Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work had as main objective the development of nanostructured formulations containing rutin, using nanoparticles prepared with alternative vegetables oils. In the first chapter it was demonstrated the feasibility of preparing nanocapsules and nanoemulsions using grape seed or almond kernel oil. Nanocapsule suspensions and nanoemulsions were prepared by the interfacial deposition of preformed polymer and spontaneous emulsification, respectively. All formulations presented nanometric mean size, polydispersity index below 0.30, negative zeta potential, pH values between 6.5 and 7.5 remaining stable after 6 storage months. These formulations promoted the protection of the active against UV degradation, regardless of the type of the oily phase or vesicle. In the second chapter, formulations prepared with grape seed oil were selected for the development of rutin-loaded nanoparticles, as well as to evaluate its in vitro antioxidant activity and photostability. All formulations presented nanometric size, low polydispersity index, acid pH values, negative zeta potential and encapsulation efficiency close to 100 %. Nanoparticles were able to protect rutin against UV photodegradation, if compared to rutin ethanolic solution. In the study of the in vitro antioxidant activity, rutin-loaded nanocapsules and nanoemulsions showed a lower rutin decay rate compared to the rutin ethanolic solution when exposed to UV radiation in the presence of OH radical. However, its presence in nanocapsules led to a prolonged in vitro antioxidant activity compared to the rutin-loaded nanoemulsions. Finally, in the third chapter we studied the development of hydrogels containing rutin (free or associated to polymeric nanocapsules). Their activity on the cutaneous wound healing in rats was evaluated. The developed formulations showed adequate properties regarding their cutaneous administration. In vivo response concerning the healing effect of hydrogels was evaluated by the regression of skin lesions after six days of treatment. Markers of oxidative stress in the lesions of rats were also evaluated, as levels of lipid peroxidation analyzed by the method of thiobarbituric acid reactive substances (TBARS), determination of protein carbonyls levels, total proteins levels, glutathione (GSH) levels, vitamin C and evaluation of the antioxidant enzyme catalase (CAT). This last chapter showed for the first time the feasibility of the dermatological use of such formulations containing rutin to promote the in vivo wound healing. / Este trabalho teve como principal objetivo o desenvolvimento de formulações nanoestruturadas contendo rutina, a partir de nanopartículas contendo óleos vegetais até então não estudados no preparo destas formulações. No primeiro capítulo foi demonstrada a viabilidade de preparar nanocápsulas e nanoemulsões contendo o óleo de semente de uva e de amêndoas doce como fase oleosa. As suspensões de nanocápsulas e nanoemulsões foram preparadas pelo método da deposição interfacial do polímero pré-formado e emulsificação espontânea, respectivamente. Todas as formulações apresentaram tamanho médio nanométrico, índice de polidispersão inferior a 0,30, potencial zeta negativo e valores de pH entre 6,5 e 7,5, permanecendo estáveis após 6 meses de armazenamento. As formulações promoveram a fotoproteção do ativo frente à degradação UV, independente do tipo de fase oleosa e do tipo de vesícula. No segundo capítulo, as formulações contendo o óleo de semente de uva foram selecionadas para o estudo do desenvolvimento de nanopartículas contendo rutina, bem como avaliação de sua atividade antioxidante in vitro e fotoestabilidade. Após o preparo, todas as formulações apresentaram tamanho nanométrico de partículas, baixo índice de polidispersão, valores de pH ácido, potencial zeta negativo e eficiência de encapsulação próxima à 100%. As nanopartículas protegeram a rutina frente à fotodegradação UV, quando comparadas à solução etanólica. No estudo da atividade antioxidante in vitro, as nanocápsulas e nanoemulsões apresentaram uma menor taxa de decaimento da rutina comparada com a solução etanólica, quando expostas à radiação UV em presença do radical ·OH. No entanto, a presença das nanocápsulas levou a uma atividade antioxidante in vitro mais prolongada comparada com as nanoemulsões contendo rutina. Finalmente, no terceiro capítulo estudamos o desenvolvimento de hidrogéis contendo rutina livre ou associada a nanocápsulas poliméricas, avaliando a sua atividade sobre a cicatrização de lesões cutâneas em ratos. As formulações desenvolvidas apresentaram propriedades adequadas para aplicação tópica. A resposta in vivo do efeito cicatrizante foi avaliada através da regressão de lesões na pele após 6 dias de tratamento. Marcadores do estresse oxidativo nas lesões dos ratos foram também avaliados, como os níveis da peroxidação lipídica através do método de TBARS, níveis de proteína carbonilada, níveis de proteínas totais, níveis de glutationa (GSH), vitamina C e avaliação da enzima antioxidante catalase (CAT). Este terceiro capítulo demonstrou pela primeira vez a potencialidade do emprego dermatológico de hidrogéis contendo rutina para a promoção de cicatrização de feridas in vivo.

