Dissertationen: „Medicinal profile“

1

Faraone, Immacolata. „Pharmacological potential and phytochemical profile of three unexplored medicinal plants“. Doctoral thesis, Universita degli studi di Salerno, 2019. http://elea.unisa.it:8080/xmlui/handle/10556/4256.

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2017 - 2018
Nature is a wide source of biologically active compounds investigated with the purpose to be used as drugs due to their biological activity and also useful in pharmaceutical discovery and drug design. Nowadays, medicinal plants play a major role in primary health care as therapeutic remedies in many developing countries. The aim of my PhD project was the phytochemical and biological investigation of three plant species, used in Bolivian traditional medicine, but few scientific studies were reported, such as: Azorella glabra Wedd., Minthostachys diffusa Epl. and Senecio clivicolus Wedd. On the basis of ethnobotanical uses, the samples were firstly analysed for their total content of polyphenols, flavonoids and terpenoids and for their in vitro antioxidant activity using different complementary assays. In particular, radical scavenging activity was tested against biological radicals such as nitric oxide (NO) and superoxide (SO) together with neutral or cationic (DPPH and ABTS) radicals; ferric reducing power and lipid peroxidation inhibitory capacity (FRAP and Beta-Carotene Bleaching tests) were also determined. Oxidative stress is involved in different diseases, such as diabetes and neurodegenerative diseases. Then, the inhibitory ability of samples was investigated against α-amylase and α-glucosidase enzymes involved in diabetes and against acetylcholinesterase and butyrylcholinesterase enzymes considered as strategy for the treatment of Parkinson’s or Alzheimer’s diseases. Moreover, cytotoxicity studies on cancer and non-cancer cell lines were carried out. The antioxidant, antidiabetic, anticholinesterase and cytotoxic activities and the phytochemical profile were performed on aerial parts of A. glabra, M. diffusa and S. clivicolus for the first time. Among all samples, the ethyl acetate fraction of S. clivicolus showed the highest antioxidant activity; instead, M. diffusa samples showed the highest antidiabetic potential and anti-cholinesterase activities. To confirm the inhibitory cholinesterase effects of the terpenes identified from M. diffusa, in silico docking analysis were also carried out. Moreover, the A. glabra samples were tested for the first time on Multiple Myeloma (MM) cell lines using several assays. The chloroform fraction of A. glabra reduced the cell viability, and arrested the cell cycle on MM cells in G0/G1 phase, characteristic feature of apoptosis. Instead, the ethyl acetate fraction of S. clivicolus was tested on hepatocellular carcinoma HepG2 cell line showed the ability to induct cell death via the mitochondrial apoptotic pathway. In conclusion, this first report on A. glabra, M. diffusa and S. clivicolus phytochemical characterization and biological activity evaluation, demonstrates as these Bolivian plant species could be considered a source of health promoting compounds. Some of the results obtained during this study might partially explain their ethnobotanical use, evidencing a potential economic added value for extract future use in the field of biotechnology applied to environmental, agricultural, health, pharmaceutical and cosmeceutical development. [edited by Author]
XXXI ciclo

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2

Labar, Reha. „Medicinal and molecular profiling of selected tea varieties of Darjeeling and Dooars“. Thesis, University of North Bengal, 2022. http://ir.nbu.ac.in/handle/123456789/5085.

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3

Pal, Arindom. „Development of a new class of ligand-targeted chemotherapeutics with enhanced safety and efficacy profile“. Scholarly Commons, 2019. https://scholarlycommons.pacific.edu/uop_etds/3642.

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The hydrophobicity of many chemotherapeutic agents usually results in their nonselective passive distribution into healthy cells and organs causing collateral toxicity. Ligand-targeted drugs (LTDs) are a promising class of targeted anticancer agents. The hydrophilicity of the targeting ligands in LTDs limits its nonselective passive tissue distribution and toxicity to healthy cells. In addition, the small size of LTDs allows for better tumor penetration, especially in the case of solid tumors. However, the short circulation half-life of LTDs, due to their hydrophilicity and small size, remains a significant challenge for achieving their full therapeutic potential. Therefore, extending the circulation half-life of targeted chemotherapeutic agents while maintaining their hydrophilicity and small size will represent a significant advance towards effective and safe cancer treatment. Here, we present a new approach for enhancing the safety and efficacy of targeted chemotherapeutic agents. By endowing hydrophobic chemotherapeutic agents with a targeting moiety and a hydrophilic small molecule that binds reversibly to the serum protein transthyretin, we generated small hydrophilic drug conjugates that displayed enhanced circulation half-life in rodents and selectivity to cancer cells. To the best of our knowledge, this is the first demonstration of a successful approach that maintains the small size and hydrophilicity of targeted anticancer agents containing hydrophobic payloads, while at the same time extending their circulation half-life. This was demonstrated by the superior in vivo efficacy and lower toxicity of our conjugates in xenograft mouse models of metastatic prostate cancer.

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4

Mandrone, Manuela <1983&gt. „Medicinal Plants from Ancient Tradition as a Source for Matrix Proteases Inhibitors. Study of Correlation between Biological Activity and Phytochemical Profile“. Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7613/1/tesi_Manuela_Mandrone_.pdf.

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Considering the crucial involvement of matrix metalloproteinases’ (MMPs) misregulated activity in the pathogenesis of several degenerative diseases, this class of enzymes has been considered a highly active set of targets for the design of new therapeutic agents. However, the scant success of synthetic MMP inhibitors, largely due to the disappointing results obtained in both clinical and preclinical studies, makes medicinal plants a valuable source of new active compounds able to modulate MMPs activity. In this work, a consistent number of plants, selected on the base of an ethnobotanical research, were tested as inhibitors of collagenase, the founding member of the MMPs family. 1H-NMR-based metabolomic analysis combined with multivariate data treatment (PLS and OPLS) was used to correlate the biological activity to the phytochemical profiles, suggesting tannins as an important class of collagenase inhibitors. Thus, a tannin-removal procedure was developed, which allowed to prove this hypothesis and to identify another class of active metabolites, the glucuronide-conjugated flavonoids (especially quercetin-3-O-β-glucoronide), whose the plant Alchemilla vulgaris was found to be a good source. In another stage of the project, different varieties of tea were investigated as collagenase inhibitors, finding black tea samples particularly potent. Then, an OPLS model was developed with the aim of correlating the biological activity to the UV-Vis spectra of teas, showing that a high activity was related to absorption values in the range 350-440 nm. A subsequent fractionation of the most active tea sample was carried out, and this approach allowed to corroborate the results obtained by the metabolomic analysis. Considering that the absorbance measurement of an extract represents a cheap and simple procedure, the proposed method can be suitable, for instance, to select the best tea variety to be developed as an anti-wrinkles cosmetic or food supplement.

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5

Mandrone, Manuela <1983&gt. „Medicinal Plants from Ancient Tradition as a Source for Matrix Proteases Inhibitors. Study of Correlation between Biological Activity and Phytochemical Profile“. Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7613/.

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Considering the crucial involvement of matrix metalloproteinases’ (MMPs) misregulated activity in the pathogenesis of several degenerative diseases, this class of enzymes has been considered a highly active set of targets for the design of new therapeutic agents. However, the scant success of synthetic MMP inhibitors, largely due to the disappointing results obtained in both clinical and preclinical studies, makes medicinal plants a valuable source of new active compounds able to modulate MMPs activity. In this work, a consistent number of plants, selected on the base of an ethnobotanical research, were tested as inhibitors of collagenase, the founding member of the MMPs family. 1H-NMR-based metabolomic analysis combined with multivariate data treatment (PLS and OPLS) was used to correlate the biological activity to the phytochemical profiles, suggesting tannins as an important class of collagenase inhibitors. Thus, a tannin-removal procedure was developed, which allowed to prove this hypothesis and to identify another class of active metabolites, the glucuronide-conjugated flavonoids (especially quercetin-3-O-β-glucoronide), whose the plant Alchemilla vulgaris was found to be a good source. In another stage of the project, different varieties of tea were investigated as collagenase inhibitors, finding black tea samples particularly potent. Then, an OPLS model was developed with the aim of correlating the biological activity to the UV-Vis spectra of teas, showing that a high activity was related to absorption values in the range 350-440 nm. A subsequent fractionation of the most active tea sample was carried out, and this approach allowed to corroborate the results obtained by the metabolomic analysis. Considering that the absorbance measurement of an extract represents a cheap and simple procedure, the proposed method can be suitable, for instance, to select the best tea variety to be developed as an anti-wrinkles cosmetic or food supplement.

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6

Xi, Jia. „Modulation of oleanolic acid dissolution profile via solid state manipulation and self-nanoemulsifying drug delivery systems (SNEDDS)“. Thesis, University of Macau, 2008. http://umaclib3.umac.mo/record=b2158690.

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7

Brown, Dustin Paul. „TARGET-DIRECTED BIOSYNTHETIC EVOLUTION: REDIRECTING PLANT EVOLUTION TO GENOMICALLY OPTIMIZE A PLANT’S PHARMACOLOGICAL PROFILE“. UKnowledge, 2015. http://uknowledge.uky.edu/neurobio_etds/13.

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The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity at this therapeutic target, i.e. the human DAT. This was achieved by expressing the human DAT protein in transgenic plant cells and selecting gain-of-function mutants for survival on medium containing a neurotoxin that is accumulated by the human DAT. This created a sub-population of mutants with increased DAT inhibitory activity. Some of the active metabolites in these mutants are novel (i.e. not detectable in wild-type cells). Others are cytoprotective, and also protect DAergic neurons against the neurotoxin. This provides proof-of-concept for a novel plant drug discovery platform, which is applicable to many different therapeutic target proteins and plant species.

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Strindhall, Jan, Mårten Skog, Jan Ernerudh, M. Bengner, S. Lofgren, A. Matussek, B. O. Nilsson und A. Wikby. „The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals : the Swedish HEXA immune study“. Linköpings universitet, Cellbiologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-93380.

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The Swedish OCTO and NONA immune longitudinal studies were able to identify and confirm an immune risk profile (IRP) predictive of an increased 2-year mortality in very old individuals, 86–94 years of age. The IRP, was associated with persistent cytomegalovirus infection and characterized by inverted CD4/CD8 ratio and related to expansion of terminally differentiated effector memory T cells (TEMRA phenotype). In the present HEXA immune longitudinal study, we have examined a younger group of elderly individuals (n = 424, 66 years of age) in a population-based sample in the community of Jönköping, Sweden, to examine the relevance of findings previously demonstrated in the very old. Immunological monitoring that was conducted included T cell subsets and CMV-IgG and CMV-IgM serology. The result showed a prevalence of 15 % of individuals with an inverted CD4/CD8 ratio, which was associated with seropositivity to cytomegalovirus and increases in the level of TEMRA cells. The proportion of individuals with an inverted CD4/CD8 ratio was significantly higher in men whereas the numbers of CD3+CD4+ cells were significantly higher in women. In conclusion, these findings are very similar to those previously found by us in the Swedish longitudinal studies, suggesting that an immune profile previously identified in the very old also exists in the present sample of hexagenerians. Therefore, it will be important to examine clinical parameters, including morbidity and mortality, to assess whether the immune profile also is a risk profile associated with higher mortality in this sample of hexagenerians.

Funding Agencies|Medical Research Council of South-East Sweden||

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9

Barrero, Franquet Anna. „Ultra-endurance triathlon: heart rate-based intensity profile, energy balance, muscle damage and race performance“. Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/362661.

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This thesis presents the results of two research studies related to the physiological demands, the energy balance and the muscle damage induced by an ultra-endurance triathlon. The first study of this thesis examined the heart rate response during an ultra-endurance triathlon race in relation with heart rate-based intensity markers derived from specific swimming, cycling and running incremental tests. We found that, contrary to what was believed until now, the absolute or relative heart rate (expressed as percentage of heart rate peak) is greater in the swimming stage than in the cycling and running stages. It was also observed that swimming at a higher intensity inversely correlated with performance during the following stages and the overall racing performance. Moreover it was found that 81% of the variance in total racing time was explained by the weight-adjusted VO2max and the heart rate difference between the running and swimming stages. Furthermore, our data support the concept of an "oxygen consumption ultra-endurance threshold". The second study provided proper characterization of the energy and fluid intake, as well as the estimated energy expenditure, of a group of male triathletes during an entire UET race. The estimated EE was aprox. 11000 kcal (46 MJ), whereas EI was only aprox. 3600 kcal (15 MJ), which resulted in an energy deficit of almost 70%. This result partially confirms our hypothesis and demonstrates the challenging metabolic demands of a UET. In this study it was as well assessed the muscle damage induced by a UET and its relationship with the hydration status. The results, beyond confirming fibre muscle damage induced by an UET race, strongly suggest that cellular structural damage predominantly affects slow fibres, and that muscle damage is related to the hydration status.
En aquesta tesi es presenten els resultats de 2 estudis d'investigació relacionats amb les demandes fisiològiques, el balanç energètic i el dany muscular en els triatlons d'ultra-resistència. L'èxit en el triatló d'ultra-resisténcia està regit per la capacitat de mantenir una velocitat absoluta superior per una donada distància, en comparació amb els altres competidors (Zaryski & Smith, 2005). Per optimitzar el rendiment i determinar els factors de rendiment és necessari conèixer la resposta fisiològica i els requeriments energètics durant la competició. El perfil d'intensitat durant un triatló pot ajudar a entendre les demandes fisiològiques i proporcionar informació essencial per a l'entrenament òptim dels triatletes que competeixen en aquests tipus d'esdeveniments. A més a més, donada la llarga durada d'aquests esdeveniments esportius, un dels principals objectius per als atletes és la gestió del consum d'aliments i begudes durant la cursa (Laursen & Rhodes, 2001) per tal de millorar el rendiment i el manteniment de l'homeòstasi del cos. La informació en aquest camp és escassa o gairebé nul•la. Un altre punt clau que afecta aquests triatlons és el dany muscular que pateixen els atletes, que pot disminuir el rendiment muscular i, per tant, afectar el rendiment final del triatló. Un programa d'entrenament de força orientat a produir adaptacions musculars podria reduir aquest dany, però primer cal conèixer quines són les fibres musculars afectades. D'acord als punts exposats, els objectius plantejats en aquesta tesi han sigut: • Proveir, per primera vegada, una caracterització comprensiva del perfil d'intensitat basat en la freqüència cardíaca durant un triatló d'ultra-resistència. Aquest perfil d'intensitat s' estimarà en funció de la relació freqüència cardíaca-consum d'oxigen obtinguda en tests específics en cadascun dels tres modes d' exercici. • Relacionar els paràmetres fisiològics de laboratori i de camp mesurats amb el rendiment en la competició. • Proveir una caracterització del consum d'energia i líquids durant la totalitat d'un triatló d'ultra-resistència. • Estimar la despesa energètica i el balanç de fluids (dipòsits intra i extracel·lulars) al llarg de la competició utilitzant les tres equacions individualitzades obtingudes de cada triatleta. • Avaluar el dany muscular produït per un triatló d’ultra-resistència mitjançant l’avaluació dels nivells de sèrum de les miosines ràpides i lentes, i dels nivells d’activitat de la creatina kinasa. • Relacionar el dany muscular amb el nivell d’hidratació dels atletes. Els resultats i conclusions derivats d’aquests dos estudis que conformen la tesis han sigut: La freqüència cardíaca mitjana durant la competició va ser superior durant el -1 segment de natació (149.2 (10.1) batecs·min ) que durant el segments de ciclisme -1 -1 (137.1 (5.7) batecs·min ) i cursa a peu (136.2 (10.5) batecs·min ). Durant aquests dos últims segments la freqüència cardíaca va estar per sota dels dos llindars ventilatoris (aprox. 11% i aprox. 27-28%) mentre que en el segment de natació la freqüència cardíaca es va situar al voltant del segon llindar ventilatori. Les diferències en la freqüència cardíaca entre el segment de natació i el segment de ciclisme van obtenir una forta correlació amb els temps dels segments de ciclisme i cursa a peu, així com també amb el temps final; com més gran va ser la diferència entre la natació i el ciclisme, pitjors resultats van obtenir els subjectes. Per tant, es pot afirmar que el segment de natació en un triatló d’ultra-resistència es desenvolupa en una intensitat relativa superior als altres dos segments i que aquesta intensitat està relacionada amb un pitjor rendiment als següents segments. El consum d’energia va ser de 3.643 (1.219) kcal i la despesa energètica estimada va ser de 11.009 (664) kcal. En conseqüència, els atletes van mostrar un dèficit d'energia de 7.365 (1.286 kcal (66,9 (11,7%)) posant de manifest les altes demandes energètiques d’aquests tipus de competició, que no són compensades per la ingesta de nutrients i líquids, resultant en un dèficit energètic de grans dimensions. La massa corporal va disminuir significativament després de finalitzar el triatló i també es van trobar pèrdues significatives en l’aigua total corporal. Aquestes pèrdues van estar més relacionades amb la reducció dels fluids extracel·lulars que amb la reducció dels fluids intracel·lulars. Els paràmetres que millor prediuen el rendiment (expressat com a temps final de cursa) en els triatlons d’ultra-resistència són el consum màxim d'oxigen relatiu i la diferència entre la freqüència cardíaca entre el segment de ciclisme i natació. Una caracterització del patró d’intensitat durant tota la cursa, especialment del segment de natació, afegeix nova informació del perfil d'intensitat i les demandes cardiovasculars d'un triatló d’ultra-resistència, la qual cosa remarca la importància de l’especificitat en els tests per avaluar el perfil fisiològic de cara a preparar els entrenaments i l’estratègia de competició. Un triatló d’ultra-resistència provoca dany muscular afectant principalment les fibres musculars ‘lentes’. Un programa d’entrenament orientat a la producció d’adaptacions a les fibres musculars lentes, pot ajudar a reduir el dany muscular produït durant un triatló d’ultra-resistència. El dany muscular produït en triatlons d’ultra-resistència està relacionat amb el grau d’hidratació durant la competició i, per tant, els triatletes haurien d’evitar la deshidratació per, entre altres coses, prevenir el deteriorament del múscul.

