Porphyrin-based supramolecular nanofibres as a dynamic and activatable photosensitiser for photodynamic therapy.

Photodynamic therapy (PDT) represents a promising treatment modality for a range of cancers and other non-malignant diseases due to its non-invasive nature arising from the light-dependent activation. However, PDT has not been the first-line treatment of cancer thus far as a consequence of, among others, the lack of effective transport and activation strategies, and the undesired side effect caused by skin photosensitisation induced by the "always on" photosensitisers. To overcome this "Achilles' heel", we present herein a non-covalent approach to construct a one-component dynamic supramolecular nanophotosensitising system based on a carefully designed porphyrin. The control of the photoactivities of the resulting supramolecular fibres lies in the spatiotemporal control of the monomer-polymer equilibrium. Both the thermodynamics and kinetics of this nanosystem have been carefully studied by different techniques. Moreover, in vitro and in vivo studies have also been performed, showing that these supramolecular aggregates exhibit facile cell internalisation and progressive disassembly after being endocyted by targeted cells, leading to activation of the photosensitising units and eventually cell death and tumour eradication under photoirradiation.

Germination response to water availability in populations of Festuca pallescens along a Patagonian rainfall gradient based on hydrotime model parameters.

Sensitivity to water availability is a key physiological trait for grassland species located in arid and semiarid environments, where successful germination is closely related to rainfall dynamics. Festuca pallescens inhabits diverse environments along a steep precipitation gradient in North Patagonia, thus offering a suitable model for the study of germination behavior in response to water availability. By analyzing germination in nine populations using a hydrotime model approach, we aimed to find within-species variation. Seed population behavior was analyzed under different hydric conditions using hydrotime model parameters (hydrotime, mean base water potential and its standard deviation). We estimated the mean base water potential for F. pallescens (ψb(50) = - 2.79 ± 0.45 MPa), which did not differ significantly between populations. However, the hydrotime parameter (θH) varied markedly, suggesting physiological adaptation to local environments. Higher values of θH were found in populations located at the extremes of the distribution gradient, indicating that germination may be prevented or delayed in conditions that are suboptimal for the species. Since the variation in hydrotime model parameters did not follow a cline, micro-environmental cues may have the greatest influence on the physiological behavior of the species, rather than the macroscale rainfall gradient.

[Does Omega-3 supplementation after the age of 65 influence cognitive function? Results of a systematic review]. / ¿La ingesta o suplementación con ácidos grasos omega-3 a partir de los 65 años influye en la función cognitiva? Resultados de una revisión sistemática.

BACKGROUND: The percentage of the older population is progressively increasing as are diseases associated with aging such as cognitive decline (CD) and dementia. Observational epidemiological studies suggest that diets rich in omega 3 polyunsaturated fatty acids (w3-PUFA) might reduce the risk of CD and dementia. The main objective was to assess whether there is sufficient scientific evidence about the relationship between w3-PUFA supplementation in patients aged 65 or older and cognitive performance. METHODS: We used the Pubmed data base to search for articles related to w3-PUFA and CD or dementia. Initially we identified 582 articles, after applying the eligibility criterion we included six studies in this systematic review. RESULTS: The studies included were heterogeneous regarding population, measurement of exposure and outcome. Therefore, it was not possible to conduct a quantitative analysis. Two studies found that w3-PUFA supplementation decreased the risk of Alzheimer and improved cognitive performance. Two studies found an improvement in only one of the domains of cognitive performance (visual analogical classification and verbal fluency) and another two did not find any evidence of protection. CONCLUSIONS: We found few studies to support or refute the evidence that w3-PUFA supplementation in patients aged 65 or older improves cognitive performance or prevents dementia.

High Blood Pressure States in Children, Adolescents, and Young Adults Associate Accelerated Vascular Aging, with a Higher Impact in Females' Arterial Properties.

