, 43% misunderstood a slogan of the government campaign. About 80% of them did not know that condoms do not protect the outside barrier area; were not able to identify herpes simplex lesions and there is no cure for this virus; considered that discrete HPV lesions could be confused with nevus; wanted to read more about STDs; and learned something about the subject. Nearly half of the students felt that a course should be offered to all undergraduates. Pre-exposure vaccination could have been offered to more than 43% of freshmen. Our findings will be useful to help define strategies for prevention and the teaching tool might be used in other learning environments / Mestrado / Ensino em Saúde / Mestra em Clínica Médica

Allergien sind häufige Erkrankungen in vielen industrialisierten Ländern. Ihre Entstehung beruht auf einem komplexen Zusammenspiel von genetischen und umweltassoziierten Einflüssen. Eine Vielzahl möglicher Faktoren ist beschrieben, die das Auftreten von AllerT gien beeinflussen können, etwa das Alter oder das Geschlecht. Es gibt allerdings nur sehr wenige Daten zur Verbreitung allergischer Erkrankungen in der älteren Bevölkerung. Das Ziel der vorliegenden Arbeit ist es, eine Übersicht zur Prävalenz allergischer ErkranT kungen und Sensibilisierungen in einer Stichprobe der 40T79Tjährigen Bevölkerung Leipzigs zu geben. Hierzu wurden insgesamt 4088 Probanden der zweiten ZwischenausT wertung (1. November 2011 bis 12. Juni 2013) der LIFETStudie untersucht. LIFE (Leipziger Forschungskomplex für Zivilisationserkrankungen) ist eine Kohortenstudie zur Erfassung von lebensstilT und umweltassoziierten Erkrankungen, beispielsweise Allergien, und mögT lichen Einflussfaktoren. In der vorliegenden Arbeit werden allergische Erkrankungen (alT lergische Rhinitis, Asthma bronchiale, atopisches Ekzem, Urtikaria, Anaphylaxie, NahT rungsmittelT und Insektengiftallergien) anhand eines AllergieTInterviews erfragt; SensibiliT sierungen werden mittels IgETDiagnostik für InhalationsT (SX1T) und NahrungsmittelallerT gene (FX5TScreeningtest) bzw. mittels Hautpricktest (Birke, Wiesenlieschgras, Beifuß, Dermatophagoides pteronyssinus, Alternaria alternata und Ambrosia) erfasst, weiterhin wird das GesamtTIgE bestimmt. Als mögliche Einflussfaktoren werden das Geschlecht, das Alter, der sozioökonomische Status und die allergologische Familienanamnese unterT sucht, hierzu werden neben den Prävalenzen auch OddsTRatios berechnet. Allergien sind häufige Erkrankungen in vielen industrialisierten Ländern. Ihre Entstehung beruht auf einem komplexen Zusammenspiel von genetischen und umweltassoziierten Einflüssen. Eine Vielzahl möglicher Faktoren ist beschrieben, die das Auftreten von Allergien beeinflussen können, etwa das Alter oder das Geschlecht. Es gibt allerdings nur sehr wenige Daten zur Verbreitung allergischer Erkrankungen in der älteren Bevölkerung. Das Ziel der vorliegenden Arbeit ist es, eine Übersicht zur Prävalenz allergischer Erkrankungen und Sensibilisierungen in einer Stichprobe der 40-79-jährigen Bevölkerung Leipzigs zu geben. Hierzu wurden insgesamt 4088 Probanden der zweiten Zwischenauswertung (1. November 2011 bis 12. Juni 2013) der LIFE-Studie untersucht. LIFE (Leipziger Forschungskomplex für Zivilisationserkrankungen) ist eine Kohortenstudie zur Erfassung von lebensstil- und umweltassoziierten Erkrankungen, beispielsweise Allergien, und möglichen Einflussfaktoren. In der vorliegenden Arbeit werden allergische Erkrankungen (allergische Rhinitis, Asthma bronchiale, atopisches Ekzem, Urtikaria, Anaphylaxie, Nahrungsmittel- und Insektengiftallergien) anhand eines Allergie-Interviews erfragt; Sensibilisierungen werden mittels IgE-Diagnostik für Inhalations- (SX1-) und Nahrungsmittelallergene (FX5-Screeningtest) bzw. mittels Hautpricktest (Birke, Wiesenlieschgras, Beifuß, Dermatophagoides pteronyssinus, Alternaria alternata und Ambrosia) erfasst, weiterhin wird das Gesamt-IgE bestimmt. Als mögliche Einflussfaktoren werden das Geschlecht, das Alter, der sozioökonomische Status und die allergologische Familienanamnese untersucht, hierzu werden neben den Prävalenzen auch Odds-Ratios berechnet. Insgesamt zeigt sich, dass allergische Erkrankungen und Sensibilisierungen in der untersuchten Stichprobe häufig sind. Die Einflussfaktoren zeigen unterschiedliche Effekte für das Risiko einer Allergie. Beispielsweise geht eine positive allergologische Familienanamnese mit einem erhöhten Risiko einher. Die möglichen Ursachen für Prävalenzunterschiede bei den allergischen Erkrankungen im Vergleich mit der Literatur und das Verhalten der Einflussfaktoren werden, ebenso wie die bestehenden Limitationen von LIFE, kritisch diskutiert. In der vorliegenden Arbeit wird erstmalig der Status quo von allergischen Erkrankungen in einer Probandengruppe der älteren Leipziger Bevölkerung gezeigt. Allergien sind bei den älteren Teilnehmern weniger häufig als bei den jüngeren, aber immer noch weit verbreitet. Weitere Untersuchungen sind notwendig, um mögliche Prävalenzänderungen zu dokumentieren und weitere Einflussfaktoren zu untersuchen. LIFE und seine geplanten Nachuntersuchungen bieten hierfür passende Möglichkeiten.

Melanoma is one of the deadliest forms of cancer. Unfortunately, its incidence rates have been increasing all over the world. One of the techniques used by dermatologists to diagnose melanomas is an imaging modality called dermoscopy. The skin lesion is inspected using a magnification device and a light source. This technique makes it possible for the dermatologist to observe subcutaneous structures that would be invisible otherwise. However, the use of dermoscopy is not straightforward, requiring years of practice. Moreover, the diagnosis is many times subjective and challenging to reproduce. Therefore, it is necessary to develop automatic methods that will help dermatologists provide more reliable diagnoses.  Since this cancer is visible on the skin, it is potentially detectable at a very early stage when it is curable. Recent developments have converged to make fully automatic early melanoma detection a real possibility. First, the advent of dermoscopy has enabled a dramatic boost in the clinical diagnostic ability to the point that it can detect melanoma in the clinic at the earliest stages. This technology’s global adoption has allowed the accumulation of extensive collections of dermoscopy images. The development of advanced technologies in image processing and machine learning has given us the ability to distinguish malignant melanoma from the many benign mimics that require no biopsy. These new technologies should allow earlier detection of melanoma and reduce a large number of unnecessary and costly biopsy procedures. Although some of the new systems reported for these technologies have shown promise in preliminary trials, a widespread implementation must await further technical progress in accuracy and reproducibility.  This thesis provides an overview of our deep learning (DL) based methods used in the diagnosis of melanoma in dermoscopy images. First, we introduce the background. Then, this paper gives a brief overview of the state-of-art article on melanoma interpret. After that, a review is provided on the deep learning models for melanoma image analysis and the main popular techniques to improve the diagnose performance. We also made a summary of our research results. Finally, we discuss the challenges and opportunities for automating melanocytic skin lesions’ diagnostic procedures. We end with an overview of a conclusion and directions for the following research plan.