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Crawshaw, Anjali Priya. „Monocyte profile and function in sarcoidosis“. Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:3378bf46-a494-45a0-b68e-81b37c1dae49.

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Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology. The immune pathology is characterised by dysregulated T cell (T_H1) activity, macrophage activation and granuloma formation, resulting in systemic inflammation, and organ dysfunction. I hypothesised that, as the systemic precursor to the macrophage, altered monocyte activity in sarcoidosis may contribute to the early immune pathology of the disease. In this thesis, I examined their phenotype, four key monocytic functions: cytokine production, suppression of T cell proliferation, phagocytosis and fusion (as a precursor to granulomagenesis); and their gene expression profile compared to monocytes from healthy controls. My data show that the expanded monocyte compartment comprise a greater proportion of the inflammatory (CD14⁺⁺CD16⁺) and patrolling (CD14⁺CD16⁺⁺) subsets, increased TNFα and IL-12 and decreased IL-10 and IL-4 production in sarcoidosis compared with healthy controls. The IL-10 deficit renders the monocytes less able to regulate T cell proliferation or their own fusion to multinucleate giant cells, potentially contributing to T cell expansion and granuloma formation respectively. Additionally, sarcoidosis monocytes are less able to phagocytose inert material. I also showed that previously reported deficiency in invariant NKT cells and low serum vitamin D levels in sarcoidosis may be linked to reduced IL-10 production by monocytes. Vitamin D treatment in vitro restored most of these deficiencies and provides a potential therapeutic method for manipulating monocyte function and disease genesis in sarcoidosis.

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11

Lu, Hung Quoc. „Lip profile preferences of Asian Americans“. VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2179.

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The aim of this study was to evaluate how Asians, non-Asians, and orthodontists in America view esthetic soft tissue Asian lip profiles. The null hypothesis was that there was no difference in the perception of lip profile esthetics of Asian patients between Asian laypersons, non-Asians laypersons, and orthodontists. A survey was constructed using the profile photographs of one adult male and one adult female Asian American patient taken from the VCU Orthodontics Clinic records. Using Dolphin Imaging 3D, the original photographs were digitally altered. The lips in each photograph were moved in increments forward and backwards to produce 5 images (-4mm, -2mm, 0mm, 4mm, 8mm). Only the lips were modified. Each evaluator was asked to rank, from 1 to 5, each collection of photographs where 1 was most preferable and 5 was least preferable. There were a total of 10 survey questions. The survey was administered to 111 Asian Americans, 115 Caucasians, and 389 Orthodontists. Results suggested that all three groups were similar in their assessment. A retrusive lip profile for the Asian male was preferred, and a slightly protrusive lip profile for the Asian female was preferred across all groups. Generally, orthodontists preferred slightly more retrusive lips compared to the other two groups. The groups of evaluators that showed statistical differences were Chinese and Filipino laypersons. Cluster analysis also revealed tremendous variation in the results, giving credence to the belief that individual patient preference should be assessed in addition to understanding social norms.

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12

Kaur, Sukhbir. „Characterisation of the expression profile and endothelial function of Rho GTPase RhoJ“. Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/1558/.

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Rho GTPases are molecular switches that regulate many aspects of cell physiology. A number of Rho GTPases are essential for the formation of new vessels from pre-existing ones, a process known as angiogenesis. RhoJ/TCL belongs to the Cdc42 subfamily of Rho GTPases. Previous bioinformatic and primary cell line analyses identified RhoJ as being highly expressed in endothelial cells. The aim of this project was to investigate the expression pattern and endothelial function of RhoJ, particularly in the processes necessary for angiogenesis. Silencing RhoJ with siRNA impaired tube formation and migration. On the cellular level, RhoJ knockdown increased focal adhesions, actin stress fibres and collagen gel contraction, suggesting increased actomyosin contractility. Pharmacological inhibition of ROCK and myosin II, two regulators of actomyosin contractility, restored motility and tube formation after RhoJ knockdown. RhoJ localised to blood vessels of developing mice and in various human normal and pathological tissues. In zebrafish embryos RhoJ was not expressed in endothelial cells, instead RhoJ was expressed in the musculature where it was involved in regulating somite formation. This study is the first to describe a role for RhoJ as a negative regulator of focal adhesion numbers and actomyosin contractility and to demonstrate a critical role of this Rho GTPase in endothelial cell migration and tube formation, thus identifying a potential new player in angiogenesis.

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Carter, Joanne. „The cardiovascular profile and pharmacology of vandetanib and pazopanib“. Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/40191/.

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Angiogenesis, a process that enables the growth of blood vessels from a pre-existing vasculature and is common to all solid tumours greater than 1 mm3 in size (Gacche and Meshram, 2014). The angiogenic process is heavily promoted by vascular endothelial growth factor (VEGF). Compounds able to inhibit VEGF signalling have been shown to reduce cancer mass (Arjaans et al., 2016). However, VEGF receptor tyrosine kinase inhibitors (RTKIs), a class of anti-VEGF treatment, have been shown to cause cardio-toxicity, with hypertension being a commonly reported, and often severe, side effect (Eskens and Verweij, 2006; Widakowich et al., 2007; Abi Aad et al., 2015). Depending on the nature of the study, the incidence of hypertension in the VEGF RTKI patient population ranges from 23% to 90% (Hamberg et al., 2010; La Vine et al., 2010; Aparicio-Gallego et al., 2011; Bible et al., 2014). Due to the increasing incidence and seriousness of hypertension observed in oncology clinics, it is clear that there are important cardiovascular issues relating to the use of RTKIs, particularly those that target VEGF, that require further exploration. This body of work set out to determine the in vitro potencies of vandetanib, pazopanib, cediranib and sorafenib at VEGFR2, alongside the in vivo cardiovascular haemodynamic and vasoactive profile of vandetanib and pazopanib, two VEGF RTKIs shown to cause hypertension in approximately 32% (Wells et al., 2012) and 33%-40% of the patient population, respectively (Bible et al., 2014). In NFAT luciferase assays cediranib, sorafenib, pazopanib and vandetanib were shown to inhibit, in a non-competitive fashion, VEGF165 mediated signalling in vitro. In haemodynamic studies, using Doppler flowmetry and telemetry methodologies, both vandetanib and pazopanib caused significant hypertension (P < 0.05, in comparision to vehicle). Pazopanib and vandetanib lead to significant vasoconstriction of the mesenteric and hindquarter vascular beds, pazopanib also produced significant vasoconstriction in the renal vascular bed (P < 0.05, in comparision to vehicle). None of the variables measured in the haemodynamic studies significantly differed between the 30 mgkg-1day-1 pazopanib and 25 mgkg-1day-1 vandetanib groups. In chronic radio-telemetric studies, vandetanib was shown to cause a significantly greater but more transient increase in mean arterial blood pressure in comparison to pazopanib (P < 0.05). Vandetanib was also shown to inhibit VEGF and ACh-mediated vessel dilatation in pressure myography experiments. Finally, vandetanib and pazopanib were shown to induce vasodilatation in the presence of a vasoconstrictor (U46619), a previously unseen finding. In conclusion, the body of work undertaken here has given novel insight into the ability of non-competative anti-VEGF RTKIs to inhibit VEGF-mediated signalling and vessel dilatation as well as produce direct effect of vessel diameter in the absence of VEGF. It has also produced a validated method of hypertension in a rat model, both in the short and long term. These models have shown that different anti-VEGF RTKIs have different regional haemodynamic and post-treatment hypertensive side effect profiles. These findings are important for understanding the mechanisms behind the therapeutic and non-therapeutic effects of VEGF RTKIs and allow for further research into the signalling mechanism involved in VEGF RKTI-mediated hypertension and the potential therapeutic treatments that could treat this.

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Athanasiadis, Paschalis. „Predicting Target Profile using Cross Venn-ABERS Predictors“. Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-440181.

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In this thesis, Cross Venn-ABERS Predictors (CVAPs) were used as aConformal Prediction technique on an Support Vector Machines (SVM)Algorithm as the underlying algorithm. The datasets, one for each target,were extracted from ChEMBL 24.1 database. After balancing the datasetsin order to get a proper format to be used as training sets, cross-validationwas followed in order to investigate whether there is a statistical significancebetween the LibLINEAR and LibSVM methods. The impact of removingduplicated set of molecular descriptors was also investigated. After decidingthat LibSVM with duplicates excluded performs best, models were trainedand used in a kinase inhibitors dataset in order to get a profile for each target.A Principal Component Analysis (PCA) was performed on those results.The variance explained was relatively low and there was no clusteringbetween the observations.

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15

Ajudua, Emmanuel Enuagwuna. „Profile of diabetic complications amongst diabetics attending internal medicine outpatient department and family medicine outpatient department in Dora Nginza Hospital, PE hospital complex“. Thesis, Stellenbosch : University of Stellenbosch, 2015. http://hdl.handle.net/10019.1/97196.

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Thesis (MFamMed)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: Introduction: Diabetes is the most prevalent endocrinology problem encountered in primary care practice. If recent trends showing a dramatic increase in prevalence (believed to be a consequence of a decline in physical activity and excessive caloric intake) continue, then the condition will soon affect nearly 20 million people in the U.S a reflection of the global trend. Effective management requires care that is thoughtful and meticulous, incorporating intensive patient education. Euglycemic control, with the level of glycosylated haemoglobin (HbA1c) kept below 7.0mmol/L, has emerged as a major treatment objective because of its association with a marked reduction in the risk for micro vascular complications. The primary physician is in the unique position to provide comprehensive care to the diabetic patient. Setting: The aim of this study is to evaluate the profile of complications arising due to diabetes mellitus among adult diabetics attending internal medicine outpatient department and family medicine/primary care outpatient department in the Dora Nginza hospital, PE hospital complex. Method: The study is a descriptive retrospective study in which names of patients were collated from clinic records of both clinics, files sought at the records department covering the period between Jan 2007 and Jan 2008 inclusive. Prevalence of statistical variables was generated using frequency tables, bar graphs, cross tabulations and chi square test. Results: Hyperglycemia was the major complication which predominantly was associated with high haemoglobin A1c (HbA1c) levels. However, some hyperglycaemic cases were also found to be associated with normal HbA1c. Complications were found to be more in type 2 diabetics. Patients with hypertension, obesity, smoking and alcohol use were observed to have a higher risk of developing diabetic complications. The findings on retinopathy in this study was inconclusive in view of the fact that patients sent for fundoscopy did not return with documented results from the sister hospital PE provincial hospital. Family Medicine outpatient department overall did better in patient care compared to the Internal Medicine outpatient department. Conclusion: The challenge for the primary care physician is to design a therapeutic program that is safe practical and acceptable to the patient. The ultimate goal of therapy is the prevention of micro vascular and macro vascular complications, consequence of diabetes that makes the condition a major risk factor for cardiovascular disease, stroke, visual impairment, renal failure, impotence, peripheral neuropathy, limb loss and ultimately death. These can be averted through appropriate education of both hospital staff, patients and their care givers. The recommendations made are based on the findings of the study.
AFRIKAANSE OPSOMMING: Nie beskikbaar.

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Tapia, Mancilla Víctor [Verfasser]. „Specificity profiles of protien recognition domains in the molecular medicine / Víctor Tapia Mancilla“. Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1052221920/34.