Hepatitis C virus (HCV) represents a global health threat. HCV is a blood-borne positive-strand RNA virus belonging to the Flaviviridae family that infects ~160 million people worldwide. About 70% of infected individuals fail to clear the virus and subsequently develop chronic hepatitis, frequently leading to liver cirrhosis and in some cases hepatocellular carcinoma. Therapeutic options for HCV infection are still limited and a protective vaccine is not yet available. Currently available therapies include administration of pegylated alpha interferon in combination with ribavirin. The recently approved protease inhibitors Boceprevir and Telaprevir are also included in the treatment regimen. However, limitations to the treatment with direct-acting antivirals (DAAs) are associated with severe side effects and low sustained virological response (SVR) rates that vary depending on the virus and host genotype. The replication step of the viral life cycle is mostly targeted by majority of DAAs. Recent findings have suggested that a combination of entry inhibitors together with DAAs exhibit a synergistic effect in the treatment of HCV. Therefore, identification of efficient HCV entry inhibitors is of high priority In vitro studies have shown that HCV attachment and subsequent entry into the host cells is mediated by E1 and E2 viral envelope proteins. HCV entry requires interaction with a number of receptors which include CD81, scavenger receptor B1 (SR-B1) and the tight junction proteins, claudin 1 (CLDN1) and occludin (OCLN). Since the E2 glycoprotein is reported to interact directly with cellular receptors, it is an attractive target for neutralisation. The present study focuses on the establishment and characterisation of entry inhibitors as antivirals for HCV. The thesis is presented in three chapters: Chapter 1- ‘Introduction’, provides a brief overview on HCV genotypes, genome organisation, life cycle including details on the entry process and therapies used for the treatment of HCV. Chapter 2 describes the generation of monoclonal antibodies (mAbs) against HCV envelope proteins as potent anti-viral agents for the prevention of HCV infection. Data on the identification and characterization of the neutralizing epitopes of HCV envelope proteins have been presented. Chapter 3 includes isolation of entry inhibitors of HCV from natural sources and identification and characterization of the active components exhibiting antiviral property. A number of studies have reported the role of neutralizing antibodies in the course of HCV infection and emerging data suggest protective effect of antibodies against HCV infection. Most of the ongoing studies are based on HCV genotype 1a which is prevalent globally. However in India, the prevalent genotype is 3a. Therefore, we established a panel of mAbs against HCV-LPs comprising of core-E1-E2 derived from genotype 3a as described in chapter 2. HCV-LP based system has been used in this study since it mimics the biophysical conformation, morphology and antigenic properties of the native virion and represents a model system for studies on viral binding and entry. MAbs were characterised and analyzed for their ability to prevent viral binding and entry into host cells. Three mAbs namely E3D8, H6D3 and A10F2 were identified to recognize the E2 viral glycoprotein which significantly inhibited HCV-LP binding to Huh7 cells in vitro. The neutralizing epitopes corresponding to the mAbs were identified using overlapping truncated fragments and synthetic peptides of the E2 protein. Our experiments suggest that the epitopes recognised by the inhibitory mAbs are unique and different from those reported till now. The synergistic effect of a combination of mAbs on virus neutralization has shown promising results for treatment of viral infections. Since in the present study the epitopes recognised by the mAbs are non-overlapping, we went ahead to determine whether a combination of these mAbs would enhance the ability to block HCV-LP binding. Indeed, flow cytometry and fluorescence microscopy studies revealed that a combination of the antibodies efficiently blocked the binding of HCV-LP to human hepatoma cells. More importantly and of relevance is the observation that the mAbs in combination inhibited viral infection (JFH1 strain) and replication in permissive human hepatocytes as determined by real time RT-PCR. Phytochemicals present in plants have been considered as conducive for prevention of several viral infections and are found to be promising antiviral agents. Natural products which are biologically active disclose drug-like properties since they are small molecules and can be easily metabolised and absorbed by the body. In our study as described in chapter 3, we evaluated extracts from Indian medicinal plants and fruits which are known to have hepato-protective effect, for natural potent attachment and entry inhibitors for HCV. Flow cytometric analysis suggested that the root extract of the herb Boerhavia diffusa and fruit extract of Prunus domestica exhibited high antiviral activity by inhibiting the binding of Hepatitis C virus like particles (HCV-LPs) to the human hepatoma cells. We went on to isolate, identify and confirm the active principles to be Boeravinone H, a dehydrorotenoid, (from Boerhavia diffusa) and Rutin, a flavonoid, (from Prunus domestica) by LC-ESI-MS, NMR, UV and IR spectral analysis. Our study revealed that the compounds block the attachment as well as entry step probably by targeting the viral particle. We also assessed the efficiency of these small molecules (Boeravinone H and Rutin) to inhibit HCV negative strand synthesis post entry by real time RT-PCR. Results suggest significant inhibition of viral entry and infection in the HCV cell culture (ex vivo). To our knowledge it is the first report on Boeravinone H and Rutin as entry inhibitor for HCV. In conclusion, our findings support the potential of employing a cocktail of neutralizing mAbs and antiviral agents from natural source in the management of HCV infection.

Covid-19 innebar nya rutiner för fastighetsmäklarna med ökat krav på användning av digitalkommunikation för att möta kunder och genomföra bostadsaffärer. Eftersomfastighetsmäklarnas intäkter helt löper på försäljningsprovision kan de nya rutinerna medförakonsekvenser för mäklares ekonomiska överlevnad. Syftet med studien var därför attanalysera hur mäklare förändrat och digitaliserat sina rutiner under Covid-19 pandemin, ijämförelse med före pandemin, för att utveckla kundrelationer, genomföra bostadsaffärersamt säkra sin ekonomiska överlevnad. Studien genomfördes med hjälp av intervjuer avmäklare, tematisering och jämförelse med rutinteorin och tidigare forskning. Resultatetvisade att mäklare genomförde färre personliga möten i hemmet och mäklarkontoret. Deutvecklade rutiner för att kombinera personliga och digitala möten, upprätthöll digitalkommunikation via hemarbete, videovisningar och sociala medier. De effektiviserade ävensina digitala rutiner genom obligatorisk föranmälan till visningar, digital avtalssignering ochanvändning av en digital plattform som kallas sälj- och köpcoachen. En av slutsatserna sommanifesterades under studien var det ökade avståndet mellan mäklare och kund, vilketkompenserades genom ökad digital användning av video, digital signering samt sälj- ochköpcoachen. Denna ökade digitalisering innebar förbättrad effektivitet i mäklarnas arbete attutveckla kundrelationer, genomföra bostadsaffärer och säkra sin ekonomiska överlevnad.Mäklarna antas därför fortsätta ompröva och effektivisera sin digitala kommunikation medkunder på nya oväntade sätt i framtiden. / Covid-19 meant new routines for real estate agents with increased requirements for the use ofdigital communication to meet customers and carry out housing transactions. A real estateagents income runs entirely on sales commission, therefore could the new routines that camealong with the pandemic have negative consequences on their financial survival. The purposeof the study was therefore to analyze how real estate agents changed and digitized theirroutines during the Covid-19 pandemic, compared to before the pandemic, to developcustomer relationships, conduct housing transactions and ensure their financial survival. Thestudy was conducted through interviews with brokers, thematization and comparison withroutine theory and previous research. The results showed that brokers conducted fewerpersonal meetings in the home and in their office. They developed routines for combiningpersonal and digital meetings, maintained digital communication via homework, video viewsand social media. They also streamlined their digital routines through mandatory pre-registration for screenings, digital contract signing and use of a digital platform called thesales and buying coach. One of the conclusions that manifested during the study was theincreased distance between broker and customer due to the pandemic. However, this wascompensated by increased usage of digital video, digital signing and the sales- and buyingcoach. The increased digitalisation meant improved efficiency in the brokers' work to developcustomer relationships, carry out housing transactions and secure their financial survival.Brokers are therefore expected to further develop and streamline their digital communicationwith customers in new unexpected ways in the future.

