Dobutamine in Paediatric Population: A Systematic Review in Juvenile Animal Models

Objective: Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/ paediatric population. Methods: Studies were identified by searching MEDLINE (1946-2012) and EMBASE (1974-2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included. Results: Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions. Conclusion: There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.

As psicoses ordinárias e suas invenções

Esta dissertação tem como proposta investigar as psicoses ordinárias e suas invenções. Partimos dos impasses de nossa prática clínica relativo ao diagnóstico diferencial, buscando identificar quais seriam os principais conceitos utilizados em referência ao mesmo. Sobretudo, apuramos de que maneira estes conceitos se mostram operativos no tratamento possível das psicoses. De forma que o esclarecimento da noção da psicose em psicanálise favorece a compreensão das psicoses ordinárias. Deduzimos que as psicoses, de forma ampla, possuem um aspecto multifacetário e, neste sentido, que as psicoses ordinárias pertencem à diversidade do campo. Estas últimas possuem uma apresentação discreta de fenômenos elementares. Embora a psicose ordinária não seja uma categoria de Jacques Lacan, averiguamos que pode ser depreendida da clínica lacaniana, extraída de uma perspectiva original do autor. Lacan nos faz avançar na ideia de uma direção de tratamento que privilegia a invenção de um significante novo que cumpre a função de sinthoma, exemplificado a partir das elaborações sobre James Joyce e o nó borromeano. O sinthoma é um artifício inventado para dar sustentação ao nó borromeano que é composto pelas instâncias separadas do imaginário, simbólico e real. Supomos que o mais específico das psicoses ordinárias se encontra no modo pelo qual ocorrem suas invenções de amarração do nó borromeano, ou seja, como surgem as compensações da foraclusão do Nome-do-Pai. Nossos dados indicam que a noção de compensação ou suplência que comportam as psicoses ordinárias produz uma forma inédita de apurar suas singularidades, facilitando não apenas o diagnóstico como também a direção do tratamento.

Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease

The neurotransmitter serotonin (5-HT) has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7) and ligand-gated ion channels (5-HT3). The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen), subthalamic nucleus (STN), internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson's disease (PD). This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA.

Pharmacogenetics of MicroRNAs and MicroRNAs Biogenesis Machinery in Pediatric Acute Lymphoblastic Leukemia

Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.

Extended bidirectional reflectance distribution function for polarized light scattering from subsurface defects under a smooth surface

By introducing the scattering probability of a subsurface defect (SSD) and statistical distribution functions of SSD radius, refractive index, and position, we derive an extended bidirectional reflectance distribution function (BRDF) from the Jones scattering matrix. This function is applicable to the calculation for comparison with measurement of polarized light-scattering resulting from a SSD. A numerical calculation of the extended BRDF for the case of p-polarized incident light was performed by means of the Monte Carlo method. Our numerical results indicate that the extended BRDF strongly depends on the light incidence angle, the light scattering angle, and the out-of-plane azimuth angle. We observe a 180 degrees symmetry with respect to the azimuth angle. We further investigate the influence of the SSD density, the substrate refractive index, and the statistical distributions of the SSD radius and refractive index on the extended BRDF. For transparent substrates, we also find the dependence of the extended BRDF on the SSD positions. (c) 2006 Optical Society of America.

One-dimensional potential for image-potential states on graphene

In the framework of dielectric theory, the static non-local self-energy of an electron near an ultra-thin polarizable layer has been calculated and applied to study binding energies of image-potential states near free-standing graphene. The corresponding series of eigenvalues and eigenfunctions have been obtained by numerically solving the one-dimensional Schrodinger equation. The imagepotential state wave functions accumulate most of their probability outside the slab. We find that the random phase approximation (RPA) for the nonlocal dielectric function yields a superior description for the potential inside the slab, but a simple Fermi-Thomas theory can be used to get a reasonable quasi-analytical approximation to the full RPA result that can be computed very economically. Binding energies of the image-potential states follow a pattern close to the Rydberg series for a perfect metal with the addition of intermediate states due to the added symmetry of the potential. The formalism only requires a minimal set of free parameters: the slab width and the electronic density. The theoretical calculations are compared with experimental results for the work function and image-potential states obtained by two-photon photoemission.

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere.

