This diploma thesis investigates the relationship between the business cycle and the alcohol consumption by using aggregate data for Czech Republic and constituent regions of Czech Republic in the period 1994-2011. The key question of this study is whether alcohol consumption is pro-cyclical or counter-cyclical. This question was asked in many works (Ruhm, Black, 2002). Unlike American studies, in which alcohol consumption is pro-cyclical, my study shows that the decrease of economic conditions has resulted in increased alcohol consumption in society and therefore indicates to me counter-cyclical. I also found that the divorce has a positive effect on alcohol consumption, while the real price has a negative effect.

Introdução: A cirrose é uma hepatopatia crônica e progressiva que constitui um estágio irreversível ou lentamente reversível de disfunção hepática, caracterizada pela formação de nódulos de fibrose no tecido hepático. Investigações devem ser realizadas para avaliar essa população a fim de que se tenha um diagnóstico mais preciso dos efeitos da doença sobre a função cardiopulmonar, a funcionalidade e a qualidade de vida desses indivíduos. Objetivo: Investigar a influência da cirrose hepática pelo vírus da hepatite C (VHC) no consumo máximo de oxigênio (VO2max.), a capacidade funcional e a qualidade de vida em indivíduos cirróticos. Materiais e métodos: Foram avaliados 36 indivíduos(18 cirróticos e 18 controles) de ambos os sexos, maiores de 18 anos. Foram avaliados e comparados entre os grupos, o consumo máximo de oxigênio através da ergoespirometria em bicicleta, a capacidade funcional pelo teste de caminhada de seis minutos e pelo time up and go test, a força do aperto de mão, a antropometria e a qualidade de vida. Foram feitas correlações em pacientes cirróticos, entre a força do aperto de mão e o VO2max e o TC6, o VO2max e o teste de caminhada de 6 minutos e a qualidade de vida e o TC6. Resultados: Os grupos doença e controle foram pareados pelo sexo e pela idade, não havendo diferença significativa entre os grupos quanto à idade e o sexo. Não foram encontradas diferenças significativas entre cirróticos e controles quanto ao Time Up And Go Test. Quanto ao Teste de Caminhada de Seis Minutos a distância percorrida foi significativamente menor nos cirróticos em comparação aos controles. Não houve diferença entre os grupos para a distância percorrida predita para cirróticos e controles. Não foi encontrada diferença para a força do aperto de mão (HGS) entre cirróticos e controles. Não foram encontradas diferenças significativas entre os grupos para avaliação antropométrica em nenhum dos itens que a contemplam. Na avaliação da qualidade de vida foram encontradas diferenças significativas entre os grupos para todos os seus domínios. O consumo máximo de oxigênio VO2max apresentou valores inferiores no grupo doença. Houveram correlações em pacientes cirróticos entre a capacidade funcional e o VO2max. e a qualidade de vida. Conclusão: Foram encontradas diferenças entre cirróticos e controles quanto ao VO2max., a capacidade funcional e a qualidade de vida. As correlações encontradas nesse estudo devem ser exploradas em novas pesquisas envolvendo esses pacientes. / Introduction: Cirrhosis is a chronic progressive liver disease is a slowly reversible or irreversible stage of liver dysfunction, characterized by the formation of nodules of fibrosis in liver tissue. investigations should be performed to evaluate this population so that it has a more accurate diagnosis of disease effects on cardiopulmonary function, functionality, and quality of life of these individuals. Objective: To investigate the influence of liver cirrhosis due to hepatitis C virus (HCV) on maximal oxygen consumption (VO2máx.), functional capacity and quality of life in individuals with cirrhosis. Materials and methods: We evaluated 36 patients (18 cirrhotic patients and 18 controls) of both sexes, aged 18 years. Were evaluated and compared between groups, the maximal oxygen uptake by cardiopulmonary exercise test on bicycle, on functional capacity by testing six-minute walk and the time up and go test, the strength of the handgrip, anthropometry and quality of life. Correlations were in cirrhotic patients, between the strength of the handshake and VO2max and 6MWT, VO2max test and 6-minute walk and the quality of life and 6MWT. Results: The disease and control groups were matched by sex and age, no significant difference between groups with respect to age and sex. No significant differences were found between cirrhotic patients and controls regarding Time Up And Go Test. How to Walk Test Six Minutes distance traveled was significantly lower in cirrhotic patients compared to controls. There was no difference between groups for the distance predicted for cirrhotic patients and controls. No difference was found for the strength of the handgrip (HGS) between cirrhotic patients and controls. No significant differences were found between groups in anthropometric assessment in any of the items that come. In assessing the quality of life were significant differences between groups for all domains. The maximal oxygen consumption VO2max values were lower in the disease group. There were correlations in cirrhotic patients between functional capacity and VO2max. and quality of life. Conclusion: We found differences between cirrhotic patients and controls regarding VO2max., Functional capacity and quality of life. The correlations found in this study should be explored in further studies involving these patients.

