Planificación anticipada de decisiones en las enfermedades crónicas avanzadas

Introduction

Advanced care planning (ACP) helps in make decisions on the health problems of people who have lost the capacity for informed consent. It has proven particularly useful in addressing the end of life. The aim of this study was to determine the prevalence of ACP in patients with severe chronic diseases.

Material and methods

Review of medical records of patients with dementia, amyotrophic lateral sclerosis, Parkinson's disease, chronic obstructive pulmonary disease or interstitial lung disease, heart failure, chronic kidney disease on dialysis and cancer, all in advanced stages. We collected data on living wills or registered prior decisions by the physician according to clinical planned.

Results

A total of 135 patients were studied. There was a record of ACP in 22 patients (16.3%). In most of them it was planned not to start any vital treatment in the event of high risk of imminent death and lacking the ability to make decisions. Only two patients were had a legal living will.

Conclusion

The registration of ACP is relatively low, and this can affect decision-making in accordance with the personal values of patients when they do not have the capacity to exercise informed consent.     

Bioavailability and potential carcinogenicity of polycyclic aromatic hydrocarbons from wood combustion particulate matter in vitro

Due to increasing energy demand and limited fossil fuels, renewable energy sources have gained in importance. Particulate matter (PM) in general, but also PM from the combustion of wood is known to exert adverse health effects in human. These are often related to specific toxic compounds adsorbed to the PM surface, such as polycyclic aromatic hydrocarbons (PAH), of which some are known human carcinogens. This study focused on the bioavailability of PAHs and on the tumor initiation potential of wood combustion PM, using the PAH CALUX® reporter gene assay and the BALB/c 3T3 cell transformation assay, respectively. For this, both cell assays were exposed to PM and their respective organic extracts from varying degrees of combustion. The PAH CALUX® experiments demonstrated a concentration–response relationship matching the PAHs detected in the samples. Contrary to expectations, PM samples from complete (CC) and incomplete combustion (IC) provided for a stronger and weaker response, respectively, suggesting that PAH were more readily bioavailable in PM from CC. These findings were corroborated via PAH spiking experiments indicating that IC PM contains organic components that strongly adsorb PAH thereby reducing their bioavailability. The results obtained with organic extracts in the cell transformation assay presented the highest potential for carcinogenicity in samples with high PAH contents, albeit PM from CC also demonstrated a carcinogenic potential. In conclusion, the in vitro assays employed emphasize that CC produces PM with low PAH content however with a general higher bioavailability and thus with a nearly similar carcinogenic potential than IC PM.     

Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K-Akt and NF-κB signaling pathways.     

Effect of Proline Mutations on the Monomer Conformations of Amylin

The formation of human islet amyloid polypeptide (hIAPP) is implicated in the loss of pancreatic β-cells in type II diabetes. Rat amylin, which differs from human amylin at six residues, does not lead to formation of amyloid fibrils. Pramlintide is a synthetic analog of human amylin that shares three proline substitutions with rat amylin. Pramlintide has a much smaller propensity to form amyloid aggregates and has been widely prescribed in amylin replacement treatment. It is known that the three prolines attenuate β-sheet formation. However, the detailed effects of these proline substitutions on full-length hIAPP remain poorly understood. In this work, we use molecular simulations and bias-exchange metadynamics to investigate the effect of proline substitutions on the conformation of the hIAPP monomer. Our results demonstrate that hIAPP can adopt various β-sheet conformations, some of which have been reported in experiments. The proline substitutions perturb the formation of long β-sheets and reduce their stability. More importantly, we find that all three proline substitutions of pramlintide are required to inhibit β conformations and stabilize the α-helical conformation. Fewer substitutions do not have a significant inhibiting effect.     

Pollen production in the Poaceae family

Total pollen production per inflorescence was studied in the most important species of the Poaceae family in the city of Córdoba in order to further our knowledge of the partial contribution of each species of this family to the total amount of pollen released into the atmosphere.

