En France et Indonésie, Sargassum est une espèce abondante mais elle algue n’a pas encore été exploitée de façon optimale. Sargassum contient de nombreux métabolites primaires ainsi que des composés bioactifs, dont les phlorotannins, ayant une large gamme de propriétés pharmacologiques intéressantes à valoriser. L’hétérogénéité et la complexité de la paroi cellulaire des algues réduisent fortement l’efficacité d’extraction conventionnelle. Cette étude a eu trois principaux objectifs (1) la caractérisation de la composition biochimique de Sargassum et ses variations saisonnières, (2) l'extraction solide-liquide et (3) l'extraction assistée par enzymes des phlorotannins et l’étude de leurs activités biologiques. Dans cette étude, les minéraux de Sargassum représentent d’une valeur importance avec une teneur qui atteint 33% suivi par les protéines avec 24% de la matière sèche. Les sucres ne représentent que 13% de la matière sèche. La composition biochimique de Sargassum, comme pour la plupart des algues, est fortement affectée par les saisons et est liée au cycle de vie de l’algue. La saisonnalité affecte également la production de phlorotannins. L’étude des différents procédés d’extraction montre que les rendements sont plus faibles pour une extraction solide-liquide traditionnelle (5 à 24% de la matière sèche de l'algue) par rapport à l'extraction assistée par enzyme (21 à 38% de la matière sèche de l'algue). L’extraction assistée par enzymes augmente le rendement d’extraction des polyphénols par rapport à l'extraction solide-liquide. Les extraits obtenus par extraction assistée par enzymes présentent une forte activité antiradicalaire. / In France and Indonesia, Sargassum is quite abundant yet this alga has not been optimally exploited. Sargassum contains macro and micro molecules and also bioactive compounds, the most known is phlorotannins, showing a wide range of pharmacological properties. Therefore, it is interesting to further valorize this alga. The heterogeneity and complexity of algal cell wall strongly reduces the extraction efficiency application of conventional extraction. Subjects of interest in this study were to characterize the seasonal variation of Sargassum biochemical composition and to extract phlorotannins using conventional and alternative method, i.e. solid-liquid and enzyme- assisted extraction. In this study, minerals represented a significant value with a content reaching 33% followed by proteins with 24% of algal dry material. In the contrary, sugars showed only 13% of algal dry material. Further, the biochemical composition of Sargassum, like most algae, was highly affected by the seasons and related to Sargassum life cycle. In terms of polyphenol compounds in Sargassum, season might be the most influential factor but suitable methods of extraction determine the efficiency to collect these compounds from Sargassum. Solid-liquid extraction, in certain extent, yielded lower (ranging from 5 to 24% of dry algal material) than the enzyme-assisted extraction (ranging from 21 to 38% of dry algal material). Concerning the polyphenol content of Sargassum extracted with these two methods, enzyme-assisted extraction, in certain extent, had higher content than the solid-liquid extraction. Enzymatic extracts showed a strong antiradical activity.

Adherence is a complex concept, with multiple definitions, over 200 possible predictors, and inconsistent measurement. This has had a detrimental impact on producing interventions to promote treatment adherence. Promoting and maintaining treatment adherence can decrease the likelihood of poor health outcomes and decrease healthcare costs for patients. This study created a conceptual model that was utilized in a secondary analysis to determine if patient factors (Income, Depression, Perceived Threat of Illness Severity, Social Support, and Treatment Beliefs) in the model predict adherence to Transcutaneous Electrical Nerve Stimulation (TENS) when used for pain control post-Total Knee Replacement (TKR). The sample included 97 patients who were randomized to TENS treatment. A higher level of Perceived Threat of Illness Severity, measured with the Pain Catastrophizing Scale, was significantly related to a Moderate level of Adherence (60-79%) versus Non-Adherence (0-59%) (OR= .260, 95% CI= .073-.992, p= .037). The other patient factors of income, depression, social support and treatment beliefs did not significantly predict adherence. This finding is clinically important, as clinicians can assess how patients are interpreting or perceiving actual (or potential) threats of illness severity, then provide education and support to help patients adhere to treatment. The effect of Daily Pain [measured with an 11-point Numeric Rating Scale (0-10)] on Daily Adherence was also investigated in this study. Daily Pain and Daily Adherence did not show a significant association in this sample. This could be attributed to the fact that Daily Adherence was maintained consistently around 70% throughout the 2-week period.