The aims of the study were to determine (1) whether the presence of High blood pressure (HBP) states in the youth associate a steeper rate of age-related change in arterial geometrical and wall properties with respect to subjects with no previous cardiovascular risk factor (CRF) exposure, (2) in which parameters and in what magnitude, and (3) the existence of a gender-related difference in the impact of this condition on arterial properties. 300 individuals (mean/range: 15/4-29 years; 133 females) were included. Two groups were assembled: (1) Reference: nonprevious exposure to traditional CRF and (2) HBP: subjects with arterial hypertension and/or elevated blood pressure (BP) levels during the study. Additionally, HBP subjects were separated in BP-related subgroups. Measured parameters were (1) central (aortic) arterial BP and aortic pulse wave analysis parameters, (2) carotid and femoral artery local (pressure-strain elastic modulus) and regional (pulse wave velocity; PWV) stiffness, and (3) arterial diameters and carotid intima-media thickness (CIMT). Age-related changes in these parameters (absolute values and z-scores) were explored by obtaining simple linear regression models for each group. HBP presented a steeper rate of change (accelerated vascular aging; VA) for most of the parameters assessed, mainly in central (aortic) hemodynamics. VA increased as the HBP level got higher. Both males' and females' aging rates were affected by this condition, but females presented a more marked relative age-related increase with HBP exposure. HBP states in the youth gradually associate accelerated VA, with a progressive hemodynamic-structural-functional onset of damage, with females presenting a more marked relative HBP-associated arterial repercussion.

Growing-Related Changes in Arterial Properties of Healthy Children, Adolescents, and Young Adults Nonexposed to Cardiovascular Risk Factors: Analysis of Gender-Related Differences.

The aims of our work were to determine normal aging rates for structural and functional arterial parameters in healthy children, adolescents, and young adults and to identify gender-related differences in these aging rates. Methods. 161 subjects (mean: 15 years (range: 4-28 years), 69 females) were studied. Subjects included had no congenital or chronic diseases, nor had they been previously exposed to traditional cardiovascular risk factors. Arterial parameters assessed were (1) central blood pressure (BP) and aortic pulse wave analysis, (2) arterial local (pressure-strain elastic modulus) and regional (pulse wave velocity, PWV) stiffness, and (3) arterial diameters and carotid intima-media thickness (CIMT). Simple linear regression models (age as the independent variable) were obtained for all the parameters and the resulting rates of change were compared between genders. Results. No gender-related differences were found in mean values of arterial structural and functional parameters in prepubertal ages (4-8 years), but they started to appear at ~15 years. Boys showed a greater rate of change for central systolic BP, central pulse pressure, CIMT, and carotid-femoral PWV. Conclusion. Gender-related differences in arterial characteristics of adults can be explained on the basis of different growing-related patterns between boys and girls, with no existing differences in prepubertal ages.

Functional diversity of phytochrome family in the control of light and gibberellin-mediated germination in Arabidopsis.

In several species, seed germination is regulated by light in a way that restricts seedling emergence to the environmental conditions that are likely to be favourable for the success of the new individual, and therefore, this behaviour is recognized to have adaptive value. The phytochromes are one of the most relevant photoreceptors involved in light perception by plants. We explored the redundancy and diversity functions of the phytochrome family in the control of seed responsiveness to light and gibberellins (GA) by using a set of phytochrome mutants of Arabidopsis. Our data show that, in addition to the well-known role of phyB in the promotion of germination in response to high red to far-red ratios (R/FR), phyE and phyD stimulate germination at very low R/FR ratios, probably by promoting the action of phyA. Further, we show that phyC regulates negatively the seed responsiveness to light, unravelling unexpected functions for phyC in seed germination. Finally, we find that seed responsiveness to GA is mainly controlled by phyB, with phyC, phyD and phyE having relevant roles when acting in a phyB-deficient background. Our results indicate that phytochromes have multiple and complex roles during germination depending on the active photoreceptor background.

On the relative stability of self-assembled metallosupramolecular subphthalocyanine capsules determined by ESI-Q-TOF tandem mass spectrometry.

A comparative study of the relative stability of subphthalocyanine metallosupramolecular capsules bearing different metals and ligands has been carried out by electrospray ionization quadrupole time-of-flight tandem mass spectrometry experiments. The results highlight the trends in the strength of metal-nitrogen bonds as well as the 'trans effect' of certain ligands.

Main results of strategic noise maps and action plans in Navarre (Spain).

According to Directive 2002/49, strategic noise maps and their correspondent action plans were carried out in the Autonomous Community of Navarre, Spain. Six strategic noise maps were produced for 120 km of major roads as well as a strategic noise map for the Agglomeration of the Region of Pamplona (ARP) with a population of 280,199 inhabitants. In the ARP, a total of 36,400 people (13.0 %) are exposed to Ln levels over 55 dBA and 42,300 people (15.1 %) are exposed to Lden levels over 65 dBA. With regard to major roads, a total of 3,900 people are exposed to Ln levels over 55 dBA and 2,400 people are exposed to Lden levels over 65 dBA. When designing action plans, different prioritisation criteria concerning rank-based effectiveness measures (mainly the amount of people benefitting from them) were taken into account.

Are urban noise pollution levels decreasing?