Background: By the year 2030 the prognosis is that one fourth of the Swedish population will be 65 years or older. An age group that today stands for 40 percent of all the daily visits in the Swedish emergency departments. Nearly half of them are 80 years or older. The frail older adults are often low prioritized due to their diffuse symptoms whereby long waiting times and healthcare-related injuries may occur. As a complement to the standard prioritizing procedure, that triage stands for, some emergency departments have introduced screening tools for detecting those individuals that are older adults and frail. Unfortunately, the introduction of new guidelines, do not always imply that the implementation comes easy because there are factors that facilitate and inhibit their intended use. Aim: To illustrate factors that affect the nurses use of the screening tool Clinical Frailty Scale (CFS) which identifies frailty in elders during triage in the emergency department. Method: A descriptive quantitative cross-sectional study where data was collected through a web-based questionnaire. The data of the study was analyzed through descriptive and analytical statistics. Results: When it came to influencing factors regarding the use of CFS in the selected emergency department, CFS as a method with its practicalities constituted as facilitators, whilst the organizational and working cultural aspects constituted as barriers. The differences in the nurses' experience and education effected the perception of CFS in different ways. Conclusion: There is a need of a working culture where responsibility is shared between stakeholders to facilitate a guideline. Advanced nurse practitioners can have a crucial role in educating, motivating and creating space for discussion relating to organizational, theoretical and practical components of the process in identifying the frail older adults. / Bakgrund: Prognosen är att år 2030 kommer en fjärdedel av den svenska populationen vara 65 år eller äldre. Åldersgruppen utgör idag cirka 40 procent av alla besök på Sveriges akutmottagningar där nästan hälften av dem är 80 år eller äldre. De sköra äldre erhåller ofta låg prioritering på grund av sina diffusa symtom, där långa väntetider och vårdrelaterade skador kan uppstå som följd. Som komplement i den vanliga prioriteringsrutinen som triagering innebär har akutmottagningar infört screeningverktyg för att upptäcka de individer som är sköra äldre. Dessvärre innebär införandet av nya rutiner att de inte alltid lätt implementeras i verksamheten eftersom det finns faktorer som främjar och hindrar dess avsedda användning. Syfte: Att belysa faktorer som påverkar sjuksköterskors användning av screeningverktyget Clinical Frailty Scale (CFS) för att identifiera sköra äldre vid triagering på akutmottagningen. Metod: En kvantitativ tvärsnittsstudie där data samlades in genom en webbenkät. Studiens data analyserades deskriptivt samt med analytisk statistisk. Resultat: När det kom till faktorer som påverkade användningen av CFS på den valda akutmottagningen utgjorde CFS som metod med dess praktiska delar en främjande faktor, medan organisatoriska och arbetskulturella aspekter utgjorde hindrande faktorer. Skillnaderna i erfarenhet och utbildning hos sjuksköterskorna påverkade uppfattningen om CFS på olika sätt. Slutsats: Det behövs en arbetskultur med ett delat ansvar mellan organisation och medarbetare för att främja följsamheten till en rutin. Specialistsjuksköterskor kan ha en betydande roll i att utbilda, motivera och skapa forum för diskussion gällande organisatoriska, teoretiska och praktiska delar i processen av att identifiera sköra äldre.

This study aims to investigate how physical planning can prevent crime and increase safety in an urban environment, with the theoretical starting point in Crime prevention through environmental design, CPTED, and the Vivalla area. Vivalla is located in Örebro and was chosen because it is a particularly vulnerable area. The district is under reconstruction with a completely renovated quarter, Visgatan. The questions and purpose are fulfilled through a literature study and document study supplemented with an interview and a location observation. The interview was held in place at Örebro Bostäder's office and the interviewees were the company's district manager and a project developer. The theoretical part of the report aims to provide an understanding of how safety, security and crime are connected to the physical urban environment. Also how planners can make use of different theories and apply these in practice to achieve as safe and secure an environment as possible. The results of the study show that the project did not follow any theoretical model in terms of physical design, but that several of the CPTED-principles can still be connected to the reconstruction of Vivalla. The analysis chapter describes how the principles have been implemented and to what extent. The case study leads to the conclusion that the safety on Visgatan has increased after the redevelopment and there are fewer crimes on Visgatan than the rest of Vivalla, which could potentially be due to the measures taken during the redevelopment. / Detta arbete syftar till att undersöka hur den fysiska planeringen kan förebygga brott och öka tryggheten i en stadsmiljö, med teoretiska utgångspunkten i Crime Prevention through environmental design, CPTED, och området Vivalla. Vivalla ligger i Örebro och valdes på grund av att det är ett särskilt utsatt område. Stadsdelen är under ombyggnation med ett färdigrenoverat kvarter, Visgatan. Frågeställningarna och syftet uppfylls genom en litteraturstudie och dokumentstudie kompletterat med en intervju och ett platsbesök. Intervjun hölls på plats på Örebro Bostäders kontor och de som intervjuades var bolagets distriktschef och en projektutvecklare.  Rapportens teoridel syftar till att ge en förståelse kring hur trygghet, säkerhet och brottslighet hänger ihop med den fysiska stadsmiljön. Även hur planerare kan ha användning av olika teorier och tillämpa dessa i praktiken för att uppnå en så trygg och säker miljö som möjligt. Studiens resultat visar att projektet inte följt någon teoretisk modell vad gäller fysisk utformning, men att flera av CPTED-principerna ändå går att koppla till ombyggnationen av Vivalla. Analysavsnittet redogör hur principerna har implementerats och i vilken utsträckning. Fallstudien leder fram till slutsatsen att tryggheten på Visgatan har ökat efter ombyggnationen och det sker färre brott på Visgatan än övriga Vivalla, vilket potentiellt skulle kunna bero på åtgärderna som vidtagits under ombyggnationen.

