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.

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.

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.

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.

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.

[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.

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.

Interferon-alpha elicits downregulation of human papillomavirus 18 mRNA in HeLa cells by selective repression of endogenous viral transcription.

We have reported that interferon-alpha inhibits HPV-18 mRNA in HeLa cells. Here we examine mechanisms by which IFN could modulate HPV expression. In northern blot experiments, we observed that interferon-alpha 2b treatment reduced HPV-18 mRNA levels in a time- and dose-dependent manner, with a maximal effect achieved at 48 h. Simultaneously, induction of 2-5A synthetase mRNA was verified as indicative of IFN action. The IFN regulatory effect on HPV-18 mRNA at 48 h required de novo protein synthesis. We performed run-on experiments to determine whether the IFN regulatory effect was at the transcriptional level. HPV-18 endogenous transcription was repressed using 200 and 1000 IU/ml. Interferon treatment did not affect HPV-18 mRNA stability, at least under our experimental conditions. To verify whether HPV-18 enhancer sequences were involved in the interferon effect, we transfected a construct containing the chloramphenicol acetyltransferase driven by the HPV-18 upstream regulatory region. The enzyme activity was unmodified on human keratinocytes and HeLa cells by interferon exposition. Our data demonstrate that interferon-alpha downregulates HPV-18 mRNA levels on HeLa cells by repressing nascent viral transcripts, possibly through regulatory cellular flanking regions.

Modulation of human papillomavirus type 16 mRNA in cervical invasive carcinoma patients by interferon-alpha therapy.

Mechanisms by which interferon produces papilloma regression remain largely unknown. We analyzed biopsies from three cervical invasive carcinoma patients treated with interferon-alpha (IFN-alpha) administered both topically and i.m. for 15 days. All specimens contained human papillomavirus (HPV-16) DNA as determined by polymerase chain reaction using specific HPV-16 E7 primers. Interestingly, in two patients. HPV-16 mRNA expression was reduced (44% and 67%, respectively) after IFN treatment. Upregulation of 2-5 A synthetase and PKR mRNA levels were indicative of the IFN effect. A larger study should be initiated to see whether IFN-alpha modulates the HPV-16 mRNA levels in tumor biopsies from cervical carcinoma patients.

Human papillomavirus type-16 (HPV-16) major transforming proteins functionally interact with interferon signaling mechanisms.

Since the IFN system has been implicated in cell growth and differentiation control mechanisms, we evaluated the influence of the expression of HPV-16 E6 and E7 oncoproteins on IFN signaling by using cotransfection experiments. Both viral oncoproteins differentially interfered with the inducibility of IFN-beta promoter by Sendai virus. The activation by IFN-gamma of a GBP ISRE reporter was dramatically affected by both viral proteins suggesting a disruption of STATs/IRFs function. Further, the inducibility of 6-16 gene ISRE reporter by IFN-alpha was decreased to varying degrees by both viral oncoproteins, implying that ISGF3 function is also impaired. Taken together, these observations suggest that HPV-16 negatively interacts with cellular targets of the IFN system, and these interactions may be implicated in cellular transformation caused by HPVs and their refractory response to IFN treatment.

The use of nonradioactive DNA probes for the characterization of Leishmania isolates from Peru.

We describe conditions for dot blot DNA hybridization studies using biotinylated kDNA probes from Leishmania. The sensitivity and specificity attained with biotinylated or 32P-labeled probes were equivalent. The lower level of detection obtained was 100 parasites that were blotted on nitrocellulose paper and then treated with Proteinase K. Studies were performed with 112 Leishmania isolates from Andean (uta) and sylvatic mucocutaneous (espundia) patients and all were determined to belong to the Leishmania braziliensis complex.

Biochemical characterization of Leishmania (Viannia) braziliensis and Leishmania (Viannia) peruviana by isoenzyme electrophoresis.

Leishmanial organisms isolated from 24 patients with Andean cutaneous leishmaniasis (uta) and from 7 with sylvatic leishmaniasis in both cutaneous and mucosal forms were characterized on the basis of their isoenzyme profiles for 13 enzymes using both cellulose acetate (CA) and thin-layer starch gel (TLS) electrophoretic techniques. Malate dehydrogenase (MDH) after electrophoresis on CA or TLS and mannose phosphate isomerase (MPI) on TLS were the only enzymes of 13 examined which discriminated between the organisms from patients with uta (L. (V.) peruviana) and those with sylvatic leishmaniasis (L. (V.) braziliensis). Mannose phosphate isomerase gave more clear-cut and reproducible discrimination than did MDH on either TLS or CA, and it is suggested that MPI is a reliable enzyme marker that can be used in routine TLS electrophoresis to distinguish between L. (V.) peruviana and L. (V). braziliensis.

Characterization of Leishmania species from Peru.

Twenty-six isolates of Leishmania parasites of Peruvian origin were studied by isoenzyme electrophoresis of four marker enzymes (ASAT, ALAT, G6PD and GPI), kinetoplast DNA hybridization and monoclonal antibody binding and compared with marker strains of the New World organisms L. b. braziliensis, L. b. guyanensis, L. m. mexicana and L. m. amazonensis. 12 of the isolates studied were of Andean origin; 11 of these were isolated from patients with Andean cutaneous leishmaniasis. The organisms originating from the Peruvian Amazonian forest were isolated from patients with cutaneous (12 cases) or mucocutaneous (2 cases) leishmaniasis. One of the Andean isolates was obtained from an infected phlebotomine vector. 25 of the new isolates were identified as L. braziliensis ssp. according to the three techniques employed. The results of monoclonal antibody binding showed that 23 of the isolates were indistinguishable from L. b. braziliensis. Two isolates identified as L. braziliensis ssp. according to their isoenzyme profiles and k-DNA hybridization patterns could not be classified at the subspecies level. The isolate obtained from the phlebotomine vector could not be identified. No evidence of the existence of parasites of the L. mexicana complex in Peruvian territory was found in this study. The results obtained show a remarkable similarity between Leishmania of Andean origin and L. b. braziliensis.

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.