Nanosensor for assessing the risk of a cardiovascular disease

The incidence of cardiovascular diseases (CVD) has been increasing according to the European and global statistics. Thus, the development of new analytical devices, such as biosensors for assessing the risk of CVD could become a valuable approach for the improvement of healthcare service. In latest years, the nanotechnology has provided new materials with improved electronic properties which have an important contribution in the transduction mechanism of biosensors. Thus, in this thesis, biosensors based on field effect transistors with single-walled carbon nanotubes (NTFET) were developed for the detection of C-reactive protein (CRP) in clinical samples, that is, blood serum and saliva from a group of control patients and a group of CVD risk patients. CRP is an acute-phase protein, which is commonly known as the best validated biomarker for the assessment of CVD, the single-walled carbon nanotubes (SWCNT) were applied as transduction components, and the immunoreaction (interaction between the CRP antigen and the antibodies specific to CRP) was used as the mechanism of molecular recognition for the label-free detection of CRP. After the microfabrication of field effect transistors (FET), the screening of the most important variables for the dispersion of SWCNT, the assemblage of NTFET, and their application on standard solutions of CRP, it was found that NTFET respond accurately to CRP both in saliva and in serum samples, since similar CRP levels were found with the NTFET and the traditional methodology (ELISA technique). On the other hand, a strong correlation between salivary and serum CRP was found with NTFET, which means that saliva could be used, based on non-invasive sampling, as an alternative fluid to blood serum. It was also shown that NTFET could discriminate control patients from CVD risk patients, allowing the determination of a cut-off value for salivary CRP of 1900 ng L-1, which corresponds to the well established cut-off of 3 mg L-1 for CRP in serum, constituting an important finding for the possible establishment of a new range of CRP levels based on saliva. According to the data provided from the volunteer patients regarding their lipoprotein profile and lifestyle factors, it was concluded that the control and the CVD risk patients could be separated taking into account the various risk factors established in literature as strong contributors for developing a CVD, such as triglycerides, serum CRP, total cholesterol, LDL cholesterol, body mass index, Framingham risk score, hypertension, dyslipidemia, and diabetes mellitus. Thus, this work could provide an additional contribution to the understanding of the association of biomarkers levels in serum and saliva samples, and above all, cost-effective, rapid, label-free, and disposable NTFET were developed, based on a noninvasive sampling, for the assessment of CVD risk, thus constituting a potential point-of-care technology.

Hemodiálise : qualidade de vida e parâmetros nutricionais

Tese de doutoramento, Ciências e Tecnologias da Saúde (Nutrição), Universidade de Lisboa, Faculdade de Medicina, 2014

Estudo exploratório da excitabilidade axonal com a "técnica threshold tracking" : controlos saudáveis e doentes com polineuropatia amilóide familiar

Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2015

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

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

The attractive female body weight and female body dissatisfaction in 26 countries across 10 world regions: results of the International Body Project I

This study reports results from the first International Body Project (IBP-I), which surveyed 7,434 individuals in 10 major world regions about body weight ideals and body dissatisfaction. Participants completed the female Contour Drawing Figure Rating Scale (CDFRS) and self-reported their exposure to Western and local media. Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across high-socioeconomic-status (SES) sites. Within cultures, heavier bodies were preferred in low-SES sites compared to high-SES sites in Malaysia and South Africa (ds = 1.94-2.49) but not in Austria. Participant age, body mass index (BMI), and Western media exposure predicted body weight ideals. BMI and Western media exposure predicted body dissatisfaction among women. Our results show that body dissatisfaction and desire for thinness is commonplace in high-SES settings across world regions, highlighting the need for international attention to this problem.

Patterns of cortisol and DHEA secretion and relationships with attachment style and psychosocial variables in female adolescents: a developmental psychopathology approach

This programme of research used a developmental psychopathology approach to investigate females across the adolescent period. A two-sided story is presented; first, a study of neuroendocrine and psychosocial parameters in a group of healthy female adolescents (N = 63), followed by a parallel study of female adolescents with anorexia nervosa (AN) (N = 8). A biopsychosocial, multi-method measurement approach was taken, which utilised self-report, interview and hypothalamic-pituitary-adrenocortical (HPA) axis measures. Saliva samples for the measurement of cortisol and DHEA were collected using the best-recommended methodology: multiple samples over the day, strict reference to time of awakening, and two consecutive sampling weekdays. The research was adolescent-orientated: specifically, by using creative and ageappropriate strategies to ensure participant adherence to protocol, as well as more generally by adopting various procedures to facilitate engagement with the research process. In the healthy females mean (± SD) age 13.9 (± 2.7) years, cortisol and DHEA secretion exhibited typical adult-like diurnal patterns. Developmental markers of chronological age, menarche status and body mass index (BMI) had differential associations with cortisol and DHEA secretory activity. The pattern of the cortisol awakening response (CAR) was sensitive to whether participants had experienced first menses, but not to chronological age or BMI. Those who were post-menarche generally reached their peak point of cortisol secretion at 45 minutes post-awakening, in contrast to the pre-menarche group who were more evenly spread. Subsequent daytime cortisol levels were also higher in post-menarche females, and this effect was also noted for increasing age and BMI. Both morning and evening DHEA were positively associated with developmental markers. None of the situational or self-report psychosocial variables that were measured modulated any of the key findings regarding cortisol and DHEA secretion. The healthy group of girls were within age-appropriate norms for all the self-report measures used, however just under half of this group were insecurely attached (as assessed by interview). Only attachment style was associated with neuroendocrine parameters. In particular, those with an anxious insecure style exhibited a higher awakening sample (levels were 7.16 nmol/l, 10.40 nmol/l and 7.93 nmol/l for secure, anxious and avoidant groups, respectively) and a flatter CAR (mean increases over the awakening period were 6.38 nmol/l, 2.32 nmol/l and 8.61 nmol/l for secure, anxious and avoidant groups, respectively). The afore-mentioned pattern is similar to that consistently associated with psychological disorder in adults, and so this may be a pre-clinical vulnerability factor for subsequent mental health problems. A group of females with AN, mean (± SD) age 15.1 (± 1.6) years, were recruited from a specialist residential clinic and compared to the above group of healthy control (HC) female adolescents. A general picture of cortisol and DHEA hypersecretion was revealed in those with AN. The mean (± SD) change exhibited in cortisol levels over the 30 minute post-awakening period was 7.05 nmol/l (± 5.99) and 8.33 nmol/l (± 6.41) for HC and AN groups, respectively. The mean (± SD) evening cortisol level for the HC girls was 1.95 nmol/l (± 2.11), in comparison to 6.42 nmol/l (± 11.10) for the AN group. Mean (± SD) morning DHEA concentrations were 1.47 nmol/l (± 0.85) and 2.25 nmol/l (± 0.88) for HC and AN groups, respectively. The HC group’s mean (± SD) concentration of 12 hour DHEA was 0.55 nmol/l (± 0.46) and the AN group’s mean level was 0.89 nmol/l (± 0.90). This adrenal steroid hypersecretion evidenced by the AN group was not associated with BMI or eating disorder symptomatology. Insecure attachment characterised by fearfulness and anger was most apparent; a style which was unparalleled in the healthy group of female adolescents. The causal directions of the AN group findings remain unclear. Examining some of the participants with AN as case studies one year post-discharge from the clinic illustrated that for one participant who was recovered, in terms of returning to ordinary school life and no longer exhibiting clinical levels of eating disorder symptomatology, her CARs were no longer inconsistent over sampling days and her DHEA levels were also now generally comparable to the healthy control group. For another participant who had not recovered from her AN one year later, the profile of her CAR continued to be inconsistent over sampling days and her DHEA concentrations over the diurnal period were significantly higher in comparison to the healthy control group. In its entirety, this work’s unique contribution lies in its consideration of methodological and developmental issues specifically pertaining to adolescents. Findings also contribute to knowledge of AN and understanding of vulnerability factors, and how these may be used to develop interventions dedicated to improving adolescent health.

Circulating pancreatic polypeptide concentrations predict visceral and liver fat content

CONTEXT AND OBJECTIVE: No current biomarker can reliably predict visceral and liver fat content, both of which are risk factors for cardiovascular disease. Vagal tone has been suggested to influence regional fat deposition. Pancreatic polypeptide (PP) is secreted from the endocrine pancreas under vagal control. We investigated the utility of PP in predicting visceral and liver fat. PATIENTS AND METHODS: Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy. RESULTS: Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01). CONCLUSIONS: Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.

Acute hypoxia reduces plasma myostatin independent of hypoxic dose

Background: Muscle atrophy is seen ~ 25 % of patients with cardiopulmonary disorders, such as chronic obstructive pulmonary disorder and chronic heart failure. Multiple hypotheses exist for this loss, including inactivity, inflammation, malnutrition and hypoxia. Healthy individuals exposed to chronic hypobaric hypoxia also show wasting, suggesting hypoxia alone is sufficient to induce atrophy. Myostatin regulates muscle mass and may underlie hypoxic-induced atrophy. Our previous work suggests a decrease in plasma myostatin and increase in muscle myostatin following 10 hours of exposure to 12 % O2. Aims: To establish the effect of hypoxic dose on plasma myostatin concentration. Concentration of plasma myostatin following two doses of normobaric hypoxia (10.7 % and 12.3 % O2) in a randomised, single-blinded crossover design (n = 8 lowlanders, n = 1 Sherpa), with plasma collected pre (0 hours), post (2 hours) and 2 hours following (4 hours) exposure. Results: An effect of time was noted, plasma myostatin decreased at 4 hours but not 2 hours relative to 0 hours (p = 0.01; 0 hours = 3.26 [0.408] ng.mL-1, 2 hours = 3.33, [0.426] ng.mL-1, 4 hours = 2.92, [0.342] ng.mL-1). No difference in plasma myostatin response was seen between hypoxic conditions (10.7 % vs. 12.3 % O2). Myostatin reduction in the Sherpa case study was similar to the lowlander cohort. Conclusions: Decreased myostatin peptide expression suggests hypoxia in isolation is sufficient to challenge muscle homeostasis, independent of confounding factors seen in chronic cardiopulmonary disorders, in a manner consistent with our previous work. Decreased myostatin peptide may represent flux towards peripheral muscle, or a reduction to protect muscle mass. Chronic adaption to hypoxia does not appear to protect against this response, however larger cohorts are needed to confirm this. Future work will examine tissue changes in parallel with systemic effects.

Translation and Psychometric Evaluation of a Standard Chinese Version of the Body Appreciation Scale-2

The present study examined the factorial and construct validity of a Standard Chinese translation of the Body Appreciation Scale (BAS-2; Tylka & Wood-Barcalow, 2015b). Participants were 191 women and 154 men from mainland China who were resident in Hong Kong at the time of recruitment. Results of confirmatory factor analysis indicated that the one-dimensional model of the BAS-2, in which all 10 items loaded onto the same factor, had adequate fit and was invariant across sex. Body appreciation scores had good internal consistency and were significantly correlated with self-esteem and life satisfaction, and, in women, with weight discrepancy and body mass index. There were no significant differences in body appreciation scores between women and men. The present findings suggest that the Standard Chinese translation of the BAS-2 has the same one-dimensional factor structure as its parent scale and may facilitate cross-cultural studies of positive body image.

Adaptação ocupacional de indivíduos obesos a partir dos conceitos de identidade e competência ocupacional: associação com os níveis de atividade física e os valores máximos de pressão plantar

A Obesidade é considerada um grave problema de saúde pública, com consequências negativas para os indivíduos obesos, nomeadamente dificuldades no desempenho de atividades de vida diária, na locomoção e na prática de exercício físico, o que pode restringir a participação em atividades sociais e de lazer. Esta investigação consiste num estudo quantitativo descritivo e tem como objetivo principal descrever de que forma os indivíduos adultos obesos classificam a sua adaptação ocupacional, a partir dos conceitos de identidade e competência ocupacional. Com este estudo, pretende-se ainda verificar se os indivíduos obesos apresentam níveis de atividade física mais baixos e valores mais elevados de pressão plantar, em relação a indivíduos com peso normal. A amostra é constituída por dez indivíduos adultos, de ambos os sexos, com índice de massa corporal igual (IMC) ou superior a 30 Kg/m2, e os instrumentos de avaliação utilizados são o Questionário Ocupacional (adaptado por N. Riopel com assistência de G. Kielhofner e J. Hawkins Watts – 1986), o IPAQ – Versão Curta e o Sistema de Palmilhas Pedar. A partir dos resultados, pode-se verificar que os indivíduos obesos apresentam uma rotina diária em que a maioria das atividades realizadas está relacionada com a casa, o trabalho e o descanso e que a percentagem de atividades de lazer em que participam é reduzida. No entanto, parecem satisfeitos com o seu desempenho na maior parte das atividades, consideram que muitas delas são importantes para si e estão motivados para as realizar. Dos resultados obtidos, podemos sugerir que os indivíduos obesos apresentam boa adaptação ocupacional. Pode-se ainda dizer que os indivíduos obesos apresentam um baixo nível de intensidade de atividade física, não se observando diferenças significativas relativamente aos indivíduos com peso normativo e que os seus valores máximos de pressão plantar normalizados são inferiores quando comparados com a população de peso normal.

