Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. METHODS: GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of CONCLUSIONS: The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

The Schr\"oder functional equation and its relation to the invariant measures of chaotic maps

The aim of this paper is to show that the invariant measure for a class of one dimensional chaotic maps, $T(x)$, is an extended solution of the Schr\"oder functional equation, $q(T(x))=\lambda q(x)$, induced by them. Hence, we give an unified treatment of a collection of exactly solved examples worked out in the current literature. In particular, we show that these examples belongs to a class of functions introduced by Mira, (see text). Moreover, as a new example, we compute the invariant densities for a class of rational maps having the Weierstrass $\wp$ functions as an invariant one. Also, we study the relation between that equation and the well known Frobenius-Perron and Koopman's operators.Comment: 9 page

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

Peer reviewedPublisher PD

Community Ecology and Population Genomics of Rhizopogon in the Madrean Sky Island Archipelago

Anthropogenic induced climate change is predicted to alter distribution of existing plant populations. As plants migrate over space and time, populations often fragment and contract, affecting basic elements of population dynamics (e.g., population size, gene flow, genetic diversity, etc.). Little is known, however, how these impacts on plant species will impact fungal symbionts of plants. Ectomycorrhizal (EcM) fungi are obligate symbionts of many forest trees. This is especially true for members of the Pinaceae, which are dominant members of temperate coniferous forests. In exchange for photosynthates, EcM provide numerous ecological services, including water and nutrient acquisition, to their host trees. EcM fungi can also serve as important food sources for forest animals and act as carbon sinks in forest ecosystems, and thus function as important links between primary producers and forest nutrient cycles. This dissertation used community ecology and population genomic approaches to characterize the impacts on historical climate events associated with the formation of the Madrean Sky Island Archipelago (Arizona, USA–Sonora, Mexico) on the community and population structure in the EcM genus Rhizopogon. The Madrean Sky Island Archipelago (MSIA) is a fragmented landscape of temperate plant communities that are the products of multiple retreats and contractions of these communities to higher elevations. During the Pleistocene glacial cycles (~90,000—20,000 years before present), temperate plant species, such as Pinus spp. were found at lower elevation forming a continuous forest across interconnected mountain ranges. Today, pine communities are only found at high elevations, isolated by a “sea” of the Sonoran Desert with limited genetic exchange among them. While there has been research conducted on the postglacial expansion of animals and plants, our understanding of populations of plant symbionts remains limited. Rhizopogon is a dominant genus of EcM that commonly associates with members of the Pinaceae. It forms truffle-like sporocarps that are dispersed by small mammals. It is also one of the dominant genera in the soil spore bank, making them critical symbionts in seedling establishment. Rhizopogon has been the subject of numerous ecological and phylogenetic studies that have advanced our understanding of competition and host specificity among EcM fungi; however, less research has been conducted on its response to climatic events and host migration. In this dissertation, data and analyses are presented that describe the structure of Rhizopogon communities of the MSIA and the population structure of the dominant species, R. salebrosus, using genome-scale data. The community structure of Rhizopogon species sampled across the MSIA is described using molecular data derived from field collected sporocarp and bioassay derived root tips. This sampling is the most comprehensive survey of an EcM system of the MSIA and employed novel sampling techniques to more effectively sample the communities and populations. These results showed that Rhizopogon communities of the MSIA are species rich and that structure is strongly influenced by the presence of Pseudotsuga menziesii, but geographic proximity of sky islands was not a predictor of community similarity. From these results a model is proposed of both deterministic (host specificity) and stochastic (ecological drift) processes that best explain the formation of Rhizopogon communities as a result of the formation of the MSIA. Community analyses revealed that R. salebrosus is the dominant EcM species in the MSIA system and served as the basis for a series of population genomic analyses involving 104 isolates distributed across nine sky islands. These analyses supported a strong sky island identity to population structure characterized by isolation by distance with none to rare occurrences of migration. Genetic diversity analyses were consistent with all islands experiencing decreases in population sizes and coalescent models that allowed for changing in population size only were sufficient to explain the demographic history. Analyses of allelic and genic diversity of mating type loci – HD MAT and P/R MAT – revealed high levels of genetic diversity across the MSIA system. However, in contrast to population genomic analyses, mating type diversity did not display any structure associated with island identity or geographic proximity (Fig. 4.5). Rather, genetic diversity at mating type loci most likely predates the formation of the sky island populations and has been maintained by a process of balancing selection known to function in fungal mating type systems

Disability evaluation after latissimus dorsi muscle transfer in breast reconstruction using DASH score