[ES] El mercado actual del vino tinto demanda vinos de gran potencia visual, elevada concentración aromática y que no resulten excesivamente astringentes ni amargos. Asimismo, el consumidor final demanda cada vez más vinos que se desarrollen en una viticultura más orgánica que garantice la sostenibilidad del cultivo. Para cumplir con estas expectativas, se está limitando la utilización de compuestos químicos en el viñedo, sustituyéndolos por otros naturales con menor impacto medioambiental, y se están utilizando en bodega técnicas como la maceración prefermentativa, que contribuye a la extracción de antocianos y aromas, o la microoxigenación, que permite estabilizar los compuestos polifenólicos en un tiempo reducido. El color de los vinos depende de su concentración en antocianos, pero también la forma y el estado en que éstos se encuentren en el vino, que depende de diferentes factores, siendo uno de ellos el fenómeno de la copigmentación como paso anterior a la polimerización y estabilización. Además, el oxígeno juega un papel crucial en la evolución del color, así como en la oxidación de los polifenoles y en la formación de complejos más estables. El aroma también es muy importante en los vinos, ya que es uno de los primeros aspectos que percibimos. Por ello, es de gran importancia la utilización de técnicas de vinificación que permitan extraer el mayor potencial aromático de los precursores que se encuentran en las uvas. Para conseguir incrementar la calidad de los vinos tintos elaborados con la variedad Monastrell, estableciendo una metodología de elaboración que permita mejorar la concentración polifenólica y aromática de estos vinos, se ha estudiado el efecto de la aplicación en la uva, 10 días antes de la vendimia, de sustancias copigmentantes, tales como, extractos vegetales (romero, trigo sarraceno y té verde) y copigmentos puros (ácido cafeico, rutina y catequina). Asimismo, los copigmentos puros también se aplicaron a la entrada en bodega. Se ensayaron dos técnicas enológicas diferentes: la vinificación tradicional y la maceración prefermentativa en frío (6-8ºC), seguida de vinificación tradicional. Por último, una vez concluida la fermentación maloláctica, los vinos obtenidos fueron sometidos a una adición controlada de acetaldehído durante 45 días, seguido de un proceso de conservación en botella de 12 meses. Los resultados mostraron que los tratamientos con copigmentos, especialmente con extractos vegetales ricos en copigmentos, incrementaron la concentración de antocianos polimerizados y totales, y de compuestos aromáticos favorables para la calidad, destacando el extracto de romero por su acción directa sobre el color de los vinos de Monastrell. Utilizar la maceración prefermentativa en la elaboración de los vinos procedentes de tratamientos de copigmentación, ha permitido incrementar la concentración de polifenoles totales y taninos condensados, así como la de ésteres y acetatos. La microoxigenación, mediante la aplicación de acetaldehído durante la conservación de los vinos tratados previamente con copigmentos, dio lugar a un incremento del porcentaje de antocianos polimerizados, de la concentración de antocianos, de taninos condensados y de polifenoles totales, no afectando a la composición aromática de los vinos. Por todo ello, se puede establecer que la combinación de tratamientos de copigmentación en el campo, especialmente con extractos vegetales, de maceración prefermentativa durante la elaboración, y de microoxigenación durante la conservación, permite elaborar vinos de Monastrell con un color más estable, mayor concentración de compuestos polifenólicos, y mayor concentración de ésteres y acetatos, compuestos relacionados con aromas positivos florales, frutales y especiados. / [CA] El mercat actual del vi negre demana vins de gran potència visual, elevada concentració aromàtica i que no siguen excessivament astringents ni amargs. Així mateix, el consumidor final demana cada vegada més vins que es desenvolupen en una viticultura més orgànica que garanteisca la sostenibilitat del cultiu. Per complir amb aquestes expectatives, s'està limitant la utilització de compostos químics a la vinya, substituint-los per altres naturals amb menor impacte mediambiental, i s'estan utilitzant al celler tècniques com la maceració prefermentativa, que contribueix a l'extracció d'antocians i aromes, o la microoxigenació, que permet estabilitzar els compostos polifenòlics en un temps reduït. El color dels vins depèn de la seua concentració en antocians, però també en la forma i l'estat en que aquests es troben en el vi, que depèn de diferents factors, siguent un d'ells el fenòmen de la copigmentació com pas anterior a la polimerització i l'estabilització. A més a més, l'oxígen juga un paper crucial en l'evolució del color, així com en l'oxidació dels polifenols i en la formació dels complexos més estables. L'aroma també és molt important en els vins, ja que és un dels primers aspectes que percebem. Per això, és de gran importància la utilització de tècniques de vinificació que permeten extraure el major potencial aromàtic dels precursors que es troben al raïm. Per aconseguir augmentar la qualitat dels vins negres elaborats amb la varietat Monastrell, establint una metodologia d'elaboració que permeta millorar la concentració polifenòlica i aromàtica d'aquests vins, s'ha estudiat l'efecte de l'aplicació en el raïm, 10 dies abans de la verema, de substàncies copigmentants, com ara, extractes vegetals (romer, blat negre i te verd) i copigments purs (àcid cafeic, rutina i catequina). Així mateix, els copigments purs també es van aplicar a l'entrada al celler. Es van assajar dos tècniques enològiques diferents: la vinificació tradicional i la maceració prefermentativa en fred (6-8ºC), seguida de vinificació tradicional. Finalment, una vegada conclosa la fermentació malolàctica, els vins obtinguts van ser sotmesos a una addició controlada d'acetaldehid durant 45 dies, seguit d'un procés de conservació en ampolla de 12 mesos. Els resultats van mostrar que els tractaments amb copigments, especialment amb extractes vegetals rics en copigments, van augmentar la concentració d'antocians polimeritzats i totals, i de compostos aromàtics favorables per a la qualitat, destacant l'extracte de romer per la seua acció directa sobre el color dels vins de Monastrell. Utilitzar la maceració prefermentativa en l'elaboració dels vins procedents de tractaments de copigmentació, ha permès augmentar la concentració de polifenols totals i tanins condensats, així com la d'èsters i acetats. La microoxigenació, mitjançant l'aplicació d'acetaldehid durant la conservació dels vins tractats prèviament amb copigments, va donar lloc a un augment del percentatge d'antocians polimeritzats, de la concentració d'antocians, de tanins condensats i de polifenols totals, no afectant a la composició aromàtica dels vins. Per tot això, es pot establir que la combinació de tractaments de copigmentació en el camp, especialment