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Introduction: Acute myocardial infarction (AMI), also known as heart attack, is a serious and potentially fatal medical condition that occurs due to interruption of blood flow to a part of the heart muscle, which causes a decrease in oxygen supply and nutrients to the heart muscle. In this context, the incidence of AMI may vary throughout the year, with evidence pointing to a relationship with seasonality. Objective: To carry out a literature review regarding the fluctuation in the incidence of AMI according to the seasons, identifying possible factors associated with these variations. Methodology: This is an integrative review, carried out by searching the electronic databases PubMed, Scielo and Google Academics, using the descriptors "Myocardial Infarction", "Seasonal Variation", "Winter" and "Summer", using the Boolean operator "AND".Conclusion: Temperature can be a risk factor for AMI, as the occurrence tends to be more common in winter, due to increased cardiac effort and changes in blood clotting. However, extreme heat in Summer can cause cardiac stress as well, sensitivity to temperature varies among individuals. [ABSTRACT FROM AUTHOR]

Orofacial nerve injuries may result in temporary or long-term loss of sensory function and decreased quality of life in patients. B vitamins are required for DNA synthesis and the repair and maintenance of phospholipids. In particular, vitamins B1, B6, and B12 are essential for neuronal function. Deficiency in vitamin B complex (VBC) has been linked to increased oxidative stress, inflammation and demyelination. Photobiomodulation (PBM) has antioxidant activity and is neuroprotective. In addition, a growing literature attests to the positive effects of PBM on nerve repair. To assess the effect of PBM and VBC on regenerative process we evaluated the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), myelin basic protein (MBP), laminin and neurofilaments (NFs) using Western blotting to identify regenerative pattern after chronic constriction injury of the infraorbital nerve (CCI IoN) treated by PBM, VBC or its combination. After CCI IoN, the rats were divided into six groups naive, sham, injured (CCI IoN), treated with photobiomodulation (904 nm, 6.23 J/cm2, CCI IoN + PBM), treated with VBC (containing B1, B6 and B12) 5 times, CCI IoN + VBC) and treated with PBM and VBC (CCI IoN + VBC + PBM). The treatments could revert low expression of BDNF, MBP and laminin. Also reverted the higher expression of neurofilaments and enhanced expression of NGF. PBM and VBC could accelerate injured infraorbital nerve repair in rats through reducing the expression of neurofilaments, increasing the expression of BDNF, laminin and MBP and overexpressing NGF. These data support the notion that the use of PBM and VBC may help in the treatment of nerve injuries. This finding has potential clinical applications. [ABSTRACT FROM AUTHOR]

Introduction: the constant evolution of cardiovascular medicine has provided significant advances in the treatment of various cardiac conditions, highlighting cardiac catheter ablation as a highly relevant intervention. Over the years, this technique has become an effective alternative for controlling cardiac arrhythmias, offering patients the prospect of an improved quality of life. Objective: this literature review provides updated information on nursing care in cardiac catheter ablation, benefiting healthcare professionals involved in the care of these patients. Methodology: the review was based on the analysis of articles present in the PubMed and Scielo databases. Conclusion: Studies emphasize the crucial role of team assistance in promoting safe recovery by addressing pain, monitoring vital signs, educating patients, and considering the emotional impact of the procedure. The conclusion highlights that, although catheter ablation is a valuable option in the management of arrhythmias, its effectiveness depends on adequate and safe performance, with the implementation of rigorous postoperative care and effective management of complications being essential. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal hypoxia is a condition that can cause irreversible damage to the newborn's brain, leading to neurological sequelae and even death. Therapeutic hypothermia has shown promising results in treating hypoxia, reducing mortality, and improving long-term prognosis. Objective: This literature review aims to provide updated information on the impact of therapeutic hypothermia, benefiting healthcare professionals involved in the care of these infants. Methodology: The review is based on the analysis of articles from PubMed and Scielo databases. Conclusion: Scientific studies indicate its effectiveness in reducing neurological injuries and other complications associated with hypoxia. However, its application requires a trained multidisciplinary team and adequate resources to monitor and maintain the patient's body temperature. The review has provided a better understanding of relevant aspects of therapeutic hypothermia, its benefits, and challenges in clinical practice. Further studies are still needed to improve the protocol and define best practices for applying therapeutic hypothermia in neonates with neonatal hypoxia. In conclusion, therapeutic hypothermia shows promise as an effective intervention, but its implementation demands specialized care and continuous research efforts to enhance its efficacy and achieve positive long-term outcomes. [ABSTRACT FROM AUTHOR]