Hansson, L. Detektion av makrolidresistens hos Mycoplasma genitalium med Panther Fusion. Examensarbete i biomedicinsk laboratorievetenskal 15 högskolepoäng. Malmö universitet: Fakulteten för hälsa och samhälle, institutionen för Biomedicinsk Vetenskap, 2023.   Mycoplasma genitalium är en sexuellt överförbar mikroorganism som infekterar både män och kvinnor, som behandlas oftast med azitromycin med ett ökande problem av antibiotikaresistens. För M. genitalium är makrolidresistens det främsta hotet mot behandling, och har kopplats till fyra punktmutationer i region V i 23S rRNA-genen: A2071G, A2072G, A2072C samt A2071T (M. genitalium G-37, GenBank NR_077054.1). Projektet har undersökt möjligheten att ersätta nuvarande in house realtids-PCR metod för makrolidresistensbestämning med ett integrerat nukleinsyra-reningssteg och realtids-PCR med Panther Fusion (Hologic) hos Klinisk mikrobiologi i Lund. Under projektet analyserades 55 patientprover som samlades under perioden januari-februari 2023 i Region Skåne, som blivit positiva vid M. genitalium testning. Dessa prover har därefter analyserats av personal med nuvarande ABI-metod för resistensbestämning och sedan analyserats på Panther Fusion. Nuvarande ABI-metod resulterade i positiv signal för 91% (50/55) av patientprover positiva vid M. genitalium analys och makrolidresistensmutation hos 25 % (14/55), medan Panther Fusion metoden resulterade i positiv signal för 81 % (45/55) av positiva M. genitalium prover och påvisade resistensmutation hos 20 % (11/55) av proverna.

The Enriching Dermatology and Aesthetics Clinic (EDAC), offering both general dermatology outpatient service in participation with National Health Insurance (NHI) and self-paid medical cosmetology service in Shulin District，New Taipei City is about to celebrate its 2-year-old birthday. The NHI business is getting on the track with stable outpatient visits; however the revenues of the cosmetology do not live up to the expectations. The business plan tries to review the company records, strategies, the competitors and market trends to propose practicable action plans to boost the revenues of the cosmetic service, while maintaining the quality and growth of NHI business.

Neural stem cells are the precursors of neurons, astrocytes and oligodendrocytes. During neural development, the division of stem cells takes place close to the lumen of the neural tube, after which they migrate to their final positions within the central nervous system (CNS). Soluble factors, including growth factors, regulate neural stem cell proliferation, survival, migration and differentiation towards specific cell lineages. This thesis describes the function of platelet-derived growth factor (PDGF) and stem cell factor (SCF) in neural stem cell regulation. PDGF was previously suggested to stimulate neuronal differentiation, but the mechanisms were not defined. This study shows that PDGF is a mitogen and a survival factor that expands a pool of immature cells from neural stem cells. The PDGF-treated cells can be stained by neuronal markers, but need further stimuli to continue their maturation. They can become either neurons or glia depending on the secondary instructive cues. Moreover, neural stem cells produce PDGF. Inhibition of this endogenous PDGF negatively affects the cell number in stem cell cultures. We find that SCF stimulates migration and supports the survival of neural stem cells, but that it has no effect on their proliferation or differentiation into neurons and glia. Intracellular signaling downstream from the receptors for PDGF and SCF includes activation of extracellular signal-regulated kinase (ERK). This investigation shows that active ERK is not needed for the differentiation of stem cells into neurons, at least not during early stages. Neural stem cells have a future potential in the treatment of CNS disorders. To be able to use neural stem cells clinically we need to understand how their proliferation, differentiation, survival and migration are controlled. The results presented in this thesis increase our knowledge of how neural stem cells are regulated by growth factors.