This chapter discusses psychopharmacological treatment for children's emotional and psychiatric disorders. It considers approaches to the selection of pharmacological agents. It then reviews the current state of psychopharmacological treatment with children and adolescents, focusing on pharmacological agents for the treatment of established psychiatric diagnoses and psychopharmacological agents selected to control or treat behaviors experienced by the child regardless of the presence of a clear diagnosis.

Alzheimer’s disease has been described long ago, yet the illness is yet to be fully understood. Though it is true that research and technological advancements have brought us closer to understanding the disease, a truly effective pharmacological cure has not been discovered. With no permanent cure to rely on, AD patients and their caregivers still go through profound struggles in navigating through life with the disease. In this thesis, current literature on the non-pharmacological interventions is presented and discusses the various options that can provide the greatest relief and reap the most health benefits for patients. In total, four different non-drug treatments come into discussion - exercise, music, diet and cognitive interventions. In terms of exercise, research suggests that anaerobic work may be more beneficial than aerobic exercises in preventing the development or progression of mild cognitive dementia and Alzheimer’s disease. This is mostly due to the fact that anaerobic exercises can shift APP processing away from the non-amyloidogenic pathway and increase BDNF levels to offer improved neural protection. Music therapy intervention is evaluated next. This unique treatment is highly valued due to its beneficial effects on AD patients’ emotional well-being. Music therapy can take the forms of singing in groups or as an individual, and it can also incorporate dancing. Not only does music promote neuroplasticity and neurogenesis, but it also alleviates mood, boosts confidence and strengthens will. Diet is another significant component that can have an incredible impact on the AD patients’ wellbeing. Research reveals that diets high in saturated fatty acid should be avoided. On the other hand, diets mirroring the Mediterranean diet, including polyunsaturated fatty acids along with high amounts of vitamin C and folic acid should be readily consumed. Moreover, spices and herbs such as capsaicin should be used in a limited manner to decrease risk for AD. Finally, cognitive therapy is still a popular method for treating mild cognitive impairment and AD. Though cognitive improvement appears to be more modest, some psychostimulation programs combined with pharmacological treatments can play an influential role in achieving cognitive stability. Further research is needed in upgrading the current non-pharmacological interventions with an emphasis on the four treatments. These are available at an affordable cost and can be easily incorporated into the lifestyles of Alzheimer’s patients.

No description available.

Human α-galactosidase (α-GAL; EC 3.2.1.22) is a lysosomal enzyme that hydrolyzes of terminal alpha-linked galactosyl residue of glycosphingolipids. Deficiencies in α-GAL leads to Fabry disease, which is characterized by the build-up of globotriaosylceramide and other neutral substrates in cells, ultimately leading to a multi-systemic organ failure in patients. Hundreds of distinct mutations have been found in the α-GAL gene of Fabry disease patients. One current treatment for Fabry disease is Enzyme Replacement Therapy (ERT), which restores the missing α-GAL function. An alternative treatment, called Pharmacological Chaperone Therapy (PCT), utilizes a small molecule substrate analogue, 1-deoxygalactonojirimycin (DGJ). In order to better understand molecular basis of Fabry disease, this work addresses structural and mechanistic studies of the α-GAL glycoprotein. First, we have determined crystal structures of each stage in the catalytic mechanism of the α-GAL enzymatic reaction. These studies reveal a novel strained conformation of the sugar when it is covalently bound to the enzyme. Second, we examine the molecular mechanism of chaperoning by pharmacological chaperones. A combination of biochemical and biophysical approaches reveals that the high potency of the DGJ chaperone is due to an interaction with α-GAL residue D170. Third, we have investigated mutant α-GAL proteins for their response to pharmacological chaperones, leading to a set of structure-based rules for predicting the effect of pharmacological chaperone on every Fabry disease patient. Fourth, we use rational design approaches to interconvert the specificity of α-GAL into that of a related enzyme, α-N-acetylgalactosaminidase (α-NAGAL). Structural and enzymatic experiments show that the engineered enzyme contains new substrate specificity, as predicted by the design. The structural and mechanistic details we present in this thesis provide better understanding of the catalysis of the human α-galactosidase enzyme as well as define the molecular basis for pharmacological chaperone therapy in Fabry patients. Since α-GAL is one of the best studied lysosomal storage disease, it might be used as a model to better understand other lysosomal storage diseases and as well as other diseases related to misfolded proteins, including Alzheimer's and Parkinson's diseases.

