GSK-3ß orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo.

Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3ß) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3ß-overexpressing newborn neurons show an increased number and altered size of Gephyrin+ postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3ß overexpression triggers a depletion of Parvalbumin+ interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3ß is dysregulated.

Structural relaxation, dynamical arrest, and aging in soft-sphere liquids.

We investigate the structural relaxation of a soft-sphere liquid quenched isochorically (ϕ = 0.7) and instantaneously to different temperatures Tf above and below the glass transition. For this, we combine extensive Brownian dynamics simulations and theoretical calculations based on the non-equilibrium self-consistent generalized Langevin equation (NE-SCGLE) theory. The response of the liquid to a quench generally consists of a sub-linear increase of the α-relaxation time with system's age. Approaching the ideal glass-transition temperature from above (Tf > Ta), sub-aging appears as a transient process describing a broad equilibration crossover for quenches to nearly arrested states. This allows us to empirically determine an equilibration timescale teq(Tf) that becomes increasingly longer as Tf approaches Ta. For quenches inside the glass (Tf ≤ Ta), the growth rate of the structural relaxation time becomes progressively larger as Tf decreases and, unlike the equilibration scenario, τα remains evolving within the whole observation time-window. These features are consistently found in theory and simulations with remarkable semi-quantitative agreement and coincide with those revealed in a previous and complementary study [P. Mendoza-Méndez et al., Phys. Rev. 96, 022608 (2017)] that considered a sequence of quenches with fixed final temperature Tf = 0 but increasing ϕ toward the hard-sphere dynamical arrest volume fraction ϕHS a=0.582. The NE-SCGLE analysis, however, unveils various fundamental aspects of the glass transition, involving the abrupt passage from the ordinary equilibration scenario to the persistent aging effects that are characteristic of glass-forming liquids. The theory also explains that, within the time window of any experimental observation, this can only be observed as a continuous crossover.

Modeling the irradiation pattern of LEDs at short distances.

A method for modeling the irradiance spatial distribution by light-emitting diodes (LEDs) on near distance targets has been developed. The model can easily handle the complex simulation of non-homogenous emitting LEDs, multichip LEDs, LED arrays, and phosphor coated LEDs. The LED irradiation profile is obtained by image processing one photograph of the emitting LED, taken with a smartphone. The method uses image convolution or image correlation between the LED image and a special kernel. The model provides the irradiation spatial pattern in function of the irradiation distance. And the model is tested both with theory and with experimental measurements.

On a fundamental description of the Kovacs' kinetic signatures in glass-forming systems.

The time-evolution equation for the time-dependent static structure factor of the non-equilibrium self-consistent generalized Langevin equation (NE-SCGLE) theory was used to investigate the kinetics of glass-forming systems under isochoric conditions. The kinetics are studied within the framework of the fictive temperature (TF) of the glassy structure. We solve for the kinetics of TF(t) and the time-dependent structure factor and find that they are different but closely related by a function that depends only on temperature. Furthermore, we are able to solve for the evolution of TF(t) in a set of temperature-jump histories referred to as the Kovacs' signatures. We demonstrate that the NE-SCGLE theory reproduces all the Kovacs' signatures, namely, intrinsic isotherm, asymmetry of approach, and memory effect. In addition, we extend the theory into largely unexplored, deep glassy state, regions that are below the notionally "ideal" glass temperature.

Anaphylaxis to Vespa velutina nigrithorax: Pattern of Sensitization for an Emerging Problem in Western Countries.

