Comparison of the Latin America Regulation Landscape and International Reference Health Authorities to Hasten Drug Registration and Clinical Research Applications.

Introduction: Promptly providing new drugs to fulfill unmet medical needs requires changes in drug development and registration processes. Health Authorities (HAs) considered as reference due to their experience and acknowledgement (Food and Drug Administration [FDA] among others) already consider innovative clinical trial (CT) designs and flexible approval procedures, but Latin America (LATAM) regulations are still far. A comparison was performed to identify gaps.

Predicting progression to Alzheimer's disease with human hippocampal progenitors exposed to serum.

Adult hippocampal neurogenesis is important for learning and memory and is altered early in Alzheimer's disease. As hippocampal neurogenesis is modulated by the circulatory systemic environment, evaluating a proxy of how hippocampal neurogenesis is affected by the systemic milieu could serve as an early biomarker for Alzheimer's disease progression. Here, we used an in vitro assay to model the impact of systemic environment on hippocampal neurogenesis.

Neuropsychological networks in cognitively healthy older adults and dementia patients.

Neuropsychological tests have commonly been used to determine the organization of cognitive functions by identifying latent variables. In contrast, an approach which has seldom been employed is network analysis. We characterize the network structure of a set of representative neuropsychological test scores in cognitively healthy older adults and MCI and dementia patients using network analysis.

The Major Allergen (Asp n 3) DNA-Specific Sequence Is a Reliable Marker to Identify Early Fungal Contamination and Postharvest Damage in Fruit.

The aim of this work was to study the value of the main allergen Asp n 3 of as a molecular marker of allergenicity and pathogenicity with the potential to be used in the identification of as a contaminant and cause of spoilage of Real-time polymerase chain reaction (RT-PCR) was used for the amplification of Asp n 3 gene. Two pairs of primers were designed: one for the amplification of the entire sequence and another one for the amplification of the most conserved region of this peroxisomal protein. The presence of was demonstrated by the early detection of the allergenic protein Asp n 3 coding gene, which could be considered a species-specific marker.

Preserved semantic categorical organization in mild cognitive impairment: A network analysis of verbal fluency.

The decline in semantic verbal fluency as we age may originate from both semantic memory degradation and executive function deficits. We investigated to what extent semantic memory is organized into categories in older adults with mild cognitive impairment (n = 81) and healthy controls (n = 83). We obtained the semantic networks automatically from the probability of co-occurrence of words in a verbal fluency test and characterized them with graph-theory tools.

Detection of early stages of Alzheimer's disease based on MEG activity with a randomized convolutional neural network.

The early detection of Alzheimer's disease can potentially make eventual treatments more effective. This work presents a deep learning model to detect early symptoms of Alzheimer's disease using synchronization measures obtained with magnetoencephalography. The proposed model is a novel deep learning architecture based on an ensemble of randomized blocks formed by a sequence of 2D-convolutional, batch-normalization and pooling layers.

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice.

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model.

Clusterin Is Required for β-Amyloid Toxicity in Human iPSC-Derived Neurons.

Our understanding of the molecular processes underlying Alzheimer's disease (AD) is still limited, hindering the development of effective treatments, and highlighting the need for human-specific models. Advances in identifying components of the amyloid cascade are progressing, including the role of the protein clusterin in mediating β-amyloid (Aβ) toxicity. Mutations in the clusterin gene (CLU), a major genetic AD risk factor, are known to have important roles in Aβ processing.

Automatic mining of symptom severity from psychiatric evaluation notes.

Objectives: As electronic mental health records become more widely available, several approaches have been suggested to automatically extract information from free-text narrative aiming to support epidemiological research and clinical decision-making. In this paper, we explore extraction of explicit mentions of symptom severity from initial psychiatric evaluation records. We use the data provided by the 2016 CEGS N-GRID NLP shared task Track 2, which contains 541 records manually annotated for symptom severity according to the Research Domain Criteria.

Evidence of eosinophil extracellular trap cell death in COPD: does it represent the trigger that switches on the disease?

In spite of the numerous studies on chronic obstructive pulmonary disease (COPD), the cellular and molecular basis of the disease's development remain unclear. Neutrophils and eosinophils are known to be key players in COPD. Recently, neutrophil extracellular trap cell death (NETosis), a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD.

Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives.

The "dysconnection hypothesis" of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated.

An efficient implementation of the synchronization likelihood algorithm for functional connectivity.

Measures of functional connectivity are commonly employed in neuroimaging research. Among the most popular measures is the Synchronization Likelihood which provides a non-linear estimate of the statistical dependencies between the activity time courses of different brain areas. One aspect which has limited a wider use of this algorithm is the fact that it is very computationally and memory demanding.

Reduction of pain thresholds in fibromyalgia after very low-intensity magnetic stimulation: a double-blinded, randomized placebo-controlled clinical trial.

Background: Exposure to electromagnetic fields has been reported to have analgesic and antinociceptive effects in several organisms.

Objective: To test the effect of very low-intensity transcranial magnetic stimulation on symptoms associated with fibromyalgia syndrome.

Methods: A double-blinded, placebo-controlled clinical trial was performed in the Sagrado Corazón Hospital, Seville, Spain.

Signal-to-noise ratio of the MEG signal after preprocessing.

Background: Magnetoencephalography (MEG) provides a direct measure of brain activity with high combined spatiotemporal resolution. Preprocessing is necessary to reduce contributions from environmental interference and biological noise.

