Motion Management for Radical Radiotherapy in Non-small Cell Lung Cancer

Intrafraction tumour motion is an issue that is of increased interest in the era of image-guided radiotherapy. It is particularly relevant for non-small cell lung cancer, for which a number of recent developments are in use to aid with motion management in the delivery of radical radiotherapy. The ability to deliver hypofractionated ablative doses, such as in stereotactic radiotherapy, has been aided by improvements in the ability to analyse tumour motion and amend treatment delivery. In addition, accounting for tumour motion can enable dose escalation to occur by reducing the normal tissue being irradiated by virtue of a reduction in target volumes. Motion management for lung tumours incorporates five key components: imaging, breath-hold techniques, abdominal compression, respiratory tracking and respiratory gating. These will be described, together with the relevant benefits and associated complexities. Many studies have described improved dosimetric coverage and reduced normal tissue complication probability rates when using motion management techniques. Despite the widespread uptake of many of these techniques, there is a paucity of literature reporting improved outcome in overall survival and local control for patients whenever motion management techniques are used. This overview will review the extent of lung tumour motion, ways in which motion is detected and summarise the key methods used in motion management.

Anatomy and Neurophysiology of Coughing: CHEST Guideline and Expert Panel Report

Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera as well as somatosensory nerves innervating the chest wall, diaphragm and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychological methods for treatment of dystussia, is high and modern imaging methods have revealed potential neural substrates for some features of cough in the human.

A Prospective Cohort Study of Body Size and Risk of Head and Neck Cancers in the NIH-AARP Diet and Health Study

Background: The association between body size and head and neck cancers (HNCA) is unclear, partly because of the biases in case–control studies. Methods: In the prospective NIH–AARP cohort study, 218,854 participants (132,288 men and 86,566 women), aged 50 to 71 years, were cancer free at baseline (1995 and 1996), and had valid anthropometric data. Cox proportional hazards regression was used to examine the associations between body size and HNCA, adjusted for current and past smoking habits, alcohol intake, education, race, and fruit and vegetable consumption, and reported as HR and 95% confidence intervals (CI). Results: Until December 31, 2006, 779 incident HNCAs occurred: 342 in the oral cavity, 120 in the oro- and hypopharynx, 265 in the larynx, 12 in the nasopharynx, and 40 at overlapping sites. There was an inverse association between HNCA and body mass index, which was almost exclusively among current smokers (HR = 0.76 per each 5 U increase; 95% CI, 0.63–0.93), and diminished as initial years of follow-up were excluded. We observed a direct association with waist-to-hip ratio (HR = 1.16 per 0.1 U increase; 95% CI, 1.03–1.31), particularly for cancers of the oral cavity (HR, 1.40; 95% CI, 1.17–1.67). Height was also directly associated with total HNCAs (P = 0.02), and oro- and hypopharyngeal cancers (P < 0.01). Conclusions: The risk of HNCAs was associated inversely with leanness among current smokers, and directly with abdominal obesity and height. Impact: Our study provides evidence that the association between leanness and risk of HNCAs may be due to effect modification by smoking. Cancer Epidemiol Biomarkers Prev; 23(11); 2422–9. ©2014 AACR.

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lactose into galactose and glucose, after weaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% among Asians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, bowel distension, cramps and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptoms vary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoid the uptake of dairy products, in doing so, they lose a readily available source of calcium and protein. In this work, gels obtained by complexation of Tetronic 90R4 with α-cyclodextrin loaded with β-galactosidase are proposed as a way to administer the enzyme immediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ, and show sustained erosion kinetics in aqueous media. The complex was characterized by FTIR that evidenced an inclusion complex between the polyethylene oxide block and α-cyclodextrin. The release profiles of β-galactosidase from two different matrices (gels and tablets) of the in situ hydrogels have been obtained. The influence of the percentage of Tetronic in media of different pH was evaluated. No differences were observed regarding the release rate from the gel matrices at pH 6 (t50 = 105 min). However, in the case of the tablets, the kinetics were faster and they released a greater amount of 90R4 (25%, t50 = 40–50 min). Also, the amount of enzyme released was higher for mixtures with 25% Tetronic. Using suitable mathematical models, the corresponding kinetic parameters have been calculated. In all cases, the release data fit quite well to the Peppas–Sahlin model equation, indicating that the release of β-galactosidase is governed by a combination of diffusion and erosion processes. It has been observed that the diffusion mechanism prevails over erosion during the first 50 minutes, followed by continued release of the enzyme due to the disintegration of the matrix.