Introduktion: Levercirros är ett medicinskt tillstånd i slutskedet som är en följd av en leversjukdom och orsakas bland annat av missbruk av alkohol, kronisk hepatit B och C, och autoimmun hepatit. Enligt rapport från Världshälsoorganisationen lider cirka 10% av befolkningen i världen av kroniska leversjukdomar, och 20 miljoner människor drabbas av levercirros eller dess följd levercancer. Den registrerade mortaliteten av levercirros i Sverige är ca 600 personer per år. För många av dessa patienter innebär det ett stort lidande både fysiskt och psykiskt. Patienterna upplever inte alltid att deras lidande har kunnat lindras, och därför är det angeläget att kunskaper om och förståelse för denna patientgrupp utifrån deras egna upplevelser förbättras och fördjupas.   Syfte: Att beskriva patienters upplevelser av att leva med levercirros och deras självskattning av sin livskvalitet.   Metod: Litteraturöversikt med en systematisk ansats baserad på sex kvalitativa och nio kvantitativa originalartiklar publicerade på engelska under åren mellan 2003 och 2020.    Resultat: Resultatet innefattar tre huvudteman: fysiskt lidande, psykologiskt lidande, och försämrad hälsorelaterad livskvalité. Individer med levercirros upplever rent generellt ett lidande, dock på olika plan samt grader. Ett fysiskt lidande förekommer men även ett psykiskt, och ofta leder det till en försämrad livskvalité.   Slutsats: Forskning har visat att patienter med levercirros möjligen inte kan uttrycka sina åsikter på samma sätt som andra patienter på grund av stigmatisering och skam. Denna litteraturstudie kommer att hjälpa såväl närstående som vårdpersonal att förstå denna patientgrupp, och minska deras lidande på ett adekvat sätt. / Introduction: Liver cirrhosis is a medical condition in the final stages that is a consequence of a liver disease and is caused by, among other things, alcohol abuse, chronic hepatitis B and C, and autoimmune hepatitis. According to a report from the World Health Organization, about 10% of the world's population suffers from chronic liver disease, and 20 million people suffer from liver cirrhosis or its consequent liver cancer. The registered mortality from liver cirrhosis in Sweden is about 600 people per year. For many of these patients, it means great suffering both physically and mentally. Patients do not always feel that their suffering has been alleviated, and therefore it is important that knowledge of and understanding of this patient group based on their own experiences is improved and deepened.   Aim: To describe patients' experiences of living with liver cirrhosis and their self-esteem of their quality of life.   Method: Literature review with a systematic approach based on six qualitative and nine quantitative original articles published in English during the years between 2003 and 2020.   Results: The results include three main themes: physical suffering, psychological suffering, and deteriorating health-related quality of life. Individuals with liver cirrhosis generally experience suffering, however, on different levels and degrees. A physical suffering occurs but also a mental one, and often it leads to a deteriorating quality of life.   Conclusion: Research has shown that patients with liver cirrhosis may not be able to express their views in the same way as other patients due to stigma and shame. This literature review will help both relatives and caregivers understand this patient group, and reduce their suffering adequately.

