Histone Acetyl Transferase 1 Is Overexpressed in Poor Prognosis, High-grade Meningeal and Glial Brain Cancers: Immunohistochemical and Aptahistochemical Study.

Primary malignancies of the central nervous system account for 2% of all cancers in adults and almost 15% in children under 15 years of age. The prognosis of brain anaplastic cancers and glioblastomas remains extremely poor, with devastating survival expectative, and new molecular markers and therapeutic targets are essential. Epigenetic changes constitute an extensive field for the development of new diagnostic and therapeutic strategies. Histone acetyl transferase-1 (HAT1) has merged as a potential prognostic marker and therapy target for different malignancies. Data repository analysis showed HAT1 mRNA overexpression in gliomas and has been described its alternative splicing in glioblastomas. Using immunohistochemical and aptahistochemical methods, we analyzed the expression of HAT1 in meningiomas, oligodendrogliomas, and astroglial cancers. We observed that HAT1 overexpression is associated with the most aggressive tumor types and the worse prognosis, as well as with a higher probability of early relapse in meningiomas. Its cytosolic localization correlates with tumor progression and prognosis. Aptamers, synthetic oligonucleotides capable to bind and inhibit a wide variety of targets, are considered as promising diagnostic and therapeutic tools. Aptahistochemistry using the aptamer apHAT610 offered superior results in comparison with the antibody used, as a good example of the potential of aptamers as diagnostic tools for histopathology.

Exocytosis-related genes and response to methylphenidate treatment in adults with ADHD.

Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD. The sample comprised 433 subjects, of which 272 (62.8%) have completed the short-term IR-MPH treatment (at least 30 days). The main outcome measure was the categorical variable of short-term response to IR-MPH based on the Swanson, Nolan and Pelham Rating Scale version 4 (SNAP-IV), and on the clinical global impression-improvement scale. Additional analyses evaluated the percentage of SNAP-IV symptom reduction for each dimension as well as short- and long- (7 years) term treatment persistence. SYT1-rs2251214 was associated with the categorical short-term response to IR-MPH (P=0.006, PFDR=0.028), and with the percentage of inattention and oppositional defiant disorder symptoms reduction (P=0.007, PFDR=0.028 and P=0.017, PFDR=0.048, respectively). SYT1-rs2251214 was also associated with short-term treatment persistence (P=0.018, PFDR=0.048), and with months of treatment (P=0.002, PFDR=0.016) in the long-term protocol. Our findings suggest that SYT1-rs2251214 presents a broad influence in IR-MPH response variability in adults with ADHD, being involved with both symptom response and treatment persistence. If such findings are replicated, SytI could represent a key element in MPH pharmacodynamics in adults with ADHD.

Trajectories of attention-deficit/hyperactivity disorder dimensions in adults.

OBJECTIVE: There is a lack of available information on the trajectories of attention-deficit/hyperactivity disorder (ADHD) dimensions during adulthood. This study investigates the course and the predictors of change for each ADHD domain in a clinical sample of adults with ADHD. METHOD: Adults with ADHD (n = 344) were followed up for 7 years, with a final retention rate of 66.0%. Trajectories of inattention, hyperactivity, and impulsivity and their potential predictors were examined. RESULTS: On average, symptoms declined in all ADHD domains during follow-up. Despite this, rises in inattentive, hyperactive, and impulsive symptoms were observed in approximately 13%, 25%, and 17% of patients respectively. Different predictors influenced the trajectory of each ADHD dimension. Oppositional defiant disorder and social phobia were associated with the maintenance of symptoms, while alcohol use disorder was associated with both maintenance and rise of symptoms. CONCLUSION: Unexpectedly, a rise in the symptoms after 7 years was not uncommon in adults with ADHD. Prevalent comorbidities have the potential to influence the neurodevelopment and the trajectory of ADHD. Therefore, such predictors should be investigated in population cohorts to better characterize the course of ADHD. Additionally, these findings may be relevant in prevention studies and in strategies for ADHD treatment.

Cross-sectional, school-based study of 14-19 year olds showed that raised blood pressure was associated with obesity and abdominal obesity.