L’évaluation visuelle de lésions cutanées est l’analyse la plus couramment réalisée par les dermatologues. Ce diagnostic s’effectue principalement à l’œil nu et se base sur des critères tels que la taille, la forme, la symétrie mais principalement la couleur. Cependant, cette analyse est subjective car dépendante de l’expérience du praticien et des conditions d’utilisation. Nous proposons dans ce manuscrit (1) le développement d’une caméra multispectrale spécialement conçue pour un usage en dermatologie. Cette caméra multispectrale se base sur la technologie de roue porte-filtres composée de filtres interférentiels et d’un algorithme basé sur les réseaux de neurones générant un cube hyperspectral de données cutanées. Cet ensemble combine l’avantage d’un spectrophotomètre (information spectrale), et celui d’une caméra (information spatiale). Son intérêt est également de délivrer une information reproductible et indépendante des conditions d’acquisition. La mise en place d’un protocole d’acquisition de données de peaux saines issues de cinq des six phototypes existants a permis la validation de notre système en comparant les spectres générés par notre système avec des spectres théoriques acquis par un spectrophotomètre professionnel. (2) La réflectance spectrale de données de peau fournit une information précieuse, car directement liée à sa composition en chromophores. La mesure quantitative des propriétés optiques du tissu cutané peut être basée sur la modélisation de la propagation de la lumière dans la peau. Pour cela, nous nous sommes appuyés sur le modèle de Kubelka-Munk, auquel nous avons associé une méthode d’optimisation basée sur les algorithmes évolutionnaires. Cette dernière apporte une réponse à l’inversion de ce modèle. A partir de cette approche, la quantification de divers paramètres de la peau peut être obtenue, tels que la mélanine et l’hémoglobine. (3) La validation de cette méthodologie est effectuée sur des données pathologiques (vitiligo et melasma) et permet de quantifier une différence de composition entre zone saine et zone affectée sur une même image. / Visual evaluation of cutaneous lesions is the analysis the most commonly performedby dermatologists. This diagnostic is mainly done by naked eye and is based on criterionsuch as the size, shape, symmetry but principally on colour of the lesions. However, thisanalysis is subjective because it depends on the practician experience and the acquisitionconditions. We propose in this dissertation (1) the development of a multispectralcamera specifically dedicated for dermatological use. This device is based on a filterwheel composed of interferential filters and a neural network-based algorithm, generatinga hyperspectral cube of cutaneous data. This setting combines advantage of both spectrophotometer(spectral information) and digital camera (spatial information). Its maininterest is also to provide reproducible information which is independent of the acquisitionconditions. The setting-up of an acquisition protocol of healthy skin data from five of thesix exisiting skin phototypes allows the validation of our system by comparing spectragenerated by our system and theoretical spectra acquired by professional spectrophotometer.(2) Skin spectral reflectance provides precious information because it is directly linkedto the skin chromophore composition. Quantitative measure of cutaneous tissue opticalproperties can be based on the modelisation of light propagation in skin. For this purpose,we based our method on Kubelka-Munk model with which we associated an optimizationmethod based on evolutionary algorithm. This method helps for the model inversion.Using this approach, quantification of diverse parameters of skin can be obtained such asmelanin and haemoglobin. (3) The validation of this model is performed on disease skindata (vitiligo and melasma) and allows to quantify difference between healthy and affectedskin area within a single image.

