Nanofibre encapsulation of limonene and modelling its release mechanisms

In this study, limonene was encapsulated by using gelatine, Na-alginate, polyvinyl alcohol, lactalbumin or xanthan gum with the uniaxial electrospinning process. The highest encapsulation efficiency was obtained for the sample containing polyvinyl alcohol. The release kinetic studies of nanofibre encapsulated limonene were carried out at 5.5, 20, and 38.5 °C. The Peppas equation expressed the release behavior of limonene for all systems very well, indicating quasi-Fickian diffusion. The modelling data suggested that maybe more than one mechanism was involved for the release at 20 °C. The activation energy for releasing limonene from the electrospun polyvinyl alcohol-alginate encapsulation system was found to be 6.2 kJ mol–1 from the Arrhenius equation

Pulpal Tissue in Bilateral Talon Cusps of Primary Central Incisors: Report of a Case

Talon cusp is a tooth anomaly that affects both the primary and the permanent dentitions. However, the occurrence of this anomalous cusp is rather infrequent in the primary dentition. Only 7 cases of bilateral talon cusps affecting the primary teeth have been reported in the dental literature. This is a case report of bilateral talon cusps on primary maxillary central incisors whose histologic evaluation revealed the existence of pulpal tissue in the anomalous cusps

Cold accretion flows and the nature of high column density H I absorption at redshift 3

Simulations predict that galaxies grow primarily through the accretion of gas that has not gone through an accretion shock near the virial radius and that this cold gas flows towards the central galaxy along dense filaments and streams. There is, however, little observational evidence for the existence of these cold flows. We use a large, cosmological, hydrodynamical simulation that has been post‐processed with radiative transfer to study the contribution of cold flows to the observed z= 3 column density distribution of neutral hydrogen, which our simulation reproduces. We find that nearly all of the H I absorption arises in gas that has remained colder than 105.5 K, at least while it was extragalactic. In addition, the majority of the H I is falling rapidly towards a nearby galaxy, with non‐negligible contributions from outflowing and static gas. Above a column density of Graphic cm−2, most of the absorbers reside inside haloes, but the interstellar medium only dominates for Graphic cm−2. Haloes with total mass below 1010 M⊙ dominate the absorption for Graphic cm−2, but the average halo mass increases sharply for higher column densities. Although very little of the H I in absorbers with Graphic cm−2 resides inside galaxies, systems with Graphic cm−2 are closely related to star formation: most of their H I either will become part of the interstellar medium before z= 2 or has been ejected from a galaxy at z > 3. Cold accretion flows are critical for the success of our simulation in reproducing the observed rate of incidence of damped Lyman‐α and particularly that of Lyman limit systems. We therefore conclude that cold accretion flows exist and have already been detected in the form of high column density H I absorbers

Mannitol polymorphs as carrier in dpis formulations: Isolation characterization and performance

The search for best performing carriers for dry powder inhalers is getting a great deal of interest to overcome the limitations posed by lactose. The aerosolization of adhesive mixtures between a carrier and a micronized drug is strongly influenced by the carrier solid-state properties. This work aimed at crystallizing kinetically stable D-mannitol polymorphs and at investigating their aerosolization performance when used in adhesive mixtures with two model drugs (salbutamol sulphate, SS, and budesonide, BUD) using a median and median/high resistance inhaler. A further goal was to assess in vitro the cytocompatibility of the produced polymer-doped mannitol polymorphs toward two lung epithelial cell lines. Kinetically stable (up to 12 months under accelerate conditions) α, and δ mannitol forms were crystallized in the presence of 2% w/w PVA and 1% w/w PVP respectively. These solid phases were compared with the β form and lactose as references. The solid-state properties of crystallized mannitol significantly affected aerosolization behavior, with the δ form affording the worst fine particle fraction with both the hydrophilic (9.3 and 6.5%) and the lipophilic (19.6 and 32%) model drugs, while α and β forms behaved in the same manner (11–13% for SS; 53–58% for BUD) and better than lactose (8 and 13% for SS; 26 and 39% for BUD). Recrystallized mannitol, but also PVA and PVP, proved to be safe excipients toward lung cell lines. We concluded that, also for mannitol, the physicochemical properties stemming from different crystal structures represent a tool for modulating carrier-drug interaction and, in turn, aerosolization performance