AIM: Gaining weight has been directly associated with an increased probability of developing high blood pressure (HBP) and metabolic abnormalities. We examined the independent and combined effects of overweight, obesity and abdominal obesity on blood pressure in adolescents. METHODS: This cross-sectional school-based study evaluated 869 adolescents (53.4% girls) from 14 to 19 years of age, and the data were collected in 2013 in the city of Imperatriz, Maranhão, Brazil. The outcome was HBP. The independent variables were overweight and obesity classified by body mass index, abdominal obesity classified by the waist-to-height ratio and the combination of obesity and overweight and abdominal obesity. The potential confounding variables were age, the socio-economic status of the family, parental education, type of school and physical activity levels. RESULTS: The prevalence ratios of HBP were higher when male and female adolescents were overweight (1.61-3.11), generally obese (3.20-4.70), had abdominal obesity (2.18-3.02) and were both generally obese and had abdominal obesity (3.28-5.16) compared with normal weight adolescents. CONCLUSION: Obesity or abdominal obesity increased the risk of HBP in adolescents aged 14-19. However, adolescents who were both generally obese and had abdominal obesity showed an even higher risk of having HBP.

Persistence and remission of ADHD during adulthood: a 7-year clinical follow-up study.

BACKGROUND: Course and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment. METHOD: A 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence. RESULTS: Retention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms [odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54-25.45, p < 0.001], number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04-1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20-8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12-11.47, p = 0.03). CONCLUSIONS: Despite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults.

Can programmed or self-selected physical activity affect physical fitness of adolescents?

The aim of this study was to verify the effects of programmed and self-selected physical activities on the physical fitness of adolescents. High school adolescents, aged between 15 and 17 years, were divided into two experimental groups: a) a self-selected physical activity group (PAS) with 55 students (aged 15.7 ± 0.7 years), who performed physical activities with self-selected rhythm at the following sports: basketball, volleyball, handball, futsal and swimming; and b) a physical fitness training group (PFT) with 53 students (aged 16.0 ± 0.7 years), who performed programmed physical fitness exercises. Both types of activity were developed during 60 min classes. To assess physical fitness the PROESP-BR protocol was used. The statistical analysis was performed by repeated measures ANOVA. The measurements of pre and post-tests showed significantly different values after PFT in: 9 minute running test, medicine ball throw, horizontal jump, abdominal endurance, running speed and flexibility. After PAS differences were detected in abdominal endurance, agility, running speed and flexibility. The intervention with programmed physical activity promoted more changes in the physical abilities; however, in the self-selected program, agility was improved probably because of the practice of sports. Therefore, physical education teachers can use PFT to improve cardiorespiratory fitness and power of lower and upper limbs and PAS to improve agility of high school adolescents.

Mass transport techniques as a tool for a better understanding of the structure of L-Dopa in aqueous solutions.

Mutual diffusion coefficients, D, densities, ρ, and viscosities, η, are reported for aqueous solutions of L-3,4-dihydroxyphenylalanine (L-Dopa) at 298.15K and 310.15K at concentrations from (0.00025 to 0.0075) moldm(-3). The aim of this study is to contribute to a better understanding of the structure of these systems and the thermodynamic behaviour of L-Dopa in solution. Thus, from these experimental data it was possible to estimate some parameters, such as the hydrodynamic radius, Rh, apparent molar volumes, ϕV, and diffusion coefficients at infinitesimal concentration, D(0), essential for a better understanding of disperse systems. From the measured diffusion coefficients, activity coefficients, γ, for aqueous L-Dopa solutions were also estimated by using Nernst-Hartley equation. The effect of the viscosity on the estimated hydrodynamic radius was also studied.

Calculations of Diffusion Coefficients of Iron Salts in Aqueous Solutions at 298.15 K: A Useful Tool for the Knowledge of the Structure of these Systems.

Diffusion coefficients, thermodynamic and mobility factors of iron salts in aqueous solutions are estimated from Onsager-Fuoss model. The influence of the ion size parameter a, "mean distance of closest approach of ions", determined from different approaches, on the variation of diffusion coefficients with concentration, is also discussed. The aim of this work is to have a better understanding of the structure of these systems and of the thermodynamic behaviour of iron salts in aqueous media.