Doenças crônicas sistêmicas, em especial o diabetes mellitus, favorecem o aparecimento e a continuidade de lesões dermo-epidérmicas, sendo o impacto econômico e social significativo. No âmbito da medicina regenerativa para o tratamento de lesões cutâneas crônicas, o emprego clínico da bioengenharia de tecidos associada à terapia celular tem sido considerado uma promissora alternativa terapêutica. Neste contexto, o estudo tem como objetivo avaliar a eficácia terapêutica no tratamento de úlceras cutâneas de pacientes diabéticos, empregando células-tronco mesenquimais do tecido adiposo (CT-TA) associadas a plasma rico em plaquetas (PRP) obtido de sangue autólogo. A pesquisa aplicada foi composta por seis pacientes diabéticos e portadores de úlceras cutâneas crônicas. A reepitelização total ocorreu em 5 das 9 lesões tratadas, sendo o índice de cicatrização médio superior a 70% após 3 meses da aplicação. Desta forma, é possível concluir que a terapia com CT-TA associadas a PRP proporciona uma redução na área ulcerosa de lesões cutâneas crônicas em pacientes diabéticos. / Systemic chronic diseases, especially diabetes mellitus, favor the emergency and continuity of dermal-epidermal lesions, being significant the economic and social impact. Within the regenerative medicine field for treatment of cutaneous chronic wounds, the clinical use of tissue bioengineering and cell therapy has been considered as a promising therapeutic alternative. In this context, the present study aims to evaluate the therapeutic efficiency, using adipose-derived mesenchymal stem cells (ADSC) associated with platelet-rich plasma (PRP) obtained from autologous blood, for the treatment of cutaneous ulcers from diabetic patients. The applied research was composed of six diabetic patients with chronic skin ulcers. The total re-epithelialization occurred in 5 of the 9 lesions treated, and the average wound healing index greater than 70% after 3 months of application. In this way, it can be concluded that ADSC therapy associated with PRP provides a reduction in ulcer area of chronic skin lesions in diabetic patients.

Wong Kin Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 151-166). / Abstracts in English and Chinese. / Chapter (I) --- ABSTRACT (IN ENGLISH) --- p.i / Chapter (II) --- Abstract (in Chinese) --- p.iv / Chapter (III) --- ACKNOWLEDGEMENTS --- p.vii / Chapter (IV) --- PERSONAL CONTRIBUTION TO THE WORK --- p.ix / Chapter (V) --- PUBLICATIONS --- p.x / Chapter (VI) --- TABLE OF CONTENTS --- p.xi / Chapter (VII) --- List of Abbreviations --- p.xvi / Chapter (VIII) --- LIST OF FIGURES --- p.xx / Chapter (IX) --- LIST OF TABLES --- p.xxii / Chapter Section 1: --- GENERAL INTRODUCTION / Chapter CHAPTER 1 --- General Introduction of Atopic Dermatitis --- p.1-8 / Chapter 1.1. --- Definition of Atopic Dermatitis --- p.1 / Chapter 1.2. --- Epidemiology and Classification --- p.3 / Chapter 1.3. --- Factors Provoking Flares of AD / Chapter 1.3.1. --- Genetics --- p.5 / Chapter 1.3.2. --- "Allergens-Food Allergens, Aeroallergens and Autoallergens" --- p.6 / Chapter 1.3.3. --- Microbial Colonization: Staphylococcus Aureus (S. aureus) --- p.7 / Chapter CHAPTER 2 --- Measurements of AD Severity and Quality of Life Impairment --- p.9-14 / Chapter 2.1. --- Scoring of Atopic Dermatitis severity and the SCORing Atopic Dermatitis (SCORAD) Index --- p.9 / Chapter 2.2. --- Quality of life Measurement --- p.10 / Chapter 2.3. --- The Children's Dermatology Life Quality Index --- p.11 / Chapter CHAPTER 3 --- Management of AD --- p.15-19 / Chapter 3.1. --- Current Management of AD and Their Drawbacks --- p.15 / Chapter 3.2. --- Traditional Chinese Herbal Medicne (TCHM) / Chapter 3.2.1. --- General Principle of TCHM --- p.17 / Chapter 3.2.2. --- Side Effects of Using TCHM --- p.18 / Chapter 3.2.3. --- Literature Reviews of TCHM Use in Treating AD --- p.18 / Chapter CHAPTER 4 --- The Pentaherbs Formula for AD Treatment --- p.20-26 / Chapter 4.1. --- Pilot study: Pentaherbs Capsule as Treatment Option of AD Children --- p.20 / Chapter 4.2. --- Literature Review: Nature of Five Herbs / Chapter 4.2.1. --- PHF as Treatment Option of AD under TCHM Concepts --- p.22 / Chapter 4.2.2. --- PHF as Treatment Option of AD from Modern Research Literature --- p.22 / Chapter CHAPTER 5 --- Pathobiology of Atopic Dermatitis --- p.27-40 / Chapter 5.1. --- Nature of Complexity of Pathogenesis --- p.27 / Chapter 5.2. --- Skin barrier-impairment of epidermal barrier --- p.28 / Chapter 5.3. --- Biphasic T cell response in skin of AD --- p.29 / Chapter 5.4. --- Nature of Immunoglobulin-E and its Role in Atopic Dermatitis --- p.32 / Chapter 5.5. --- Innate Immunity Defect in AD --- p.33 / Chapter 5.6. --- Role of Superantigen in Pathogenesis of AD --- p.35 / Chapter 5.7. --- "Cytokines, Chemokines and Inflammatory Mediators in Pathogenesis of Atopic Dermatitis" / Chapter 5.7.1. --- Proinflammatory Cytokines --- p.37 / Chapter 5.7.2. --- Th1/Th2 Cytokines --- p.37 / Chapter 5.7.3. --- Chemokines --- p.38 / Chapter 5.7.4. --- Pruritus Mediators --- p.39 / Chapter Section 2: --- CLINICAL TRIAL OF PENTAHERBS / Chapter CHAPTER 1 --- Objective --- p.41 / Chapter CHAPTER 2 --- Materials and Methods (RCT) --- p.42-51 / Chapter 2.1. --- Materials / Chapter 2.1.1. --- SCORAD worksheet --- p.42 / Chapter 2.1.2. --- CDLQI questionnaire --- p.42 / Chapter 2.1.3. --- Allergic Rhinitis Score (ARS) --- p.43 / Chapter 2.1.4. --- ELISA Assay Kits --- p.43 / Chapter 2.1.5. --- EDTA blood collestion tubes --- p.43 / Chapter 2.2. --- Methods / Chapter 2.2.1. --- Design --- p.45 / Chapter 2.2.2. --- Intervention --- p.45 / Chapter 2.2.3. --- Treatment / Chapter 2.2.3.1 --- The Pentaherbs Formula --- p.45 / Chapter 2.2.3.2 --- Randomization --- p.48 / Chapter 2.2.3.3 --- Concomitant Treatment in Study Period --- p.48 / Chapter 2.2.4. --- Participants --- p.49 / Chapter 2.2.5. --- Outcome Measures --- p.50 / Chapter 2.2.6. --- Statistical Analysis --- p.50 / Chapter CHAPTER 3 --- Results (RCT) --- p.52-67 / Chapter 3.1. --- Demographics --- p.52 / Chapter 3.2. --- Drug Compliance --- p.55 / Chapter 3.3. --- Efficacy / Chapter 3.3.1. --- SCORAD Score --- p.56 / Chapter 3.3.2. --- Quality of Life Score --- p.56 / Chapter 3.3.3. --- Duration and Amount of CS Usage --- p.59 / Chapter 3.3.4. --- Amount of Antihistamine Usage --- p.61 / Chapter 3.3.5. --- Allergic Rhinitis Score --- p.61 / Chapter 3.3.6. --- Blood chemistry and Haematology --- p.63 / Chapter 3.3.7. --- Plasma TARC and BDNF level --- p.63 / Chapter 3.4. --- Tolerability --- p.65 / Chapter Section 3: --- IN VITRO STUDY OF PENTAHERBS / Chapter CHAPTER 1 --- Objectives and Study Design --- p.68 / Chapter CHAPTER 2 --- Materials and Methods (In vitro Study) --- p.69-86 / Chapter 2.1. --- Materials for in vitro study / Chapter 2.1.1. --- Preparation of the Water Extracts of PHF Capsules --- p.69 / Chapter 2.1.2. --- Endotoxin Assay --- p.69 / Chapter 2.1.3. --- Cell isolation and culture ofPBMC / Chapter 