The E3 ubiquitin ligase Pellino3 protects against obesity-induced inflammation and insulin resistance

Diet-induced obesity can induce low-level inflammation and insulin resistance. Interleukin-1β (IL-1β) is one of the key proinflammatory cytokines that contributes to the generation of insulin resistance and diabetes, but the mechanisms that regulate obesity-driven inflammation are ill defined. Here we found reduced expression of the E3 ubiquitin ligase Pellino3 in human abdominal adipose tissue from obese subjects and in adipose tissue of mice fed a high-fat diet and showing signs of insulin resistance. Pellino3-deficient mice demonstrated exacerbated high-fat-diet-induced inflammation, IL-1β expression, and insulin resistance. Mechanistically, Pellino3 negatively regulated TNF receptor associated 6 (TRAF6)-mediated ubiquitination and stabilization of hypoxia-inducible factor 1α (HIF1α), resulting in reduced HIF1α-induced expression of IL-1β. Our studies identify a regulatory mechanism controlling diet-induced insulin resistance by highlighting a critical role for Pellino3 in regulating IL-1β expression with implications for diseases like type 2 diabetes.

Estudo biométrico do caranguejo-de-profundidade de Angola (Chaceon maritae) e determinação do tamanho de primeira maturação sexual

Dissertação de Mestrado, Biologia Marinha, Especialização em Pescas e Aquacultura, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2008

Reações adversas gastrointestinais: causas, prevenção e tratamento

Dissertação de mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Processos de cuidar em enfermagem:idosos com hipertenção arterial

Tese de doutoramento, Enfermagem, Universidade de Lisboa, com a participação da Escola Superior de Enfermagem, 2014

Estudo da relação entre o estado nutricional e défice cognitivo em idosos

Tese de mestrado, Nutrição Clínica, Faculdade de Medicina, Universidade de Lisboa, 2014

Evaluation and Potential Cost-Effectiveness of Active Surveillance Pharmacovigilance for First-Line HAART in Namibia

Thesis (Ph.D.)--University of Washington, 2016-02

Preterm nutritional intake and MRI phenotype at term age: a prospective observational study

Objective: To describe (1) the relationship between nutrition and the preterm-at-term infant phenotype, (2) phenotypic differences between preterm-at-term infants and healthy term born infants and (3) relationships between somatic and brain MRI outcomes. Design: Prospective observational study. Setting: UK tertiary neonatal unit. Participants: Preterm infants (<32 weeks gestation) (n=22) and healthy term infants (n=39) Main outcome measures: Preterm nutrient intake; total and regional adipose tissue (AT) depot volumes; brain volume and proximal cerebral arterial vessel tortuosity (CAVT) in preterm infants and in term infants. Results: Preterm nutrition was deficient in protein and high in carbohydrate and fat. Preterm nutrition was not related to AT volumes, brain volume or proximal CAVT score; a positive association was noted between human milk intake and proximal CAVT score (r=0.44, p=0.05). In comparison to term infants, preterm infants had increased total adiposity, comparable brain volumes and reduced proximal CAVT scores. There was a significant negative correlation between deep subcutaneous abdominal AT volume and brain volume in preterm infants (r=−0.58, p=0.01). Conclusions: Though there are significant phenotypic differences between preterm infants at term and term infants, preterm macronutrient intake does not appear to be a determinant. Our preliminary data suggest that (1) human milk may exert a beneficial effect on cerebral arterial vessel tortuosity and (2) there is a negative correlation between adiposity and brain volume in preterm infants at term. Further work is warranted to see if our findings can be replicated and to understand the causal mechanisms.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.

OBJECTIVE: The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. DESIGN: To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. RESULTS: Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. CONCLUSIONS: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.

Comportamento motor do tronco e membro superior, num sistema de posicionamento rígido e dinâmico, durante atividade

