Prevalencia de la hipomineralización incisivo molar en una muestra de 772 escolares de la provincia de Barcelona

La hipomineralización incisivo molar es una alteración del desarrollo dentario que involucra a los primeros molares permanentes pudiendo estar comprometidos, también, los incisivos permanentes. La prevalencia de HIM varía en la literatura entre 2,5 a 40 % en la población infantil mundial. El objetivo de este estudio fue determinar la prevalencia de la HIM en una población de 772 niños catalanes entre 6,9 y 14,11 años de edad. Se estableció el diagnóstico de acuerdo a los criterios de la Academia Europea de Odontopediatría y la prevalencia encontrada fue del 7,94 % siendo comparable a la obtenida en estudios realizados a nivel mundial

Poli (ADP-Ribosa) Polimerasa-1: una proteína nuclear implicada en procesos inflamatorios, muerte celular y cáncer

Numerosos estudios en modelos experimentales han puesto de manifiesto que el bloqueo genético o lainhibición farmacológica de poli-ADP-ribosa-polimerasa-1, proteína nuclear implicada en fenómenos deseñalización celular a través de modificaciones postraduccionales mediante poli-ADP-ribosilación, confiereprotección frente a procesos citolíticos derivados que tienen lugar durante el desarrollo de la respuestainflamatoria. Un denominador común en todos los procesos inflamatorios es la secreción de diversosmediadores proinflamatorios y la formación de radicales libres que van a desencadenar la activación de poli-ADP-ribosa-polimerasa-1 y simultáneamente se potencia la activación de diversos factores de transcripcióncomo NF-kB y AP-1, dando lugar a la expresión de genes dependientes de éstos. Es bien conocido que lainflamación en el cáncer, como proceso de estrés oxidativo continuo, actúa como un fuerte promotor tumoralfavoreciendo el desarrollo del tumor. Esta revisión pretende dar una visión general sobre el conocimientoactual de esta proteína tanto a nivel celular como en procesos patológicos tan importantes como el cáncer. PALABRAS CLAVE: PARP-1, Inflamación, Cáncer, Factores de Transcripción

Exploring and challenging the network of angiogenesis

Angiogenesis is one of the hallmarks of cancer and, as such, one of the alternative general targets for anticancer therapy. Since angiogenesis is a complex process involving a high number of interconnected components, a network approach would be a convenient systemic way to analyse responses to directed drug attacks. Herein we show that, although the angiogenic network is easily broken by short combinations of directed attacks, it still remains essentially functional by keeping the global patterns and local efficiency essentially unaltered after these attacks. This is a clear sign of its high robustness and resilience and stresses the need of directed, combined attacks for an effective blockade of the process. The results of this theoretical study could be relevant for the design of new antiangiogenic therapies and the selection of their targets

Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition

ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after γ-irradiation. ATM is also modified by PARP-1 during DNA damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATM-kinase activity and have found that while PARP-1 deficient cells display a defective ATM-kinase activity and reduced γ-H2AX foci formation in response to γ-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced γ H2AX foci accumulation, in an ATM-dependent manner. Inhibition of PARP also induces DNA double strand breaks which were dependent on the presence of ATM. As consequence ATM deficient cells display an increased sensitivity to PARP inhibition. In summary our results show that while PARP-1 is needed in the response of ATM to gamma irradiation, the inhibition of PARP induces DNA double strand breaks (which are resolved in and ATM-dependent pathway) and activates ATM kinase

Prevalence of Symptomatic and Asymptomatic Peripheral Arterial Disease and the Value of the Ankle-brachial Index to Stratify Cardiovascular Risk