amb extractes vegetals de maceració prefermentativa durant l'elaboració, i de microoxigenació durant la conservació, permet elaborar vins de Monastrell amb un color més estable, més concentració de compostos polifenòlics, i major concentració d'èsters i acetats, compostos relacionats amb aromes positus florals, fruitals i especiats. / [EN] The current red wine market demands wines with high visual power, great aromatic concentration and that are not excessively astringent or bitter. Furthermore, the final consumer increasingly demands developed wines in a more organic viticulture in order to ensure the sustainability of the crop. To meet these expectations, the use of chemical compounds in the vineyard is being limited, replacing them by another natural ones with less environmental impact, and techniques such as pre-fermentation maceration are being used in the winery, which contributes to the extraction of anthocyanins and aromas, or micro-oxygenation, that allows polyphenolic compounds to be stabilized in a reduced time. The colour of wines depends on their concentration in anthocyanins, but also the form and state in which they are found in the wine, which depends on several factors, one of them being the phenomenon of copigmentation as a previous step to polymerization and stabilization. In addition, the oxygen has a crucial role in colour's evolution, as well as, in the oxidation of polyphenols and in the formation of more stable complexes. Aroma is also very important in wines, due to the fact that is one of the first aspects that we perceive. For this reason, the use of vinification techniques that allow extracting the greatest aromatic potential of the precursors found in the grapes, is of great importance. In order to increase the quality of red wines made with the Monastrell variety, establishing a production methodology that allows improving the polyphenolic and aromatic concentration of these wines, the effect of the application on the grape, 10 days before harvest, has been studied, of copigmenting substances such as plant extracts (rosemary, buckwheat and green tea) and pure copigments (caffeic acid, rutin and catechin). Likewise, pure copigments were also applied in the cellar entrance. Two different enological techniques were tested: traditional vinification and cold pre-fermentation maceration (6-8ºC), followed by traditional vinification. Finally, once the malolactic fermentation was concluded, the wines obtained were subjected to a controlled addition of acetaldehyde for 45 days, followed by a 12-month bottle preservation process. The results showed that treatments with copigments, especially with plant extracts rich in copigments, increased the concentration of polymerized and total anthocyanins, and aromatic compounds favorable for quality, highlighting rosemary extract for its direct action on the colour of wines of Monastrell. Using pre-fermentation maceration in the production of wines from copigmentation treatments has made it possible to increase the concentration of total polyphenols and condensed tannins, as well as that of esters and acetates. Micro-oxygenation through the application of acetaldehyde during the conservation of wines previously treated with copigments gave rise to an increase in the percentage of polymerized anthocyanins, in the concentration of anthocyanins, in condensed tannins and in total polyphenols, without affecting the aromatic composition of the wines. For all of these reasons, it can be established that the combination of copigmentation treatments in the field, particularly with plant extracts, pre-fermentation maceration during production and micro-oxygenation during storage, allows the production of Monastrell wines with a more stable colour, higher concentration of polyphenolics, and higher concentration of esters and acetates, compounds related to positive floral, fruity and spicy aromas. / Anaya Martínez, JA. (2022). Efecto de la aplicación de copigmentos vegetales sobre la composición fenólica y aromática de vinos tintos de Monastrell elaborados con diferentes técnicas de vinificación [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/185126 / TESIS

A rutina é empregada como antioxidante e na prevenção da fragilidade capilar. Pode ser veiculada em emulsões tópicas adequadas para atingir o local de ação. Estudos de penetração in vitro através da pele humana seria a situação ideal, entretanto, há dificuldades de sua obtenção e manutenção de sua viabilidade. Entre os demais modelos de membrana, a muda de pele de cobra apresenta-se como estrato córneo puro, fornecendo barreira similar ao humano e é obtida sem a morte do animal. Os objetivos desta pesquisa foram: (1) desenvolver e avaliar a estabilidade de emulsões cosméticas, contendo rutina e promotores de penetração cutânea, tais como, uréia (U), isopropanol (IP) e propilenoglicol (PG); (2) avaliar a liberação da referida substância ativa das emulsões e; (3) avaliar a penetração e a retenção cutânea in vitro da rutina da formulação de melhor desempenho. Emulsões foram desenvolvidas com rutina a 5,0% p/p e U, IP e PG, associados ou não e em proporções distintas, segundo planejamento fatorial com dois níveis com ponto central. Quantificou-se a rutina das emulsões por espectrofotometria a 361,0 nm, método previamente validado. A liberação da rutina nas formulações foi realizada em células de difusão vertical com membrana de acetato de celulose e água destilada e álcool etílico absoluto 99,5% (1:1), como fluido receptor. O experimento foi conduzido em um período de seis horas, a 37,0 ±. 0,5 °C e agitação constante de 300 rpm.>f. emulsão de melhor desempenho quanto à liberação foi estudada quanto à estabilidade (Testes de Estabilidade Acelerada). Para o estudo de penetração e retenção cutânea da rutina dessa formulação foi utilizada muda de pele de cobra de Crotalus durissus. Empregou-se o método espectrofotométrico validado a 410,0 nm para a quantificação da rutina após liberação, penetração e retenção cutânea. Todas as emulsões foram consideradas adequadas após desenvolvimento das formulações. A uréia (isolada e em associação com IP e PG) e o isopropanol (isolado e em associação com PG) influenciaram negativamente a liberação da rutina das emulsões em diversos parâmetros. A rutina liberada e acumulada da formulação contendo PG a 5,0% p/p possuiu valor de 648,80 ±. 53,01 &#181g/cm2. Fora do esperado, a preparação contendo o número maior de promotores (U 5,0% p/p, IP 5,0% p/p e PG 5,0% p/p) resultou em liberação de menor magnitude igual a 419,76 ±. 17,98 &#181g/cm2. A presença do PG apresentou-se mais eficiente na liberação da rutina, mas não na sua penetração através da muda de pele de C. durissus, retendo 0,931 ± 0,0391 µg de rutina/mg de muda de pele de cobra. Nas condições de armazenamento a 25,0 ±2,0 °C; 5,0 ±0,5 °C e 45,0 ±. 