Background: Breast reconstruction with latissimus dorsi muscle transfer is one of the most frequent procedures at our hospital. The objective is to evaluate if there is any functional impairment after the surgery with a potential impact of patient´s daily life. Methods: Functional morbidity was analyzed applying the disabilities of the arm, shoulder and hand (DASH) questionnaire and shoulder range of motion with goniometer in 42 patients whose breast reconstruction was between 2016 and 2022 at our hospital. We collected data using Microsoft excel V16.47.1 and analyzed data with statistical package for the social sciences (SPSS) software, v23.0. Results: There was statistically significant difference for disability/symptom DASH score in cases of bilateral reconstruction and for cases undergoing a procedure on the right side versus left side. Conclusions: In patients with bilateral breast reconstruction, we found a greater DASH score in dysfunction and symptoms which associates with poor quality of life, as well as when the flap is on the contralateral extremity of the hand dominance; in those cases, there are other reconstructive procedures that provide greater safety and less disability to the patient. For evaluating extension, we need more prospective and comparative studies with strict follow up of the patients and same series of rehabilitation

Nitrate Reduction Functional Genes and Nitrate Reduction Potentials Persist in Deeper Estuarine Sediments. Why?

Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are processes occurring simultaneously under oxygen-limited or anaerobic conditions, where both compete for nitrate and organic carbon. Despite their ecological importance, there has been little investigation of how denitrification and DNRA potentials and related functional genes vary vertically with sediment depth. Nitrate reduction potentials measured in sediment depth profiles along the Colne estuary were in the upper range of nitrate reduction rates reported from other sediments and showed the existence of strong decreasing trends both with increasing depth and along the estuary. Denitrification potential decreased along the estuary, decreasing more rapidly with depth towards the estuary mouth. In contrast, DNRA potential increased along the estuary. Significant decreases in copy numbers of 16S rRNA and nitrate reducing genes were observed along the estuary and from surface to deeper sediments. Both metabolic potentials and functional genes persisted at sediment depths where porewater nitrate was absent. Transport of nitrate by bioturbation, based on macrofauna distributions, could only account for the upper 10 cm depth of sediment. A several fold higher combined freeze-lysable KCl-extractable nitrate pool compared to porewater nitrate was detected. We hypothesised that his could be attributed to intracellular nitrate pools from nitrate accumulating microorganisms like Thioploca or Beggiatoa. However, pyrosequencing analysis did not detect any such organisms, leaving other bacteria, microbenthic algae, or foraminiferans which have also been shown to accumulate nitrate, as possible candidates. The importance and bioavailability of a KCl-extractable nitrate sediment pool remains to be tested. The significant variation in the vertical pattern and abundance of the various nitrate reducing genes phylotypes reasonably suggests differences in their activity throughout the sediment column. This raises interesting questions as to what the alternative metabolic roles for the various nitrate reductases could be, analogous to the alternative metabolic roles found for nitrite reductases

Análisis y autoevaluación de las competencias tutoriales en un programa de posgrado en enfermería

Introducción: El tutor es fundamental en la formación de estudiantes del posgrado, su trabajo no se enfoca únicamente en la dirección de la tesis; además debe fomentar el desarrollo de otras habilidades en el alumno al incorporarlo al conocimiento tácito en comunidades de investigación. Esto implica que el tutor muestre competencias en la tutoría, de ahí la importancia de reconocerlas y autoevaluarlas tanto en forma crítica como reflexiva para su mejora. Objetivo: Analizar y autoevaluar las competencias de los tutores de un posgrado en enfermería. Método: Los tutores fueron invitados a participar de manera libre y voluntaria en grupos focales, con el propósito de analizar, discutir y autoevaluar sus competencias; se empleó una rúbrica como elemento detonador, que describe cualitativamente diez competencias que deben tener los tutores de posgrado, en cuatro niveles de dominio. Resultados: La discusión sostenida al interior de los grupos focales fue documentada para su codificación y análisis, se obtuvieron categorías que aludieron a: 1) aspectos éticos y el respeto a las autorías de los estudiantes en publicaciones; 2) la relevancia de la transferencia del conocimiento a problemas específicos del campo de enfermería; 3) la relación tutor-alumno destacando vínculos de menor y mayor dependencia. Conclusiones: Se identificó el reconocimiento de las competencias que requieren los tutores en este nivel, se generó una autoevaluación crítica y reflexiva, sobre lo que se ha realizado en la práctica educativa. Los tutores ubicaron sus niveles de competencia en desarrollo y consumado

Safety of Levetiracetam in paediatrics: a systematic review

Objective To identify adverse events (AEs) associated with Levetiracetam (LEV) in children. Methods Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis. Results Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems. Conclusion Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research