New Method: The effect on the signal-to-noise ratio of different preprocessing techniques is evaluated.

Increased brain responses during subjectively-matched mechanical pain stimulation in fibromyalgia patients as evidenced by MEG.

Objective: The precise pathophysiology of fibromyalgia, a syndrome characterized by chronic widespread pain, remains to be clarified. When subjected to the same amount of stimulation, patients show enhanced brain responses as compared to controls, providing evidence of central pain augmentation in this syndrome. We aimed to characterize brain response differences when stimulation is adjusted to elicit similar subjective levels of pain in both groups.

Estimation of functional connectivity from electromagnetic signals and the amount of empirical data required.

An increasing number of neuroimaging studies are concerned with the identification of interactions or statistical dependencies between brain areas. Dependencies between the activities of different brain regions can be quantified with functional connectivity measures such as the cross-correlation coefficient. An important factor limiting the accuracy of such measures is the amount of empirical data available.

Reorganization of functional networks in mild cognitive impairment.

Whether the balance between integration and segregation of information in the brain is damaged in Mild Cognitive Impairment (MCI) subjects is still a matter of debate. Here we characterize the functional network architecture of MCI subjects by means of complex networks analysis. Magnetoencephalograms (MEG) time series obtained during a memory task were evaluated by synchronization likelihood (SL), to quantify the statistical dependence between MEG signals and to obtain the functional networks.

Brain activity patterns in stable and progressive mild cognitive impairment during working memory as evidenced by magnetoencephalography.

It has been reported that mild cognitive impairment (MCI) patients, when compared with controls, show increased activity in different brain regions within the ventral pathway during memory tasks. A key question is whether this profile of increased activity could be useful to predict which patients will develop dementia. Herein, we present profiles of brain magnetic activity during a memory task recorded with magnetoencephalography from MCI patients (N = 10), Alzheimer's disease (AD) patients (N = 10), and healthy volunteers (N = 17).

Functional connectivity in mild cognitive impairment during a memory task: implications for the disconnection hypothesis.

Mild cognitive impairment (MCI) has been considered an intermediate state between healthy aging and dementia. The early damage in anatomical connectivity and progressive loss of synapses that characterize early Alzheimer's disease suggest that MCI could also be a disconnection syndrome. Here, we compare the degree of synchronization of brain signals recorded with magnetoencephalography from patients (22) with MCI with that of healthy controls (19) during a memory task.

Increased biomagnetic activity in healthy elderly with subjective memory complaints.

Objective: Subjective memory complaints (SMCs) are frequently reported by elderly people with or without objective cognitive impairment (OMI) as assessed by neuropsychological tests. We investigate whether SMCs are associated with altered brain biomagnetic patterns even in the absence of OMI.

Methods: We report spatio-temporal patterns of brain magnetic activity recorded with magnetoencephalography during a memory task in 51 elderly participants divided into the following groups: patients with mild cognitive impairment (MCI) with SMC and OMI, individuals with SMC but not OMI, and healthy controls without neither SMC nor OMI.

Cortical oscillatory activity associated with the perception of illusory and real visual contours.

We used magnetoencephalography (MEG) to examine the nature of oscillatory brain rhythms when passively viewing both illusory and real visual contours. Three stimuli were employed: a Kanizsa triangle; a Kanizsa triangle with a real triangular contour superimposed; and a control figure in which the corner elements used to form the Kanizsa triangle were rotated to negate the formation of illusory contours. The MEG data were analysed using synthetic aperture magnetometry (SAM) to enable the spatial localisation of task-related oscillatory power changes within specific frequency bands, and the time-course of activity within given locations-of-interest was determined by calculating time-frequency plots using a Morlet wavelet transform.

Can we observe collective neuronal activity from macroscopic aggregate signals?

The fundamental problem faced by noninvasive neuroimaging techniques such as EEG/MEG(1) is to elucidate functionally important aspects of the microscopic neuronal network dynamics from macroscopic aggregate measurements. Due to the mixing of the activities of large neuronal populations in the observed macroscopic aggregate, recovering the underlying network that generates the signal in the absence of any additional information represents a considerable challenge. Recent MEG studies have shown that macroscopic measurements contain sufficient information to allow the differentiation between patterns of activity, which are likely to represent different stimulus-specific collective modes in the underlying network (Hadjipapas, A.

Brain imaging of acupuncture: comparing superficial with deep needling.

The difference between superficial and deep needling at acupuncture points has yet to be mapped with functional magnetic resonance imaging (fMRI). Using a 3T MRI, echo planar imaging data were acquired for 17 right-handed healthy volunteer participants. Two fMRI scans of acupuncture needling were taken in random order in a block design, one for superficial and one for deep needling on the right hand at the acupuncture point LI-4 (Hegu), with the participant blind to the order.

Spatio-temporal prediction and inference by V1 neurons.

In normal vision, visual scenes are predictable, as they are both spatially and temporally redundant. Evidence suggests that the visual system may use the spatio-temporal regularities of the external world, available in the retinal signal, to extract information from the visual environment and better reconstruct current and future stimuli. We studied this by recording neuronal responses of primary visual cortex (area V1) in anaesthetized and paralysed macaques during the presentation of dynamic sequences of bars, in which spatio-temporal regularities and local information were independently manipulated.