Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111964/1/cpt127.pd

Assessment of nutritional status in children with kidney diseases-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

In children with kidney diseases, an assessment of the child’s growth and nutritional status is important to guide the dietary prescription. No single metric can comprehensively describe the nutrition status; therefore, a series of indices and tools are required for evaluation. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations (CPRs) for the nutritional management of children with kidney diseases. Herein, we present CPRs for nutritional assessment, including measurement of anthropometric and biochemical parameters and evaluation of dietary intake. The statements have been graded using the American Academy of Pediatrics grading matrix. Statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. Audit and research recommendations are provided. The CPRs will be periodically audited and updated by the PRNT

Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host

The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell. Our model explains the experimentally observed shortening of a second infection when cross-reactivity is present, and shows that memory in the cellular adaptive immune response is necessary to protect against a second infection.Comment: 35 pages, 12 figure

Evolutionary pressures on simple sequence repeats in prokaryotic coding regions

Simple sequence repeats (SSRs) are indel mutational hotspots in genomes. In prokaryotes, SSR loci can cause phase variation, a microbial survival strategy that relies on stochastic, reversible on–off switching of gene activity. By analyzing multiple strains of 42 fully sequenced prokaryotic species, we measure the relative variability and density distribution of SSRs in coding regions. We demonstrate that repeat type strongly influences indel mutation rates, and that the most mutable types are most strongly avoided across genomes. We thoroughly characterize SSR density and variability as a function of N→C position along protein sequences. Using codon-shuffling algorithms that preserve amino acid sequence, we assess evolutionary pressures on SSRs. We find that coding sequences suppress repeats in the middle of proteins, and enrich repeats near termini, yielding U-shaped SSR density curves. We show that for many species this characteristic shape can be attributed to purely biophysical constraints of protein structure. In multiple cases, however, particularly in certain pathogenic bacteria, we observe over enrichment of SSRs near protein N-termini significantly beyond expectation based on structural constraints. This increases the probability that frameshifts result in non-functional proteins, revealing that these species may evolutionarily tune SSR positions in coding regions to facilitate phase variation

Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome

Glucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and are ineffective in ~20-50% of patients. Thiazolidinediones have recently been suggested to be renoprotective, and to modulate podocyte glucocorticoid-mediated nuclear receptor signaling. We hypothesized that thiazolidinediones could enhance glucocorticoid efficacy in NS. We found that puromycin aminonucleoside-induced proteinuria in rats was significantly reduced by both high-dose glucocorticoids (79%) and pioglitazone (61%), but not low-dose glucocorticoids (25%). Remarkably, pioglitazone + low-dose glucocorticoids also reduced proteinuria (63%) comparably to high-dose glucocorticoids, whereas pioglitazone + high-dose glucocorticoids reduced proteinuria to almost control levels (97%). Molecular analysis revealed that both glucocorticoids and pioglitazone enhanced glomerular synaptopodin and nephrin expression, and reduced COX-2 expression, after injury. Furthermore, the glomerular phosphorylation of glucocorticoid receptor and Akt, but not PPARγ, correlated with treatment-induced reductions in proteinuria. Notably, clinical translation of these findings to a child with refractory NS by the addition of pioglitazone to the treatment correlated with marked reductions in both proteinuria (80%) and overall immunosuppression (64%). These findings together suggest that repurposing pioglitazone could potentially enhance the proteinuria-reducing effects of glucocorticoids during NS treatment

Percepção de estudantes de psicologia sobre a informática em sua formação profissional