The majority of acoustic impact studies developed over the last 50 years have used a similar acoustic parameter (L(eq), L(dn)) but the noise mapping methodology has been very uneven. The selection of the measurement points, the measurement periods, or the evaluation indices have not followed a unique criterion. Therefore, it is not possible to compare the sound pollution levels between different cities from those studies, at least in a rigorous sense. Even more, different studies carried out in the same city by different researchers during different years and using different methodologies are not conclusive whether the acoustic pollution increases or decreases. The present paper shows results, with statistical significance, about the evolution of the acoustic pollution obtained for two Spanish cities, Pamplona and Madrid. In both cases, it can be concluded that noise pollution decreases over time (P<0.01).

Strategic noise map of a major road carried out with two environmental prediction software packages.

The main objective of this study is to analyze the differences found in the results of noise mapping using two of the most popular software techniques for the prediction of environmental noise. The location selected to conduct the comparative study is an area encompassed by the ring road that surrounds the city of Pamplona and on a grid, with a total of 6 x 10(5) points, approximately. In fact, and as the Environmental Noise Directive points out, it is a major road designated by a Member State (Spain). Configuration of the calculation parameters (discretization of the sources, ground absorption, reflection order, etc.) was as equivalent as possible as far as programs allow. In spite of that, a great number of differences appear in the findings. Although in 95.5% of the points the difference in the noise level calculated from the two programs was less than 3 dB, this general statistic result concealed some great differences. These are due to the various algorithms that programs implement to evaluate noise levels. Most differences pertain to highly screened receivers or remote ones. In the former, the algorithm of visibility is the main cause of such differences. In the latter, differences are mainly brought about by a different implementation of the propagation under homogeneous and favorable atmospheric conditions from both software systems.

Post-assembly error-checking in subphthalocyanine based M3L2 metallosupramolecular capsules.

A kinetic mixture of self-assembled subphthalocyanine-based capsules was shown to gradually reorganize into its more stable symmetrical components by electrospray mass spectrometry.

Incidence and timing of infections after liver transplant in Italy.

BACKGROUND: Infections are one of the main complications that cause high morbidity and mortality in transplant recipients. This study sought to estimate the incidence of infections and their main determinants in liver transplant recipients in the first year after transplantation. PATIENTS AND METHODS: A prospective study was conducted on 103 consecutive patients (72% men) who underwent transplantation in three centers in Northern (Bologna) and Central (Rome) Italy in 2005. Person-years (PY) at risk, incidence rates (IR), IR ratios and 95% confidence intervals were computed for viral, fungal, and bacterial infections. RESULTS: The 103 patients (median age 55 years) contributed a total of 78.2 PYs, with a median follow-up of 286 days (interquartile range: 194 to 365 days). Fifty-eight patients (56.3%) experienced one or more infections, namely, 151 events (IR = 193.2 infections/100 PYs). IR for bacterial, fungal, and viral infections were 110.0, 56.3, and 26.9 infections/100 Pys, respectively. Within the first 30 days after transplantation, 37.9% patients (39/103) developed one or more events. Bacterial infections represented the most frequent event (86/151, 57.0%). Risk factors significantly associated with increased IR were gender (female), age (>50 years), prolonged intensive care stay volume of blood transfused during surgery and posttransplant, and need for retransplantation. CONCLUSIONS: These preliminary results showed the relevance of infectious events after liver transplantation especially those of bacterial etiology, and identified factors mainly associated with their occurrence.

Differential regulation of Th1/Th2 in relevant tissues for sepsis pathogenesis with a Limulus anti-LPS factor-derived peptide increases survival in Gram-positive sepsis.

Severe sepsis and septic shock are important causes of death in intensive care units. Although Gram-negative infections were predominant in the 1960s, Gram-positive infections have increased in the past two decades and now account for about half of the cases of severe sepsis. In this study, we examined the effect of a Limulus anti-LPS factor (LALF)-derived peptide on lung and liver Th1/Th2 cytokine mRNA levels during a Gram-positive sepsis. We also examined the morphopathological changes observed in these organs during the disease. Mice challenged with a high dose of Staphylococcus haemolyticus showed severe damage in lung. In contrast, the liver of challenged mice showed an accumulation of bacterial particles in the sinusoids, associated with a severe inflammatory response due to high levels of tissue mRNA proinflammatory cytokines. Treatment with the peptide LALF(32-51) ameliorated the sepsis-induced effects in the lung and liver and increased the survival of mice in a dose- and time-dependent manner. Pretreatment with the peptide LALF(32-51) differentially regulates TNF-alpha, IFN-gamma, IL-12p40, IL-2 and IL-10 mRNA levels in lung and liver of peptide-treated mice, and limits the systemic inflammatory response. These findings support for the first time the effectiveness of an LALF-derived peptide in the treatment of a Gram-positive sepsis. Modulation of the Th1/Th2 pattern in tissues relevant for sepsis correlates with an improved outcome of the disease as denoted by increased survival.