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Mendes, Wiviany Thaise de Lima. „Medicine use in institutions of long permanence for aged of Fortaleza-CearÃ: profile, risks and necessities“. Universidade Federal do CearÃ, 2006. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=372.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Many of the elderly that lives in Nursing Homes (ILPI) have health problems, are very fragile and frequently need polypharmacy, being exposed to health risks like medical lapsing errors, dispensation or drug administration. Thus, the rational drug use in these ILPI is essentially linked to its drugs dispensary and to one adjusted Pharmaceutical Assistance. To investigate the conditions of the drugs dispensary and the Pharmaceutical Assistance, moreover, to evaluate the quality of the prescribed drugs to the elderly in ILPI in Fortaleza. A descriptive study was carried out in two ILPI (A and B) at Fortaleza-CE. On the first study, were observed and evaluated the conditions of functioning of the drug dispensary, the profile of the existing products in the dispensary, the employees and the routines related to the processes of election, acquisition, storage, control and distribution of drugs in those institutions. The data collected were inserted and analyzed on a data base developed on the Microsoft Excel 2002 program. On the second study, an analysis of the quality of medicines prescribed to the aged residents in the ILPI was carried out, considering the essentiality, the drug association in fixed doses, the pharmacological interaction potential, the drug-food interaction potential, the redundancy of pharmacotherapy and the therapeutic value of the drug. The data collected were inserted and analyzed in the statistical program SPSS 12.0 for Windows. The project was submitted to the Committee of Ethics in Research at the Hospital Complex of the Federal University of the CearÃ, receiving approval. First Study: In the dispensary of the ILPI-A there was an infestation of insects in the drugs; lack of illumination control, ventilation and temperature of the environment; and, storage of not-recommended products (cigarette, match sticks and others). Moreover, among the 776 pharmaceutical specialties found in the dispensary, 67.9% needed medical lapsing, 75.5% were monodrugs and 21.2% were essential. And, of the total of 195.177 pharmaceutical units, almost 30% were in improper conditions for consumption. The storage of the products was not standardized. The election and standardization of drugs were not realized and the acquisition of drugs was realized without logistic evaluation of supply. The collective system of drug distribution was used. The dispensary was managed by employees without training. In the ILPI-B, there was a lack of illumination control, ventilation and temperature in the environment; windows without protecting screens against the entrance of rodents and insects; and a lack of routine for cleaning the place. 104 pharmaceutical specialties were found, 51.9% needed medical lapsing, 87.5% were monodrugs and 58.7% were essential. In the 21.447 pharmaceutical units, only 1.7% was improper for consumption. The storage of the products obeyed alphabetical order for generic name, being registered the entrance and exit in proper card indices. The election and standardization of drugs were realized, and, were annually acquired. The collective system of drug distribution was used. The dispensary was managed by trained employees. Second Study: In ILPI-A, 50.8% were female, 51.6% were functional dependents individuals and 53.2% were between 60 and 75 years old. Of the 347 pharmaceuticals specialties prescribed, 5.5% were associatiated to drugs in fixed dose, 30.5% was not essential and, 34.9% was for the central nervous systems (CNS). It was observed that 25.6% of drugs presented unacceptable therapeutic value for the elderly. Among the medical lapsings with 2 or more drugs, 52.6% presented potential drug interactions. In ILPI-B, 58.3% were female, 100% were functional dependents individuals and 65% were between 60 and 75 years old. Of the 205 pharmaceuticals specialties prescribed, 2.9% were associatated to drugs in fixed dose, 32.2% was not essential and, 55.1% were to the CNS. It was observed that 36.6% presented unacceptable therapeutic value for the elderly. Among the medical lapsings with 2 or more drugs, 58.0% presented potential drug interactions. In both ILPI, the potential risks to health of the elderly, due to the drug use, were related to the lack of technician-administrative orientation concerning the drug, the dispensary management and the Pharmaceutical Assistance. The profile of the dispensaries and prescribed medicines suggests that the elderly of these ILPI are in constant risk of health, maximized or increased by incorrect and irrational use of drugs. The development of a structuralized Pharmaceutical Assistance, starting with the observance the effective good practices of the legislation in the country about the processes related to the Cycle of the Pharmaceutical Assistance, the implantation and implementation of steps of prevention as the reduction of the polypharmacy, reduction of the unacceptable drug use by the elderly, the evaluation of the quality of prescribed medicines and the practice of the Pharmaceutical Attention and the Clinical Pharmacy are fundamental.
Muitos dos idosos que vivem em InstituiÃÃo de Longa PermanÃncia para Idosos (ILPI) apresentam diversos problemas de saÃde e necessitam de mÃltiplos fÃrmacos, estando freqÃentemente expostos aos riscos Ã saÃde como erros de prescriÃÃo, dispensaÃÃo ou administraÃÃo de medicamentos. O uso racional de medicamentos nessas ILPI estÃ essencialmente interligado ao seu dispensÃrio de medicamentos e a uma adequada AssistÃncia FarmacÃutica. Investigar as condiÃÃes do dispensÃrio de medicamentos e da AssistÃncia FarmacÃutica e, avaliar a qualidade dos medicamentos prescritos aos idosos residentes em ILPI do municÃpio de Fortaleza. Foram realizados estudos descritivos em duas instituiÃÃes, identificadas como ILPI-A e ILPI-B, do municÃpio de Fortaleza. No primeiro estudo, foram observadas e avaliadas as condiÃÃes de funcionamento do dispensÃrio de medicamentos, o perfil dos produtos existentes no dispensÃrio, os funcionÃrios e as rotinas relacionadas aos processos de seleÃÃo, aquisiÃÃo, armazenamento e distribuiÃÃo de medicamento nessas ILPI. Os dados obtidos foram inseridos e analisados num banco de dados desenvolvido no programa Microsoft Excel 2002. No segundo estudo, foi realizada uma anÃlise da qualidade dos medicamentos prescritos aos 124 idosos residentes na ILPI-A e aos 60 na ILPI-B, considerando a essencialidade, a associaÃÃo de medicamentos em doses fixas, a interaÃÃo farmacolÃgica potencial, a interaÃÃo medicamento-alimento potencial, a redundÃncia de farmacoterapia e o valor terapÃutico do medicamento. Os dados obtidos foram inseridos e analisados num banco de dados desenvolvido no programa estatÃstico SPSS 12.0 para Windows. O trabalho foi aprovado pelo ComitÃ de Ãtica em Pesquisa do Complexo Hospitalar da Universidade Federal do CearÃ. RESULTADOS: Primeiro Estudo: No dispensÃrio de medicamentos da ILPI-A havia resÃduos de insetos nos medicamentos; falta de controle de iluminaÃÃo, ventilaÃÃo e temperatura do ambiente; e, armazenamento de produtos nÃo recomendados (cigarro, fÃsforo, etc). Das 776 especialidades farmacÃuticas encontradas no dispensÃrio, 67,9% necessitavam de prescriÃÃo mÃdica, 75,5% eram monofÃrmacos e 21,2% eram essenciais. Do total de 195.177 unidades farmacÃuticas identificadas, quase 30% estavam em condiÃÃes imprÃprias para consumo. A guarda dos produtos nÃo era padronizada. NÃo havia seleÃÃo e padronizaÃÃo dos medicamentos, nem tampouco controle de estoque e movimentaÃÃo dos produtos. A aquisiÃÃo de medicamentos era realizada por compra direta, sem avaliaÃÃo logÃstica de estoque. Utilizava-se o sistema de distribuiÃÃo coletivo de medicamentos. O dispensÃrio era gerenciado por um funcionÃrio de nÃvel mÃdio nÃo capacitado. Na ILPI-B, havia falta de controle de iluminaÃÃo, ventilaÃÃo e temperatura do ambiente; janela sem tela de proteÃÃo contra entrada de roedores e insetos; e falta de rotina para limpeza do local. Foram encontradas 104 especialidades farmacÃuticas, sendo que 51,9% necessitavam de prescriÃÃo mÃdica, 87,5% eram monofÃrmacos e 58,7%, essenciais. Das 21.447 unidades farmacÃuticas, apenas 1,7% estava imprÃpria para consumo. A guarda dos produtos obedecia ,Ã ordem alfabÃtica por nome genÃrico, sendo a entrada e saÃda registradas em fichÃrios prÃprios. Havia seleÃÃo e padronizaÃÃo dos medicamentos, bem como controle de estoque e movimentaÃÃo dos produtos. A aquisiÃÃo de medicamentos era realizada por licitaÃÃo anual, com avaliaÃÃo logÃstica de estoque. Utilizava-se o sistema de distribuiÃÃo coletivo de medicamentos. O dispensÃrio era gerenciado por um funcionÃrio de nÃvel mÃdio treinado pelo farmacÃutico, sendo este Ãltimo responsÃvel pela seleÃÃo e aquisiÃÃo dos produtos. Segundo Estudo: Na ILPI-A, 50,8% dos indivÃduos eram do sexo feminino, 51,6% eram dependentes funcionais e 53,2% estavam na faixa etÃria de 60 a 75 anos. Das 347 especialidades farmacÃuticas prescritas 5,5% eram associaÃÃo de fÃrmacos em dose fixa, 30,5% nÃo eram essenciais e 34,9% destinavam-se ao tratamento do sistema nervoso central (SNC). Em mÃdia, foram prescritas 2,8 (dp=1,5) especialidades farmacÃuticas/idoso. 25,6% dos medicamentos apresentavam valor terapÃutico inaceitÃvel para idosos. Entre as prescriÃÃes mÃdicas com 2 ou mais medicamentos, 52,6% apresentavam interaÃÃes medicamentosas potenciais (IMP). NA ILPI-B, 58,3% dos indivÃduos eram do sexo feminino, 100% eram dependentes funcionais e 65% estavam na faixa etÃria de 60 a 75 anos. Das 205 especialidades farmacÃuticas prescritas 2,9% eram associaÃÃo de fÃrmacos em dose fixa, 32,2% nÃo eram essenciais e 55,1% destinavam-se ao tratamento do SNC. Foram prescritas 3,4 (dp = 1,9) especialidades farmacÃuticas/idoso, em mÃdia. 36,6% dos medicamentos apresentavam valor terapÃutico inaceitÃvel para idosos. Em prescriÃÃes com 2 ou mais medicamentos, 58,0% na apresentavam IMP. Em ambas as ILPI, a maioria dos riscos potenciais a saÃde dos idosos das ILPI, relacionados a medicamentos, eram decorrentes da falta de orientaÃÃo tÃcnico-administrativa acerca do medicamento, do gerenciamento do dispensÃrio e da AssistÃncia FarmacÃutica. O perfil dos dispensÃrios e dos medicamentos prescritos sugere que os idosos residentes nas ILPI estudadas estÃo em constante risco de saÃde, provocado ou aumentado pelo uso incorreto e irracional de medicamentos. A estruturaÃÃo de uma AssistÃncia FarmacÃutica adequada, a comeÃar pela observÃncia da legislaÃÃo, das boas prÃticas vigentes no paÃs quanto aos processos do Ciclo da AssistÃncia FarmacÃutica, e, a avaliaÃÃo rotineira das terapÃuticas empregadas nesses idosos, bem como a implantaÃÃo e implementaÃÃo de medidas preventivas como a reduÃÃo da polifarmÃcia, reduÃÃo da utilizaÃÃo de medicamentos inaceitÃveis para idosos, a avaliaÃÃo da qualidade dos medicamentos prescritos e a prÃtica da AtenÃÃo FarmacÃutica e da FarmÃcia ClÃnica sÃo fundamentais para um bom atendimento desses idosos.

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Aquino, Ranniere Gurgel Furtado de. „Pathological profile of ductal carcinomas in areference service of 2005 to 2014: correlation with age and with the axillary metastasis“. Universidade Federal do CearÃ, 2016. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16572.

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Breast cancer is the most common cancer in women worldwide, and its morphological characteristics, despite the current molecular classification, also provide important information about the pattern of this disease. In order to standardize the morphological classification of breast cancer and to refine the clinical applicability of anatomopathological reports, the histological grade of Scarff-Bloom-Richardson (SBR) system was proposed, which, later was modified by Nottingham group, in which tumors are graded 1, 2 and 3 according to the structural and cellular findings. In 1991, its prognostic value was demonstrated for the first time and, since then, several studies have validated it, which has made it a classification system recommended worldwide. The aim of this study was to understand the pathological profile of ductal carcinomas of the Maternidade Escola Assis Chateubriant, correlating with age and with axillary metastases. They studied 302 cases of ductal carcinoma patients from Mastology service of Universidade Federal do CearÃ - UFC in the period 2005-2014, aged ≤ 50 years and above 50 years. The following morphological characteristics were analyzed: larger diameter of the tumor, axillary metastasis and histological grade. It was determinate histological grade, tubular grade, nuclear grade and mitotic index in axillary metastasis to compare with primary tumor. The average age of patients was 55.6 years. The average tumor size was 3.4 cm. 40 % of the tumors have diameter ≤ 2cm and 60% > 2cm. According to the histological grade, 23.7 % were grade 1, 32.1 % grade 2 and 42% grade 3. 66 % of the cases showed axillary metastasis and 34 % didnât show. Women with age ≤ 50 years had fewer tumors grade 1 (p = 0.002) compared to grades 2 and 3. Women older than 50 years had more grade 3 tumors (p = 0.002) and more tumors larger than 2 cm of diameter (p <0.001). The presence of metastasis predominated in both age groups when analyzed alone (p < 0.001). When compared to the primary tumor, the axillary metastases showed a higher frequency of histological grade 3 (66,7%), tubular grade 3 (85,5%), nuclear grade 3 (58%) and mitotic index 2 (58%). The tubular formation was minor in axillary metastasis (p=0,04). Based on the above, it is concluded that women older than 50 years had larger and more undifferentiated tumors and women aged ≤ 50 years had less well-differentiated tumors. There was no difference in morphology between these two groups when compared each other. The axillary implants revealed a more disorganized tissue morphology, which formed a lower number of tubules when compared to the breast primary tumors.
O cÃncer de mama Ã o que mais acomete mulheres no mundo; e suas caracterÃsticas morfolÃgicas, a despeito da atual classificaÃÃo molecular, ainda fornecem informaÃÃes importantes sobre comportamento desta doenÃa. No intuito de padronizar a classificaÃÃo morfolÃgica do cÃncer de mama e de refinar a aplicabilidade clÃnica dos laudos anatomopatolÃgicos, foi proposta a classificaÃÃo do grau histolÃgico de Scarff-Bloom- Richardson que, posteriormente, foi modificada pelo grupo de Nottingham, onde os tumores recebem graus 1, 2 e 3 de acordo com os achados estruturais e celulares. Em 1991, seu valor prognÃstico foi demonstrado pela primeira vez e, desde entÃo, diversos estudos a validaram, o que a tornou um sistema de classificaÃÃo recomendado mundialmente. O objetivo deste estudo foi conhecer o perfil anatomopatolÃgico dos carcinomas ductais de pacientes tratadas na Maternidade Escola Assis Chateubriant, correlacionando com a faixa etÃria e com as metÃstases axilares. Foram estudados 302 casos de carcinoma ductal de pacientes do serviÃo de Mastologia da Universidade Federal do CearÃ - UFC, no perÃodo de 2005 a 2014, tendo como ponto de corte a idade: ≤ 50 anos e acima de 50 anos. Foram analisadas as caracterÃsticas morfolÃgicas: maior diÃmetro do tumor, presenÃa de metÃstase axilar e grau histolÃgico. Em seguida, foram determinados os graus histolÃgico, tubular e nuclear e o Ãndice mitÃtico na metÃstase axilar para comparaÃÃo com os achados do tumor primÃrio. A idade mÃdia das pacientes foi 55,6 anos. O tamanho mÃdio dos tumores foi 3,4 cm. 40% dos tumores possuÃam diÃmetro ≤ 2cm e 60% > 2cm. Quanto ao grau histolÃgico, 23,7% eram grau 1, 32,1% grau 2 e 42% grau 3. 66% dos casos apresentaram metÃstase axilar e 34% nÃo. Mulheres com idade ≤ 50 anos apresentaram menos tumores grau 1 (p=0,002) em relaÃÃo aos graus 2 e 3. Mulheres acima de 50 anos apresentaram mais tumores grau 3 (p=0,002) e mais tumores com mais de 2 centÃmetros de diÃmetro (p<0,001). A presenÃa de metÃstase predominou nas duas faixas etÃrias quando analisadas isoladamente (p<0,001). Quando comparadas ao tumor primÃrio, as metÃstases axilares evidenciaram uma frequÃncia maior de grau histolÃgico 3 (66,7%), tubular 3 (85,5%), nuclear 3 (58%) e Ãndice mitÃtico 2 (58%). A formaÃÃo tubular foi menor nas metÃstases axilares (p=0,04). Diante do exposto, conclui-se que mulheres acima de 50 anos apresentaram tumores maiores e de morfologia mais indiferenciada e as com idade ≤ 50 anos apresentaram menos tumores bem diferenciados. NÃo houve diferenÃa da morfologia entre as faixas etÃrias quando comparadas entre si e os implantes axilares apresentaram morfologia tecidual mais desorganizada formando menos tÃbulos quando comparados aos tumores primÃrios.