The contribution of grasses in a given area was estimated by counting the number of inflorescences in an area of one square meter. Four different representative areas of the city were selected. The number of pollen grains per anther and flowers per inflorescence was also estimated in order to obtain total pollen production per inflorescence.

Pollen production per inflorescence ranged from 14,500 to more than 22,000,000 pollen grains, the amount being clearly higher in the perennial species. Pollen production per square meter was higher in the mountains near the city and lower in areas of abandoned crops.

Only a few species are responsible for the majority of pollen produced. A phenological study is necessary in order to determine the temporal distribution of this pollen production and subsequent shedding.     

Pollen biology in four Mediterranean Quercus species

Potential pollen production, viability and germination were studied in the most important species of Quercus in the mountains of Córdoba to determine the contribution of each species to the total amount of airborne pollen. The results were compared over two consecutive years with different rainfall patterns. The viability of pollen grains was determined at anther opening, and during the pollination period, in order to determine potential pollination capacity. Results indicated that there were differences in the number of pollen grains produced by stamen in the four species. Equally, there were differences in the number of flowers among the species, being Q. suber the species with higher number of catkins groups and flowers per individual tree. Total pollen production per tree can be summarized in the following proportion: 1: 3: 3: 6 (Q. coccifera, Q. ilex ssp. ballota, Q. faginea and Q. suber). Potential pollen viability was estimated using the Fluorochromatic Reaction (FCR) and a germination assay. The results have shown that Quercus potential pollen viability is high and declines slowly with time. Q. coccifera was the species with the highest percentage of germination, with Q. suber being the lowest.     

Agroecosystems and conservation of migratory waterbirds: importance of coastal pastures and factors influencing their use by wintering shorebirds

Coastal pastures are common agroecosystems adjacent to estuarine areas that can provide valuable habitat for wildlife, particularly for migratory shorebirds. Disentangling the factors that influence coastal pasture use by wintering shorebirds will provide new insights into its role for buffering human disturbances and habitat loss in intertidal areas. We examined whether numbers of two shorebirds (Eurasian curlew and Black-tailed godwit) foraging actively on coastal pastures was affected by weather conditions, tidal stage (low/high tide) and number of harvesters at intertidal areas throughout winter. Both species frequently used coastal pastures and most individuals foraged actively there. The average percentage of the total wintering population of curlews and godwits foraging on coastal pastures was 27.4 and 7.8 %, respectively, and was significantly higher during high tide compared to low tide. The number of harvesters on mudflats also had a positive significant effect in explaining the presence of curlews, and to a lesser extent for godwits, on coastal pastures, and accumulated rainfall had a positive effect for both species too. These supratidal areas were consistently used as alternative foraging grounds during low tide by curlews, as well as supplementary foraging areas during high tide by wintering populations of both large shorebirds. By supplementary foraging, wintering curlews, and probably godwits, seemed to compensate for a negative effect of the presence of harvesters on their foraging activity. We recommend managing of those coastal agricultural fields adjacent to intertidal foraging grounds in order to increase the availability of supratidal foraging habitats for declining shorebird populations. These habitats may thus have a beneficial role in sustaining populations of wintering shorebirds, but further studies are needed to estimate if birds can compensate for any shortfall in daily energy budget by supplementary foraging on coastal pastures, thus providing insights into whether they are involved in large-scale population regulation of migratory birds.     

PEG conjugates of potent α4 integrin inhibitors,maintaining sustained levels and bioactivity in vivo,following subcutaneous administration

Mitsunobu reactions were employed to link t-butyl esters of α4 integrin inhibitors at each of the termini of a three-arm, 40 kDa, branched PEG. Cleavage of the t-butyl esters using HCO₂H provided easily isolated PEG derivatives, which are potent α4 integrin inhibitors, and which achieve sustained levels and bioactivity in vivo, following subcutaneous administration to rats.