2.1.3.1 . --- Cell Isolation from Human Peripheral Blood --- p.70 / Chapter 2.1.3.2. --- Culture of Peripheral Blood Mononuclear Cells --- p.70 / Chapter 2.1.4. --- Trypan Blue Exclusion Assay --- p.72 / Chapter 2.1.5. --- [3H]-Thymidine incorporation Assay --- p.72 / Chapter 2.1.6. --- Supernatant Collection and ELISA --- p.72 / Chapter 2.1.7. --- RNA Extraction and RT-PCR / Chapter 2.1.7.1. --- Reagents for RNA Extraction --- p.73 / Chapter 2.1.7.2. --- Reagents for Reverse Transcription --- p.73 / Chapter 2.1.7.3. --- Reagents for Polymerase Chain Reaction --- p.74 / Chapter 2.1.7.4. --- Reagents for Gel Electrophoresis --- p.74 / Chapter 2.2. --- Methods / Chapter 2.2.1. --- Isolation and Culture PBMC / Chapter 2.2.1.1. --- Isolation of PBMC --- p.76 / Chapter 2.2.1.2. --- Culture of Isolated PBMC --- p.76 / Chapter 2.2.1.3. --- PHA/SEB Treatment --- p.77 / Chapter 2.2.2. --- Preparation of PHF Water Extracts and Endotoxin Level / Chapter 2.2.2.1. --- Hot Water Extraction --- p.78 / Chapter 2.2.2.2. --- Limulus Amebocyte Lysate Assay --- p.78 / Chapter 2.2.3. --- Study on the Cytotoxic and Mitogenic Effects of PHF on PBMC / Chapter 2.2.3.1. --- Trypan Blue Exclusion Assay --- p.80 / Chapter 2.2.3.2. --- [3H]-Thymidine Incorporation Assay --- p.80 / Chapter 2.2.4. --- Study on the Effect of PHF on PBMC Inflammatory Mediator Production / Chapter 2.2.4.1. --- Determination of Inflammatory Mediator Expression Levels by ELISA --- p.82 / Chapter 2.2.4.2. --- Semi-quantification of Inflammatory Mediator mRNA Levels by RT-PCR --- p.83 / Chapter 2.2.5. --- Statistical Analysis --- p.86 / Chapter CHAPTER 3 --- Results(In vitro) --- p.87-114 / Chapter 3.1. --- preparation of PHF Water Extracts and Endotxin Level --- p.87 / Chapter 3.2. --- Cytotoxicity Effect of PHF on PBMC --- p.88 / Chapter 3.3. --- Mitogenicity Effect of PHF on PBMC --- p.93 / Chapter 3.4. --- Effects of PHF on Expression of Inflammatory Mediators from PBMC Following Mitogen (PHA) Stimulation / Chapter 3.4.1. --- Effects of PHF on mRNA Expression of Inflammatory Mediators from PHA-stimulated PBMC --- p.98 / Chapter 3.4.2. --- Effects of PHF on Secretion of Inflammatory Mediators from PHA-stimulated PBMC --- p.101 / Chapter 3.5 --- Effects of PHF on Expression of Inflammatory Mediators from SEB-stimulated PBMC / Chapter 3.5.1. --- Effects of PHF on mRNA Expression of Inflammatory --- p.106 / Chapter 3.5.2. --- Effescts of PHF on secretion of inflammatory Mediatorsfrom SEM-Stimulated PBMC --- p.109 / Chapter 3.6. --- Summarization of Effects of PHF on Expression of Inflammatory Mediators from PHA- and SEB-stimulated PBMC / Chapter 3.6.1. --- Mitogen (PHA) Stimulation --- p.114 / Chapter 3.6.2. --- Superantigen (SEB) Stimulation --- p.114 / Chapter Section 4: --- DISCUSSIONS / Chapter CHAPTER 1 --- Discussions on RCT of PHF --- p.115-122 / Chapter 1.1. --- Clinical Efficacy and Tolerability of PHF for Treatment of Children AD: a RCT study / Chapter 1.2. --- Efficacy of PHF for Treatment of Children with AD --- p.117 / Chapter 1.3. --- Safety and Tolerability of PHF Use for Treatment of Children with AD --- p.119 / Chapter 1.4. --- Rounding up --- p.121 / Chapter CHAPTER 2 --- Discussions on In vitro Immunomodulatory Activities of PHF --- p.123-130 / Chapter 2.1. --- General Effects of PHF on PBMC --- p.123 / Chapter 2.2. --- Effects of PHF on Inflammatory Mediators Expression in PBMC --- p.124 / Chapter CHAPTER 3 --- Limitations of the Present Study --- p.131-132 / Chapter Section 5: --- CONCLUSIONS AND FUTURE PROSPECTS / Chapter CHAPTER 1 --- Conclusions --- p.133 / Chapter CHAPTER 2 --- Future Prospects --- p.134-135 / Chapter Section 6: --- APPENDICES / Appendix1 --- p.137 / Appendix2 --- p.142 / Appendix3 --- p.149 / Chapter Section 7: --- BIBLIOGRAPHY --- p.151-166