AbstractObjectivesTo determine the prevalence of ankle-brachial index (ABI)<0.9 and symptomatic peripheral arterial disease (PAD), association with cardiovascular risk factors (CVRF), and impact of adding ABI measurement to coronary heart disease (CHD) risk screening.DesignPopulation-based cross-sectional survey of 6262 participants aged 35–79 in Girona, Spain.MethodsStandardized measurements (CVRF, ABI, 10-year CHD risk) and history of intermittent claudication (IC), CHD, and stroke were recorded. ABI<0.9 was considered equivalent to moderate-to-high CHD risk (≥10%).ResultsABI<0.9 prevalence was 4.5%. Only 0.62% presented low ABI and IC. Age, current smoker, cardiovascular disease, and uncontrolled hypertension independently associated with ABI<0.9 in both sexes; IC was also associated in men and diabetes in women. Among participants 35–74 free of cardiovascular disease, 6.1% showed moderate-to-high 10-year CHD risk; adding ABI measurement yielded 8.7%. Conversely, the risk function identified 16.8% of these participants as having 10-year CHD risk>10%. In participants 75–79 free of cardiovascular disease, the prevalence of ABI<0.9 (i.e., CHD risk≥10%) was 11.9%.ConclusionsABI<0.9 is relatively frequent in those 35–79, particularly over 74. However, IC and CHD risk≥10% indicators are often missing. Adding ABI measurement to CHD-risk screening better identifies moderate-to-high cardiovascular risk patients

In Vitro and In Vivo Efficacy of Ether Lipid Edelfosine against Leishmania spp. and SbV-Resistant Parasites

Leishmaniasis represents a major international health problem, has a high morbidity and mortality rate, and is classified as an emerging and uncontrolled disease by the World Health Organization. The migration of population from endemic to nonendemic areas, and tourist activities in endemic regions are spreading the disease to new areas. Unfortunately, treatment of leishmaniasis is far from satisfactory, with only a few drugs available that show significant side-effects. Here, we show in vitro and in vivo evidence for the antileishmanial activity of the ether phospholipid edelfosine, being effective against a wide number of Leishmania spp. causing cutaneous, mucocutaneous and visceral leishmaniasis. Our experimental mouse and hamster models demonstrated not only a significant antileishmanial activity of edelfosine oral administration against different wild-type Leishmania spp., but also against parasites resistant to pentavalent antimonials, which constitute the first line of treatment worldwide. In addition, edelfosine exerted a higher antileishmanial activity and a lower proneness to generate drug resistance than miltefosine, the first drug against leishmaniasis that can be administered orally. These data, together with our previous findings, showing an anti-inflammatory action and a very low toxicity profile, suggest that edelfosine is a promising orally administered drug for leishmaniasis, thus warranting clinical evaluation

Long-term decline of the Amazon carbon sink

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades1, 2, with a substantial fraction of this sink probably located in the tropics3, particularly in the Amazon4. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity5. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale1, 2, and is contrary to expectations based on models6

Dynamical downscaling of historical climate over CORDEX Central America domain with a regionally coupled atmosphere–ocean model

The climate in Mexico and Central America is influenced by the Pacific and the Atlantic oceanic basins and atmospheric conditions over continental North and South America. These factors and important ocean–atmosphere coupled processes make the region’s climate a great challenge for global and regional climate modeling. We explore the benefits that coupled regional climate models may introduce in the representation of the regional climate with a set of coupled and uncoupled simulations forced by reanalysis and global model data. Uncoupled simulations tend to stay close to the large-scale patterns of the driving fields, particularly over the ocean, while over land they are modified by the regional atmospheric model physics and the improved orography representation. The regional coupled model adds to the reanalysis forcing the air–sea interaction, which is also better resolved than in the global model. Simulated fields are modified over the ocean, improving the representation of the key regional structures such as the Intertropical Convergence Zone and the Caribbean Low Level Jet. Higher resolution leads to improvements over land and in regions of intense air–sea interaction, e.g., off the coast of California. The coupled downscaling improves the representation of the Mid Summer Drought and the meridional rainfall distribution in southernmost Central America. Over the regions of humid climate, the coupling corrects the wet bias of the uncoupled runs and alleviates the dry bias of the driving model, yielding a rainfall seasonal cycle similar to that in the reanalysis-driven experiments.Universidad de Costa Rca/[805-B7-507]/UCR/Costa RicaCRYOPERU/[144-2015]//PerúUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline