Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Objective: To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.

Design: Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.

Setting: General population.

Participants: 26 018 men and women aged 50-79 years

Main outcome measures: All-cause, cardiovascular, and cancer mortality.

Results: 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.

Conclusions: Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Models of Mortality - Analysing the Residuals

The area of mortality modelling has received significant attention over the last 20 years owing to the need to quantify and forecast improving mortality rates. This need is driven primarily by the concern of governments, professionals, insurance and actuarial professionals and individuals to be able to fund their old age. In particular, to quantify the costs of increasing longevity we need suitable model of mortality rates that capture the dynamics of the data and forecast them with sufficient accuracy to make them useful. In this paper we test several of those models by considering the fitting quality and in particular, testing the residuals of those models for normality properties. In a wide ranging study considering 30 countries we find that almost exclusively the residuals do not demonstrate normality. Further, in Hurst tests of the residuals we find evidence that structure remains that is not captured by the models.

Minimal intervention dentistry and older patients part 2: minimally invasive operative interventions

As described in the first paper of this two part series, the expansion of our older population and the concomitant reduction in levels of edentulism will result in an increase in the number of patients presenting in general practice with complex restorative challenges. The application of the concepts of minimal intervention dentistry and minimally invasive operative techniques may offer a powerful armamentarium to the general dentist to provide ethical and conservative treatment to older patients.

Clinical Relevance: When it is unavoidable, operative intervention should be as minimally invasive as practicable in older patients to preserve the longevity of their natural dentition.

Living long and ageing well: is epigenomics the missing link between nature and nurture?

Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50 % of the variability in human lifespan with another 25 % explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages.

Cellular responses to genome mistranslation

Low level protein synthesis errors can have profound effects on normal cell physiology and disease development, namely neurodegeneration, cancer and aging. The biology of errors introduced into proteins during mRNA translation, herein referred as mistranslation, is not yet fully understood. In order to shed new light into this biological phenomenon, we have engineered constitutive codon misreading in S. cerevisiae, using a mutant tRNA that misreads leucine CUG codons as serine, representing a 240 fold increase in mRNA translational error relative to typical physiological error (0.0001%). Our studies show that mistranslation induces autophagic activity, increases accumulation of insoluble proteins, production of reactive oxygen species, and morphological disruption of the mitochondrial network. Mistranslation also up-regulates the expression of the longevity gene PNC1, which is a regulator of Sir2p deacetylase activity. We show here that both PNC1 and SIR2 are involved in the regulation of autophagy induced by mistranslation, but not by starvation-induced autophagy. Mistranslation leads to P-body but not stress-granule assembly, down-regulates the expression of ribosomal protein genes and increases slightly the selective degradation of ribosomes (ribophagy). The study also indicates that yeast cells are much more resistant to mistranslation than expected and highlights the importance of autophagy in the cellular response to mistranslation. Morpho-functional alterations of the mitochondrial network are the most visible phenotype of mistranslation. Since most of the basic cellular processes are conserved between yeast and humans, this study reinforces the importance of yeast as a model system to study mistranslation and suggests that oxidative stress and accumulation of misfolded proteins arising from aberrant protein synthesis are important causes of the cellular degeneration observed in human diseases associated to mRNA mistranslation.

Anodes for protonic ceramic fuel cells (PCFCs)

One of the more promising possibilities for future “green” electrical energy generation is the protonic ceramic fuel cell (PCFC). PCFCs offer a low-pollution technology to generate electricity electrochemically with high efficiency. Reducing the operating temperature of solid oxide fuel cells (SOFCs) to the 500-700°C range is desirable to reduce fabrication costs and improve overall longevity. This aim can be achieved by using protonic ceramic fuel cells (PCFCs) due to their higher electrolyte conductivity at these temperatures than traditional ceramic oxide-ion conducting membranes. This thesis deals with the state of the art Ni-BaZr0.85Y0.15O3-δ cermet anodes for PCFCs. The study of PCFCs is in its initial stage and currently only a few methods have been developed to prepare suitable anodes via solid state mechanical mixing of the relevant oxides or by combustion routes using nitrate precursors. This thesis aims to highlight the disadvantages of these traditional methods of anode preparation and to, instead, offer a novel, efficient and low cost nitrate free combustion route to prepare Ni-BaZr0.85Y0.15O3-δ cermet anodes for PCFCs. A wide range of techniques mainly X-ray diffraction (XRD), scanning electron microscopy (SEM), environmental scanning electron microscopy, (ESEM) and electrochemical impedance spectroscopy (EIS) were employed in the cermet anode study. The work also offers a fundamental examination of the effect of porosity, redox cycling behaviour, involvement of proton conducting oxide phase in PCFC cermet anodes and finally progresses to study the electrochemical performance of a state of the art anode supported PCFC. The polarisation behaviour of anodes has been assessed as a function of temperature (T), water vapour (pH2O), hydrogen partial pressures (pH2) and phase purity for electrodes of comparable microstructure. The impedance spectra generally show two arcs at high frequency R2 and low frequency R3 at 600 °C, which correspond to the electrode polarisation resistance. Work shows that the R2 and R3 terms correspond to proton transport and dissociative H2 adsorption on electrode surface, respectively. The polarization resistance of the cermet anode (Rp) was shown to be significantly affected by porosity, with the PCFC cermet anode with the lowest porosity exhibiting the lowest Rp under standard operating conditions. This result highlights that porogens are not required for peak performance in PCFC anodes, a result contrary to that of their oxide-ion conducting anode counterparts. In-situ redox cycling studies demonstrate that polarisation behaviour was drastically impaired by redox cycling. In-situ measurements using an environmental scanning electron microscopy (ESEM) reveal that degradation proceeds due to volume expansion of the Ni-phase during the re-oxidation stage of redox cycling.The anode supported thin BCZY44 based protonic ceramic fuel cell, formed using a peak performing Ni-BaZr0.85Y0.15O3-δ cermet anode with no porogen, shows promising results in fuel cell testing conditions at intermediate temperatures with good durability and an overall performance that exceeds current literature data.

O apoio domiciliário e os cuidadores informais

Dissertação de Mestrado, Psicologia, Especialização em Psicologia da Saúde, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2009

NAA and STS effects on bract survival time, carbohydrate content, respiration rate and carbohydrate balance of potted Bougainvillea spectabilis Willd

The aims of this work were to deepen the knowledge on the physiology of bract abscission in Bougainvillea spectabilis ‘Killie Campbell’ plants, in what relates to respiration and carbon balance. Using the effects induced by Silver Thiosulphate (STS) and/or Naphtalene Acetic Acid (NAA, at high concentration: 500 mg.l-1) on bract abscission under interior conditions, the relationship between bract survival time (longevity) and, respiration rate or carbohydrate levels, was investigated. Treatments that included NAA were the ones that reduced significantly bract abscission. Unexpectedly, the higher the levels of bract soluble and total carbohydrates, measured at day 10 postproduction (PP), the higher the abscission of bracts. These results show, for the first time, that abscission can positively correlate with non structural carbohydrates levels in the organ that abscise. Bract respiration rate was significantly affected by treatment and postproduction day (PP). Treatments that had higher bract respiration rates (WATER and STS) also had higher levels of non structural carbohydrates in the bracts. Bract respiration rate decreased from day 10 to day 17 PP by approximately 50% (on average of all treatments) and was negatively correlated with bract survival time. In the carbon balance per gram of bract dry weight, the treatments WATER and STS, showed the largest decrease in the content of total carbohydrates and had the highest consumption of carbohydrates through respiration. So, these were the bracts that needed to import a higher amount of carbohydrates per gram of bract dry weight. In the carbon balance for the whole mass of bracts and adjacent stems in an average plant, the treatments WATER and STS continued to allow for the largest decreases in total carbohydrate during postproduction. However, and contradicting the results per gram of bract dry weight, the highest total consumption of carbohydrates by respiration was obtained for the NAA and STS+NAA treatments. It makes sense that bracts that last longer have lower individual carbon consumption while, at the plant level, the increased number of remaining bracts causes a higher overall expenditure. Respiration rate has been used as an indicator of flower longevity, this correlation is here extended for the flower+bract system. Plants that had higher bract respiration rates, most probably, had a higher flow of carbohydrates through the bracts (and flowers), which, in the end, was sensed as a higher carbohydrate level.

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

Copy number variation and Huntington’s disease

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2014

Regulatory interactions between the metabolic sensors SIRT1 and AMPK in modulating PPARα linked functions, in obesity-dependent type 2 diabetes mellitus

Tese de doutoramento, Ciências Biomédicas (Ciências Funcionais), Universidade de Lisboa, Faculdade de Medicina, 2014

Relationship between happiness, stress and musculoskeletal disorders in portuguese dentists

Tese de doutoramento, Medicina Dentária (Dentisteria Conservadora), Universidade de Lisboa, Faculdade de Medicina Dentária, 2016

Purity of Blood and Caste. Identity Narratives among Early Modern Goan Elites

This essay analyses the roles played by purity of blood and caste in seventeenth-and eighteenth-century identity narratives of Goan clites. Goa and its population are usually excluded from the mainstream literature of Indian social history, and seldom related to the early-modern Atlantic world, making this case study all the more valuable as a place to think the topic of blood and caste. The early establishment and the longevity of the Portuguese imperial presence (1510-1961) in Goa, its location at the crossroads of multiple cultural geographies (Iberian and Indian, and later, also Dutch, British and French), as well as the systematic process of religious conversion of its inhabitants and the questions of legal equality that conversion entailed, all intensified the types, textures, layers and meanings of experiences of social differentiation in this colonial context. This mapping of the experiences of purity of blood and caste in early-modem Goa therefore illuminates from a new angle the role of European imperial powers in the mUltiple expressions of racial classification.