A funcionalidade dos indivíduos com Paralisia Cerebral está muitas vezes comprometida devido às alterações do movimento e do controlo postural. Dadas estas alterações, a posição de sentado oferece uma maior estabilidade sendo muitas das atividades de vida diária desempenhadas nesta posição. O objetivo mais importante de intervenção é obter o máximo de funcionalidade na posição de sentado, particularmente do membro superior. Este objectivo, na maioria das vezes, só pode ser atingido com o uso de sistemas de posicionamento que tentam colmatar as alterações posturais e do movimento. Assim, o objetivo deste estudo de caso é verificar se existem diferenças no comportamento motor do tronco e do membro superior, com um sistema de posicionamento rígido e com um sistema de posicionamento dinâmico, numa jovem com Paralisia Cerebral, aquando da ativação manual de um switch. Foi realizado um estudo de caso único em que foi feita uma análise cinemática do movimento do tronco e membro superior na ativação de um switch BigMack, em três posições de teste com distâncias diferentes. Simultaneamente mediu-se a distribuição do peso durante o movimento, através do mapa de pressão e foi registada, bilateralmente a atividade dos músculos trapézio (porção média), longuíssimo, recto abdominal e oblíquo externo. Os resultados obtidos apontam, neste caso em particular, para uma melhoria na qualidade do movimento e da distribuição de peso, com o sistema de posicionamento dinâmico, sem diferenças entre os dois sistemas relativamente à ativação muscular.

Relação entre a unidade de biofeedback de pressão, deslocamento do centro de pressão e atividade eletromiográfica durante o active straight leg raising em indivíduos com e sem dor lombo-pélvica.

Introdução: A unidade de biofeedback de pressão, em indivíduos com dor lombo-pélvica, é utilizada durante exercícios de estabilização segmentar, no entanto ainda carece de evidência científica. Objetivo: Determinar a relação entre a unidade de biofeedback de pressão (UBFP), o deslocamento do centro de pressão no sentido médio-lateral (COPml) e a atividade eletromiográfica abdominal durante o active straight leg raising (ASLR) em indivíduos com e sem dor lombo-pélvica, bem como identificar diferenças entre os grupos. Metodologia: Estudo transversal analítico em 18 estudantes universitários voluntários com dor lombo-pélvica crónica inespecífica (GCD) e em 20 sem dor (GSD). Durante o ASLR (desafio postural dinâmico) foram avaliadas as variações máxima e média da pressão (recorrendo à UBFP) e do deslocamento do COPml (através da plataforma de forças), bem como a atividade muscular abdominal, bilateralmente, com recurso à eletromiografia de superfície. Estatisticamente recorreu-se à correlação de Spearman e ao teste Mann-Whitney U, ambos com um nível de significância de 0,05. Resultados: No GCD, ao contrário do GSD, não foi verificada uma relação entre a UBFP e a atividade do transverso abdominal/obliquo interno (TrA/OI) contra-lateral. Correlações moderadas, mas com sentidos opostos, foram evidenciadas em ambos os grupos, entre o deslocamento do COPml e a atividade do TrA/OI contra-lateral. Em ambos os grupos, a UBFP demonstrou estar fortemente correlacionada com o COPml. Não foram observadas diferenças significativas entre os grupos nas variáveis avaliadas. Conclusão: A UBFP, no GCD, não se apresentou relacionada com a atividade do TrA/OI. Contudo, demonstrou uma relação com o deslocamento do COPml, em ambos os grupos, sendo portanto um indicador de estabilidade do tronco e assim, uma ferramenta útil em ambiente clínico. No GCD observou-se que uma maior atividade muscular TrA/OI pressupõe maior deslocamento do COPml, sendo uma relação contrária à verificada no GSD, podendo ser um indicador da perda da sua ação tónica.

Clay body wrap with microcurrent: effects in central adiposity

Introduction Increased fat mass is becoming more prevalent in women and its accumulation in the abdominal region can lead to numerous health risks such as diabetes mellitus. The clay body wrap using compounds such as green clay, green tea and magnesium sulfate, in addition to microcurrent, may reduce abdominal fat mass and minimize or prevent numerous health problems. Objective This study aims at measuring the influence of the clay body wrap with microcurrent and aerobic exercise on abdominal fat. Methods Nineteen female patients, randomized into intervention (n = 10) and control (n = 9) groups, were evaluated using ultrasound for visceral and subcutaneous abdominal fat, calipers and abdominal region perimeter for subcutaneous fat and bioimpedance for weight, fat mass percentage and muscular mass. During 10 sessions (5 weeks, twice a week) both groups performed aerobic exercise in a cycloergometer and a clay body wrap with microcurrent was applied to the intervention group. Results When comparing both groups after 5 weeks of protocol, there was a significant decrease in the subcutaneous fat around left anterior superior iliac spine in the intervention group (ρ = 0.026 for a confidence interval 95%). When comparing initial and final abdominal fat in the intervention group, measured by ultrasound (subcutaneous and visceral fat) and by skinfold (subcutaneous fat), we detected a significant abdominal fat reduction. Conclusion This study demonstrated that the clay body wrap used with microcurrent and aerobic exercise can have a positive effect on central fat reduction.