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Wright, Rachael Deborah. „Modulation of galectin expression and glycosylation profile of immune cells during inflammation“. Thesis, Queen Mary, University of London, 2015. http://qmro.qmul.ac.uk/xmlui/handle/123456789/9014.

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Galectins-1, -3 and -9, are endowed with many immune-regulatory properties, with galectins-1 and -9 largely regarded as anti-inflammatory and galectin-3 as pro-inflammatory. Expression levels increase in activated adaptive immune cells, with peak expression often correlating with peak inflammation. Galectin actions are not only determined by their expression levels but also target tissue permissibility to galectin binding, which is in turn determined by the profile of specific carbohydrate residues, namely N-acetyllactosamine, recognised by these lectins. How expression levels and actions are modulated in innate immune cells during inflammation has not been systematically characterised. This study therefore set out to delineate the effects of inflammation on neutrophil glycophenotype, as well as elucidate the temporal and spatial modulation of galectins during resolving inflammation. The neutrophil glycophenotype was modulated during trafficking with decreased levels of all terminal glycan residues assessed. However, this did not correlate with galectin binding permissibility suggesting this is not a useful indicator in this model. The overall change in glycosylation may theoretically be a consequence of rapid modulation of cell surface glycoproteins by activated neutrophils (i.e. CD62L shedding) rather than the actions of specific glycosylation enzymes as demonstrated in T- and endothelial cells. Assessment of galectin levels in leukocytes over a 96h zymosan-induced resolving peritonitis demonstrated alterations both spatially and temporally with increased galectin-3 expression in neutrophils at the inflammatory site compared to the periphery and a peak expression at 24h adding supporting evidence that modulation of galectin expression allows delineation of galectin responses by neutrophils. This study also demonstrated a novel pro-resolution effect of galectin-3 with defective resolution observed in galectin-3 null mice. In conclusion this work demonstrated that neutrophil permissibility for galectins-1, -3 and -9 binding is more likely a consequence of the exposure to galectins at specific time points in the resolving inflammatory response rather than due to a modulation of the glycophenotype upon activation. This study also 3 demonstrated that as well as an important role in the induction of an inflammatory response galectin-3 is involved in resolution, a novel finding which may lead to a better understanding of the resolution process.

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Bagherisadeghi, Golshan. „Real life dose emission characterization using patient inhalation profiles“. Thesis, University of Huddersfield, 2016. http://eprints.hud.ac.uk/id/eprint/30322/.

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The aerodynamic characteristics of the dose emitted from dry powder inhalers (DPIs) varies from patient to patient depending on their peak inhalation flow (PIF) and may also be affected by other factors such as the inhaled volume (Vin) and the initial acceleration of the inhalation manoeuvre (ACIM). Compendial methods for the in-vitro determination of the dose emitted from inhalers recommend using a vacuum pump to simulate an inhalation but this is not representative of that made by a patient. In this study a new in-vitro methodology has been developed by adapting a mixing inlet with the Andersen Cascade Impactor (ACI) to use COPD patient inhalation profiles in place of a vacuum pump. The aim was to investigate the effect of inhalation manoeuvre parameters (PIF, Vin and ACIM) on the dose emission performance of both Symbicort® Turbuhaler® and DuoResp® Spiromax®. The medium (200 μg/6 μg budesonide[BUD]/formoterol[FORM]) and high strength (400 μg/12 μg BUD/FORM) products have been used. In the first part of this thesis a comparison has been made between the Alberta Idealised Throat (AIT) and the traditional USP Induction Port (IP) using standard in-vitro compendial methodology. The medium strength version of the Symbicort® Turbuhaler® was used. The results show that the AIT captured more drug compared to the USP IP throat (p<0.05). Regardless of the inhalation volume, no significant change was observed for the FPD at 28.3 L/min between the two throats, although there was a significant difference in the FPD when the flow was increased to 60 L/min (p<0.05). In contrast to an inhalation flow of 28.3 L/min, at 60 L/min the MMAD reduced significantly (p<0.05). No significant change was observed for TED at both inhalation flows while changing the size of the throats regardless of the inhalation volume. In the second and the last but major part, the performance of the Symbicort® Turbuhaler® and DuoResp® Spiromax® was evaluated using the medium and high strength products. The results of both inhalers indicate the importance of PIF on the dose emission characteristics as it increased from <30 to >60 L/min. As a result, both FPD and TED increased and MMAD decreased significantly (p<0.05). The Vin and ACIM showed different effects on the medium and high strength of both inhalers. Generally, Vin had a small effect on both FPD and TED which increased and no change was observed with MMAD. The ACIM also had a small impact on FPD, TED and MMAD for Symbicort® Turbuhaler® and only FPD and MMAD for DuoResp® Spiromax®. The results highlights the potential of this methodology to characterise the dose a patient receive during real life use by using these inhalation profiles in place of the inhalation provided by a vacuum pump. Overall, PIF was the dominant inhalation manoeuver parameter for the dose emission from the Symbicort® Turbuhaler® and DuoResp® Spiromax®.

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Cruz, Maria de Fatima Silveira Lopes [UNIFESP]. „Portfólio do Discente: Resgatando uma Experiência no Curso de Medicina da UNIMONTES“. Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/9945.

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A avaliação e os instrumentos avaliativos continuam sendo um grande desafio no processo ensino-aprendizagem. Partindo desse entendimento, esta pesquisa tem como objetivo conhecer a importância[Otilia Se1] do portfólio no processo de ensino-aprendizagem, a partir da perspectiva dos estudantes e mentores que vivenciaram essa experiência no período do primeiro semestre de 2005 até o primeiro semestre de 2007, no[Otilia Se2][Microsoft3] Curso de Medicina da UNIMONTES. O desenho metodológico compreendeu os seguintes procedimentos: pesquisa bibliográfica e documental (os portfólios dos estudantes e as avaliações realizadas pelos mentores acerca dos estudantes) e questionário de perguntas abertas e fechadas. Os dados foram analisados pela técnica da Análise de Conteúdo com uso da Análise Temática. Os sujeitos da pesquisa foram os estudantes que iniciaram o Curso de Medicina em fevereiro de 2005 e um mentor que desenvolveu o portfólio com essa turma. Os resultados evidenciam que os estudantes estão comprometidos com o processo de ensinoaprendizagem. O portfólio possibilitou as percepções pessoais dos desempenhos dos discentes nos aspectos cognitivos, de habilidades e de atitudes e forneceu informações sobre as atividades curriculares. Os dados indicam que o portfólio atuou em vários níveis de avaliação: deu suporte ao processo de aprendizagem e autoaprendizagem; possibilitou a reflexão dos estudantes sobre seu próprio trabalho, identificando seus avanços e dificuldades; demonstrou o desempenho dos professores, das atividades pedagógicas e dos serviços de ensino, possibilitando um rico conhecimento sobre o caminhar de todo o curso. Segundo a pesquisa, o mentor tem relevante papel, ao mediar o desenvolvimento do desempenho do estudante. Assim, é evidente a necessidade de formação continuada por parte dos mentores e dos estudantes acerca dessa ferramenta avaliativa. Nesse contexto, o estudo aponta para a necessidade de reaprender conceitos e ressignificar a avaliação com a finalidade de torná-la mais efetiva e homogênea por parte dos docentes e dos discentes. Avaliar é importante para aperfeiçoar a pessoa, projetá-la, descobrir pontos positivos, que possam melhorá-la ainda mais, conhecer o que o estudante ainda não aprendeu para estimulá-lo a aprender, para mudar, transformar a sua forma de ser, pensar e agir. Palavras-chave: Portfólio, Avaliação Formativa, Autoavaliação, Perfil do Estudante, Curso de Medicina.
The evaluation process and evaluative instruments still remain a great challenge in the teaching-learning process. Based on this fact, the aim of this study was to identify the importance of the portfolio in the teaching-learning process, from the student´s and professor´s point of view who attend the Medical Course fin the first semester of 2005. The methodological design involved the following procedures: document research (students portfolio and the evaluation processes performed by tutors) and open closed format questions. Data were analyzed by means of Content Analysis with the aid of thematic analysis. The subjects of this research were students who started the Medical Course on February 2005 and a tutor who gave support during the course. The results showed that students are involved in the teaching-learning process. This instrument allowed personal perceptions of the student´s development regarding cognitive aspects, abilities, attitudes and also allowed to obtain information on curricular activities. Data showed that the portfolio operated in several levels of the evaluation process; gave support to the teaching-learning process and self-learning; allowed the students to make considerations on their own work environment, identifying improvements and difficulties; showed the professor´s performance, regarding pedagogical activities and teaching services, and brought a rich knowledge about development during the course. According to the research, the tutor had an important role when mediating the student´s development. It was obvious the need of a continuous education for tutor and students about evaluative instruments, emphasizing the necessity of reflections, readings and discussion on this issue. In this context, this study showed the importance to re-learn concepts and re-meaning the evaluation process aiming to make this process more effective and homogeneous by the professors and students. Evaluation helps the individual to develop, to project, to be able to discover positive points in order to improve oneself, also to get to know the student, stimulating him to learn, to change, to transform the way somebody thinks and acts.
TEDE
BV UNIFESP: Teses e dissertações

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Hasan, Ahmed Ali Ahmed. „A profile of handballers and physiological responses to exercise related to the game“. Thesis, Liverpool John Moores University, 1998. http://researchonline.ljmu.ac.uk/4955/.

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Papadopoulou, Georgia. „Cognitive profile in advanced Duchenne Muscular Dystrophy (DMD) and the effects of hypoventilation on cognition“. Thesis, University of Hull, 2010. http://hydra.hull.ac.uk/resources/hull:3471.

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The portfolio has three parts.Part One is a systematic literature review concerning the nature and severity of the psychological distress experienced by carers (primarily parents) of people with Muscular Dystrophy. Quantitative and qualitative studies investigating distress in these carers have been reviewed and critically evaluated to draw conclusions and implications for clinical practice. Part Two is an empirical paper aimed at creating a cognitive profile for people suffering from Duchenne Muscular Dystrophy in the advanced stages of the illness. The focus of this cross-sectional study is placed on the investigation of whether hypoventilation, inevitably seen to develop in this population, is related to permanent cognitive deficits in memory and/or executive functioning. The participants who have been identified to suffer from hypoventilation (N=17) are compared on measures of memory and executive functioning to a group of DMD participants of similar age (N=16) who have not yet developed hypoventilation. Other measures are also taken in the form of questionnaires to compare the groups on, including demographics, mood (depression and anxiety), health-related quality of life, sleepiness, and beliefs about sleep. Part Three comprises the Appendices.

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Pierucci, Lucirleia Alves Moreira. „Os novos cursos de medicina fazem mal a saude?“ [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/251660.

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Orientador: Ana Maria Fonseca de Almeida
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação
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Resumo: Esta pesquisa focaliza o debate sobre a formação médica contemporânea na sociedade brasileira por meio do estudo das lutas materiais e simbólicas que cercam a transformação do modo comunitário de medicina em currículo incentivado pelo estado. Interroga-se, particularmente, sobre os efeitos da circulação internacional dos médicos nesse processo.
Abstract: The research looks into the medical education reform in course in contemporary Brazil by examining the process by which a new model, called "communitarian" approach, came to be endorsed by the Health aud Education Departaments, of State. It shows how the international circulation of doctors played a role in this process.
Mestrado
Educação, Conhecimento, Linguagem e Arte
Mestre em Educação

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Coleman, Grant Gordon. „Lip Profile Preferences in Varying Sagittal Mandibular Positions“. VCU Scholars Compass, 2003. http://scholarscompass.vcu.edu/etd/1474.

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The purpose of this study was to determine the influence of sagittal mandibular position on preferred lip position in profile. Five androgynous silhouette profiles differing only in the degree of mandibular retro- or prognathism (-25º, -18º, -11º, -4º, & +3º facial contour angles) were created. Using a computer animation program, evaluators moved the lips independently into the position deemed to be the most esthetic for each profile. Evaluators included adolescent orthodontic patients, parents of patients, and orthodontists. In general, no differences in preferred lip position were found between the 11º & -4º profiles or between the 18º & +3º profiles, but preferences for each of the three profile groupings (-11º & -4º, -18º & +3º, and 25º) were different. No differences were found among the three evaluator groups or between male and female evaluators. Scattered and inconsistent differences were found among lip preferences for male and female profiles.

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Almeida, Maria Teresa da Conceição Malheiro Pinto de. „Tyrosine phosphorylation profile of Listeria monocytogenes infected cells:Identification of new host factors hijacked to promote infection“. Master's thesis, Faculdade de Medicina da Universidade do Porto, 2008. http://hdl.handle.net/10216/22084.

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Osório, Catarina Raquel de Sousa. „Angiogenic profile in Myelodysplastic Syndromes and genetic characterization of the endothelial compartment - biologic and clinic relevance“. Master's thesis, Faculdade de Medicina da Universidade do Porto, 2006. http://hdl.handle.net/10216/22115.

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Osório, Catarina Raquel de Sousa. „Angiogenic profile in Myelodysplastic Syndromes and genetic characterization of the endothelial compartment - biologic and clinic relevance“. Dissertação, Faculdade de Medicina da Universidade do Porto, 2006. http://hdl.handle.net/10216/22115.

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Almeida, Maria Teresa da Conceição Malheiro Pinto de. „Tyrosine phosphorylation profile of Listeria monocytogenes infected cells:Identification of new host factors hijacked to promote infection“. Dissertação, Faculdade de Medicina da Universidade do Porto, 2008. http://hdl.handle.net/10216/22084.

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Chang, Wei Chao. „Impact of Preoperative Patient Profiles on Elective Open Intestinal Resection Outcomes“. Diss., NSUWorks, 2015. https://nsuworks.nova.edu/hpd_hs_stuetd/2.

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There are a myriad of risk factors for surgical mortality, intraoperative and postoperative complications, and prolonged length of stay. Effectively identifying possible risk factors in the preoperative patient profiles that may impact the outcome of elective open intestinal resection has significant implications on the quality of care, the safe delivery of surgical care, and the speedy recovery of patients undergoing elective open intestinal resection. Few studies specifically focused on the construction of individual preoperative patient risk profile used only preoperative patient profiles in elective open intestinal resection. A retrospective cohort predictive study was conducted to assess the impact of preoperative patient profiles on surgical outcomes in patients undergoing elective open intestinal resection using 2009-2011 Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) databases. This study aimed to identify independent predictors in the preoperative patient profiles for the development of preoperative patient risk profiling tool for the construction of an individual preoperative patient risk profile for risk stratification, surgical planning, and care coordination for patients undergoing elective open intestinal resection. The results of this study showed that independent predictors in the preoperative patient profiles could predict the risks of increased adverse surgical outcomes in terms of in-hospital mortality, in-hospital complications, and prolonged length of stay in patients undergoing elective open intestinal resection. Independent predictors of increased adverse surgical outcomes were identified in the personal domain, the social history domain, and the comorbidity domain of preoperative patient profiles. In the personal domain profile, advanced age was an independent predictor of increased in-hospital mortality, prolonged length of stay (LOS), and six of the eight categories of in-hospital complications studied, except mechanical wound complications and infection complications. The 18 to 39 age group was more likely to develop the latter two complications. Male gender was an independent predictor of in-hospital mortality, prolonged LOS, and six of the eight in-hospital complications except intraoperative complication and systemic complications. Asian/Pacific Islanders were more likely to have intraoperative bleeding complication while black patients were more likely to have gastrointestinal complications and prolonged LOS compared to white patients. In the social history domain profile, patients with alcohol abuse were more likely to suffer pulmonary complications and have prolonged LOS. Patients with illicit drug abuse were more likely to have prolonged LOS as well. Four comorbidities, fluid and electrolyte disorders, weight loss, coagulopathy, and congestive heart failure, were identified as the strongest independent predictors of increased adverse surgical outcomes overall, except in the cardiovascular complications. Pulmonary circulation disorders were the strongest independent predictors of cardiovascular complications. Other comorbidities that were statistically significant and unique predictors of adverse outcomes were also identified. Patients without comorbidity were less likely to have increased in-hospital mortality, prolonged LOS, and in-hospital complications. These findings have significant implications in developing preoperative patient risk profiling tools for the construction of an individual preoperative patient risk profile for risk stratification, surgical planning, and care coordination in patients undergoing elective open intestinal resection.

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Biržietis, Tomas. „Ultragarsinio ir lipidų apykaitos tyrimų vertė vaisiaus svorio prognozei gestacinio diabeto atvejais“. Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2006. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2006~D_20060125_130632-69676.

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The term “gestational diabetes” first was used in 1967 by J.Pedersen [J.Pedersen, 1967]. Up till then a number of other names was used to describe this pathology in scientific literature. During the last four decades a lot of reseach was done on this pregnancy related metabolic disturbance, but it is discussed up till now if this condition is worth of attention in general and if setting the diagnose is more beneficial or more harmful. Controversy exists also concerning diagnosing methods and criteria of gestational diabetes (GD). It is still discussed about the usefullness of global screening, though the majority of authors agree that by examining only the women who have predisposing factors for GD, up till 25% of GD cases would remain undiagnosed with consequently worse pregnancy outcome compared to the diagnosed and treated cases [K.M.Adams et al., 1998; D.Baliutavičienė et al., 2005]. The major complication of GD – fetal macrosomy, appears 2-4 times more frequently compared to healthy pregnant women [O.Langer et al., 2000] and is related not only to higher probability of labour trauma to mother and newborn, but also with a higher incidence of obesity in childhood and adulthood [B.Vohr et al., 1997; D.Dabelea et al., 1999; M.W.Gillman et al., 2003]. Even though it was succeded to decreace the mortality and morbidity of newborns by normalising glucose level in blood in GD patients, the incidence of macrosomy in these risky pregnancies remains higher compared to healthy... [to full text]

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Siversten, Otilia. „Psychological Profile in Patients with Pathologic Gastroscopic Findings andFunctional Dyspepsia:A Pilot Study“. Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-66822.

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Fukushima, André Rinaldi. „Desenvolvimento de métodos analíticos com finalidade forense aplicados à medicina veterinária legal: ênfase na identificação de agentes anticolinesterásicos“. Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-04032016-150046/.

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As intoxicações letais, via de regra, estão comumente relacionadas com a área médico-legal; alguns agentes tóxicos ocupam lugar de destaque como os principais responsáveis pela ocorrência desses óbitos. Em medicina legal, tanto humana quanto animal, o grande desafio enfrentado é a elucidação da causa mortis e do tempo da ocorrência da morte quando os cadáveres são encontrados, indicando possível exposição aos agentes tóxicos, os quais são adicionados intencionalmente, na maior parte das vezes, com a finalidade de causar danos irreversíveis à vítima. No último relatório do Sistema Nacional de Informações Tóxico-Farmacológicas (SINITOX), no ano de 2012, foram relatadas no Brasil 102.854 intoxicações envolvendo seres humanos e animais, sendo que desse total 1.199 (1,17%) intoxicações foram relatadas em animais. Dentre os principais agentes responsáveis por intoxicação, tanto em seres humanos, como em animais, estão os praguicidas e, em particular, os nticolinesterásicos, sendo importante causa de óbitos intencionais e não intencionais em animais. Métodos de análises toxicológicas envolvendo intoxicações em seres humanos são amplamente estudados e divulgados, o que é menos usual na medicina veterinária legal. Portanto, a existência de laboratórios que atendam as legislações relacionadas as análises toxicológicas forenses, bem como a pesquisa das características da forma de apresentação e do potencial toxicológico dos anticolinesterásicos e o desenvolvimento e validação de técnicas analíticas mais sofisticadas se fazem necessária e contribuirão para os avanços nesse aspecto forense da toxicologia veterinária. Assim, o presente trabalho foi distribuído em quatro capítulos distintos. No primeiro capítulo discute-se o recebimento de amostras e um modelo de formulário de Requisição de Análise Toxicológica num laboratório veterinário de análises toxicológicas que recebe amostras biológicas de interesse forense. O segundo capítulo apresenta a possibilidade de utilização de uma técnica enzimática com a finalidade de avaliar o potencial de inibição dos praguicidas anticolinesterásicos; o método se mostrou eficiente para avaliar a inibição da atividade da acetilcolinesterase (AChE) causada pelo aldicarbe e pelo seu metabólito, o aldicarbe-sulfona. O terceiro capítulo trata-se do teste de dissolução in vitro da forma acabada do grânulo comercial do praguicida aldicarbe (Temik 150®), a fim de avaliar a cinética de liberação do princípio ativo tóxico, bem como a cinética de formação dos seus principais metabólitos ativos, considerando que cães e gatos encontrados mortos com suspeita de intoxicação exógena apresentam chumbinho no conteúdo estomacal. O perfil de dissolução dos grânulos do Temik 150® em meio ácido foi capaz mostrar a presença in vitro dos metabólitos aldicarbe-sulfóxido e o aldicarbe-sulfona, o que não ocorre quando apenas o princípio ativo passou pelo mesmo perfil de dissolução, mostrando que essa forma disponível no comércio contribui para a toxicidade deste praguicida. O quarto capítulo apresenta o desenvolvimento de um método para determinação de praguicidas anticolinesterásicos, bem como os seus produtos biotransformados em diversas matrizes biológicas, baseada em cromatografia líquida de alta eficiência (CLAE) com detecção por arranjo de diodos (DAD). Foi, então, desenvolvido e validado um método de extração e identificação de praguicidas anticolinesterásicos em matrizes biológicas, cujas figuras de mérito atendem a RDC 27 de 2012 da ANVISA (Brasil, 2012). O método permitiu a extração e identificação de aldicarbe e seus metabólitos (aldicarbe-sulfóxido e aldicarbe-sulfona), carbofurano e seu metabólito (3-OH carbofurano), forato e seu metabólito (forato-sulfóxido) e aldicarbe. Esse método foi aplicado em amostras reais encaminhadas ao Laboratório de Diagnóstico Toxicológico (LADTOX) e se mostrou eficiente para identificação de aldicarbe
Lethal poisonings, as a rule, are commonly related to the forensic area; some toxic agents are commonly found as the main agent responsible for these deaths. In forensic medicine, both human and animal, the major challenge faced is the elucidation of cause of death and the time elapsed when the bodies are found, indicating possible exposure to toxic agents, which are intentionally added, most of the times in order to cause irreversible damage to the victim. In the latest report of the Toxic-Pharmacologic National Information System (SINITOX) in the year 2012, 102 854 poisonings involving humans and animals were reported in Brazil, and of this total 1,199 (1.17%) poisonings have been reported in animals. Among the main agents responsible for toxicity, both in humans and in animals, pesticides are common and, in particular, cholinesterase inhibitors, which is important because of intentional and unintentional deaths in animals. Methods of toxicological analyzes involving poisoning in humans are widely studied and published, but less so in legal veterinary medicine. Therefore, the existence of laboratories that meet the legislation related to forensic toxicological analysis and research of the characteristics of the presentation and toxicological potential of cholinesterase inhibitors and the development and validation of more sophisticated analytical techniques are necessary and can contribute to advances in the forensic aspect of veterinary toxicology. Thus, this work was distributed into four distinct chapters. The first chapter discusses the receipt of samples and a Request Form template for Toxicological analysis in a Toxicological analysis veterinary laboratory that receives biological samples of forensic interest. The second section presents the possibility of using an enzymatic technique in order to assess the potential inhibition of cholinesterase inhibitors pesticides; the method was efficient to evaluate the inhibition of the activity of acetylcholinesterase (AChE) caused by aldicarb and its metabolite, aldicarb sulfone. The third chapter it is the in vitro dissolution test of the finished form of commercial bead pesticide aldicarb (Temik 150®) in order to assess the kinetics of release of toxic active ingredient, as well as the formation kinetics of its main metabolites assets, whereas dogs and cats found dead with suspected exogenous intoxication present \"pellets\" in the stomach contents. The dissolution profile of the Temik 150® beads in acid was able to show the presence of in vitro metabolites aldicarb sulfoxide and aldicarb sulfone, which does not occur when only the active ingredient went through the same dissolution profile, showing that this market-available form contributes to the toxicity of this pesticide. The fourth chapter presents the development of a method for determining cholinesterase inhibitors pesticides, as well as their biotransformation products in various biological matrices, based on high-performance liquid chromatography (HPLC) with diode array detection (DAD).Then, a method of extraction and identification of anticholinesterase pesticides in biological matrices was developed and validated, meeting current standards RDC 27, 2012 ANVISA (Brazil, 2012). The method allowed the extraction and identification of aldicarb and its metabolites (aldicarb sulfoxide and aldicarb sulfone), carbofuran and its metabolite (3-OH carbofuran), phorate and its metabolite (phorate sulfoxide) and aldicarb. This method was applied to real samples sent to the Toxicology Laboratory Diagnostics (LADTOX) and was efficient in aldicarb identification

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Cavalcante, Janio Emanuel Andrade. „Influence of polymorphisms in cytokine genes TNFα, IFNγ, TGFβ, IL-6 and IL-10 in clinical laboratory profile of sickle cell patients“. Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=11699.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Sickle cell anemia (SCA) is caused by a point mutation leading the substitution of glutamic acid for valine at the sixth position of the beta globin chain. Associations between single nucleotide polymorphisms (SNPs) and several clinical events have been described in sickle cell patients. The aim of this study was to determine the polymorphisms frequency in the cytokine genes TNFα, IFNγ, TGFβ, IL-6 e IL-10 in sickle cell patients and healthy controls, and to investigate the cytokines genotypes influence in clinical and laboratory profile in sickle cell patients. The sickle cell patients group was composed by 41 adultsâ patients with molecular diagnosis, of both sexes, in outpatients care at the Hematology Center of CearÃ (HEMOCE), from march 2011 to july 2012. The study included 90 healthy blood donors matched for age and sex. We collected 5 mL of venous blood for DNA extraction kit using the GFX Genomic Blood DNA Purification (GE Healthcare) and typing of cytokine genes polymorphisms by kit from One-Lambda (Canoga Park, CA, USA). The polymorphisms frequencies analysis and associations between polymorphisms and clinical events were performed using the two-tailed Fisher exact test. To check the genotypes influence in laboratory parameters were used parametric test ANOVA and non-parametric Kruscal Wallis test. The clinical and laboratory data were obtained by active search in the medical records. Sickle cell patients typified for TGFβ genotypes showed a tendency to appear a lower frequency of TGFβ T/T G/G genotype than control group. Sickle cell patients typified for CC GC/ CC CC /TT CC/TC CC TGFβ genotypes (low producer) obtained a leukocytes median number greater than patients typified for TT GG/TC GG TGFβ group (high producer). A significant difference on IL-6 genotypes frequency was observed between patient group and control group. Regarding IL-6, patients typified for CC genotype exhibited an average/median MCHC higher than patients typified for GC or GG genotypes. Patients typified for CC genotype showed evident tendency to lower fetal hemoglobin levels and higher reticulocytes percentages. We find an association between ACC ATA + ATA ATA + ACC ACC IL-10 group, lower IL-10 producer, and acute chest syndrome (ACS). It is concluded that genotypes associated with low IL-10 production may play a role in the predisposition to ACS in sickle cell patients.
A anemia falciforme (AF) Ã causada por uma mutaÃÃo pontual que leva a substituiÃÃo do Ãcido glutÃmico pela valina na sexta posiÃÃo da cadeia de beta globina. A associaÃÃo entre polimorfismos de nucleotÃdeos Ãnicos (SNPs) e diversos eventos clÃnicos tem sido descrita em pacientes com AF. O objetivo do presente estudo foi verificar a frequÃncia dos polimorfismos nos genes das citocinas TNFα, IFNγ, TGFβ, IL-6, e IL-10 nos pacientes com AF e controles saudÃveis, e investigar o impacto dos genÃtipos dessas citocinas no perfil clÃnico-laboratorial dos pacientes. 41 IndivÃduos adultos com diagnÃstico molecular de AF, de ambos os sexos, em acompanhamento ambulatorial no Centro de Hematologia e Hemoterapia do CearÃ (HEMOCE) participaram do estudo, no perÃodo de marÃo de 2011 a julho de 2012. Um grupo controle foi constituÃdo por 90 indivÃduos saudÃveis pareados quanto Ã idade e o sexo. Foram coletados 5 mL de sangue venoso para extraÃÃo do DNA atravÃs do kit GFX Genomic Blood DNA Purification (GE Healthcare) e para tipificaÃÃo dos polimorfismos dos genes das citocinas atravÃs do âkitâ da âOne-Lambdaâ (Canoga Park, CA, EUA). A anÃlise das frequÃncias dos polimorfismos e as associaÃÃes com os eventos clÃnicos foram realizadas pelo teste exato de Fisher bicaudal. Para verificar a influÃncia dos genÃtipos nos parÃmetros laboratoriais foram utilizados o teste paramÃtrico ANOVA e o nÃo paramÃtrico de Kruscal Wallis. Os dados clÃnicos e laboratoriais foram obtidos por busca ativa nos prontuÃrios mÃdicos. Pacientes com AF tipificados para os genÃtipos de TGFβ CC GC/ CC CC /TT CC/TC CC (baixo produtor) obtiveram um nÃmero mediano de leucÃcitos maior do que os pacientes do grupo TT GG/TC GG (alto produtor). Houve diferenÃa significativa na frequÃncia dos genÃtipos de IL-6 entre o grupo de pacientes e o grupo controle. Ainda em relaÃÃo a IL-6, os pacientes tipificados para o genÃtipo CC apresentaram valores mÃdios/medianos de CHCM maiores que os pacientes portadores dos genÃtipos GC ou GG. Foi evidenciada tendÃncia dos pacientes tipificados para o genÃtipo C/C apresentarem menores nÃveis de hemoglobina fetal (HbF) e maiores porcentagens de reticulÃcitos. Houve uma associaÃÃo entre o grupo de genÃtipos de IL-10 ACC ATA + ATA ATA + ACC ACC, grupo baixo produtor de IL-10, e a sÃndrome torÃcica aguda (STA). Conclui-se que genÃtipos associados com a baixa produÃÃo de IL-10 possam desempenhar um papel importante na predisposiÃÃo Ã STA em adultos com AF.