Yes / Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis.

Yes / An influential review in 2010 concluded that non-pharmacological multi-component interventions have positive effects on cognitive functioning, activities of daily living, behaviour and mood of people with dementia. Our aim here is to provide an up-to-date overview of research into psychosocial interventions and their impact on psychosocial outcomes. We focused on randomised controlled trials, controlled studies and reviews published between October 2008 and August 2015, since the earlier review. The search of PsychInfo, Medline and the Cochrane database of systematic reviews yielded 61 relevant articles, organised into four themes echoing key phases of the care pathway: Living at home with dementia (five reviews, eight studies), carer interventions (three reviews, four studies), interventions in residential care (16 reviews, 12 studies) and end-of-life care (three reviews, two studies), along with an additional group spanning community and institutional settings (six reviews, two studies). Community findings suggested that appointment of dementia specialists and attention to case management can produce positive outcomes; physical therapies, cognitive training and modified cognitive behaviour therapy also had a range of benefits. There was more limited evidence of positive benefits for people with dementia through interventions with family carers. Thirty-two articles focused on the management of ‘behavioural symptoms’ through a range of interventions all of which had some evidence of benefit. Also a range of multi-component and specific interventions had benefits for cognitive, emotional and behavioural well-being of people with dementia in residential settings, as well as for quality of life. Overall, interventions tended to be short term with impact only measured in the short term. We recommend further research on interventions to promote living well in the community post-diagnosis and to address end-of-life care. Development of psychosocial interventions would benefit from moving beyond the focus on control of behaviours to focus on wider aspects of life for people with dementia.

Yes / Objectives: Inconsistency in outcome measurement in dementia care trials impedes the comparisons of effectiveness between trials. The key aim of this study is to establish an agreed standardised core outcome set (COS) for use when evaluating non-pharmacological health and social care interventions for people with dementia living at home. Method: We used a mixed-methods research design, including substantive qualitative research with five key stakeholders groups. We consulted with people living with dementia for many aspects of this research. We applied a modified two-round 54 item Delphi approach to attain consensus on core outcomes. The COS was finalised in a face-to-face consensus meeting in 2018. Results: Of the 288 who completed round 1 (21 people living with dementia, 58 care partners, 137 relevant health and social care professionals, 60 researchers, 12 policy makers), 246 completed round 2 (85% response rate). Twenty participants attended the consensus meeting. We reached consensus for the inclusion of 13 outcome items. Conclusion: We identified 13 outcome items which are considered core; many relate to social health. Providing there are adequate measures, measuring these core outcome items will enhance comparisons for effectiveness making trial evidence more useful. The items will provide commissioners and service planners with information on what types of interventions are most likely to be valued highly by people living with dementia. / This study was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR). ESRC is part of UK Research and Innovation.