BACKGROUND: After proteolysis, the majority of released amino acids from dietary protein are transported to the liver for gluconeogenesis or to peripheral tissues where they are used for protein synthesis and eventually catabolized, producing ammonia as a byproduct. High ammonia levels in the brain are a major contributor to the decreased neural function that occurs in several pathological conditions such as hepatic encephalopathy when liver urea cycle function is compromised. Therefore, it is important to gain a deeper understanding of human ammonia metabolism. The objective of this study was to predict changes in blood ammonia levels resulting from alterations in dietary protein intake, from liver disease, or from partial loss of urea cycle function. METHODS: A simple mathematical model was created using MATLAB SimBiology and data from published studies. Simulations were performed and results analyzed to determine steady state changes in ammonia levels resulting from varying dietary protein intake and varying liver enzyme activity levels to simulate liver disease. As a toxicity reference, viability was measured in SH-SY5Y neuroblastoma cells following differentiation and ammonium chloride treatment. RESULTS: Results from control simulations yielded steady state blood ammonia levels within normal physiological limits. Increasing dietary protein intake by 72% resulted in a 59% increase in blood ammonia levels. Simulations of liver cirrhosis increased blood ammonia levels by 41 to 130% depending upon the level of dietary protein intake. Simulations of heterozygous individuals carrying a loss of function allele of the urea cycle carbamoyl phosphate synthetase I (CPS1) gene resulted in more than a tripling of blood ammonia levels (from roughly 18 to 60 μM depending on dietary protein intake). The viability of differentiated SH-SY5Y cells was decreased by 14% by the addition of a slightly higher amount of ammonium chloride (90 μM). CONCLUSIONS: Data from the model suggest decreasing protein consumption may be one simple strategy to decrease blood ammonia levels and minimize the risk of developing hepatic encephalopathy for many liver disease patients. In addition, the model suggests subjects who are known carriers of disease-causing CPS1 alleles may benefit from monitoring blood ammonia levels and limiting the level of protein intake if ammonia levels are high.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第17974号 / 医博第3838号 / 新制||医||1001(附属図書館) / 80818 / 京都大学大学院医学研究科医学専攻 / (主査)教授 羽賀 博典, 教授 坂井 義治, 教授 千葉 勉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18457号 / 医博第3912号 / 新制||医||1004(附属図書館) / 31335 / 京都大学大学院医学研究科医学専攻 / (主査)教授 坂井 義治, 教授 羽賀 博典, 教授 武藤 学 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18508号 / 医博第3928号 / 新制||医||1005(附属図書館) / 31394 / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 稲垣 暢也, 教授 千葉 勉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

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Hepatitis C is the most common chronic bloodbourne infection in the United States, with an estimated prevalence of 2.7 million. The total cost of care for this patient population was estimated to be $6.5 billion in 2013. Since 1998, the Centers for Disease Control (CDC) have recommended hepatitis C screening for specific high risk populations, but until recently there was no recommendation for age-based screening. The recent advent of new, more efficacious therapies for hepatitis C have made early identification significantly more important. Consequently, the CDC updated its recommendations in 2012 based on recent evidence to include one-time screening for all individuals born between 1945 and 1965. In 2013, the US Preventive Services Task Force (USPSTF) also incorporated this recommendation into their hepatitis C screening guidelines. In spite of this, there is some debate in the medical community regarding cohort screening for hepatitis C, and some data indicates widespread misunderstanding of current screening recommendations among primary care providers. The purpose of this project was to evaluate current knowledge and understanding of hepatitis C screening guidelines among a group of family medicine residents at East Tennessee State University, and to improve their knowledge in order to promote more appropriate screening practices in their patient population. To accomplish this, 13 question surveys were administered to residents to assess their current knowledge. Following these surveys, residents attended an education session covering current recommendations from the CDC and USPSTF. The 13 question survey was administered again in the post-intervention period. A t-test revealed that post-intervention survey scores increased significantly on 8 out of 13 questions. The intervention was successful at improving knowledge of current hepatitis C screening recommendations in the target population. Future research should be directed at broadening the intervention to include a variety of other providers, and at assessing the impact on execution of screening in the patient population, particularly regarding application to people born in the specified birth cohort.

Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors, resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation. This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and hepatocellular carcinoma (HCC). AGEs and RAGE are upregulated in liver fibrosis, and the silencing of RAGE reduced collagen deposition and the tumor growth of HCC. Nevertheless, data relating to Glo-I in fibrosis and cirrhosis are preliminary. Glo-I expression was found to be reduced in early and advanced cirrhosis with a subsequent increase of MGO-levels. On the other hand, pharmacological modulation of Glo-I resulted in the reduced activation of hepatic stellate cells and therefore reduced fibrosis in the CCl4-model of cirrhosis. Thus, current research highlighted the Glo-I/AGE/RAGE system as an interesting therapeutic target in chronic liver diseases. These findings need further elucidation in preclinical and clinical studies.