Neste artigo analisa-se uma pesquisa de natureza qualitativa, cujo objetivo era explorar a percepção de 45 alunos de psicologia de diferentes universidades da cidade de Santiago do Chile, sobre a incorporação da informática como apoio para a aprendizagem em sua formação profissional. A informação foi coletada através de entrevistas semiestruturadas e analisou-se mediante o processo de codificação da Teoría Fundamentada. Os resultados mostram como categorias principais, o conhecimento da informática, a valoração da informática, e os fatores que obstaculizam o uso desta. Da codificação seletiva se desprende uma alta valoração da informática como ferramenta econômica e cômoda, mas também se observa uma alta reticência dos alunos diante de sua utilização no trabalho profissional tradicional do psicólogo. Encontraram-se fatores pessoais e institucionais nos que se baseia a valoração, a motivação e o nível de conhecimento dos estudantes diante do uso de ferramentas informáticas.This paper analyses a qualitative research aimed to exploring the perception of 45 psychology students from different universities in Santiago de Chile, about incorporating information systems to support learning in their professional training. Data were collected through semi structured interviews and their analysis was based on Grounded Theory's coding process. Results show that the major categories are computer knowledge, appreciation of computers and factors that hinder their use. From the selective coding a positive evaluation emerges of information systems as an economic and useful tool. However, there is also a high reluctance on the part of the students regarding the use of such tools in the psychologist' traditional professional work. Personal and organizational factors were found as bases for students' assessment, motivation and level of knowledge facing the use of these tools.En este artículo se analiza una investigación de naturaleza cualitativa, cuyo objetivo era explorar la percepción de 45 alumnos de psicología de diferentes universidades de la ciudad de Santiago de Chile, sobre la incorporación de la informática como apoyo para el aprendizaje en su formación profesional. La información se recolectó a través de entrevistas semiestructuradas y se analizó mediante el proceso de codificación de la Teoría Fundamentada. Los resultados muestran como categorías principales, el conocimiento de la informática, la valoración de la informática, y los factores que obstaculizan el uso de ésta. De la codificación selectiva se desprende una alta valoración de la informática como herramienta económica y cómoda, pero también se observa una alta reticencia de los alumnos frente a su utilización en el trabajo profesional tradicional del psicólogo. Se encontraron factores personales e institucionales en los cuales se fundamenta la valoración, la motivación y el nivel de conocimiento de los estudiantes frente al uso de herramientas informáticas

Neoantigen quality predicts immunoediting in survivors of pancreatic cancer.

Cancer immunoediting1 is a hallmark of cancer2 that predicts that lymphocytes kill more immunogenic cancer cells to cause less immunogenic clones to dominate a population. Although proven in mice1,3, whether immunoediting occurs naturally in human cancers remains unclear. Here, to address this, we investigate how 70 human pancreatic cancers evolved over 10 years. We find that, despite having more time to accumulate mutations, rare long-term survivors of pancreatic cancer who have stronger T cell activity in primary tumours develop genetically less heterogeneous recurrent tumours with fewer immunogenic mutations (neoantigens). To quantify whether immunoediting underlies these observations, we infer that a neoantigen is immunogenic (high-quality) by two features-'non-selfness'  based on neoantigen similarity to known antigens4,5, and 'selfness'  based on the antigenic distance required for a neoantigen to differentially bind to the MHC or activate a T cell compared with its wild-type peptide. Using these features, we estimate cancer clone fitness as the aggregate cost of T cells recognizing high-quality neoantigens offset by gains from oncogenic mutations. With this model, we predict the clonal evolution of tumours to reveal that long-term survivors of pancreatic cancer develop recurrent tumours with fewer high-quality neoantigens. Thus, we submit evidence that that the human immune system naturally edits neoantigens. Furthermore, we present a model to predict how immune pressure induces cancer cell populations to evolve over time. More broadly, our results argue that the immune system fundamentally surveils host genetic changes to suppress cancer

Imaging of the urinary tract: the role of CT and MRI

Computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly valuable tools for assessing the urinary tract in adults and children. However, their imaging capabilities, while overlapping in some respects, should be considered as complementary, as each technique offers specific advantages and disadvantages both in actual inherent qualities of the technique and in specific patients and with a specific diagnostic question. The use of CT and MRI should therefore be tailored to the patient and the clinical question. For the scope of this article, the advantages and disadvantages of these techniques in children will be considered; different considerations will apply in adult practice