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Sápia, Tatiana. „Perfis comportamentais e estilos de mobilização de enfermeiros gestores de um serviço de medicina diagnóstica“. Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/7/7131/tde-14082009-095956/.

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O mercado de trabalho para os enfermeiros vem sofrendo mudanças, constatando-se que os profissionais têm ampliado seus papéis profissionais, requerendo que desenvolvam um leque maior de competências. Nesse contexto, este estudo objetivou caracterizar demograficamente os enfermeiros gestores de um serviço de medicina diagnóstica; identificar os perfis comportamentais e estilos de mobilização dos enfermeiros gestores; relacionar os perfis comportamentais com as competências individuais dos enfermeiros gestores, conforme definidas pela empresa; e, por fim, subsidiar políticas de treinamento e desenvolvimento de enfermeiros que atuam nesse setor. A investigação caracteriza-se como pesquisa exploratória, do tipo descritiva, desenvolvida na modalidade de estudo de caso. O cenário do estudo foi uma organização privada, prestadora de serviços de saúde, com a particularidade de atuar no campo da medicina diagnóstica. Os sujeitos da pesquisa foram constituídos pela totalidade dos 36 enfermeiros gestores atuantes nas unidades de atendimento, assessoria e diretoria de educação da empresa. A coleta de dados foi realizada em duas etapas, entre agosto e outubro de 2008. A primeira etapa consistiu de uma pesquisa documental. Na segunda etapa houve a aplicação de um questionário com questões norteadoras que permitissem caracterizar demograficamente os enfermeiros gestores e também foi entregue o questionário diagnóstico M.A.R.E.® das orientações motivacionais, visando identificar os perfis comportamentais e os estilos de mobilização dessas lideranças. Participaram do estudo 35 dentre os 36 gestores de enfermagem, representando 97,22% do grupo. O tratamento estatístico dos dados relacionados às respostas das questões desse instrumento permitiu apresentar os seguintes resultados: o estilo de mobilização com maior representatividade no grupo de gestores de enfermagem é o Negociador, totalizando 25,71%, o que representa nove gestores; seguido pelo Mantenedor, 17,14%, o que representa seis gestores; 14,29%, cinco gestores, têm estilo de mobilização Especialista; 14,29%, cinco gestores, têm estilo de mobilização Conquistador; 11,43%, quatro gestores, têm estilo de mobilização Realizador; 8,57%, representando três gestores, têm estilo de mobilização Competidor e, por fim, 8,57%, três gestores, têm estilo de mobilização Colaborador. Em relação às características de cada estilo, destaca-se que a competência inteligência emocional, ressaltada nos diferentes estilos de mobilização, é, e será sempre, um indicador de tendência e não algo que possa ser considerado adquirido. Considerando as características dos elementos específicos dos processos de trabalho, assistencial e gerencial, e a forte articulação que os mesmos devem ter entre si no trabalho desenvolvido pelo grupo de enfermeiros gestores, os dados do estudo revelam que os perfis de mobilização apresentados favorecem o desempenho das funções de liderança que são peculiares no serviço, bem como o atendimento de expectativas da empresa no alcance de metas. Cabe destacar que os pontos de fragilidade de cada perfil precisam continuamente de investimentos na forma de educação permanente, bem como os pontos fortes precisam de feedback constante por parte da cúpula que define metas estratégicas
The work market for the nurses is changing, confirming that the professionals have amplified their professional roles, requiring that they develop a higher gamma of competences. In this context, this study aimed to characterize demographically the managing nurses of diagnostic medicine service; identify the behavioral profiles and mobilization styles of the managing nurses; relate the behavioral profiles to the individual competences of the managing nurses; as defined by the company and, finally, finance policies of training and development of nurses, who act in this sector. The investigation is characterized as exploratory research, descriptive type, developed in the modality of case study. The setting of the study was a private organization, health services rendering company, with the particularity of acting in the diagnostic medicine field. The subjects of the research were constituted by the total of 36 managing nurses in the units of healthcare advisory and board of directors of education of the company. The data collection was performed in two steps, between August and October, 2008. The first step was constituted of documentary research. In the second step, there was an application of a questionnaire with guiding questions, which allow to characterize demographically the managing nurses and, also, was delivered the diagnostic questionnaire of the motivational guidance, aiming to identify the behavioral profiles and mobilization styles of these leaderships. Thirty-five out of 36 managing nurses participated in the study, representing 97,22% of the group. The statistical treatment of the data, related to the answers of the questions of this instrument allowed to present the following results: the mobilization style with higher representativity in the nursing managers group is the negotiator, totalizing 25,71%, which represents nine managers; followed by the supporter, 17,14%, which represents six managers; 14,29%, five managers have specialist mobilization style; 14,29%, five managers have conqueror mobilization style; 11,43%, four managers have creator mobilization style; 8,57%, representing three managers, have competitor mobilization style and, finally, 8,57%, three managers have cooperator mobilization style. Regarding to the characteristics of each style, it is highlighted that the competence emotional intelligence, underscored in the different mobilization styles is, and will always be, an indicative of trend and not something which may be deemed as acquired. Considering the specific elements characteristics of the work processes, attendance and managerial, and the strong articulation, which the same should have among themselves, in the work developed by the managing nurses group, the study data reveal that the mobilization profiles presented favor the development of the leadership functions, which are peculiar in the service, as well, the company expectations achievement, in the satisfaction of goals. It should be highlighted that the fragile points of each profile need continually of investments as permanent education, as well, the strong points need the constant feedback by the board of directors, which defines strategic goals

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Tam, Christine. „Defining microenvironment-induced transcription profiles in breast cancer liver metastases“. Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=123094.

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Breast cancer is the most common type of cancer diagnosed in Canadian women, with metastatic spread contributing to the majority of cancer-related deaths. The liver is the third most frequent site of breast cancer metastasis, but not much is known about the hepatic microenvironment's role in regulating the growth and survival of metastatic cells in the liver. In order to elucidate these interactions, we used laser capture microdissection and microarray analysis to compare gene expression patterns of liver metastases and primary tumors. We employed liver-aggressive 4T1 breast cancer cells derived from an in vivo selection process to generate mammary tumors and liver metastases in female Balb/c mice. Mice with liver metastases were kept for three different time periods post-injection to assess the changes in gene expression during metastatic development. Laser capture microdissection was used to isolate cores and margins of tumors and liver metastases, as well as tumor-adjacent and –distal normal liver. Transcription profiling revealed significant gene expression changes within breast cancer cells growing in the fat pad and the liver microenvironments. We identified a set of immune-related genes overexpressed in the liver metastases that may represent putative myeloid/granulocytic cell markers. Lcn2 and S100a8/S100a9 were found to be exclusively expressed in the immune compartment of liver metastases, particularly within smaller lesions. Since concurrent studies in our laboratory have revealed a similar recruitment of Gr1+/NE+ cells around breast cancer liver metastases, Lcn2 and S100a8/a9 represent interesting avenues with which to investigate the role that these infiltrating cell types play in supporting breast cancer liver metastasis.
Le cancer du sein est le cancer le plus fréquent chez la femme au Canada. Les métastases demeurent la principale cause de décès associée au cancer du sein. Chez ces patients, le foie est le troisième site le plus fréquent pour la formation de métastases. À ce jour, très peu est connu concernant les interactions éventuelles entre le microenvironnement hépatique et les cellules cancéreuses qui y croissent. Pour ce faire, nous avons utilisé un processus de sélection in vivo pour générer, à partir des cellules 4T1, des sous-populations de cellules murines de cancer du sein. Ainsi, les cellules obtenues ont pour caractéristique principale de former des tumeurs mammaires mais surtout de préférentiellement former des métastases hépatiques dans les souris Balb/c. Dans le but de déterminer les changements d'expression des gènes qui se produisent pendant le processus de développement des métastases au foie, nous avons initialement collecté des tumeurs primaires et des métastases hépatiques après trois différentes périodes de temps. Par la suite, nous avons utilisé la microdissection par capture laser pour isoler différentes régions dans les tumeurs ou les métastases, soit le centre des lésions, la périphérie des lésions ou des régions de foie non cancéreuses adjacentes ou distales aux lésions. L'analyse de l'expression des gènes a révélé de nombreuses différences dans l'expression des gènes entre les tumeurs mammaires et les métastases hépatiques. Ainsi, en comparant les métastases hépatique aux tumeurs primaires, nous avons identifié la surexpression d'un ensemble de gènes normalement exprimés par les cellules myéloïdes ou granulocytaires. Parmi ces gènes, Lcn2 et S100a8/S100a9 sont exprimé exclusivement par les cellules immunitaires présentes au niveau des métastases, surtout au niveau des plus petites lésions. Considérant que des études conduites dans notre laboratoire ont également démontré un recrutement similaire de cellules immunitaire Gr1+/NE+ (neutrophiles) au niveau des métastases au foie, il appert que Lcn2 et S100a8/a9 représentent des candidats intéressants pour l'étude des interactions entre système immunitaire et cellules cancéreuses pour le développement de métastases hépatiques dérivées du cancer du sein.

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Borkum, Megan Sara. „Chronic kidney disease prevalence and ambulatory blood pressure profile in healthy HIV positive subjects pre and post anti-retroviral therapy“. Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/19881.

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Introduction: Few studies have been done in South Africa to establish the extent of chronic kidney disease (CKD) in stable outpatients infected with the human immunodeficiency virus (HIV). Both HIV and the anteretroviral therapy (ART) used to treat HIV have been associated with abnormal metabolic profile, increased cardiovascular risk and renal disease1,2,3. Hypertension has been found to be common in HIV infected individuals, in European and American cohorts, with a prevalence ranging from 13- 34%2. Nocturnal blood pressure (BP) is superior to daytime or office BP as a predictor of cardiovascular disease4. However, the relationship between circadian BP patterns, measured via ambulatory blood pressure (ABP) monitoring, and HIV has never been documented in the South African HIV infected population. Individuals with an abnormal diurnal rhythm and a blunted nocturnal decline in systolic BP (SBP), i.e. ≤ 10%, are referred to as 'non- dippers' and have the highest risk of cardiovascular complications4. HIV itself has been associated with a non- dipping status and may play a role in the HIV related increase in cardiovascular risk5.

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DI, VARA NICOLAS. „Study of time profiles of heavy scintillating crystals“. Doctoral thesis, Università degli Studi di Milano-Bicocca, 2014. http://hdl.handle.net/10281/54672.

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In the field of particle therapy Positron Emission Tomography has proven to be the most reliable three dimensional imaging technique for beam monitoring. The standard solution for future PET scanners is to make use of heavy scintillating crystals coupled to Silicon PhotoMultipliers. This thesis is devoted to the full characterization of the parameters that influence time resolution in a scintillator/photodetector setup, with particular attention focused on the impact of time profiles of heavy scintillators on the performance. Moreover a time resolved study of rise time is proposed.

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Fessenden, Sean D. „Torsional Testing of Race, K3 and Profile Nickel Titanium Endodontic Files“. VCU Scholars Compass, 2004. http://scholarscompass.vcu.edu/etd/1012.

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Rotary endodontic instruments have different cross sectional designs that may effect their resistance to torsional stress. The purpose of this study is to evaluate the static torsional properties of two nickel titanium files that have recently been introduced for use in endodontics and compare them to the same size Profile instruments. Ten new files of each brand and size were tested. The files tested were: RaCe 25 tip 0.02, 0.04, 0.06 taper, K3 and Profile 25 and 40 tip in 0.02, 0.04 and 0.06 taper. The diameter of each file was measured at 3mm from tip. The last three millimeters of the working area of the file was grasped with a non-rotating stainless steel chuck and the handle was held in freely rotating chuck. Torque was applied with the Instron Universal Tester in a counter-clockwise direction to simulate the direction of torque encountered clinically. The crosshead speed was set to produce 2 rotations per minute until fracture occurred. The maximum torque achieved and the rotations to fracture were recorded. A multi-way ANOVA of rotations revealed that RaCe 25-0.02 exhibited significantly less rotations to fracture than Profile and K3 of the same size (p<0.0001). RaCe 25 tip exhibited lower maximum torque in all tapers than corresponding K3 and Profile instruments. The mean diameter was significantly smaller for the RaCe files. In this study the RaCe file series exhibited lower values for maximum torque and rotations to fracture. These results should be taken into account while using these files clinically, however further testing is indicated.

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Babb, Lisa. „Influence of facial profile on social perceptions: a 3D video imaging study“. VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/2979.

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The purpose of this study was to evaluate the influence of facial convexity on the perception of social attributes in a young adult population. Nine models were asked to pose for a 3 dimensional photograph that was then modified to represent ideal, retrognathic, and prognathic facial convexity angles. Survey evaluators were shown digital videos of models with ideal and non-ideal profiles and asked to rate their perception of the following 4 social attributes: intelligence, athleticism, popularity, and leadership ability using a visual analog scale. Results gathered from 271 evaluators showed that the model images with ideal facial convexity angles were rated higher on average than the same model images with retrognathic and prognathic profiles. The differences in ratings between ideal and non-ideal profiles were significant for intelligence (P = 0.0009), athleticism (P = 0.0002), and leadership ability (P = 0.0008). Differences in perceived popularity (P = 0.2169) showed no significant differences among facial convexities.

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Higer, Samantha B. „Pressure-time profile analysis to select surfaces that effectively redistribute pediatric occipital pressure“. Thesis, Tufts University, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1589455.

