Spelling problems after early oral language difficulties.

Recent research has stated that early oral language acquisition difficulties are related to reading and writing difficulties. Children with developmental language disorder (DLD) experience difficulties with several dimensions of language. In this study we focus on the specific difficulties of children with DLD in spelling. We examine the impact of lexicality and length in written production of Spanish-speaking children with DLD. A total of 18 children with language difficulties (Mage = 8;4) were compared with age-matched children (Mage = 8;2). Participants completed a spelling-to-dictation task of words and pseudo-words, where length was manipulated. A digital tablet was used to collect data and obtain measures of accuracy, latencies and total writing durations. Results showed that children with DLD produced more errors, longer latencies and longer writing durations than age-matched children. Regarding accuracy, analysis of the errors shows that children in the control group produce few errors, most being substitutions, while children with DLD made more errors and of more varied categories. Moreover, they were more affected by length on writing accuracy than the control group. WHAT THIS PAPER ADDS: What is already known on this subject Children with language difficulties are more likely to present reading difficulties. There are fewer studies analysing the impact of oral language difficulties in writing skills. What this paper adds to existing knowledge The study suggests that children with oral language difficulties also have impairments in spelling, impacting on accuracy, duration and reaction time, possibly related to poor phonological working memory. What are the potential or actual clinical implications of this work? This study highlights the need to emphasize early oral intervention and language-related processing skills to help prevent written language difficulties.

High delayed mortality after the first episode of Clostridium difficile infection.

Clostridium difficile infection (CDI) is characterized by a high delayed and unrelated mortality. Predicting delayed mortality in CDI patients could allow the implementation of interventions that could reduce these events. A prospective multicentric study was carried out to investigate prognostic factors associated with mortality. It was based on a cohort (July 2015 to February 2016) of 295 patients presenting with CDI. Logistic regression was used and the model was calibrated using the Hosmer-Lemeshow test. The mortality rate at 75 days in our series was 18%. Age (>65 years), comorbidity (defined by heart failure, diabetes mellitus with any organ lesion, renal failure, active neoplasia or immunosuppression) and fecal incontinence at clinical presentation were associated with delayed (75-day) mortality. When present, each of the aforementioned variables added one point to the score. Mortalities with 0, 1, 2 and 3 points were 0%, 9.4%, 18.5% and 38.2%, respectively. The area under the ROC curve was 0.743, and the Hosmer-Lemeshow goodness-of-fit test p value was 0.875. Therefore, the prediction of high delayed mortality in CDI patients by our scoring system could promote measures for increasing survival in suitable cases.

Peroxisome proliferator activated receptor gamma 2 modulates late pregnancy homeostatic metabolic adaptations.

Pregnancy requires the adaptation of maternal energy metabolism including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPARγ) controls adipogenesis, glucose and lipid metabolism and insulin sensitivity. The PPARγ2 isoform is mainly expressed in adipocytes and is thus likely to contribute to adipose tissue adaptation during late pregnancy. In the present study, we investigated the contribution of PPARγ2 to the metabolic adaptations occurring during the late phase of pregnancy in the context of IR. Using a model of late pregnancy in PPARγ2 knockout (KO) mice, we found that deletion of PPARγ2 exacerbated IR in association with lower serum adiponectin levels, increased body weight and enhanced lipid accumulation in liver. Lack of PPARγ2 provoked changes in the distribution of fat mass and preferentially prevented the expansion of the perigonadal depot while at the same time exacerbating inflammation. PPARγ2KO pregnant mice presented adipose tissue depot-dependent decreased expression of genes involved in lipid metabolism. Collectively, these data indicate that PPARγ2 is essential to promote healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term.

Combined theoretical and experimental study of the photophysics of asulam.