The relationship between obesity and human brain structure is incompletely under)stood. Using diffusion-weighted MRI from ∼30,000 UK Biobank participants, we test the hypothesis that obesity (waist-to-hip ratio, WHR) is associated with regional differences in two micro-structural MRI metrics: isotropic volume fraction (ISOVF), an index of free water, and intra-cellular volume fraction (ICVF), an index of neurite density. We observed significant associations with obesity in two coupled but distinct brain systems: a prefrontal/temporal/striatal system associated with ISOVF and a medial temporal/occipital/striatal system associated with ICVF. The ISOVF~WHR system colocated with expression of genes enriched for innate immune functions, decreased glial density, and high mu opioid (MOR) and other neurotransmitter receptor density. Conversely, the ICVF~WHR system co-located with expression of genes enriched for G-protein coupled receptors and decreased density of MOR and other receptors. To test whether these distinct brain phenotypes might differ in terms of their underlying shared genetics or relationship to maps of the inflammatory marker C-reactive Protein (CRP), we estimated the genetic correlations between WHR and ISOVF (rg = 0.026, P = 0.36) and ICVF (rg = 0.112, P < 9×10−4) as well as comparing correlations between WHR maps and equivalent CRP maps for ISOVF and ICVF (P<0.05). These correlational results are consistent with a two-way mechanistic model whereby genetically determined differences in neurite density in the medial temporal system may contribute to obesity, whereas water content in the prefrontal system could reflect a consequence of obesity mediated by innate immune system activation. [ABSTRACT FROM AUTHOR]

Mescaline derivative (2C phenethylamines) drugs have been modified by the introduction of a N-2-methoxybenzyl group to originate a new series of compounds with recognized and potent psychedelic effects, the NBOMe-drugs. Although they are prevalent in unregulated drug markets, their toxicity profile is still poorly understood, despite several reports highlighting cases of acute intoxication, with brain and liver toxicity. Thus, in this study, mescaline, 2C-N (insertion of a nitro in the para position of the 2C phenethylamines aromatic ring) and 2C-B (insertion of a bromide in the para position of the 2C phenethylamines aromatic ring) and their corresponding NBOMe counterparts, mescaline-NBOMe, 25N-NBOMe and 25B-NBOMe, were synthetized and the in vitro neuro- and hepatocytotoxicity evaluated in differentiated SH-SY5Y and HepG2 cell lines, respectively. Cytotoxicity, oxidative stress, metabolic and energetic studies were performed to evaluate the main pathways involved in their toxicity. Our results demonstrated that the presence of the N-2-methoxybenzyl group significantly increased the in vitro cytotoxicity of 2C phenethylamines drugs in both cell lines, with the NBOMe drugs presenting lower EC50 values when compared to their counterparts. Consistently, our data showed a correlation between the drug's lipophilicity and the EC50 values, except for 2C-B. The 2C-B presented higher cytotoxic effects in both cell lines than mescaline-NBOMe, a result that can be explained by its higher passive permeability. All the NBOMe derivatives were able to cross the blood–brain barrier. Considering metabolic studies, the cytotoxicity of these drugs was shown to be influenced by inhibition of cytochrome P450 (CYP), which suggests a potential role of this enzyme complex, especially CYP3A4 and CYP2D6 isoenzymes in SH-SY5Y cells, in their detoxification or bioactivation. Furthermore, in differentiated SH-SY5Y cells, the drugs were able to induce mitochondrial membrane depolarization, and to disrupt GSH and ATP intracellular levels, these effects being concentration dependent and more pronounced for the NBOMe derivatives. No ROS overproduction was detected for any of the drugs in the tested experimental conditions. A correlation between a drug's lipophilicity and the EC50 values in both cell lines, except for 2C-B, was also obtained. In summary, the introduction of a NBOMe moiety to the parent drugs significantly increases their lipophilicity, brain permeability and cytotoxic effects, with GSH and ATP homeostasis disruption. The inhibition of CYP3A4 and CYP2D6 emphasized that CYP-mediated metabolism impacts the toxicity of these drugs. [ABSTRACT FROM AUTHOR]

The aim of this present work is to compare the performance in public management among Brazilian federal universities, from indicators, which deal with the levels of efficiency, efficacy and effectiveness extracted directly from the performance management reports of the Federal Court of Auditors. Conducting the research, secondary data comprising a universe of 63 federal universities were used within a time frame between the years 2015 to 2019. Through the application of multivariate statistical techniques of data, such as multiple linear regression and analysis of clusters (conglomerates), it was possible to compare the performance between each Brazilian federal university with the public management indicators adopted by the TCU. The comparative analysis allowed the development of groupings between the federal universities according to the results of each management indicator, in such a way that it made it possible to know the performance of each group by levels of efficiency, effectiveness and effectiveness. [ABSTRACT FROM AUTHOR]