OBJECTIVE: To define the sensitization pattern of patients with anaphylaxis to Vespa velutina nigrithorax (VVN). METHODS: We studied 100 consecutive Spanish patients with anaphylaxis to Hymenoptera venom and systematically determined specific IgE (sIgE) to whole venoms (Vespula species, Polistes dominula, Apis mellifera, Vespa crabro, and Dolichovespula maculata) and their molecular components (rApi m 1, rApi m 5, rApi m 10, rVes v 1, rVes v 5, rPol d 5, and cross-reactive carbohydrates). Specific IgE to VVN venom and its antigen 5 (nVesp v 5) were measured in a subsample. RESULTS: Seventy-seven patients had anaphylaxis to VVN. Of these, only 16 (20.8%) reported previous VVN stings, but were stung by other Hymenoptera. Positive sIgE (>0.35 kUA/L) to each of the whole venoms was detected in >70% of patients (Vespula species in 100%). The components showing >50% positivity were rApi m 5 (51.4%), rPol d 5 (80.0%), and rVes v 5 (98.7%). This pattern was similar to that of Vespula species anaphylaxis (n=11) but different from that of A mellifera anaphylaxis (n=10). Specific IgE to nVesp v 5 was positive in all patients (n=15) with VVN anaphylaxis and was correlated with sIgE to both rVes v 5 (R=0.931) and rPol d 5 (R=0.887). CONCLUSIONS: VVN has become the commonest cause of Hymenoptera anaphylaxis in our area. Most cases report no previous VVN stings. Their sensitization pattern is similar to that of patients with anaphylaxis to other Vespidae. Specific IgE to antigen-5 from VVN, Vespula species, and P dominula are strongly correlated in patients with VVN anaphylaxis.

First-principles prediction of multiple stationary states in glass-forming liquids.

In the present work, the Non-Equilibrium Self-Consistent Generalized Langevin Equation (NESCGLE) theory is used to predict the final state of glass-forming liquids subjected to different cooling processes. We show that the NESCGLE theory correctly describes two essential features of the glass transition. Such features are the structural recovery and the dependence of the final state with the cooling rate. We demonstrate that below a particular temperature Tc, the system is unable to equilibrate, independently of the cooling rate. We show that the equilibrium state is only reached for the quasistatic process. Additionally, we show how, from the NESCGLE theory, it is possible to deduce a relaxation model of structural recovery, for which we obtain molecular expressions of the parameters.

Utility of the Spanish version of the Everyday Cognition scale in the diagnosis of mild cognitive impairment and mild dementia in an older cohort from the Argentina-ADNI.

INTRODUCTION: The performance of activities of daily living in elderly patients with memory disorders is directly related to living independently and to autonomy. Documenting and assessing functional capacity through detailed scales is important for both diagnostic and treatment recommendations. The Everyday Cognition (ECog) scale is a relatively new informant-rated measure of cognitive and functional abilities. In the present study, the discriminant validity of the ECog scale was evaluated in cognitively intact controls (CN) and in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) from the Argentina-ADNI cohort to establish diagnostic accuracy. In addition, we compared the sensitivity and specificity of ECog against Functional Assessment Questionnaire (FAQ) scale to discriminate among the three groups. METHODS: We evaluated 15 CN, 28 MCI, and 13 mild AD subjects. External, convergent and divergent validity and internal consistency were examined. RESULTS: The average total score on the ECog was significantly different across the three diagnostic syndromes (p < .05). The ECog was more sensitive than FAQ in discriminating between CN and MCI patients and between MCI and AD subjects. The ECog showed a strong correlation with FAQ, and moderate correlations with neuropsychological tests. Cronbach's alpha was .98. CONCLUSIONS: The ECog scale is an efficient instrument for the differentiation of individuals with mild dementia or MCI from normal older adults, with good accuracy and good correlation with other tests measuring daily and cognitive functions. Comparing against FAQ, ECog was more useful in assessing changes in functionality in MCI patients.

Randomized, double-blind study comparing percutaneous electrolysis and dry needling for the management of temporomandibular myofascial pain.

BACKGROUND: To assess whether the techniques of percutaneous needle electrolysis (PNE) and deep dry needling (DDN) used on trigger points (TrP) of lateral pterygoid muscle (LPM) can significantly reduce pain and improve function in patients with myofascial pain syndrome (MPS) compared to a control group treated with a sham needling procedure (SNP). MATERIAL AND METHODS: Sixty patients diagnosed with MPS in the LPM were selected and randomly assigned to one of three groups. The PNE group received electrolysis to the LPM via transcutaneous puncture. The DDN group received a deep puncture to the TrP without the introduction of any substance. In the SNP group, pressure was applied to the skin without penetration. Procedures were performed once per week for 3 consecutive weeks. Clinical evaluation was performed before treatment, and on days 28, 42 and 70 after treatment. RESULTS: Statistically significant differences (p <0.01) were measured for the PNE and DDN groups with respect to pain reduction at rest, during chewing, and for maximum interincisal opening (MIO). Values for the PNE group showed significantly earlier improvement. Differences for PNE and DDN groups with respect to SNP group were significant (p <0.05) up to day 70. Evaluation of efficacy as reported by the patient and observer was better for PNE and DDN groups. No adverse events were observed for either of the techniques. CONCLUSIONS: PNE and DDN of the LPM showed greater pain reduction efficacy and improved MIO compared to SNP. Improvement was noted earlier in the PNE group than in the DDN group.

Discovering key residues of dengue virus NS2b-NS3-protease: New binding sites for antiviral inhibitors design.

The NS2B-NS3 protease is essential for the Dengue Virus (DENV) replication process. This complex constitutes a target for efficient antiviral discovery because a drug could inhibit the viral polyprotein processing. Furthermore, since the protease is highly conserved between the four Dengue virus serotypes, it is probable that a drug would be equally effective against all of them. In this article, a strategy is reported that allowed us to identify influential residues on the function of the Dengue NS2b-NS3 Protease. Moreover, this is a strategy that could be applied to virtually any protein for the search of alternative influential residues, and for non-competitive inhibitor development. First, we incorporated several features derived from computational alanine scanning mutagenesis, sequence, structure conservation, and other structure-based characteristics. Second, these features were used as variables to obtain a multilayer perceptron model to identify defined groups (clusters) of key residues as possible candidate pockets for binding sites of new leads on the DENV protease. The identified residues included: i) amino acids close to the beta sheet-loop-beta sheet known to be important in its closed conformation for NS2b ii) residues close to the active site, iii) several residues evenly spread on the NS2b-NS3 contact surface, and iv) some inner residues most likely related to the overall stability of the protease. In addition, we found concordance on our list of residues with previously identified amino acids part of a highly conserved peptide studied for vaccine development.

Algorithm for early discharge after total thyroidectomy using PTH to predict hypocalcemia: prospective study.

PURPOSE: Hypocalcemia is the most common complication after total thyroidectomy. The aim of this study was to determine whether postoperative parathyroid hormone (PTH) levels predict hypocalcemia in order to design an algorithm for early discharge. METHODS: We present a prospective study including patients who underwent total thyroidectomy. Hypocalcemia was defined as serum ionized calcium < 1.09 mmol/L or clinical evidence of hypocalcemia. PTH measurement was performed preoperatively and at 1, 3, and 6 h postoperatively. The percent decline of preoperative values was calculated for each time point. RESULTS: One hundred and six patients were included. Thirty-six (33.9%) patients presented hypocalcemia. A 50% decline in PTH levels at 3 h postoperatively showed the highest sensitivity and specificity to predict hypocalcemia (91 and 73%, respectively). No patients with a decrease <35% developed hypocalcemia (100% sensitivity), and all patients with a decrease >80% had hypocalcemia (100% specificity). CONCLUSIONS: PTH determination at 3 h postoperatively is a reliable predictor of hypocalcemia. According to the proposed algorithm, patients with less than 80% drop in PTH levels can be safely discharged the day of the surgery.

Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology clinic of a tertiary hospital.

INTRODUCTION: Anisocorias are a relatively frequent reason for consultation in neuro-ophthalmology units. They remain a diagnostic challenge for specialists as they may be due to several etiological factors. In the absence of other accompanying symptoms, anisocorias are usually due to benign processes. Benign episodic mydriasis (BEM) is an isolated cause of intermittent pupil asymmetry, in which the pathophysiology is still not fully understood, and is predominant in young women with migraine. SUBJECTS, MATERIAL AND METHODS: We describe the epidemiological and clinical characteristics of patients with BEM, assessed in a neuro-ophthalmology unit in a tertiary hospital. RESULTS: A total of 7 patients were diagnosed with BEM, all of them females, with a mean age of 33 ± 10 yrs. The patients presented with pupil asymmetry (n = 5) and blurred vision (n = 2), and 6 of the 7 patients had unilateral involvement. The duration of impairment varied from a few minutes to 48 hrs. Four patients (57%) had a clinical history of migraine without aura. The episodes in these 4 patients were recurrent (75%), often lasted for a few minutes (75%), and had associated blurred vision (50%). The neuroimaging studies were normal. DISCUSSION: BEM appears predominantly in young women. It is frequently related to a previous history of migraine, and the specialist must consider if it is a concomitant symptom of common migraine, migraine with aura, or ophthalmoplegic migraine. Although BEM has unilateral predominance, there may be alternation of the affected eye or even bilateral impairment during the same episode, which makes us question the adequacy of the term to describe the process. Imaging tests are not recommended in the absence of other accompanying symptoms, or in short-term episodes.

Monte Carlo computer simulation of sedimentation of charged hard spherocylinders.

In this article we present a NVT Monte Carlo computer simulation study of sedimentation of an electroneutral mixture of oppositely charged hard spherocylinders (CHSC) with aspect ratio L/σ = 5, where L and σ are the length and diameter of the cylinder and hemispherical caps, respectively, for each particle. This system is an extension of the restricted primitive model for spherical particles, where L/σ = 0, and it is assumed that the ions are immersed in an structureless solvent, i.e., a continuum with dielectric constant D. The system consisted of N = 2000 particles and the Wolf method was implemented to handle the coulombic interactions of the inhomogeneous system. Results are presented for different values of the strength ratio between the gravitational and electrostatic interactions, Γ = (mgσ)/(e(2)/Dσ), where m is the mass per particle, e is the electron's charge and g is the gravitational acceleration value. A semi-infinite simulation cell was used with dimensions Lx ≈ Ly and Lz = 5Lx, where Lx, Ly, and Lz are the box dimensions in Cartesian coordinates, and the gravitational force acts along the z-direction. Sedimentation effects were studied by looking at every layer formed by the CHSC along the gravitational field. By increasing Γ, particles tend to get more packed at each layer and to arrange in local domains with an orientational ordering along two perpendicular axis, a feature not observed in the uncharged system with the same hard-body geometry. This type of arrangement, known as tetratic phase, has been observed in two-dimensional systems of hard-rectangles and rounded hard-squares. In this way, the coupling of gravitational and electric interactions in the CHSC system induces the arrangement of particles in layers, with the formation of quasi-two dimensional tetratic phases near the surface.

A state-of-art-review on emerging contaminants: Environmental chemistry, health effect, and modern treatment methods.

Pollution problems are increasingly becoming e a priority issue from both scientific and technological points of view. The dispersion and frequency of pollutants in the environment are on the rise, leading to the emergence have been increasing, including of a new class of contaminants that not only impact the environment but also pose risks to people's health. Therefore, developing new methods for identifying and quantifying these pollutants classified as emerging contaminants is imperative. These methods enable regulatory actions that effectively minimize their adverse effects to take steps to regulate and reduce their impact. On the other hand, these new contaminants represent a challenge for current technologies to be adapted to control and remove emerging contaminants and involve innovative, eco-friendly, and sustainable remediation technologies. There is a vast amount of information collected in this review on emerging pollutants, comparing the identification and quantification methods, the technologies applied for their control and remediation, and the policies and regulations necessary for their operation and application. In addition, This review will deal with different aspects of emerging contaminants, their origin, nature, detection, and treatment concerning water and wastewater.

Computer simulation of sedimentation of ionic systems using the Wolf method.

We present computer simulation results for 1:1 and 2:1 electrolyte solutions in the presence of a gravitational field, using the Monte Carlo method in the NVT ensemble for the restrictive primitive model. Coulombic interactions were taken into account comparing the Ewald and Wolf methods. Three variations of Ewald summations were considered: the exact method for slab geometries (EW2D), and the three-dimensional (3D) versions with and without a dipolar correction (EW3DC and EW3D, respectively). The equivalent 3D Wolf protocols were applied under the same conditions (WF3DC and WF3D, respectively). The Wolf and Ewald methods agree accurately in the prediction of several thermodynamic and structural properties for these inhomogeneous systems: excess internal energies, isochoric heath capacities, and density and electrostatic potential profiles. The main advantage using the Wolf method is the significant saving in computing time, which is approximately six times faster than EW3D and EW3DC, and sixty times faster than EW2D.

Formation and structure of colloidal halos in two-dimensional suspensions of paramagnetic particles.

Different Monte Carlo simulation approaches are used here to study the static structure induced by a spherical neutral substrate inserted in the midst of a two-dimensional suspension of paramagnetic particles. It is then observed that in some instances some of these particles are adsorbed to the surface of the substrate, forming colloidal halos. We investigate the necessary conditions for the formation of these halos and the dependence of the number of adsorbed particles on the relevant parameters of the system. The angular distribution of the adsorbed particles around the perimeter of the substrate is analyzed here too.

Biomarkers of Alzheimer's disease in mild cognitive impairment: Experience in a memory clinic from Latin America. / Biomarcadores de enfermedad de Alzheimer en deterioro cognitivo leve: experiencia en una clínica de memoria de Latinoamérica.

OBJECTIVE: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America. METHODS: We studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aß1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration. RESULTS: Amyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non-Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia. CONCLUSIONS: This study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice.

Effects of DC Magnetic Fields on Magnetoliposomes.

The potential use of magnetic nanoparticles (MNPs) in biomedicine as magnetic resonance, drug delivery, imagenology, hyperthermia, biosensors, and biological separation has been studied in different laboratories. One of the challenges on MNP elaboration for biological applications is the size, biocompatibility, heat efficiency, stabilization in physiological conditions, and surface coating. Magnetoliposome (ML), a lipid bilayer of phospholipids encapsulating MNPs, is a system used to reduce toxicity. Encapsulated MNPs can be used as a potential drug and a gene delivery system, and in the presence of magnetic fields, MLs can be accumulated in a target tissue by a strong gradient magnetic field. Here, we present a study of the effects of DC magnetic fields on encapsulated MNPs inside liposomes. Despite their widespread applications in biotechnology and environmental, biomedical, and materials science, the effects of magnetic fields on MLs are unclear. We use a modified coprecipitation method to synthesize superparamagnetic nanoparticles (SNPs) in aqueous solutions. The SNPs are encapsulated inside phospholipid liposomes to study the interaction between phospholipids and SNPs. Material characterization of SNPs reveals round-shaped nanoparticles with an average size of 12 nm, mainly magnetite. MLs were prepared by the rehydration method. After formation, we found two types of MLs: one type is tense with SNPs encapsulated and the other is a floppy vesicle that does not show the presence of SNPs. To study the response of MLs to an applied DC magnetic field, we used a homemade chamber. Digitalized images show encapsulated SNPs assembled in chain formation when a DC magnetic field is applied. When the magnetic field is switched off, it completely disperses SNPs. Floppy MLs deform along the direction of the external applied magnetic field. Solving the relevant magnetostatic equations, we present a theoretical model to explain the ML deformations by analyzing the forces exerted by the magnetic field over the surface of the spheroidal liposome. Tangential magnetic forces acting on the ML surface result in a press force deforming MLs. The type of deformations will depend on the magnetic properties of the mediums inside and outside the MLs. The model predicts a coexistence region of oblate-prolate deformation in the zone where χ = 1. We can understand the chain formation in terms of a dipole-dipole interaction of SNP.

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine.

Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2',2'-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment (P< 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression (P=0.044) and overall survival (P=0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P=0.049), time to progression (9.9 vs 2.3 months; P=0.003) and overall survival (15.4 vs 3.6; P=0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy.

WITHDRAWN: Role of NCAM in Spine Dynamics and Synaptogenesis.

Increasing evidence indicates that adhesion molecules are critically involved in the regulation of mechanisms of synaptic plasticity including synapse formation, but also synaptic remodeling associated to changes in synaptic strength. Among these, the Neural Cell Adhesion Molecule (NCAM) and its polysialylated form PSA-NCAM are important candidates. Here we review recent results that point to a possible role of these two molecules in regulating the structural properties of excitatory synapses and namely the composition and stability of the postsynaptic density, thereby accounting for their contribution to mechanisms of synaptogenesis and activity-dependent synaptic plasticity.

Choroidal metastasis of a minor salivary gland adenoid cystic carcinoma: A case report. / Metástasis coroideas de un carcinoma adenoide quístico de glándula salival menor: caso clínico.

CASE REPORT: A 61-year-old man with a lower lip minor salivary gland adenoid cystic carcinoma, suffered from a unilateral progressive visual acuity loss due to choroidal metastasis. DISCUSSION: Adenoid cystic carcinoma is a rare primary tumour with significant metastatic potential. Our patient presented with a unilateral choroidal metastasis. According to the current literature, 8 cases of choroidal metastasis of salivary gland adenoid cystic carcinoma have been reported. This is the second case reported of choroidal metastasis with origin in a minor salivary gland, and the first one with origin in the minor salivary glands of the lower lip.