The burdened life of adults with ADHD: impairment beyond comorbidity.

Since approximately 70% of adult patients with attention-deficit/hyperactivity disorder (ADHD) have at least one comorbid disorder, rating of impairment specifically attributable to ADHD is a hard task. Despite the evidence linking environmental adversities with negative outcomes in ADHD, life events measures have not been used to rate the disorder impairment. The present study tested for the first time the hypothesis that increased ADHD severity is associated with an increase in negative recent life events, independently of comorbidity status. The psychiatric diagnoses of 211 adult ADHD outpatients were based on DSM-IV criteria assessed through structured interviews (K-SADS-E for ADHD and ODD, MINI for ASPD and SCID-IV-R for other comorbidities). ADHD severity was evaluated with the Swanson, Nolan and Pelham rating scale (SNAP-IV) and recent life events with the Life Experience Survey. Higher SNAP-IV inattention and hyperactivity scores, female gender, lower socioeconomic status and the presence of comorbid mood disorders were associated with negative life events. Poisson regression models with adjustment for possible confounders confirmed the effect of inattention and hyperactivity severity on negative life events. Our results suggest that the negative life events experienced by these patients are associated to the severity of ADHD independently from comorbid psychiatric disorders.

Estimation of the mean distance of closest approach of actinides and lanthanides ions in aqueous solutions: some experimental and theoretical calculations.

The estimation of numerical values of the mean distance of closest approach of ions, a, of lanthanides and actinides ion salts in aqueous solutions, determined from activity coefficients, as well as from different theoretical approaches, is presented and discussed.

Diffusion coefficients of sodium fluoride in aqueous solutions at 298.15 k and 310.15 k.

Mutual diffusion coefficients (interdiffusion coefficients) have been measured for sodium fluoride in water at 298.15 K and 310.15 K at concentrations between 0.003 mol dm-3 and 0.05 mol dm-3. The diffusion coefficients were measured using a conductimetric cell. The experimental mutual diffusion coefficients are discussed on the basis of the Onsager-Fuoss model. The limiting molar conductivity of the fluoride ion in these solutions at 310.15 K has been estimated using these results.

Aqueous solution behavior of anionic fluorene-co-thiophene-based conjugated polyelectrolytes.

Two anionic fluorene-thiophene alternating copolymers, poly[9,9-bis(4-sulfonylbutoxyphenyl)fluorene-2,7-diyl-2,5-thienylene] (PBS-PFT) and poly[9,9-bis(4-sulfonylbutoxyphenyl)fluorene-2,7-diyl-2,2'-bithiophene-5,5'-diyl] (PBS-PF2T), have been synthesized and their solution behaviors in water studied by UV-vis absorption spectroscopy, fluorescence, and electrical conductivity and compared with that of the previously studied conjugated polyelectrolyte (CPE) poly[9,9-bis(4-sulfonylbutoxyphenyl)fluorene-2,7-diyl-1,4-phenylene] (PBS-PFP). These conjugated polymers do not form solutions at the molecular level in water but instead form clusters. Information on the structure of these clusters for PBS-PF2T comes from small-angle X-ray and neutron scattering. The relative ease of dispersing the copolymers in water increases with an increase in the number of thiophene rings in these alternating copolymers. Semiempirical calculations on the structure suggest that this results from bending of the chains and increased conformational flexibility, decreasing interchain interactions. These CPEs can be dissolved in water at the molecular level using the nonionic surfactants n-dodecylpentaoxyethylene glycol ether (C12E5) or Triton X-100 to obtain systems with increased photoluminescence quantum yield and increased electrical conductivity that can be solution-processed for potential applications as components of sensory or optoelectronic devices.

Aggregation and micellization of sodium dodecyl sulfate in the presence of Ce(III) at different temperatures: a conductometric study.