Biotic vs. Abiotic Control of Decomposition: A Comparison of the Effects of Simulated Extinctions and Changes in Temperature

The loss of species is known to have significant effects on ecosystem functioning, but only recently has it been recognized that species loss might rival the effects of other forms of environmental change on ecosystem processes. There is a need for experimental studies that explicitly manipulate species richness and environmental factors concurrently to determine their relative impacts on key ecosystem processes such as plant litter decomposition. It is crucial to understand what factors affect the rate of plant litter decomposition and the relative magnitude of such effects because the rate at which plant litter is lost and transformed to other forms of organic and inorganic carbon determines the capacity for carbon storage in ecosystems and the rate at which greenhouse gasses such as carbon dioxide are outgassed. Here we compared how an increase in water temperature of 5 degrees C and loss of detritivorous invertebrate and plant litter species affect decomposition rates in a laboratory experiment simulating stream conditions. Like some prior studies, we found that species identity, rather than species richness per se, is a key driver of decomposition, but additionally we showed that the loss of particular species can equal or exceed temperature change in its impact on decomposition. Our results indicate that the loss of particular species can be as important a driver of decomposition as substantial temperature change, but also that predicting the relative consequences of species loss and other forms of environmental change on decomposition requires knowledge of assemblages and their constituent species' ecology and ecophysiology

A note on the von Bertalanffy growth function concerning the allocation of surplus energy to reproduction

We propose an extended form of the von Bertalanffy growth function (VBGF), where the allocation of surplus energy to reproduction is considered. Any function can be used in our model to describe the ratio of energy allocation for reproduction to that for somatic growth. As an example, two models for energy allocation were derived: a step-function and a logistic function. The extended model can jointly describe growth in adult and juvenile stages. The change in growth rate between the two stages can be either gradual or steep; the latter gives a biphasic VBGF. The results of curve fitting indicated that a consideration of reproductive energy is meaningful for model extension. By controlling parameter values, our comprehensive model gives various growth curve shapes ranging from indeterminate to determinate growth. An increase in the number of parameters is unavoidable in practical applications of this new model. Additional information on reproduction will improve the reliability of model estimates.

Effects of rapid decompression and exposure to bright light on visual function in black rockfish (Sebastes melanops) and Pacific halibut (Hippoglossus stenolepis)

Demersal fishes hauled up from depth experience rapid decompression. In physoclists, this can cause overexpansion of the swim bladder and resultant injuries to multiple organs (barotrauma), including severe exophthalmia (“pop-eye”). Before release, fishes can also be subjected to asphyxia and exposure to direct sunlight. Little is known, however, about possible sensory deficits resulting from the events accompanying capture. To address this issue, electroretinography was used to measure the changes in retinal light sensitivity, flicker fusion frequency, and spectral sensitivity in black rockfish (Sebastes melanops) subjected to rapid decompression (from 4 atmospheres absolute [ATA] to 1 ATA) and Pacific halibut (Hippoglossus stenolepis) exposed to 15 minutes of simulated sunlight. Rapid decompression had no measurable influence on retinal function in black rockfish. In contrast, exposure to bright light significantly reduced retinal light sensitivity of Pacific halibut, predominately by affecting the photopigment which absorbs the green wavelengths of light (≈520–580 nm) most strongly. This detriment is likely to have severe consequences for postrelease foraging success in green-wavelength-dominated coastal waters. The visual system of Pacific halibut has characteristics typical of species adapted to low light environments, and these characteristics may underlie their vulnerability to injury from exposure to bright light.

An allometric smoothing function to describe the relation between otolith and somatic growth over the lifespan of walleye pollock (Theragra chalcogramma)

We propose a new equation to describe the relation between otolith length (OL) and somatic length (fork length [FL]) of fish for the entire lifespan of the fish. The equation was developed by applying a mathematical smoothing method based on an allometric equation with a constant term for walleye pollock (Theragra chalcogramma) —a species that shows an extended longevity (>20 years). The most appropriate equation for defining the relation between OL and FL was a four-phase allometric smoothing function with three inflection points. The inflection points correspond to the timing of settlement of walleye pollock, changes in sexual maturity, and direction of otolith growth. Allometric smoothing functions describing the relation between short otolith radius and FL, long otolith radius and FL, and FL and body weight were also developed. The proposed allometric smoothing functions cover the entire lifespan of walleye pollock. We term these equations “allometric smoothing functions for otolith and somatic growth over the lifespan of walleye pollock.”

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-beta 3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.