The photophysics of the neutral molecular form of the herbicide asulam has been described in a joint experimental and theoretical, at the CASPT2 level, study. The unique π → π* aromatic electronic transition (f, ca. 0.5) shows a weak red-shift as the polarity of the solvent is increased, whereas the fluorescence band undergoes larger red-shifts. Solvatochromic data point to higher dipole moment in the excited state than in the ground state (µ(g) < µ(e)). The observed increase in pKa in the excited state (pKa* - pKa, ca. 3) is consistent with the results of the Kamlet-Abboud-Taft and Catalán et al. multiparametric approaches. Fluorescence quantum yield varies with the solvent, higher in water (ϕ(f) = 0.16) and lower in methanol and 1-propanol (approx. 0.02). Room temperature fluorescence lifetime in aqueous solution is (1.0 ± 0.2) ns, whereas the phosphorescence lifetime in glassy EtOH at 77 K and the corresponding quantum yield are (1.1 ± 0.1) s and 0.36, respectively. The lack of mirror image symmetry between modified absorption and fluorescence spectra reflects different nuclear configurations in the absorbing and emitting states. The low value measured for the fluorescence quantum yield is justified by an efficient nonradiative decay channel, related with the presence of an easily accessible conical intersection between the initially populated singlet bright (1)(L(a) ππ*) state and the ground state (gs/ππ*)(CI). Along the main decay path of the (1)(L(a) ππ*) state the system undergoes an internal conversion process that switches part of the population from the bright (1)(L(a) ππ*) to the dark (1)(L(b) ππ*) state, which is responsible for the fluorescence. Additionally, singlet-triplet crossing regions have been found, a fact that can explain the phosphorescent emission detected. An intersystem crossing region between the phosphorescent state (3)(L(a) ππ*) and the ground state has been characterized, which contributes to the nonradiative deactivation of the excitation energy.

Reading in English as a Foreign Language by Spanish Children With Dyslexia.

It has been reported that children with dyslexia have difficulties with learning a second language. The English alphabetic code is opaque, and it has been stated that deep orthographies cause important problems in children with dyslexia. Considering the strong differences between the Spanish and English orthographic systems, we predicted English reading problems in Spanish-speaking children with dyslexia. The current study focused on English as a foreign language in a group of 22 Spanish children with dyslexia (8-12 year olds), compared to a control group matched for age, gender, grade, and socioeconomic status. The objective was to identify the main difficulties that Spanish-speaking children with dyslexia demonstrate during English reading, to develop specific teaching programs. Participants were given four tasks related to reading: discrimination of phonemes, visual lexical decision, reading aloud, and oral vs. written semantic classification. The results suggest that children with dyslexia demonstrate problems in using English grapheme-phoneme rules, forcing them to employ a lexical strategy to read English words. However, they also showed difficulties in developing orthographic representations of words. Finally, they also exhibited problems with oral language, demonstrating difficulties accessing semantic information from an auditory presentation.

Dynamics of Sentence Handwriting in Dyslexia: The Impact of Frequency and Consistency.

Previous literature has indicated that linguistic and motor processes influence each other during written sentence production, and that the scope of this influence varies according to spelling ability or cognitive resources available. This study investigated how the spelling deficits associated with dyslexia affect the dynamics of the interaction between central and peripheral processes and the level of anticipation that can be observed in word spelling in the context of a sentence to dictation task. Children 9-12-year-olds with and without dyslexia wrote sentences to dictation in which the lexical frequency and phonology-to-orthography consistency of the last word (target) were manipulated. Analyses of kinematic measures (writing durations, in-air pen duration, and peaks of speed) revealed that children with dyslexia showed lexical frequency effects evident in within-word pauses (in-air pen) in the article and noun production. In addition, both children with and without dyslexia showed a phonology-to-orthography consistency effect in the pause before the target word. This effect tended to continue affecting the execution of the syllable prior to the inconsistency only in the group with dyslexia. Results support the influence of linguistic processes on motor execution. In addition, the study provides evidence of the impact of spelling deficits on the dynamics of handwriting in children with dyslexia.

Morpheme-Based Reading and Writing in Spanish Children with Dyslexia.

It has been well documented that morphemic structure (roots and affixes) have an impact in reading, but effects seem to depend on the reading experience of readers and lexical characteristics of the stimuli. Specifically, it has been reported that morphemes constitute reading units for developing readers and children with dyslexia when they encounter a new word. In addition, recent studies have stated that the effect of morphology is also present in spelling, as morphological information facilitates spelling accuracy and influences handwriting times. The goal of this study was to investigate the role of morphology in reading and spelling fluency in Spanish children with dyslexia. For that purpose, a group of 24 children with dyslexia was compared with an age-matched group of 24 children without reading disabilities in performing a word naming task and a spelling-to-dictation task of isolated words. Morphological condition (high frequency base, low frequency base, simple) and lexicality (words vs. pseudowords) were manipulated. We considered, for the naming task, reading latencies, reading durations, reading critical segment (three first phonemes) durations and naming accuracy; and, for the spelling task, written latencies, writing durations for the whole word, writing critical segment (three first letters) durations and spelling accuracy. Results showed that Spanish children (with and without dyslexia) benefit from a high frequency base to initiate reading and writing responses, showing that they are familiar with the letter chunks that constitute a morpheme. In addition, base frequency impacts reading critical segment duration only for children with dyslexia, but for both groups in writing. In summary, children with dyslexia benefit from a high frequency base to read and spell unfamiliar stimuli.