A Limulus anti-LPS factor-derived peptide modulates cytokine gene expression and promotes resolution of bacterial acute infection in mice.

Sepsis in experimental animals and humans has been associated with perturbed immune response. A major event contributing to the decrease in immune functions in septic disorders seems to be the inadequate balance of cytokines mediating the interactions between the innate and adaptive immune systems. We previously observed that a cyclic peptide derived from the Limulus anti-LPS factor (LALF), which partially protect mice from endotoxic shock lethality, has the ability to modulate cytokine secretion in vitro. We herein examined the effects of the LALF(31-52) peptide in an experimental model of Gram-negative peritoneal sepsis and analyzed the cytokine gene expression in the spleen and liver of peptide-treated mice. The prophylactic administration of LALF(31-52) abrogated the systemic TNF-alpha response, reduced organ damage and increased the survival of infected mice. Histological examination of spleen and liver in peptide-treated mice showed prevention of tissue damage induced by the high dose of Pseudomonas aeruginosa. This treatment modulates the cytokine gene expression in these tissues, stimulating IL-2, IL-12 and IL-13 mRNA synthesis, while IL-4 and IL-10 mRNA expression was not modified. This cytokine profile induced by the LALF-derived peptide seems to be favorable for host resistance against Gram-negative bacteria acute infection. In addition, peptide treatment was effective after the initiation of the systemic inflammatory response, promoting a significant increase in mice survival. These results further demonstrate the immunomodulatory potential of LALF(31-52) and are relevant for the design of prophylactic and therapeutic strategies for acute bacteria infection and sepsis, especially for preventing or ameliorating host immunity defects in these disorders.

Identification of single amino acid residues essential for the binding of lipopolysaccharide (LPS) to LPS binding protein (LBP) residues 86-99 by using an Ala-scanning library.

Lipopolysaccharide binding protein (LBP) is a 60 kDa acute phase glycoprotein capable of binding to LPS of Gram-negative bacteria and facilitating its interaction with cellular receptors. This process is thought to be of great importance in systemic inflammatory reactions such as septic shock. A peptide corresponding to residues 86-99 of human LBP (LBP86-99) has been reported to bind specifically with high affinity the lipid A moiety of LPS and to inhibit the interaction of LPS with LBP. We identified essential amino acids in LBP86-99 for binding to LPS by using a peptide library corresponding to the Ala-scanning of human LBP residues 86-99. Amino acids Trp91 and Lys92 were indispensable for peptide-LPS interaction and inhibition of LBP-LPS binding. In addition, several alanine-substituted synthetic LBP-derived peptides inhibited LPS-LBP interaction. Substitution of amino acids Arg94, Lys95 and Phe98 by Ala increased the inhibitory effect. The mutant Lys95 was the most active in blocking LPS binding to LBP. These findings emphasize the importance of single amino acids in the LPS binding capacity of small peptides and may contribute to the development of new drugs for use in the treatment of Gram-negative bacterial sepsis.

[Nutritional status in the pediatric population of a rural area on the Ecuadorian coast]. / Estudio del estado nutricional de la población infantil de la zona rural de la costa ecuatoriana.