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Pressure ulcers are a hospital-acquired condition with reported incidence of up to 27% in acutely ill infants and children, who are particularly vulnerable during long periods of immobilization. Pressure is a key risk factor for pressure ulcer formation and pressure-redistributing surfaces are used in the clinical setting to mitigate this risk. However, there is a lack of information on the most effective surfaces available to redistribute pressure in pediatric patients, especially because the occiput is the highest risk location for pediatric patients, while the sacrum and heels are at highest risk for adults. The aim of this research is to evaluate the pressure-redistributing properties of surfaces used to redistribute pressure under the bony prominence of the occiput of hospitalized pediatric patients through pressure mapping experiments on healthy children.

A commercially available pressure mapping system is validated for use in the pediatric population through studies on sensitivity, accuracy, creep and repeatability. Then, the capacitive pressure sensor is used to measure mean peak pressure and contact area between the occipital region of the skull of children under 6 years old and each of four pressure-redistributing surfaces: gel, foam, fluidized, and air cushion. Lastly, finite element analysis is performed to simulate the pressure generated on the occiput during contact with a foam surface for two loading conditions. Predictions from the finite element model are compared to experimental pressure mapping data. The results of this study provide clinical recommendations for pediatric pressure ulcer prevention protocols.

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Alayadhi, Nadyah Y. A. H. „Establishing an essential medicine list for the State of Kuwait“. Thesis, University of Bradford, 2017. http://hdl.handle.net/10454/15742.

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The Health Sector at the state of Kuwait is facing many challenges. One of which is public expectations in health are high, and thus, the Ministry of Health (MOH) in Kuwait has amplified the health expenditure by 86% since 2007. And since the medicine budget represents half of the total MOH budget, it is proposed that the development in health policy might be a suitable tool to control the inflation within the health budget. This thesis examines the opportunities and challenges of introducing an EML in Kuwait and the factors influencing its effectiveness. A mixed-methodology approach has been used to enhance and validate the data, in the form of interviews, comparative studies and questionnaires. One major limitation to the research was the lack of previous data relating to this work, and the information should be gathered in person in the form of hard copies, and later, the data was analysed using qualitative and quantitative approaches. It has been attained that, the EML might be a valuable tool if adopted and implemented appropriately, EML adjustment to country health situation is crucial for successful utilisation and fulfilling the concept objectives. Standard Treatment Guidelines are fundamental part of EM selection process, in Kuwait there were lack in the uniformity of the local STG, but fortunately, there is an eagerness to innovate, and the medicine situation might benefit from a type of organisation, overall, if the EML implemented efficiently in Kuwait, it might help in improving the general health and control the inflation in MOH budget.

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Fitzpatrick, Martin Antony. „Do differentiated macrophages display distinct metabolic profiles reflecting their different functions?“ Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/7036/.

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Macrophages are key players in both regulatory and inflammatory immune responses. They are implicated in the pathogenesis of rheumatoid arthritis (RA) where they accumulate in the synovium and produce pro-inflammatory cytokines including TNFα and IL-6. The rheumatoid synovium is metabolically distinctive, with low oxygen perfusion and high concentrations of lactate and reactive oxygen species (ROS). Macrophages are known to respond to metabolic signals, therefore we wanted to explore whether metabolic phenotypes of differentiated macrophages could play a role in the persistence of RA. We used an in vitro model of pro-inflammatory “classically activated” and “alternatively activated” macrophages to study macrophage behaviour using metabolomic and transcriptomic techniques. Differentiation with GMCSF and M-CSF produced macrophages with distinctive profiles. GM-CSF macrophages were metabolically active, metabolising glucose, glutamine and fatty acids, while M-CSF macrophages utilised fatty acid β-oxidation alone. Activation of macrophages with LPS, LPS+IFNγ or IL-4 produced metabolic changes, however, differences between MCSF groups were modest. LPS activation of GM-CSF macrophages drove both depletion of intracellular metabolites and transcriptional downregulation. In contrast, IL-4 activation of M-CSF macrophages was metabolically activating. We propose that the metabolic adaptability of GM-CSF macrophages may put them at an energetic advantage in the hypoxic, ROS-enriched rheumatoid synovium.

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Salle-Essoo, Maya de. „Le profane et le sacré dans les tradipratiques à l’île Maurice“. Thesis, La Réunion, 2011. http://www.theses.fr/2011LARE0010/document.

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Dans cette thèse nous avons abordé les tradipratiques à l'île Maurice et nous avons tenté de délimiter une zone d'interculturalité où se situent ces tradipratiques, partagées par les différentes communautés religieuses et ethnoculturelles de l'île et s'insérant dans un fonds commun mauricien. Ainsi, nous avons constaté qu'il existe une conception commune de la maladie, du corps, des Invisibles et des traitements qui font partie de cette zone interculturelle, issue du contact de cultures et de la créolisation. Nous avons ainsi été amenée à envisager l'imbrication du sacré et du profane au sein des tradipratiques et fait le constat que ces deux facettes sont indissociables et nécessaires à l'efficacité des traitements. Nous avons également envisagé les rituels de soins sous leur aspect identitaire, mettant en évidence le rôle central joué par les ancêtres dans les traitements, la transmission transgénérationnelle du don de guérison et de voyance, mais également comme agents à l'origine de certains syndromes. Ce qui nous amène à souligner l'aspect identitaire des rituels de soins venant répondre à la nécessité de réaffirmer les liens aux ancêtres, la filiation du patient et celle de sa famille, l'insérant dans un groupe et renforçant ainsi son identité
In this PhD thesis, the traditional medicinal practices were considered within the context of Mauritius Island and we have attempted to delimitate an area of interculturality where traditional medicinal practices are taking place and are shared by the different religious and ethnocultural communities of the island and are inserted in a common Mauritian ground. Thus, we have discovered that there is a common conception of the disease, the body, the invisibles, treatments, making part of this intercultural zone and resulting from the contact with cultures and creolization. We have thus considered the interweaving of the sacred and the secular within the traditional practices and made the statement that these two aspects were inseparable and necessary for the efficiency of treatments. We have also considered the healing rituals from the angle of identity while revealing the central role played by the ancestors in these treatments, in the inter-generational transmission of the gift of healing and clairvoyance but also as agents causing specific syndromes. This leads us to stress out the necessity to reaffirm the links toward the ancestors, the filiation of the patient and his family, inserting him in a group and therefore reinforcing his identity

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GIUDICI, FABIOLA. „Metodi statistici per la stima di profili di rischio personalizzati basati sulla medicina di precisione del cancro nei pazienti oncologici“. Doctoral thesis, Università degli studi di Padova, 2022. http://hdl.handle.net/11577/3458751.

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Precision medicine is beginning to emerge as a well-defined discipline with specific goals, areas of focus, and tailored methodology. Specifically, the primary goal is to discover treatment rules that leverage heterogeneity to improve clinical decision making in a manner that is reproducible, generalizable, and adaptable as needed. This endeavor spans a broad range of scientific areas including drug discovery, genetics/genomics, health communication, and causal inference, all in support of evidence-based, i.e., data-driven, decision making. Precision Medicine allows patients to be discriminated according to their level of risk (e.g. low or high) and identifies subgroups of patients according to their characteristics in order to assign the treatment to those who are likely to benefit. Statistics research in precision medicine is broadly focused on methodological development for estimation of and inference for treatment regimens that maximize some cumulative clinical outcome. The process for using statistical inference to establish personalized treatment strategies requires specific techniques for data-analysis that optimize the combination of competing therapies with candidate genetic features and characteristics of the patient and disease. The present dissertation focuses on the implementation and application of statistical methods for establishing optimal treatment rules for personalized medicine and discuss specific examples in various medical contexts with oncology as an emphasis. I have focused my research activity mainly in the study of the following topics. 1) Statistical methods to analyze continuous biomarkers. Several approaches were considered according to the design of study: from classical approach - median or mean value, percentiles, optimal cut-point identified by means standard receiver operating characteristic (ROC) analysis-to more complex analysis - time-dependent ROC, conditional inferential tree and subpopulation Treatment Effect Pattern (STEPP) method. 2) Statistical methods for time-to-event endpoints. Competing risks occur commonly in medical research. In the analysis of competing risks data, methods of standard survival analysis lead to incorrect and biased results. In the presence of competing risks, data analysis has to be performed including methods to calculate the cumulative incidence of an event of interest, to compare cumulative incidence curves in the presence of competing risks, and to perform competing risks regression analysis. 3) Meta-analysis for synthesizing evidence. 4) An important topic reviews to use of several statistical methods that handle the issue of treatment switching. The contribution aims at assessing tamoxifen treatment effect taking into account treatment switches, in order to provide a robust assessment of treatment effect applying causal inference methods. 5) The last topic deals with the use of population-based registry and administrative databases. The objective of this project is to develop an acceptable claims-based algorithm to identify second breast cancer events during a 10-year follow-up through a record-linkage of two data sources:the Friuli Venezia Giulia population based-cancer registry and the administrative individual-record FVG database.
Precision medicine is beginning to emerge as a well-defined discipline with specific goals, areas of focus, and tailored methodology. Specifically, the primary goal is to discover treatment rules that leverage heterogeneity to improve clinical decision making in a manner that is reproducible, generalizable, and adaptable as needed. This endeavor spans a broad range of scientific areas including drug discovery, genetics/genomics, health communication, and causal inference, all in support of evidence-based, i.e., data-driven, decision making. Precision Medicine allows patients to be discriminated according to their level of risk (e.g. low or high) and identifies subgroups of patients according to their characteristics in order to assign the treatment to those who are likely to benefit. Statistics research in precision medicine is broadly focused on methodological development for estimation of and inference for treatment regimens that maximize some cumulative clinical outcome. The process for using statistical inference to establish personalized treatment strategies requires specific techniques for data-analysis that optimize the combination of competing therapies with candidate genetic features and characteristics of the patient and disease. The present dissertation focuses on the implementation and application of statistical methods for establishing optimal treatment rules for personalized medicine and discuss specific examples in various medical contexts with oncology as an emphasis. I have focused my research activity mainly in the study of the following topics. 1) Statistical methods to analyze continuous biomarkers. Several approaches were considered according to the design of study: from classical approach - median or mean value, percentiles, optimal cut-point identified by means standard receiver operating characteristic (ROC) analysis-to more complex analysis - time-dependent ROC, conditional inferential tree and subpopulation Treatment Effect Pattern (STEPP) method. 2) Statistical methods for time-to-event endpoints. Competing risks occur commonly in medical research. In the analysis of competing risks data, methods of standard survival analysis lead to incorrect and biased results. In the presence of competing risks, data analysis has to be performed including methods to calculate the cumulative incidence of an event of interest, to compare cumulative incidence curves in the presence of competing risks, and to perform competing risks regression analysis. 3) Meta-analysis for synthesizing evidence. 4) An important topic reviews to use of several statistical methods that handle the issue of treatment switching. The contribution aims at assessing tamoxifen treatment effect taking into account treatment switches, in order to provide a robust assessment of treatment effect applying causal inference methods. 5) The last topic deals with the use of population-based registry and administrative databases. The objective of this project is to develop an acceptable claims-based algorithm to identify second breast cancer events during a 10-year follow-up through a record-linkage of two data sources:the Friuli Venezia Giulia population based-cancer registry and the administrative individual-record FVG database.

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Ribeiro, Helena Isabel Canejo Lalanda. „Rinotraqueíte Infecciosa Bovina num efectivo de bovinos de carne: uma análise multifactorial na perspectiva da Medicina de Grupo“. Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2010. http://hdl.handle.net/10400.5/2072.

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Dissertação de Mestrado Integrado em Medicina Veterinária
A produção tradicional Ribatejana de bovinos de carne em regime extensivo baseia-se em pastos naturais, dependentes das condições climáticas mediterrânicas, e na distribuição sazonal de suplementação alimentar (Verão e Inverno). Na realidade agropecuária de Portugal, a abordagem técnica e científica à bovinicultura de carne extensiva é ainda incipiente, não se encontrando muitas publicações científicas subordinadas a este tema. Os serviços médico-veterinários são uma ferramenta essencial no fomento da produtividade, sendo exigido um perfil multivalente ao médico veterinário, que se estende para além da formação veterinária básica. Só assim poderá prestar um bom serviço aos produtores, apoiando-os na tomada de decisões fundamentadas em análises multifactoriais do desempenho dos animais e do ambiente que os rodeia. Na perspectiva de melhorar o conhecimento acerca desta temática, pretendeu-se demonstrar, com um estudo de caso, que se podem aplicar fundamentos técnico-científicos na produção de bovinos de carne em extensivo. A partir de uma suspeita de Rinotraqueíte Infecciosa Bovina (IBR), descreve-se a abordagem a um problema reprodutivo num efectivo, integrando, à luz dos princípios da Medicina de Grupo, conhecimentos multidisciplinares, com vista à optimização do estado hígido dos animais e da sua produtividade. Recorrendo a técnicas de regressão linear, identificaram-se como factores com maior impacto na fertilidade deste efectivo, a condição corporal e a seropositividade à IBR. Determinou-se ainda a viabilidade económica de um potencial aumento do encabeçamento deste efectivo, com vista a uma maior rentabilização da exploração.
ABSTRACT - Infectious Bovine Rhinotracheitis in a beef herd: a multifactorial analysis under the principles of herd health - Ribatejo’s traditional beef herd breeding is based on a grazing system, having natural pasture as background, which nutritional value depends on the Mediterranean climatic conditions, as well as seasonal supplementation of feed (Summer and Winter). In the Portuguese agricultural and cattle breeding reality, the technical and scientific approach to the grazing beef herd is yet incipient, and it is difficult to find scientific studies about this issue. Veterinary services are an essential tool for increasing productivity. This means an additional demand on the veterinarians: a multivalent profile that goes beyond basic veterinary qualifications. This is the only way to provide good quality services to farmers, supporting them in the decision-making process with multifactorial analysis of animal performance and their surrounding environment. With the purpose of improving the existing knowledge about this issue, it was the aim of this case-study to demonstrate that it is possible to apply technical and scientific principles to the grazing beef cattle production. The approach to a reproductive problem is described, starting with an Infectious Bovine Rhinotracheitis (IBR) suspicion, integrating, under Herd Health principles, knowledge relative to several disciplines, regarding optimization of animal higid state and productivity. Concerning fertility reduction, it was possible to identify, based on linear regression techniques, body condition and IBR seropositivity as the main contributing factors. The economic viability of increasing stocking rate was also determined, which leads to interest increase.