Lipotoxicity as a trigger factor of renal disease.

In the last few decades, rapid changes in lifestyle have led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance, dyslipidemia, type 2 diabetes and kidney disease. The surplus of calories is normally stored as triglycerides in adipose tissue. However, excess lipids can also accumulate ectopically in other organs, including the kidney, contributing to their damage through toxic processes named lipotoxicity. The kidney is negatively affected by dyslipidemia, lipid accumulation and changes in circulating adipokines that bring about alterations in renal lipid metabolism and promote insulin resistance, generation of reactive oxygen species and endoplasmic reticulum stress, ultimately leading to alterations in the glomerular filtration barrier and renal failure. This review focuses on the pathogenic molecular mechanisms associated with renal lipotoxicity, and presents new insights about potential new therapeutic targets and biomarkers such as microRNAs and long non-coding RNAs, of relevance for the early detection of lipid-associated kidney disease.

Renal Lipotoxicity-Associated Inflammation and Insulin Resistance Affects Actin Cytoskeleton Organization in Podocytes.

In the last few decades a change in lifestyle has led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance (IR), dyslipidemia, type 2 diabetes and renal disease. The excess calories are stored as triglycerides in adipose tissue, but also may accumulate ectopically in other organs, including the kidney, which contributes to the damage through a toxic process named lipotoxicity. Recently, the evidence suggests that renal lipid accumulation leads to glomerular damage and, more specifically, produces dysfunction in podocytes, key cells that compose and maintain the glomerular filtration barrier. Our aim was to analyze the early mechanisms underlying the development of renal disease associated with the process of lipotoxicity in podocytes. Our results show that treatment of podocytes with palmitic acid produced intracellular accumulation of lipid droplets and abnormal glucose and lipid metabolism. This was accompanied by the development of inflammation, oxidative stress and endoplasmic reticulum stress and insulin resistance. We found specific rearrangements of the actin cytoskeleton and slit diaphragm proteins (Nephrin, P-Cadherin, Vimentin) associated with this insulin resistance in palmitic-treated podocytes. We conclude that lipotoxicity accelerates glomerular disease through lipid accumulation and inflammation. Moreover, saturated fatty acids specifically promote insulin resistance by disturbing the cytoarchitecture of podocytes. These data suggest that renal lipid metabolism and cytoskeleton rearrangements may serve as a target for specific therapies aimed at slowing the progression of podocyte failure during metabolic syndrome.

Accelerated renal disease is associated with the development of metabolic syndrome in a glucolipotoxic mouse model.

Individuals with metabolic syndrome are at high risk of developing chronic kidney disease (CKD) through unclear pathogenic mechanisms. Obesity and diabetes are known to induce glucolipotoxic effects in metabolically relevant organs. However, the pathogenic role of glucolipotoxicity in the aetiology of diabetic nephropathy is debated. We generated a murine model, the POKO mouse, obtained by crossing the peroxisome proliferator-activated receptor gamma 2 (PPARγ2) knockout (KO) mouse into a genetically obese ob/ob background. We have previously shown that the POKO mice showed: hyperphagia, insulin resistance, hyperglycaemia and dyslipidaemia as early as 4 weeks of age, and developed a complete loss of normal ß-cell function by 16 weeks of age. Metabolic phenotyping of the POKO model has led to investigation of the structural and functional changes in the kidney and changes in blood pressure in these mice. Here we demonstrate that the POKO mouse is a model of renal disease that is accelerated by high levels of glucose and lipid accumulation. Similar to ob/ob mice, at 4 weeks of age these animals exhibited an increased urinary albumin:creatinine ratio and significantly increased blood pressure, but in contrast showed a significant increase in the renal hypertrophy index and an associated increase in p27(Kip1) expression compared with their obese littermates. Moreover, at 4 weeks of age POKO mice showed insulin resistance, an alteration of lipid metabolism and glomeruli damage associated with increased transforming growth factor beta (TGFß) and parathyroid hormone-related protein (PTHrP) expression. At this age, levels of proinflammatory molecules, such as monocyte chemoattractant protein-1 (MCP-1), and fibrotic factors were also increased at the glomerular level compared with levels in ob/ob mice. At 12 weeks of age, renal damage was fully established. These data suggest an accelerated lesion through glucolipotoxic effects in the renal pathogenesis in POKO mice.

Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass.

BACKGROUND: The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion RESULTS: Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell. CONCLUSIONS: Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-ß signaling and decreased oxidative phosphorylation.