Every year more than 72,000 adolescents and young adults (AYAs) in the United States (US) aged 15-39 years are diagnosed with cancer. AYAs represent a population that falls into a care gap between pediatric and adult medical services. Additionally, AYAs have experienced increased cancer incidence and decreased five-year survival rates compared to other age groups. The spectrum of tumors seen in AYAs differs from children and older adults, with 90% of the tumors stemming from ten cancer types. Melanoma of the skin, characterized by the uncontrolled growth of pigment-producing cells, is the third most common cancer diagnosed among AYAs in the US. Overexposure to ultraviolet (UV) radiation from sunlight or artificial sources is the greatest risk factor for melanoma. AYAs seem to be particularly at risk for developing melanoma due to increased UV exposure early in life. This study’s objectives were to understand the unique characteristics of melanoma in AYAs in Tennessee and identify the predictors of late- stage diagnosis. The sample for this study includes all incident melanoma cancer cases (N=1109) in AYAs from the Tennessee Cancer Registry (TCR) for the years 2004-2008, inclusive. AYA cases were defined as cancer cases that were diagnosed in individuals ages 15-39 years, inclusive. Melanoma cases were defined according to the International Classification of Diseases- Oncology (ICD-O-3) site codes C440-C449. Melanoma cases that had a specified stage at diagnosis were included for final analysis (N= 315). Stage of diagnosis was determined through the SEER Summary Stage 2000 variable and coded into in situ, localized, and combined regional & distant stage. Univariate and multivariate analyses were performed for the following predictor variables: insurance status (private insurance vs. other), age group (5- year groups), and sex (male vs. female). The majority of the sample was white (96.5%), female (63.8%), had private insurance (85%) and was diagnosed with localized stage melanoma (69.4%). Individuals with government insurance were eight times more likely to be diagnosed with late stage melanoma compared to individuals with private insurance (OR 8.4, CI 3.0-23.3, p < 0.01). AYAs in the 15-19 year old age group were six times more likely to be diagnosed with late stage melanoma compared to 35-39 year olds (OR 6.3, CI 1.7-22.9, p=0.01). Females were 57% less likely to be diagnosed with late stage melanoma compared to males (OR 0.53, CI 0.30-0.93, p < 0.05). These findings indicate that individuals with government insurance may not receive adequate melanoma screening and preventative care compared to individuals with private insurance. While females were less likely to be diagnosed with late stage melanoma, females have a much greater risk of being diagnosed with melanoma at any stage. Finally, the increased risk of late stage diagnosis in the 15-19 year old age group may be associated with greater UV exposure from indoor and outdoor tanning. These data suggest the need for targeted cancer awareness and control activities specific to AYAs. Future studies are needed to explore the variations in late stage diagnosis of melanoma in AYAs in Tennessee.