Pathological relevance of post-translationally modified alpha-synuclein (pSer87, pSer129, nTyr39) in idiopathic Parkinson’s disease and Multiple System Atrophy

Aggregated alpha-synuclein (a-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of a-synuclein exist, including phosphorylated and nitrated forms. It is unclear which a-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant a-synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three a-synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology- affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 a-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 a- synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 a- synuclein in MSA. Quantification of the LB scores revealed that pS129 a-synuclein was the dominant and earliest a-synuclein PTM followed by nY39 a-synuclein, while lower amounts of pSer87 a-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments

Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers

Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D-2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D-2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D-2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model.Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilAssociacao Fundo Incent Pesquisa, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilWeb of Scienc

Reverse Engineering Gene Networks with ANN: Variability in Network Inference Algorithms

Motivation :Reconstructing the topology of a gene regulatory network is one of the key tasks in systems biology. Despite of the wide variety of proposed methods, very little work has been dedicated to the assessment of their stability properties. Here we present a methodical comparison of the performance of a novel method (RegnANN) for gene network inference based on multilayer perceptrons with three reference algorithms (ARACNE, CLR, KELLER), focussing our analysis on the prediction variability induced by both the network intrinsic structure and the available data. Results: The extensive evaluation on both synthetic data and a selection of gene modules of "Escherichia coli" indicates that all the algorithms suffer of instability and variability issues with regards to the reconstruction of the topology of the network. This instability makes objectively very hard the task of establishing which method performs best. Nevertheless, RegnANN shows MCC scores that compare very favorably with all the other inference methods tested. Availability: The software for the RegnANN inference algorithm is distributed under GPL3 and it is available at the corresponding author home page (http://mpba.fbk.eu/grimaldi/regnann-supmat

Evaluation and Validation of a Method for Determining Platelet Catecholamine in Patients with Obstructive Sleep Apnea and Arterial Hypertension

Background: Measurements of plasma and urinary catecholamine are susceptible to confounding factors that influence the results, complicating the interpretation of sympathetic nervous system (SNS) activity in the Obstructive sleep apnea (OSA) and arterial hypertension (HYP) conditions.Objective: in this study, we validated a test for platelet catecholamine and compared the catecholamine levels (adrenaline and noradrenaline) in urine, plasma and platelets in patients with OSA and HYP compared with controls.Methods: in the validation, 30 healthy, nonsmoking volunteers who were not currently undergoing treatment or medication were selected as the control group. One hundred fifty-four individuals (114 OSA, 40 non-OSA) were consecutively selected from the outpatient clinic of the Sleep Institute and underwent clinical, polysomnographic and laboratory evaluation, including the urinary, plasma and platelet levels of adrenaline (AD) and noradrenaline (NA). Patients were then allocated to groups according to the presence of OSA and/or hypertension.Results: A logistic regression model, controlled for age and BMI, showed that urinary AD and urinary NA were risk factors in the OSA+HYP group and the HYP group; however, the model showed higher levels of platelet NA for OSA without HYP. After 1 year of CPAP (continuous upper airway pressure) treatment, patients (n = 9) presented lower levels of urinary NA (p = 0.04) and platelet NA (p = 0.05).Conclusion: Urinary NA and AD levels were significantly associated with the condition of hypertension with and without OSA, whereas platelet NA with OSA without comorbidity. These findings suggest that platelet catecholamine levels might reflect nocturnal sympathetic activation in OSA patients without hypertension.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Associacao Fundo de Pesquisa a Psicobiologia (AFIP), BrazilConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Cardiol, São Paulo, BrazilAssoc Fundo Incent & Pesquisa, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Cardiol, São Paulo, BrazilWeb of Scienc

Rethinking Hypothesis Tests

Null Hypothesis Significance Testing (NHST) have been a popular statistical tool across various scientific disciplines since the 1920s. However, the exclusive reliance on a p-value threshold of 0.05 has recently come under criticism; in particular, it is argued to have contributed significantly to the reproducibility crisis. We revisit some of the main issues associated with NHST and propose an alternative approach that is easy to implement and can address these concerns. Our proposed approach builds on equivalence tests and three-way decision procedures, which offer several advantages over the traditional NHST. We demonstrate the efficacy of our approach on real-world examples and show that it has many desirable properties