OBJECTIVES: To determine the effects of a diet based on carbohydrates on the nutritional status of a pediatric population through a study performed in a rural area of the province of Los Ríos (Ecuador). PATIENTS AND METHODS: We evaluated 871 Ecuadorian children from a rural environment in an ambulatory medical clinic created for the purposes of the study. Basic anthropometric measurements (weigh, height, head circumference and upper arm circumference) and clinical data from physical examination were recorded. The anthropometric measurements were compared with the growth charts used in Spanish children, which were taken as the standard reference measurements. Information on nutrition was obtained from interviews with the mothers. RESULTS: A total of 871 children were evaluated (53 % boys; 47 % girls). Mean age was 6.39 years (range: 0-14 years; mode 4). Comparison of the data obtained with the standard growth charts for the Spanish pediatric population revealed significant differences in body mass index in boys aged 5-14 years and in girls aged 3-12 years and highly significant differences in boys aged 6-13 years and in girls aged 3-12 years. Significant differences in middle upper arm circumference were found in boys and girls aged 1-14 years and highly significant differences were found in boys aged 1-12 years and in girls aged 2-12 years. A middle upper arm circumference of less than 14 cm (slight malnutrition) was found in 6.67 % of boys and in 9.15 % of girls; a middle upper arm circumference of less than 12.5 cm (serious malnutrition) was found in 1.82 % of boys and in 2.82 % of girls. Nutritional interviews revealed that the overall caloric intake was approximately 1,500 cal/ day. Eight percent of calories came from carbohydrates, 15 % from fats and 5 % from proteins. CONCLUSIONS: A poor diet affects the child population's nutritional status qualitatively but not quantitatively. Nutritional deficit favors the prevalence of childhood diseases that could be avoided by suitable feeding and hygiene. Because of the lack of economic and health resources, prevention is the fundamental weapon for maintaining health in underdeveloped countries. Childhood nutritional status is influenced by diet, which in turn is influenced by physical, climatic, cultural and political factors, and by stress, which is provoked by infections and parents' behavior. Nutritional status in children is a clear reflection of the socioeconomic status of a given population.

Influence of close-up dry period protein supplementation on productive and reproductive performance of Holstein cows in their subsequent lactation.

Holstein cows on a commercial dairy were assigned to close-up dry groups and offered an 11.7% crude protein (CP) ration based on corn silage, alfalfa cubes, oat hay, corn, and barley grain without (Control; C) or with (Supplemented; S) 0.8 kg/d per cow of a high CP supplement of SoyPass, distillers dried grains, ring dried blood meal, feather meal, and corn gluten meal. Heifers (C: 37, S: 44) and mature cows (C: 96, S: 81) were allocated to one of four groups based upon their time in the close-up groups (i.e., 1 to 4, 5 to 8, 9 to 12, and 13 to 19 d) within parity (i.e., heifers or mature) for statistical analysis. Full lactation means of all response parameters for cows confirmed to be pregnant that completed a lactation (i.e., lactating at 305 d in milk or dried off before 305 d in milk but not culled; C: 28, S: 23 for heifers and C: 48, S: 43 for mature cows) were analyzed by ANOVA. Lactation curves were evaluated by parallel curve analysis to assess differences in lactation curve shape, and curve separation, due to treatments. Protein supplementation had no impact on full-lactation milk or milk component yields of heifers, determined by ANOVA, although parallel curve analysis showed higher milk and milk protein yield with protein supplementation. As the number of days cows spent consuming their assigned close-up dry rations increased, heifers produced more milk, milk fat and milk protein, although the maximum yield for milk and milk protein occurred for those fed close-up rations for 9 to 12 d. For mature cows, neither time close up or close-up period protein supplementation influenced any mean response parameter, by ANOVA, although parallel curve analysis showed higher milk and protein yield for supplemented cows as time close up increased. Overall, results suggest the optimum close-up period length was 9 to 12 d, with a protein content intermediate between 11.7 and 14.4% of DM, for heifers. In contrast, results do not support any substantive benefit of a close up period, or protein contents above 11.7%, for mature cows.

Seroprevalence of human Trypanosoma cruzi infection in diferent geografic zones of Chiapas, Mexico.

A serologic survey was carried out in four different geographic zones of Chiapas, Mexico. A total of 1,333 samples were collected from residents of thirteen communities located on the Coast, Central Mountain, Lacandon Forest and a zone called Mesochiapas. One hundred and fifty one seropositive individuals (11.3%) were identified. Human Trypanosoma cruzi infection was influenced by geography. In the Lacandon Forest and Central Mountains there was a higher seroprevalence 32.1 and 13.8% respectively, than on the coast (1.2%). In Mesochiapas there were no seropositive individuals among the 137 persons tested. An active transmission is probably continuing because seropositive cases (13.8%) were detected in children under 10 years of age. The vector recognized on the Coast was Triatoma dimidiata while in the Lacandon Forest it was Rhodnius prolixus.

Synthesis of a new 5'-O-triphosphate analog of 5-methyl 2'-O-deoxycytidine. Preliminary in vitro labelling for non-radioactive detection of DNA.

We report the synthesis of the triphosphate of 5-methyl 4-N-[6-(p-bromobenzamido)hex-1-yl]-2'-O-deoxycytidine 3A. We also analyzed the formation of intramolecular H-bonds of 5-methyl 4-N-[n-[6-(p-bromobenzamido) caproyl amino]alk-1-yl]-2'-deoxycytidine compounds, and confirmed their presence by 1H-NMR studies. In vitro DNA labeling with modified nucleotides is preliminarily evaluated.