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Castaño, Villadiego Faider Alberto. „Parâmetros reprodutivos e produtivos em vacas leiteiras em free- stall“. Universidade Federal de Viçosa, 2013. http://locus.ufv.br/handle/123456789/5137.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico
This study was aimed to evaluate the productive and reproductive performance of dairy cows, in free stalls, immediately after postpartum. The herd was composed of 51 Holstein primiparous and multiparous cows, aged 3 to 7 years and mean body weight of 594.4±65.1 kg. The dairy farm managed all the nutrition, leasing, health, as well as milking times. After calving, cows were supplemented with 6 kg of concentrate/cow/day and corn silage for the 1st 20 days of lactation. Subsequently 1 kg of concentrate was supplied for every 3 kg milk/day, taking in consideration the average of the animals. Corn silage was supplemented ad-libitum. The variables studied were: birth intervals until first ovulation, first service or first IA; pregnancy rate to first service, number of services per conception and service period, parity, body condition score, body weight at calving, calf sex, absence or presence of retained placenta, uterine infection, total milk yield, days in milk, and daily milk production. The statistical program SAEG-2007 was used to analyze the descriptive data (means and standard deviations), and ANOVA for quantitative data and chi-square for a categorical variable (pregnancy rate). Not normal and homologous data was analyzed by nonparametric analysis and compared by Kruskall Wallis test or Wilcoxon test. A 5% significance level was adopted for all analyses. The mean values obtained were: body condition score at calving of 3.47±0.4; calving interval to first ovulation of 5.89±3.4 weeks postpartum, first artificial insemination of 112.5±57.0 days postpartum, no difference was found in these parameters between delivery times of parturition (P>0.05). The pregnancy rate to first service was 43.6% and pregnancy rate in the experimental period was of 76.4%, with no difference between delivery times of parturition (P>0.05). Milk production accumulated in conception was of 3335.6±1488.4 liters and an average accumulated in conception was of 25.8±5.4 liters per day and Milk production adjusted to 305 days was of 7424.0±1877.8 liters. Management of production employed in free-stalls for all reproductive and productive traits observed was considered satisfactory. Detection of estrus, measured here by the number of first insemination estrus, might have been the biggest limiting factor to achieve lower values of service period and reproductive efficiency.
Este trabalho teve como objetivo avaliar os parâmetros produtivos e reprodutivos em vacas de aptidão leiteira no pós-parto imediato, criados em manejo de free-stall. O grupo estudado foi composto por 51 vacas da raça holandês entre primíparas e pluríparas, com idade entre 3 a 7 anos e peso corporal médio de 594,4±65,1 kg. O manejo nutricional, sanitário e manejo de locação e de ordenha das vacas foram os mesmos adotados pela granja leiteira. Após o parto, as vacas foram suplementadas com 6 kg de concentrado/vaca/dia e silagem de milho a vontade foi fornecidos até completar 20 dias de lactação. Posteriormente foi fornecido 1 kg de concentrado para cada 3 kg de leite/dia, considerado a média do lote e silagem de milho a vontade para todos os animais. As variáveis estudadas foram: intervalos do parto à primeira ovulação, ao primeiro serviço ou primeira IA; taxa de gestação ao primeiro serviço; número de serviços por concepção e período de serviço, ordem de parto, escore de condição corporal, peso corporal ao parto, sexo do bezerro, presença ou ausência de retenção de placenta, infecção uterina, produção de leite total, dias de lactação e produção de leite diária. O programa estatístico SAEG-2007 foi empregado para analisar os dados, onde se efetuou a estatística descritiva (médias e desvios-padrão) e ANOVA para os dados quantitativos e Qui-Quadrado para a variável categórica (taxa de gestação). Os dados que não apresentaram normalidade e homocidacidade foram analisados por analise não paramétrica e comparadas pelos testes de Kruskall Wallis ou Wilcoxon. Adotou-se 5% de significância para todas as analises. Os valores médios obtidos foram: escore de condição corporal ao parto de 3,47±0,4; intervalo de parto a primeira ovulação de 5,89±3,4 semanas pós-parto; primeira inseminação artificial aos 112,5±57,0 dias pós-parto, não sendo observada diferença destes parâmetros entre as ordens de parto (P>0,05). A taxa de gestação ao primeiro serviço foi de 43,6% e taxa de gestação no período experimental de 76,4%, não havendo diferença entre as ordens de parto (P>0,05). A produção de leite acumulada à concepção, produção diária leite até a concepção e produção de leite ajustado para 305 (PRODL305) foi respectivamente de 3.335,6±1.488,4; 25,8±5,4 e 7.424,0±1.877,8 litros. Conclui-se que no manejo de produção empregado Free-Stall, os valores observados para todas as características reprodutivas e produtivas são consideradas satisfatórias; a detecção de estro, aqui avaliado pelo numero de estro a primeira inseminação, talvez possa ter sido o maior fator limitante para alcançar valores menores de período de serviço e eficiência reprodutiva.

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Corti, P. „Afasia Progressiva Primaria: identificazione di n profilo neuropsicologico predittivo e correlazione con biomarcatori liquorali e neuroimaging“. Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/218465.

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Un gruppo internazionale di clinici, esperti in disturbi progressivi del linguaggio, si riunì per tre volte tra il 2006 ed il 2009, con lo scopo di creare un classificazione definitiva delle PPA e delle sue tre varianti, utilizzando come punto di partenza i criteri esistenti in letteratura (Tabella 1 - Mesulam, 2003) ma integrandoli alla luce delle informazioni fornite dalle strumentazioni più recenti (neuroimaging, dosaggio liquorale). Le linee guida cosi delineate prevedono che, affinché la diagnosi di PPA sia verosimile, l'insorgenza del disturbo linguistico deve apparire insidiosa e dall'andamento ingravescente; l'afasia deve essere evidente sia nel linguaggio spontaneo che in seguito ad una valutazione neuropsicologica e deve rappresentare, almeno nella fase iniziale, il sintomo d’esordio, nonché il segno clinico più evidente. L'autonomia nelle attività di base ed in quelle strumentali della vita quotidiana deve essere preservata, ad eccezione di quelle attività strettamente correlate all'utilizzo del linguaggio. Tutte le altre funzioni cognitive dovrebbero risultare coinvolte solo successivamente, ma l'afasia rappresenterà comunque il deficit cognitivo più evidente per tutta la durata della malattia. I principali criteri di esclusione includono un disturbo mnesico o visuo-spaziale nelle fasi iniziali della malattia, marcati disturbi comportamentali e la presenza di lesioni focali (ictus, tumori). La recente classificazione della PPA proposta da Gorno-Tempini in tre differenti varianti: non-fluente (NFPA), semantica (SVPA) e logopenica (LPA) (Gorno-Tempini et al., 2011), richiede un processo diagnostico complesso, che si articola su tre livelli differenti: l’assessment neuropsicologico, il neuroimaging e l’analisi liquorale. In questo studio abbiamo correlato i risultati ottenuti in test specifici, scelti per indagare le caratteristiche linguistiche tipiche di ogni variante di PPA, con i livelli liquorali delle proteine Aβ, Tau e Ptau, ed il pattern atrofico riscontrato alla risonanza magnetica. Lo scopo della ricerca è quello di creare una batteria neuropsicologica in grado di effettuare ipotesi diagnostiche e realizzare diagnosi differenziale tra le singole varianti di PPA già nelle fasi iniziali della malattia. Lo scopo della nostra ricerca è proprio questo: individuare test cognitivi che più di altri siano predittivi nell’individuare la possibile presenza di PPA già nelle fasi inziali della patologia. Si è partiti dalla consapevolezza che i domini cognitivi maggiormente compromessi siano la capacità di denominazione, la comprensione, la scrittura, la lettura, la ripetizione e la capacità di fruibilità lessicale. Si sono, infatti, selezionate cinque prove: la batteria di Milano II, per l’indagine delle competenza linguistiche, il Token Test, per valutare la comprensione di ordini verbali, le fluenze verbali, per indagare la fruibilità lessicale, il Boston Naming Test per la capacità di denominazione e il Mini Mental State Examination per l’efficienza cognitiva globale. Analizzando la correlazione tra i tre diversi marcatori considerati (test neuropsicologici, localizzazione delle aree atrofiche e dosaggio liquorale) è emerso che la presenza di agrammatismo, e di aprassia verbale rappresentano i deficit neuropsicologici più sensibili per la diagnosi di NFPA già nelle fasi iniziali della patologia. Punteggi al di sotto del range normativi, ottenuti nelle prove di ripetizione (sia di parole, non parole che di frasi complesse), rappresenta un buon predittore per la diagnosi di LPA. Infine, punteggi patologici nelle prove di lettura (soprattutto di frasi) e di denominazione di stimoli visivi (Boston Naming Test) potrebbe essere un indicatore precoce per la diagnosi di SPA. Obiettivo futuro sarà quello di ampliare il campione e proseguire con follow-up longitudinali a 6-8 mesi per delineare il progredire della patologia. Inoltre, per ciascuno dei test somministrati si cercherà di determinare dei valori soglia specifici per la diagnosi di PPA in modo da consentirne pieno utilizzo diagnostico, già nelle fasi iniziali della malattia, soprattutto in contesti clinici in cui non sia possibile determinare i biomarcatori liquorali.

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49

Lau, Whitney Charlena. „Temperamental Profiles of Children with Communication Impairment“. Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etd/1323.

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The temperament literature available that involves children with communication impairments is limited but promising. The purpose of this study was to investigate the temperamental profiles of children with autism spectrum disorders, primary language impairments, phonological/articulation impairments, and combined phonological and language impairments. Participants included 38 children who attended the East Tennessee State University Speech-Language-Hearing Clinic at the time of the study or in the past 10 years. Parents of eligible participants were asked to complete demographic and temperament questionnaires about their children. Results indicated that the temperamental profiles of children with communication impairments differed significantly from typically developing children in terms of the superdimensions Negative Emotionality, Effortful Control, and Sociability/Affiliation. Temperamental differences were also noted between diagnostic groups. While the results of this pilot study are promising, further research is necessary to investigate the intricacies of the relationships identified in this study.

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Hanekom, Susan. „The profile of a surgical ICU in a public sector tertiary hospital in South Africa“. Thesis, Stellenbosch : University of Stellenbosch, 2004. http://hdl.handle.net/10019.1/16335.

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Thesis (MScFisio)--University of Stellenbosch, 2004.
ENGLISH ABSTRACT: Objective: To describe the baseline data of a surgical ICU in South Africa before the implementation of an evidence-based physiotherapy practice protocol. Design: Prospective cohort observational study Setting: Ten-bed closed surgical unit in a university affiliated tertiary hospital. Patients: All adult ICU admissions from 16 June - 30 September 2003. Measurements: The patient’s clinical data including demographic information, admission diagnosis, surgery classification and co-morbidities were recorded on admission to the unit. APACHE II score was calculated. The physiotherapy techniques, positions and functional activities used, the frequency and duration of physiotherapy treatment sessions, the provision of after-hours service and the diagnosis of pulmonary complications were also recorded daily. The time of mechanical ventilation was calculated and the number of re-intubations documented. The ICU length of stay or mortality was recorded. Results: 160 patients were admitted. Patients were 49 +/- 19.95 years of age. The mean APACHE II score was 12.3 +/ 7.19 and a 12.3% mortality was observed. Thirty seven percent of patients were admitted to the unit following elective surgery. Patients stayed in the unit for 5.94 +/- 6.55 days. Hypertension was the most frequent co-morbidity found in this cohort (42%), and 21% of patients tested, tested positive for HIV. Co-morbidities had no significant association with ICU LOS or mortality. Nine hundred and twenty seven physiotherapy records were obtained. Students were responsible for 39% (n=366) of treatment sessions, the unit therapist for 34% (n=311) and the on-call therapists for 27% (n=250). Despite routine daily physiotherapy for all patients in the unit, 39% (n=62) developed excessive secretions, 30% (n=48) of patients developed pneumonia and 27% (n=43) of patients were diagnosed with basal atelectasis. Nineteen patients (12%) died in the ICU. Patients spent a mean of 5.94 (SD 6.55) days in the unit. One hundred patients (63%) were ventilated. Almost a third of ventilated patients (31%) were intubated more than once. The patients spent a mean time of 3.8 days (SD 6.30) on the ventilator every time they were re-intubated. The development of pulmonary complications significantly increased the time on the ventilator and the LOS. Conclusions: This baseline study of a surgical ICU presents a picture of a unit providing care comparable to first world environments. The picture of the physiotherapy service provided in this unit is of a “traditional” service based neither on the available evidence regarding the prevention or management of pulmonary complications, nor on the incorporation of early rehabilitation into the management of mechanically ventilated adult patients in ICU.
AFRIKAANSE OPSOMMING: Doel: Om die basis lyn van ‘n chirurgiese intensiewe sorg eenheid in Suid Afrika te beskryf voor die implementering van ‘n bewysgesteunde fisioterapie protokol in die eenheid. Studie struktuur: Prospektiewe kohort observerende studie. Eenheid: Tien bed geslote eenheid in ‘n tertiêre opleidingshospitaal. Pasiënte: Alle volwasse pasiënte opgeneem in die eenheid tussen 16 Junie en 30 September 2003. Meetings: Demografiese data, diagnose met opname, chirurgie klassifikasie en ko-morbiditeite is aangeteken by opname. APACHE II is bereken. Die fisioterapie tegnieke, pasiënt posisies en funksionele aktiwiteite gebruik in behandelingssessies, die frekwensie en duur van behandelingssessies, die verskaffing van na-ure diens aan die eenheid asook die komplikasies gediagnoseer is daagliks aangeteken. Die tyd wat pasiënte geventileer is asook die aantal kere geher-intubeer is bereken. Die tydsduur van eenheid verblyf asook mortaliteit is aangeteken. Results: 160 pasiënte is opgeneem, met ‘n gemiddelde ouderdom van 49 +/- 19.95. Die gemiddelde APACHE II telling was 12.3 +/ 7.19 en die mortaliteit was 12.3%. Sewe en dertig persent van pasiënte is opgeneem na elektiewe chirurgie. Pasiënte bly in die eenheid gemiddeld vir 5.94 +/- 6.55 dae. Hipertensie was die mees algemene ko-morbiditeit (42%), en 21% van die pasiënte wat getoets is, het positief getoets vir HIV. Ko-morbiditeite het geen beduidende verband getoon met die tyd in die eenheid of mortaliteit nie. 927 Fisioterapie rekords is aangeteken. Studente was verantwoordelik vir 39% (n=366) van die behandelingssessies, die eenheid terapeut vir 34% (n=311) en die op-roep fisioterapeute vir 27% (n=250). Ten spyte van daaglikse roetine fisioterapie behandeling van alle pasiënte in die eenheid het 39% (n=62) oormatige sekresies ontwikkel, 30% (n=48) is met pneumonie gediagnoseer en 27% (n=43) met basale atelektase. Negentien pasiënte (12%) is dood in die eenheid. Die tydsduur van eenheid verblyf was 5.94 (SD 6.55) dae. Een honderd pasiënte (63%) is geventileer. Byna een derde (31%) van pasiënte is geher-intubeer. Met elke her-intubasie het die pasiënte gemiddeld 3.8 (SD 6.30) dae langer op die ventilator gebly. Pulmonale komplikasies het beide die tydsduur in die eenheid as op die ventilator betekenisvol verleng. Gevolgtrekkings: Hierdie basislyn studie beskryf ‘n eenheid waar pasiënte mediese sorg ontvang soortgelyk aan eerste wêreld lande. Die fisioterapeutiese diens wat gelewer word is egter nie gebasseer op die nuutste bewyse in die literatuur nie. Nog, in die voorkoming of in die behandeling van pulmonale komplikasies, nog in die vroëere inkorporasie van rehabilitasie in die hantering van volwasse pasiënte in ‘n intensiewe sorg eenheid.

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Dissertationen zum Thema „Medicinal profile“

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