O impacto do excesso de gordura corporal sobre a remodelação óssea de adolescentes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise do padrão motor em pessoas com diagnóstico de esquizofrenia: uma abordagem em tempo real

A esquizofrenia é uma perturbação mental grave caracterizada pela coexistência de sintomas positivos, negativos e de desorganização do pensamento e do comportamento. As alterações motoras são consistentemente observadas mas, ainda pouco estudadas na esquizofrenia, sendo relevantes para o seu diagnóstico. Neste quadro, o presente estudo tem como objetivo verificar se os indivíduos com esquizofrenia apresentam alterações na coordenação motora, comparativamente com o grupo sem esquizofrenia, bem como analisar se as disfunções dos sinais neurológicos subtis (SNS) motores se encontram correlacionadas com o funcionamento executivo e com os domínios psicopatológicos da perturbação. No total participaram 29 indivíduos (13 com diagnóstico de esquizofrenia e 16 sem diagnóstico) equivalentes em termos de idade, género, escolaridade e índice de massa corporal. Para avaliar o desempenho motor recorreu-se ao sistema Biostage de parametrização do movimento em tempo real, com a tarefa de lançameto ao alvo; a presença de SNS foi examinada através da Brief Motor Scale; o funcionamento executivo pela aplicação do subteste do Vocabulário e da fluência verbal e a sintomatologia clínica através da Positive and Negative Sindrome Scale. Pela análise cinemática do movimento constatou-se que os indivíduos com esquizofrenia recrutam um padrão motor menos desenvolvido e imaturo de movimento, com menor individualização das componentes (principalmente do tronco e pélvis), necessitando de mais tempo para executar a tarefa, comparativamente com os sujeitos sem a perturbação que evidenciaram um movimento mais avançado de movimento. Os indivíduos com esquizofrenia mostraram índices elevados de disfunção dos SNS (média =6,01) estabelecendo este domínio uma relação boa e negativa com o desempenho verbal (rho Spearman=-0,62) e uma relação forte e positiva com todos os domínios psicopatológicos (rho Spearman=0,74). O estudo da existência de alterações motoras como parte intrínseca da esquizofrenia revela-se pertinente uma vez que possibilita uma compreensão mais aprofundada da sua fisiopatologia e permite que se desenvolvam práticas mais efetivas na área da saúde e reabilitação.

The effect of long-chain polyunsaturated fatty acids intake during pregnancy on adiposity of healthy full-term offspring at birth

Objective - The adjusted effect of long-chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy on adiposity at birth of healthy full-term appropriate-for-gestational age neonates was evaluated. Study Design - In a cross-sectional convenience sample of 100 mother and infant dyads, LCPUFA intake during pregnancy was assessed by food frequency questionnaire with nutrient intake calculated using Food Processor Plus. Linear regression models for neonatal body composition measurements, assessed by air displacement plethysmography and anthropometry, were adjusted for maternal LCPUFA intakes, energy and macronutrient intakes, prepregnancy body mass index and gestational weight gain. Result - Positive associations between maternal docosahexaenoic acid intake and ponderal index in male offspring (β=0.165; 95% confidence interval (CI): 0.031–0.299; P=0.017), and between n-6:n-3 LCPUFA ratio intake and fat mass (β=0.021; 95% CI: 0.002–0.041; P=0.034) and percentage of fat mass (β=0.636; 95% CI: 0.125–1.147; P=0.016) in female offspring were found. Conclusion - Using a reliable validated method to assess body composition, adjusted positive associations between maternal docosahexaenoic acid intake and birth size in male offspring and between n-6:n-3 LCPUFA ratio intake and adiposity in female offspring were found, suggesting that maternal LCPUFA intake strongly influences fetal body composition.