0,5 °C, a emulsão com PG e rutina apresentou-se quimicamente estável durante 30 dias. De acordo com os resultados, a emulsão contendo PG apresentou liberação mais expressiva da rutina, no entanto, não ocorreu a penetração cutânea, mas apenas sua retenção no estrato córneo de C. durissus. A preparação manteve-se estável em todas as condições de armazenamento. / Rutin is employed as antioxidant and to prevent the capillary fragility and, when incorporated in cosmetic emulsions, it must target the action site. In vitro cutaneous penetration studies through human skin is the ideal situation, however, there are difficulties to obtain and to maintain this tissue viability. Among the membrane models, the shed snake skin presents itself as pure stratum corneum, providing barrier function similar to human and it is obtained without the animal sacrifica. The objectives of this research were: (1) development and stability evaluation of cosmetic emulsions containing rutin and penetration enhancers, as urea (U), isopropanol (IP) and propylene glycol (PG); (2) release evaluation of the mentioned active substance from the emulsions and; (3) evaluation of rutin in vitro cutaneous penetration and retention from the emulsion of the best performance. Emulsions were developed with rutin 5.0% w/wand U, IP and PG, associated or not according to factorial design with two levels and central point. Active substance on the formulations was quantified by a validated spectrophotometric method at 361.0 nm. Rutin release from emulsions was performed in vertical diffusion cells with cellulose acetate membrane and distilled water and ethanol 99.5% (1:1), as receptor fluid. The experiment was conducted for six hours, at 37.0 ± 0.5 °c with constant stirring of 300 rpm. Formulation with best profile of rutin release had its stability studied by the Accelerated Stability Assays. Rutin cutaneous penetration and retention from the mentioned emulsion was performed with shed snake skin from Crotalus durissus. Spectrophotometry at 410.0 nm, previously validated, determined the active substance after release and cutaneous penetration/retention. Ali emulsions were considered apparently stables after development. Urea (isolated and associated with IP and PG) and isopropanol (isolated and associated with PG) have influenced negatively the rutin release in several parameters. Emulsion with PG 5.0% w/w presented rutin released and accumulated equal to 648.80 ± 53.01 µg/cm2. Unexpectedly, the formulation containing all enhancers (U 5.0% w/w, IP 5.0% w/w and PG 5.0% w/w) has decreased the amount released of the active substance (419.76 ± 17.98 µg/cm2). Emulsion with PG presented more adequate for rutin release, but PG did not provide rutin cutaneous penetration through C. durissus skin, retaining 0.931 ± 0.0391 &$181;g rutin/mg shed snake skin. The referred formulation was chemically stable for 30 days after they have been stored at 25.0 ± 2.0 °c, 5.0 ± 0.5 °c and 45.0 ± 0.5 °C. In conclusion, emulsion with PG provided rutin release more expressively, although, it has not been verified the active cutaneous penetration, but only its retention on the Crotalus durissus stratum corneum. Formulation was stable in all storage conditions.

A rutina é empregada como antioxidante e na prevenção da fragilidade capilar. Pode ser veiculada em emulsões tópicas adequadas para atingir o local de ação. Estudos de penetração in vitro através da pele humana seria a situação ideal, entretanto, há dificuldades de sua obtenção e manutenção de sua viabilidade. Entre os demais modelos de membrana, a muda de pele de cobra apresenta-se como estrato córneo puro, fornecendo barreira similar ao humano e é obtida sem a morte do animal. Os objetivos desta pesquisa foram: (1) desenvolver e avaliar a estabilidade de emulsões cosméticas, contendo rutina e promotores de penetração cutânea, tais como, uréia (U), isopropanol (IP) e propilenoglicol (PG); (2) avaliar a liberação da referida substância ativa das emulsões e; (3) avaliar a penetração e a retenção cutânea in vitro da rutina da formulação de melhor desempenho. Emulsões foram desenvolvidas com rutina a 5,0% p/p e U, IP e PG, associados ou não e em proporções distintas, segundo planejamento fatorial com dois níveis com ponto central. Quantificou-se a rutina das emulsões por espectrofotometria a 361,0 nm, método previamente validado. A liberação da rutina nas formulações foi realizada em células de difusão vertical com membrana de acetato de celulose e água destilada e álcool etílico absoluto 99,5% (1:1), como fluido receptor. O experimento foi conduzido em um período de seis horas, a 37,0 ±. 0,5 °C e agitação constante de 300 rpm.>f. emulsão de melhor desempenho quanto à liberação foi estudada quanto à estabilidade (Testes de Estabilidade Acelerada). Para o estudo de penetração e retenção cutânea da rutina dessa formulação foi utilizada muda de pele de cobra de Crotalus durissus. Empregou-se o método espectrofotométrico validado a 410,0 nm para a quantificação da rutina após liberação, penetração e retenção cutânea. Todas as emulsões foram consideradas adequadas após desenvolvimento das formulações. A uréia (isolada e em associação com IP e PG) e o isopropanol (isolado e em associação com PG) influenciaram negativamente a liberação da rutina das emulsões em diversos parâmetros. A rutina liberada e acumulada da formulação contendo PG a 5,0% p/p possuiu valor de 648,80 ±. 53,01 &#181g/cm2. Fora do esperado, a preparação contendo o número maior de promotores (U 5,0% p/p, IP 5,0% p/p e PG 5,0% p/p) resultou em liberação de menor magnitude igual a 419,76 ±. 17,98 &#181g/cm2. A presença do PG apresentou-se mais eficiente na liberação da rutina, mas não na sua penetração através da muda de pele de C. durissus, retendo 0,931 ± 0,0391 µg de rutina/mg de muda de pele de cobra. Nas condições de armazenamento a 25,0 ±2,0 °C; 5,0 ±0,5 °C e 45,0 ±. 0,5 °C, a emulsão com PG e rutina apresentou-se quimicamente estável durante 30 dias. De acordo com os resultados, a emulsão contendo PG apresentou liberação mais expressiva da rutina, no entanto, não ocorreu a penetração cutânea, mas apenas sua retenção no estrato córneo de C. durissus. A preparação manteve-se estável em todas as condições de armazenamento. / Rutin is employed as antioxidant and to prevent the capillary fragility and, when incorporated in cosmetic emulsions, it must target the action site. In vitro cutaneous penetration studies through human skin is the ideal situation, however, there are difficulties to obtain and to maintain this tissue viability. Among the membrane models, the shed snake skin presents itself as pure stratum corneum, providing barrier function similar to human and it is obtained without the animal sacrifica. The objectives of this research were: (1) development and stability evaluation of cosmetic emulsions containing rutin and penetration enhancers, as urea (U), isopropanol (IP) and propylene glycol (PG); (2) release evaluation of the mentioned active substance from the emulsions and; (3) evaluation of rutin in vitro cutaneous penetration and retention from the