Aggregation properties of sodium dodecyl sulfate (SDS) in the presence of cerium(III) chloride, at various temperatures (298.15-323.15 K) have been measured by the electrical conductance technique. The experimental data on aqueous solutions as a function of SDS concentration show the presence of two inflexion points indicating the presence of two distinct interaction mechanisms: the first, occurring at SDS concentrations below the critical micelle concentration of the pure surfactant, which can be explained by the formation of aggregates between dodecyl sulfate (DS-) and Ce(III), while the second one, at SDS concentrations around the critical micelle concentration (cmc) of the pure surfactant which is due to the SDS micellization. The aggregation between DS- and Ce(III) was confirmed by static light scattering. The binding ratio of DS-/Ce(III) changes from 6 to 4, shows a slight dependence on the Ce(III) concentration and is independent of the temperature. The thermodynamic micellization parameters, Gibbs energy, enthalpy and entropy of micellization were calculated on the basis of the experimental data for the aggregation concentration, and the degree of counterion dissociation of the micelles. The SDS micellization is energetically favoured by increasing either the concentration of CeCl3 or the temperature. Such behaviour is clearly dominated by a decrease of the micellization (exothermic) enthalpy. The entropy of micellization approaches zero as the cerium(III) chloride concentration and temperature increase.

Modulating the emission intensity of poly-(9,9-bis(6'-N,N,N-trimethylammonium)hexyl)-fluorene phenylene) bromide through interaction with sodium alkylsulfonate surfactants.

The interaction between the cationic HTMA-PFP (Poly-(9,9-bis(6'-N,N,N-trimethylammonium)hexyl-fluorene phenylene) bromide) and oppositely charged sodium n-alkyl sulfonate surfactants of different chain lengths has been studied in DMSO-water solutions (4% v/v) by UV-visible absorption, fluorescence spectroscopy, fluorescence lifetimes, electrical conductivity, and (1)H NMR spectroscopy. Polymer-surfactant interactions lead to complex spectroscopic behaviors which depends on surfactant concentration. At low surfactant concentrations, the observed strong static fluorescence quenching of fluorescence seems to be associated with formation of aggregates between polymer chains neutralized through interaction with surfactants. This is supported by conductivity and by analysis of absorption spectra deconvoluted at each surfactant concentration using an adapted iterative method. In contrast, above the surfactant critical micelle concentration, there is a strong fluorescence enhancement, leading in some cases to higher intensities than in the absence of surfactants. This is attributed to the transformation of the initially formed aggregates into some new aggregate species involving surfactant and polymer. These changes in HTMA-PFP fluorescence as a function of n-alkyl sulfonate concentration are important for the general understanding of polymer-surfactant interactions, and the aggregates formed may be important as novel systems for applications of these conjugated polyelectrolytes.

Serotonin transporter gene polymorphism and the phenotypic heterogeneity of adult ADHD.

The present study investigates possible associations between the 5-HTT control region polymorphism (5-HTTLPR) with adult ADHD, including subtypes, severity, temperament profile and comorbidities. The polymorphic site was genotyped in 312 adult patients with ADHD and 236 controls, all of them Brazilians of European descent. The interviews followed the DSM-IV criteria, using the K-SADS-E for ADHD and oppositional defiant disorder, SCID-I and MINI for comorbidities and the TCI for temperament dimensions. The 5-HTTLPR polymorphism was not associated with ADHD. Carriers of the S allele presented slightly higher inattention and novelty seeking scores, and a higher frequency of drug dependence. These differences do not persist after correction for multiple comparisons. These results suggest that the 5-HTTLPR polymorphism does not have a direct role in the predisposition to adult ADHD. There is suggestive evidence for a small effect in some behavioral phenotypes related to ADHD.

First total synthesis of aspinolide B, a new pentaketide produced by Aspergillus ochraceus.

The first asymmetric total synthesis of Aspinolide B (1), a new 10-membered lactone discovered by chemical screening methods in the cultures of Aspergillus ochraceus, has been accomplished. The key steps included a selective Felkin-type addition of TMS-acetylene to aldehyde 3a and a Nozaki-Hiyama-Kishi coupling reaction to build the required 10-membered ring. This synthesis confirmed the absolute stereochemistry of aspinolide B, established through Helmchen's method and corrected its previously reported specific optical rotation.