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Betablockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and aldosterone antagonists have been widely used, as they were proven to reduce morbi/mortality in heart failure. Patient adherence has been studied all over the world in the last years in acute and chronic heart failure. Many factors knownly can influence the patient adherence to treatment. This study purpose was to evaluate pharmacological treatment in patients diagnosed with heart failure in outpatient follow up in a university hospital. Different methods were used to get to this objective, comparing each other and also clustering patients in more adherent and less adherent to pharmacological treatment, furthermore, we described the factors influencing patient adherence to pharmacological treatment. Thereunto, the Morisky questionnaire was used. Also a questionnaire made by the author and a form to collect data in patient’s chart were applied. Data frequency was described and then hierarchic clusters analysis was performed. Adherence measured by the Morisky questionnaire resulted in 71% of patients more adherent to pharmacological treatment and 26% less adherent. A different result and with more expressive values was found in the self-report adherence to pharmacological treatment by the patient, where 90% of the patients considered themselves as more adherent to pharmacological treatment and 8% considered themselves as less adherent. When comparing treatment prescribed and treatment reported by the patients, the majority of patients (78%) reports at least one drug different from the prescription. When measured by different methods, adherence can show not uniform results. The clinical factors and factors related to the satisfaction with the service did not influence the patient adherence to pharmacological treatment. In the other hand, some sociodemographics factors, like age (p = 0,0476), employment condition (p = 0,0132), schooling (p = 0,0167), marriage status (p = 0,011), family income (p = 0,0123), and factors related to the use of medications, as having family help to the the medications (p = 0,006), use medication alone (p = 0,0186) and have medical orientation bout the use of medication (p = 0,0077) had influence in patient adherence to pharmacological treatment. Thus, it was observed that patients being followed up in the Heart Failure Clinic of Hospital das Clínicas da Universidade Federal de Goiás are well medicated and have satisfactory adherence to pharmacological treatment. / O tratamento medicamentoso da insuficiência cardíaca evoluiu nas últimas décadas. Os betabloqueadores (BB), inibidores da enzima conversora de angiotensina (IECA), bloqueadores dos receptores de angiotensina II (BRA) e antagonistas de aldosterona são classes fundamentais pois comprovadamente diminuem morbi/mortalidade na IC. A adesão ao tratamento vem sendo amplamente estudado em insuficiência cardíaca aguda como crônica. Vários são os fatores que podem influenciar a adesão. O objetivo deste estudo foi avaliar a adesão ao tratamento medicamentoso, em pacientes diagnosticados com Insuficiência Cardíaca em acompanhamento ambulatorial em um hospital universitário. Foram utilizados diferentes métodos para este fim, comparando-os entre si, assim como agrupou-se os pacientes em mais aderentes e menos aderentes, além de se descrever os fatores que influenciaram na adesão ao tratamento medicamentoso. Para isso, utillizou-se o teste de Morisky de quatro perguntas. Além dele, também foi utilizado um questionário confeccionado pela autora e um formulário de coleta de dados no prontuário. Descreveu-se a frequência dos dados e posteriormente, a análise hierárquica de clusters foi aplicada. A adesão medida por meio do teste de Morisky resultou em 71% dos pacientes mais aderentes e 26% menos aderentes. Um resultado diferente, e também com valores mais expressivos, foi encontrado no autorrelato de adesão ao tratamento medicamentoso pelo paciente, em que 90% dos pacientes se consideraram mais aderentes e 8% menos aderentes. Quando se compara os medicamentos prescritos e relatados, a maioria dos pacientes (78%) relata pelo menos um medicamento diferente da prescrição. Quando medida por métodos diferentes, a adesão pode apresentar resultados não uniformes. Os fatores clínicos e os relacionados à satisfação com o serviço não influenciam na adesão ao tratamento medicamentoso. Já alguns fatores sociodemográficos, como idade (p=0,0476), condições de emprego (p=0,0132), escolaridade (p=0,0167), estado marital (p=0,0110), renda familiar (p=0,0123) e fatores relacionados ao uso do medicamento, como ter ajuda da família para retirar os medicamentos (p=0,0060), utilizar os medicamentos sozinhos (p=0,0186) e ter orientação médica quanto aos medicamentos (p=0,0077), influenciam na adesão ao tratamento medicamentoso. Assim, observou-se que os pacientes atendidos no Ambulatório de Insuficiência Cardíaca do Hospital das Clínicas da Universidade Federal de Goiás (HC/UFG) possuem adesão satisfatória ao tratamento medicamentoso prescrito.