emulsion of the best performance. Emulsions were developed with rutin 5.0% w/wand U, IP and PG, associated or not according to factorial design with two levels and central point. Active substance on the formulations was quantified by a validated spectrophotometric method at 361.0 nm. Rutin release from emulsions was performed in vertical diffusion cells with cellulose acetate membrane and distilled water and ethanol 99.5% (1:1), as receptor fluid. The experiment was conducted for six hours, at 37.0 ± 0.5 °c with constant stirring of 300 rpm. Formulation with best profile of rutin release had its stability studied by the Accelerated Stability Assays. Rutin cutaneous penetration and retention from the mentioned emulsion was performed with shed snake skin from Crotalus durissus. Spectrophotometry at 410.0 nm, previously validated, determined the active substance after release and cutaneous penetration/retention. Ali emulsions were considered apparently stables after development. Urea (isolated and associated with IP and PG) and isopropanol (isolated and associated with PG) have influenced negatively the rutin release in several parameters. Emulsion with PG 5.0% w/w presented rutin released and accumulated equal to 648.80 ± 53.01 µg/cm2. Unexpectedly, the formulation containing all enhancers (U 5.0% w/w, IP 5.0% w/w and PG 5.0% w/w) has decreased the amount released of the active substance (419.76 ± 17.98 µg/cm2). Emulsion with PG presented more adequate for rutin release, but PG did not provide rutin cutaneous penetration through C. durissus skin, retaining 0.931 ± 0.0391 &$181;g rutin/mg shed snake skin. The referred formulation was chemically stable for 30 days after they have been stored at 25.0 ± 2.0 °c, 5.0 ± 0.5 °c and 45.0 ± 0.5 °C. In conclusion, emulsion with PG provided rutin release more expressively, although, it has not been verified the active cutaneous penetration, but only its retention on the Crotalus durissus stratum corneum. Formulation was stable in all storage conditions.

Background: We live in a world where not everyone is employed; numerous people havelost their jobs due to several factors where one of them is the economic crisis. This has hada huge impact on Sweden and the unemployment rate. Previous research has shown thatinflation, unemployment, and high interest rates represent risks to consumer welfare. We all consume daily, or on occasions, but how do unemployed consumers consume, what do they consume and why? In this area, the authors have found a knowledge gap in literature; therefore exploring this phenomenon is of interest.   Purpose: The purpose of this study is to explore and illustrate how consumers who have experienced a life transition, from employment to unemployment, are affected by this and how it has an impact on their consumption.   Method: This is an exploratory study performed with a qualitative and an abductive approach, where the authors used primary data collection through semi-structured in-depth interviews in Swedish with 16 unemployed consumers. These unemployed consumers were selected at Arbetsförmedlingen, the public employment service, in Jönköping.   Results: By living in unemployment the consumers have been affected psychologically, physically, financially and socially. Their identity has changed for each of them since they have to adapt to the new circumstances in their life. The new life situation has had an impact on the consumer’s well-being where depression, anxiety, and a feeling of being the underdog in the society is present. Their new life situation has implied a change in their consumption behavior since they nowadays have to prioritize the basic needs. Many of the respondents used explicit and implicit shopping-list in order to reduce their impulse buying. The contribution that the authors have done to the theory of resistance is a fourth category called ‘Everyday life resistance’ which explains the behavior of people who live in unemployment, i.e. they always have to think about resisting temptations, wants, desires, and avoiding situations where the result may be unnecessary consumption. The consumers in this study are highly involved in their consumption behavior, which the authors have chosen to call ‘reversed habitual decision making’. This kind of involvement is very high despite the high- or low risk category of the product. Their new life situation has made them more aware of product alternatives, market supply, prices, and also knowledge about their own resistance in the marketplace. / Bakgrund: Vi lever i en värld där inte alla har en anställning, en omfattande andel av befolkningen har förlorat sitt jobb på grund av flera faktorer, där en av dem är den ekonomiska krisen. Detta har haft en stor påverkan på Sverige och dess arbetslöshet. Föregående studier har visat att inflation, arbetslöshet och hög räntesats representerar risk för konsumentens välbefinnande. Vi alla konsumerar dagligen eller vid speciella tillfällen, men hur konsumerar en arbetslös konsument, vad konsumerar dem och varför? Inom detta område har författarna funnit ett kunskaps gap i litteraturen, därav är en undersökning av detta fenomen av intresse.   Syfte: Syftet med denna studie är att utforska och illustrera hur konsumenter som har genomgått en livsförändring, från att ha varit anställd till att vara arbetslös, är påverkade av detta och hur detta har inverkat på deras konsumtion.   Metod: Detta är en explorativ studie genomförd med en kvalitativ och abduktiv tillvägagångssätt där författarna har använt sig av primär information samlad genom, till viss del, strukturerade djupgående intervjuer på svenska med 16 arbetslösa konsumenter. Dessa var utvalda vid Arbetsförmedlingen i Jönköping.   Resultat: Att leva som arbetslös har påverkat konsumenterna psykologiskt, fysiskt, finansiellt och socialt. Deras identitet har förändrats då de måste anpassa sig till den nya livssituationen. Den nya situationen har påverkat konsumenternas hälsa då de känner av depression, ängslan och känner sig mindre värda i samhället. Deras nya livssituation har inneburit en det förändringar i deras konsument beteende eftersom de numera måste prioritera sina primära behov. Många av studiens deltagare använde sig av explicita och implicita inköpslistor för att minimera spontanköp. Författarnas bidrag till teorin om motstånd är en fjärde kategori kallad ‘Vardagligt motstånd’ vilket förklarar beteendet hos arbetslösa personer dvs. de måste hela tiden tänka på att motstå frestelser, begär och försöka undvika situationer där onödiga inköp kan uppstå. Konsumenterna i denna studie är synnerligen involverade i sitt konsument beteende, detta har författarna valt att benämna ’omvänt rutin besluts genomförande’. Denna typ av involvering är väldigt hög oavsett om produktkategorin innebär hög- eller låg risk. Deras nya livssituation har gjort dem mer medvetna om alternativa produkter, marknadens utbud, priser och ny kunskap om deras egna motstånd inom konsumtionssamhället.

