Infection after intramedullary nailing of femoral and tibial diaphyseal fractures.

PURPOSE: Management of fracture-related infection (FRI) after intramedullary fixation (IF) is a challenge. The aim of the present study is to describe a series of 26 patients with FRI after IF and to evaluate factors possibly related to the outcome. METHODS: Baseline variables were obtained at the time of IF: age, sex, body mass index, affected bone, open fracture, substance abuse, use of an external fixator, type of nail, reaming, soft-tissue reconstruction and surveillance culture result. After diagnosis of the infection, information was obtained about the time interval between IF and diagnosis and classification according to both the Willeneger and Roth and Makridis systems. Treatment modalities were grouped and analysed according to: use of antimicrobials, surgical debridement, nail removal or retention and spacer use. Cultures of bone or deep soft tissues were performed. Patients were followed up for 12 months, and outcomes (remission, relapse, death and loss of follow-up) were evaluated, as well as fracture consolidation. RESULTS: Remission was observed in 42.3% of patients. There was no significant association between any baseline variable and outcome. There was a significant association between Makridis stage 2 classification and recurrence or death. Treatment strategy was not significantly associated with outcome, and 65.4% of cases had positive culture results, with Enterobacter cloacae as the predominant agent. Consolidation was observed in 81.8% of patients and was not significantly related to the outcome. CONCLUSION: There was a significant association between Makridis classification and the outcome. Consolidation rate was not associated with the outcome regarding the treatment of the infection.

How Good Is the Phoneme Elision Test in Assessing Reading, Spelling and Arithmetic-Related Abilities?

OBJECTIVE: The aim of this study was to investigate the psychometric properties and diagnostic accuracy of phoneme elision task (PET). METHOD: We assessed cross-sectionally 470 Brazilian children (54.3% girls) aged between 7 and 11 years (mean age = 8.83, sd = 0.85), from the 2nd to 4th grades. Children were assessed in their phonemic awareness ability, as well as intelligence, general school achievement, both verbal and visuospatial working memory, single-word reading, and nonsymbolic magnitude comparison. Beyond the psychometric properties and diagnostic accuracy of PET, we also provided reference values. RESULTS: Our data suggest that PET is composed mainly of one single construct, with high item reliability and precision (KR-20 above 0.90). In general, items have acceptable discriminability, considering item-total correlations. Overall PET is generally a good screening tool for reading and spelling difficulties (SD), as well as to identify children with learning difficulties in the early grades. However, it is not a reliable measure for screening math learning difficulties. Finally, PET shows good convergent and divergent validity. CONCLUSIONS: We provide evidence about the psychometric properties and diagnostic accuracy of a PET. Results contribute to the assessment of phonemic awareness in Brazilian children, in both clinical and research contexts. The PET can be used as a screening tool for reading and SD, which could lead to early interventions.

The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis.

Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation.

Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus. Maternally deprived rats had a depressive-like behavior in the forced swimming test and an increase in the HDAC and DNMT activities in the hippocampus and NAc. Treatment with quetiapine reversed depressive-like behavior and reduced the DNMT activity in the hippocampus. This is the first study to show the antidepressant-like effect of quetiapine in animals subjected to MD and a protective effect by quetiapine in reducing epigenetic changes induced by stress in early life. These results reinforce an important role of quetiapine as therapy for MDD.

Ketamine Exhibits Different Neuroanatomical Profile After Mammalian Target of Rapamycin Inhibition in the Prefrontal Cortex: the Role of Inflammation and Oxidative Stress.

Studies indicated that mammalian target of rapamycin (mTOR), oxidative stress, and inflammation are involved in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been identified as a novel MDD therapy; however, the antidepressant mechanism is not fully understood. In addition, the effects of ketamine after mTOR inhibition have not been fully investigated. In the present study, we examined the behavioral and biochemical effects of ketamine in the prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens after inhibition of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol) or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). Immobility was assessed in forced swimming tests, and then oxidative stress parameters and inflammatory markers were evaluated in the brain and periphery. mTOR activation in the PFC was essential to ketamine's antidepressant-like effects. Ketamine increased lipid damage in the PFC, hippocampus, and amygdala. Protein carbonyl was elevated in the PFC, amygdala, and NAc after ketamine administration. Ketamine also increased nitrite/nitrate in the PFC, hippocampus, amygdala, and NAc. Myeloperoxidase activity increased in the hippocampus and NAc after ketamine administration. The activities of superoxide dismutase and catalase were reduced after ketamine administration in all brain areas studied. Inhibition of mTOR signaling pathways by rapamycin in the PFC was required to protect against oxidative stress by reducing damage and increasing antioxidant enzymes. Finally, the TNF-α level was increased in serum by ketamine; however, the rapamycin plus treatment group was not able to block this increase. Activation of mTOR in the PFC is involved in the antidepressant-like effects of ketamine; however, the inhibition of this pathway was able to protect certain brain areas against oxidative stress, without affecting inflammation parameters.

Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex.

Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol), or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) - alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures.

What Is Specific and What Is Shared Between Numbers and Words?

Reading and spelling performance have a significant correlation with number transcoding, which is the ability to establish a relationship between the verbal and Arabic representations of numbers, when a conversion of numerical symbols from one notation to the other is necessary. The aim of the present study is to reveal shared and non-shared mechanisms involved in reading and writing of words and Arabic numerals in Brazilian school-aged children. One hundred and seventy-two children from second to fourth grades were evaluated. All of them had normal intelligence. We conducted a series of hierarchical regression models using scores on word spelling and reading single words and Arabic numerals, as dependent variables. As predictor variables we investigated intelligence, the phonological and visuospatial components of working memory (WM) and phonemic awareness. All of the writing and reading tasks (single word spelling and reading as well as number reading and number writing) were significantly correlated to each other. In the regression models, phonological WM was specifically associated to word reading. Phonemic awareness was the only cognitive variable that systematically predicted all of the school skills investigated, both numerical and word tasks. This suggests that phonemic awareness is a modular cognitive ability shared by several school tasks and might be an important factor associated to the comorbidity between dyslexia and dyscalculia.

Phonemic awareness as a pathway to number transcoding.

Although verbal and numerical abilities have a well-established interaction, the impact of phonological processing on numeric abilities remains elusive. The aim of this study is to investigate the role of phonemic awareness in number processing and to explore its association with other functions such as working memory and magnitude processing. One hundred seventy-two children in 2nd grade to 4th grade were evaluated in terms of their intelligence, number transcoding, phonemic awareness, verbal and visuospatial working memory and number sense (non-symbolic magnitude comparison) performance. All of the children had normal intelligence. Among these measurements of magnitude processing, working memory and phonemic awareness, only the last was retained in regression and path models predicting transcoding ability. Phonemic awareness mediated the influence of verbal working memory on number transcoding. The evidence suggests that phonemic awareness significantly affects number transcoding. Such an association is robust and should be considered in cognitive models of both dyslexia and dyscalculia.

Contributions from specific and general factors to unique deficits: two cases of mathematics learning difficulties.

Mathematics learning difficulties are a highly comorbid and heterogeneous set of disorders linked to several dissociable mechanisms and endophenotypes. Two of these endophenotypes consist of primary deficits in number sense and verbal numerical representations. However, currently acknowledged endophenotypes are underspecified regarding the role of automatic vs. controlled information processing, and their description should be complemented. Two children with specific deficits in number sense and verbal numerical representations and normal or above-normal intelligence and preserved visuospatial cognition illustrate this point. Child H.V. exhibited deficits in number sense and fact retrieval. Child G.A. presented severe deficits in orally presented problems and transcoding tasks. A partial confirmation of the two endophenotypes that relate to the number sense and verbal processing was obtained, but a much more clear differentiation between the deficits presented by H.V. and G.A. can be reached by looking at differential impairments in modes of processing. H.V. is notably competent in the use of controlled processing but has problems with more automatic processes, such as nonsymbolic magnitude processing, speeded counting and fact retrieval. In contrast, G.A. can retrieve facts and process nonsymbolic magnitudes but exhibits severe impairment in recruiting executive functions and the concentration that is necessary to accomplish transcoding tasks and word problem solving. These results indicate that typical endophenotypes might be insufficient to describe accurately the deficits that are observed in children with mathematics learning abilities. However, by incorporating domain-specificity and modes of processing into the assessment of the endophenotypes, individual deficit profiles can be much more accurately described. This process calls for further specification of the endophenotypes in mathematics learning difficulties.

Count on dopamine: influences of COMT polymorphisms on numerical cognition.

Catechol-O-methyltransferase (COMT) is an enzyme that is particularly important for the metabolism of dopamine. Functional polymorphisms of COMT have been implicated in working memory and numerical cognition. This is an exploratory study that aims at investigating associations between COMT polymorphisms, working memory, and numerical cognition. Elementary school children from 2th to 6th grades were divided into two groups according to their COMT val158met polymorphism [homozygous for valine allele (n = 61) vs. heterozygous plus methionine homozygous children or met+ group (n = 94)]. Both groups were matched for age and intelligence. Working memory was assessed through digit span and Corsi blocks. Symbolic numerical processing was assessed through transcoding and single-digit word problem tasks. Non-symbolic magnitude comparison and estimation tasks were used to assess number sense. Between-group differences were found in symbolic and non-symbolic numerical tasks, but not in working memory tasks. Children in the met+ group showed better performance in all numerical tasks while val homozygous children presented slower development of non-symbolic magnitude representations. These results suggest COMT-related dopaminergic modulation may be related not only to working memory, as found in previous studies, but also to the development of magnitude processing and magnitude representations.