Similar clinical improvement and maintenance after rTMS at 5 Hz using a simple vs. complex protocol in Alzheimer's disease.

BRACKGROUND: Current treatments for Alzheimer's disease (AD) have a limited clinical response and methods, such as repetitive transcranial magnetic stimulation (rTMS), are being studied as possible treatments for the clinical symptoms with positive results. However, there is still seldom information on the type of rTMS protocols that deliver the best clinical improvement in AD. Objetive: To compare the clinical response between a simple stimulation protocol on the left dorsolateral prefrontal cortex (lDLPFC) against a complex protocol using six regions of interest. METHODS: 19 participants were randomized to receive any of the protocols. The analysis of repeated measures evaluated the change. RESULTS: Both protocols were equally proficient at improving cognitive function, behavior and functionality after 3 weeks of treatment, and the effects were maintained for 4 weeks more without treatment. CONCLUSION: We suggest rTMS on the lDLPFC could be enough to provide a clinical response, and the underlying mechanisms should be studied.

The circadian transcriptome of marine fish (Sparus aurata) larvae reveals highly synchronized biological processes at the whole organism level.

The regulation of circadian gene expression remains largely unknown in farmed fish larvae. In this study, a high-density oligonucleotide microarray was used to examine the daily expression of 13,939 unique genes in whole gilthead sea bream (Sparus aurata) larvae with fast growth potentiality. Up to 2,229 genes were differentially expressed, and the first two components of Principal Component Analysis explained more than 81% of the total variance. Clustering analysis of differentially expressed genes identified 4 major clusters that were triggered sequentially, with a maximum expression at 0 h, 3 h, 9-15 h and 18-21 h zeitgeber time. Various core clock genes (per1, per2, per3, bmal1, cry1, cry2, clock) were identified in clusters 1-3, and their expression was significantly correlated with several genes in each cluster. Functional analysis revealed a daily consecutive activation of canonical pathways related to phototransduction, intermediary metabolism, development, chromatin remodeling, and cell cycle regulation. This daily transcriptome of whole larvae resembles a cell cycle (G1/S, G2/M, and M/G1 transitions) in synchronization with multicellular processes, such as neuromuscular development. This study supports that the actively feeding fish larval transcriptome is temporally organized in a 24-h cycle, likely for maximizing growth and development.

Strategies for a direct characterization of phosphoproteins on hydroxyapatite surfaces.

We show in this work how systems formed by phosphoproteins on calcium phosphate surfaces can be directly characterized, in real time, in liquid medium, without the need for elution or labeling. Specifically, we show how this is possible by applying three different techniques: ellipsometry, quartz crystal microbalance with dissipation, and atomic force microscopy-based friction force spectroscopy. We apply these techniques to study two different model systems, i.e. those formed upon the adsorption of two model phosphoproteins (κ- and ß-casein) on hydroxyapatite (HA) surfaces. Information on the kinetics of adsorption, surface excess, viscoelasticity, water content, thickness of the layers, and protein-surface interaction is provided. Results indicate that both phosphoproteins form homogeneous elastic highly hydrated monolayers on the HA surfaces, the strength of ß-casein layers being higher by approximately a factor of 4. Based on the experimental results, models for the conformation of κ- and ß-casein molecules adsorbed on HA surfaces are proposed.

Nanowear of salivary films vs. substratum wettability.

The pellicle serves as a multifunctional protective layer, providing, e.g., lubrication and remineralization and also acting as a diffusion barrier. In addition, since the formation of the pellicle precedes the adhesion of micro-organisms, it is also important as a conditioning film. We present a novel approach to study the influence of the water wettability of solid surfaces on the strength of adsorbed salivary films. It is based on studying the wear resistance of the films with an atomic force microscope operated in the friction force spectroscopy mode. This methodology provides the strength of the films in terms of the forces needed for breaking and removing them. Our results indicate that these forces are highly dependent on the water wettability of the underlying substrata, decreasing with increasing hydrophobicity. Thus, this study provides valuable information for the design of materials exposed in the oral cavity, i.e., materials that will minimize plaque formation and be easy to clean.

AFM imaging and analysis of electrostatic double layer forces on single DNA molecules.

Electrical double layer (EDL) forces develop between charged surfaces immersed in an electrolyte solution. Biological material surrounded by its physiological medium constitutes a case where these forces play a major role. Specifically, this work is focused on the study of the EDL force exerted by DNA molecules, a standard reference for the study of single biomolecules of nanometer size. The molecules deposited on plane substrates have been characterized by means of the atomic force microscope operated in the force spectroscopy imaging mode. Force spectroscopy imaging provides images of the topography of the DNA molecules, and of the EDL force spectrum. Due to the size of the molecule being much smaller than that of the tip, both the tip-substrate and tip-molecule interactions need to be considered in the analysis of the experimental results. We solve this problem by linearly superposing the two contributions. EDL force images are presented where DNA molecules are clearly resolved. The lateral resolution of the EDL force is discussed and compared with that of the topography. The method also allows the estimation of the DNA surface charge density, thereby obtaining reasonable values.

Jumping mode AFM imaging of biomolecules in the repulsive electrical double layer.

We present a method to image single biomolecules in aqueous media by atomic force microscope (AFM) without establishing any mechanical contact between the tip and the sample. It works by placing the feedback set point in the repulsive electrical double-layer curve just before the mechanical instability occurs. We use the jumping operation mode, where the set point is controlled at every image point and a stable imaging is achieved for several hours. This is a necessary condition for this method to be operative, otherwise the tip can fall in contact in a short time. The method is applied to image single-avidin protein molecules deposited on cleaved mica. In addition, the dependence of the height of avidin molecules as a function of ion concentration, due to differences in surface charge density of mica and avidin, is tentatively used to deduce relative values of these quantities.

Construcción, validez y fiabilidad de la escala de tamizaje «FASCT» para el trastorno por déficit de atención en adultos (versión autoaplicada y del observador) / Construction, validity and realiability, of the screening scale «FASCT» for attention deficit hyperactivity disorder in adults (self-reported and observer versions)

Introducción. La fiabilidad de las escalas autoaplicadas retrospectivamente para tamizar a adultos con trastorno por déficit de atención con hiperactividad (TDAH) se ha investigado de manera limitada.Método. Se construyó un instrumento denominado «FASCT», el cual consta de dos versiones: autoaplicada y del observador. Se aplicó la primera versión a un total de 393 personas y la versión del observador a 377. Se realizó un análisis factorial exploratorio y confirmatorio para obtener las versiones finales del instrumento. Finalmente se aplicó la versión autoaplicada junto con una entrevista estructurada a 205 sujetos. La versión del observador fue aplicada a 105 de sus familiares de primer grado.Resultados. La versión autoaplicada obtuvo un alfa de Cronbach de 0,84 y la versión del observador de 0,87. El punto de corte con mejor balance entre sensibilidad y 1-especificidad fue de 23 puntos para cada versión. El coeficiente de correlación entre ambas versiones fue de 0,88. El coeficiente de correlación entre la escala de Wender-UTHA y la versión autoaplicada de la «FASCT» fue de 0,71 y para la versión del observador fue de 0,66. El grado de acuerdo entre la calificación dicotomizada de la «FASCT» con el diagnóstico de la entrevista estructurada fue de 0,82 para la versión autoaplicada y de 0,88 para la versión del observador. Asimismo se obtuvieron los siguientes índices para la versión autoaplicada: sensibilidad, 80,36; especificidad, 97,9. Los valores para la versión del observador fueron: 95,4 y 96,3, respectivamente.Conclusiones. Ambas versiones de la escala «FASCT» demostraron ser válidas y confiables para el tamizaje del TDAH en adultos

Introduction. Research about the reliability of retrospective self-report rating scales for attention deficit hyperactivity disorder (ADHD) in adults has been limited.Method. A self-report scale named «FASCT» was created with two versions: self-reported and observer. The self-reported version was applied to 393 subjects and the observer version to 377. An exploratory and confirmatory factorial analysis was made in order to obtain the final adaptation of both versions. Finally they were applied to 205 subjects and 105 of their first degree relatives.Results. Cronbach's alpha for the self-reported version was 0.84 and 0.87 for the observer version. The total score that had the best balance between sensitivity and 1-specificity was 23 points for each version of the «FASCT». Correlation between both versions was 0.88. The correlation coefficient between the Wender-UTAH scale and self-reported version was 0.71 and for the observer version was 0.66. Agreement degree between dichotomized total score and the diagnosis made by structured interview was 0.82, for the self-reported version and 0.88 for the observer version. Sensitivity and specificity for the self-reported version were 80.36 and 97.9, respectively. Sensitivity and specificity values for the observer version were 95.4 and 96.3 respectively.Conclusions. Both versions of the «FASCT» scale were shown to be valid and reliable for adult ADHD screening

[Construction, validity and reliability, of the screening scale "FASCT" for attention deficit hyperactivity disorder in adults (self-reported and observer versions)]. / Construcción, validez y fiabilidad de la escala de tamizaje "FASCT" para el trastorno por déficit de atención en adultos (versión autoaplicada y del observador).

INTRODUCTION: Research about the reliability of retrospective self-report rating scales for attention deficit hyperactivity disorder (ADHD) in adults has been limited. METHOD: A self-report scale named "FASCT" was created with two versions: self-reported and observer. The self-reported version was applied to 393 subjects and the observer version to 377. An exploratory and confirmatory factorial analysis was made in order to obtain the final adaptation of both versions. Finally they were applied to 205 subjects and 105 of their first degree relatives. RESULTS: Cronbach's alpha for the self-reported version was 0.84 and 0.87 for the observer version. The total score that had the best balance between sensitivity and 1-specificity was 23 points for each version of the "FASCT". Correlation between both versions was 0.88. The correlation coefficient between the Wender-UTAH scale and self-reported version was 0.71 and for the observer version was 0.66. Agreement degree between dichotomized total score and the diagnosis made by structured interview was 0.82, for the self-reported version and 0.88 for the observer version. Sensitivity and specificity for the self-reported version were 80.36 and 97.9, respectively. Sensitivity and specificity values for the observer version were 95.4 and 96.3 respectively. CONCLUSIONS: Both versions of the "FASCT" scale were shown to be valid and reliable for adult ADHD screening.

Relation of serum cholesterol, lipid, serotonin and tryptophan levels to severity of depression and to suicide attempts.

OBJECTIVE: To determine if there is a relation to low serum cholesterol, lipoprotein, serotonin or tryptophan levels in patients with depression who have recently attempted suicide. DESIGN: Biochemical and behavioural study. SETTING: Inpatient and outpatient treatment at the Instituto Mexicano de Psiquiatría. PARTICIPANTS: Thirty-three patients with a diagnosis of major depressive episode. Eighteen of these patients had attempted suicide in the month before the start of the study; 15 patients had never attempted suicide. OUTCOME MEASURES: Serum levels of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, serotonin (5-HT) and tryptophan. Scores on Hamilton Depression Rating Scale, Carroll Depression Rating Scale, Beck Hopelessness Scale and Beck Suicide Attempt Severity Scale. RESULTS: There were no significant differences between patients who had attempted suicide and those who had not in terms of serum cholesterol, HDL, LDL and triglyceride levels. Serum levels of 5-HT and tryptophan were significantly lower in patients with depression who had a recent suicide attempt than in those patients who had never attempted suicide. A comparison of patients not taking antidepressant medication found serum 5-HT levels to be more than 3 times lower in those patients with a recent suicide attempt than in patients with no history of suicide attempt. CONCLUSIONS: The study found no difference in lipid profiles between patients who had attempted suicide and those who had not. Low serum levels of 5-HT may increase the risk of suicide attempt in patients who are depressed.

High-dose naloxone (1.0 mg/kg): psychological and endocrine effects in normal male subjects pretreated with one milligram of dexamethasone.

The possible participation of the endogenous opioid system (EOS) in the negative feedback of the hypothalamic-pituitary-adrenal axis (HPA-a) activated by low doses (1 mg) of dexamethasone (Dex) was investigated. Ten male healthy subjects (mean age 31.5 +/- 1.9 SEM) were studied on 2 separate days, in a double-blind, cross-over and placebo-controlled design. All subjects were pretreated with 1.0 mg Dex orally the night (2300 h) before both test days. On the study days, subjects were admitted at 0700 h for cannula insertion; the administration of an i.v. bolus of either naloxone (Nal) (1.0 mg/kg) or saline solution (Sal) i.v. was started at 0900 h. Before and following each infusion, mood was measured by a Visual Analogue Scales (VAS) and by the Affective Quality Scale (AQS) every 30 min and blood samples were taken at 15-min intervals. Blood pressure and heart rate were also monitored. Before Dex administration, plasma cortisol levels were within the normal range in all subjects (210.4 +/- 13 ng/ml), while after 9 h after Dex cortisol levels showed the expected significant (p < 0.01) decrease (11.5 +/- 1.9 and 15.04 +/- 0.7 ng/ml for Sal and Nal test days respectively). There were no detectable increases in plasma cortisol levels following either Nal nor Sal administration. However, there was a Nal-induced significant increase in LH (p < 0.01) thus indicating that an effective opioid blockade at the level of the hypothalamic-pituitary unit occurred. There were also a mild and selective Dex + Nal-induced dysphoric (mood factors related to subjects perception of their cognition) and bradycardic effects (p < 0.05). These results suggest that the EOS is not directly involved in the negative feedback triggered by low doses of Dex of the HPA-a, and that there might be a possible glucocorticoid-opioid interaction for the modulation of some aspects of mood.