<p><strong>Background:</strong> We live in a world where not everyone is employed; numerous people havelost their jobs due to several factors where one of them is the economic crisis. This has hada huge impact on Sweden and the unemployment rate. Previous research has shown thatinflation, unemployment, and high interest rates represent risks to consumer welfare. We all consume daily, or on occasions, but how do unemployed consumers consume, what do they consume and why? In this area, the authors have found a knowledge gap in literature; therefore exploring this phenomenon is of interest.</p><p> </p><p><strong>Purpose:</strong> The purpose of this study is to explore and illustrate how consumers who have experienced a life transition, from employment to unemployment, are affected by this and how it has an impact on their consumption.</p><p> </p><p><strong>Method:</strong> This is an exploratory study performed with a qualitative and an abductive approach, where the authors used primary data collection through semi-structured in-depth interviews in Swedish with 16 unemployed consumers. These unemployed consumers were selected at Arbetsförmedlingen, the public employment service, in Jönköping.</p><p> </p><p><strong>Results:</strong> By living in unemployment the consumers have been affected psychologically, physically, financially and socially. Their identity has changed for each of them since they have to adapt to the new circumstances in their life. The new life situation has had an impact on the consumer’s well-being where depression, anxiety, and a feeling of being the underdog in the society is present. Their new life situation has implied a change in their consumption behavior since they nowadays have to prioritize the basic needs. Many of the respondents used explicit and implicit shopping-list in order to reduce their impulse buying. The contribution that the authors have done to the theory of resistance is a fourth category called ‘Everyday life resistance’ which explains the behavior of people who live in unemployment, i.e. they always have to think about resisting temptations, wants, desires, and avoiding situations where the result may be unnecessary consumption. The consumers in this study are highly involved in their consumption behavior, which the authors have chosen to call ‘reversed habitual decision making’. This kind of involvement is very high despite the high- or low risk category of the product. Their new life situation has made them more aware of product alternatives, market supply, prices, and also knowledge about their own resistance in the marketplace.</p> / <p><strong>Bakgrund:</strong> Vi lever i en värld där inte alla har en anställning, en omfattande andel av befolkningen har förlorat sitt jobb på grund av flera faktorer, där en av dem är den ekonomiska krisen. Detta har haft en stor påverkan på Sverige och dess arbetslöshet. Föregående studier har visat att inflation, arbetslöshet och hög räntesats representerar risk för konsumentens välbefinnande. Vi alla konsumerar dagligen eller vid speciella tillfällen, men hur konsumerar en arbetslös konsument, vad konsumerar dem och varför? Inom detta område har författarna funnit ett kunskaps gap i litteraturen, därav är en undersökning av detta fenomen av intresse.</p><p> </p><p><strong>Syfte:</strong> Syftet med denna studie är att utforska och illustrera hur konsumenter som har genomgått en livsförändring, från att ha varit anställd till att vara arbetslös, är påverkade av detta och hur detta har inverkat på deras konsumtion.</p><p> </p><p><strong>Metod:</strong> Detta är en explorativ studie genomförd med en kvalitativ och abduktiv tillvägagångssätt där författarna har använt sig av primär information samlad genom, till viss del, strukturerade djupgående intervjuer på svenska med 16 arbetslösa konsumenter. Dessa var utvalda vid Arbetsförmedlingen i Jönköping.</p><p> </p><p><strong>Resultat:</strong> Att leva som arbetslös har påverkat konsumenterna psykologiskt, fysiskt, finansiellt och socialt. Deras identitet har förändrats då de måste anpassa sig till den nya livssituationen. Den nya situationen har påverkat konsumenternas hälsa då de känner av depression, ängslan och känner sig mindre värda i samhället. Deras nya livssituation har inneburit en det förändringar i deras konsument beteende eftersom de numera måste prioritera sina primära behov. Många av studiens deltagare använde sig av explicita och implicita inköpslistor för att minimera spontanköp. Författarnas bidrag till teorin om motstånd är en fjärde kategori kallad ‘Vardagligt motstånd’ vilket förklarar beteendet hos arbetslösa personer dvs. de måste hela tiden tänka på att motstå frestelser, begär och försöka undvika situationer där onödiga inköp kan uppstå. Konsumenterna i denna studie är synnerligen involverade i sitt konsument beteende, detta har författarna valt att benämna ’omvänt rutin besluts genomförande’. Denna typ av involvering är väldigt hög oavsett om produktkategorin innebär hög- eller låg risk. Deras nya livssituation har gjort dem mer medvetna om alternativa produkter, marknadens utbud, priser och ny kunskap om deras egna motstånd inom konsumtionssamhället.</p>