Drug checking services (DCS) allow people who use drugs to submit drug samples for chemical analysis and provide feedback of results and counseling. Our study tested the validity of behavioral intention measures against reports of actual behavior and the adoption of protective behavioral strategies. DCS patrons at Boom Festival 2018 completed three surveys during the festival (pre-drug analysis 343 participants submitted 671 drug samples, post-drug analysis 290 participants reported on 341 drug sample results, three-day follow-up 145 participants reported on 195 drug sample results) and another survey after six months (n = 71). At third-day follow-up, when the results were 'not the expected substance' (N = 35), 86% (n = 30) reported they 'didn't take the substance'; 11% (n = 4) 'took a smaller dose than initially planned' and only 3% (n = 1) 'took it as planned'. In 71% (n = 63) of the matched post-test and third-day follow-up answers (N = 89), the behavior reported at third-day matched the behavioral intention reported during post-test. After six months, there was a slight increase in most harm-reduction behaviors; however, there was a substantial drop-out among respondents. Results support the hypothesis that DCS promote the adoption of safer drug use practices; however, further research is needed to evaluate the medium- and long-term effects of DCS. [ABSTRACT FROM AUTHOR]

The present study was undertaken to explore the relative contributions of Cav3.2 T-type channels to mediating the antihyperalgesic activity of joint manipulation (JM) therapy. We used the chronic constriction injury model (CCI) to induce peripheral neuropathy and chronic pain in male mice, followed by JM. We demonstrate that JM produces long-lasting mechanical anti-hyperalgesia that is abolished in Cav3.2 null mice. Moreover, we found that JM displays a similar analgesic profile as the fatty acid amide hydrolase inhibitor URB597, suggesting a possible converging mechanism of action involving endocannabinoids. Overall, our findings advance our understanding of the mechanisms through which JM produces analgesia. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disease that can result in disability. Until now, there is no antiviral treatment against CHIKV, demonstrating that there is a need for development of new drugs. Studies have shown that thiosemicarbazones and their metal complexes possess biological activities, and their synthesis is simple, clean, versatile, and results in high yields. Here, we evaluated the mechanism of action (MOA) of a cobalt(III) thiosemicarbazone complex named [CoIII(L1)2]Cl based on its in vitro potent antiviral activity against CHIKV previously evaluated (80% of inhibition on replication). Furthermore, the complex has no toxicity in healthy cells, as confirmed by infecting BHK-21 cells with CHIKV-nanoluciferase in the presence of the compound, showing that [CoIII(L1)2]Cl inhibited CHIKV infection with the selective index of 3.26. [CoIII(L1)2]Cl presented a post-entry effect on viral replication, emphasized by the strong interaction of [CoIII(L1)2]Cl with CHIKV non-structural protein 4 (nsP4) in the microscale thermophoresis assay, suggesting a potential mode of action of this compound against CHIKV. Moreover, in silico analyses by molecular docking demonstrated potential interaction of [CoIII(L1)2]Cl with nsP4 through hydrogen bonds, hydrophobic and electrostatic interactions. The evaluation of ADME-Tox properties showed that [CoIII(L1)2]Cl presents appropriate lipophilicity, good human intestinal absorption, and has no toxicological effect as irritant, mutagenic, reproductive, and tumorigenic side effects. [ABSTRACT FROM AUTHOR]

Herein, a series of polymeric copper(II) complexes were obtained using four different triazoles: 3‐amino‐1,2,4‐triazole (HL1), 3,5‐diamino‐1,2,4‐triazole (HL2), 3‐amino‐1,2,4‐triazole‐5‐carboxylic acid (H2L3) and 1,2,4‐triazole‐3‐carboxylic acid (H2L4); through solvothermal conditions, under controlled pressure and high temperature, following usual procedures described in the literature. These triazoles were chosen to exploit their different coordination modes to copper(II) metal centres to obtain interesting structures and varied gas adsorption selectivity. The isolated materials were characterized by common spectroscopic techniques (IR, diffuse reflectance UV‐Vis, EPR), CHN analyses, X‐ray diffraction (XRD), thermogravimetric analyses, and SQUID magnetometry to give an insight into their structure and composition. Besides, they had their BET surface area determined by nitrogen adsorption‐desorption isotherms, to assess their porosity. At last, their capacity to adsorb carbon dioxide selectively was also evaluated, in line with those reported for similar systems in the literature. Although having small surface area, these compounds are able to adsorb CO2 selectively at very low pressure (under 600 mbar). [ABSTRACT FROM AUTHOR]

A new nitronyl‐nitroxide ligand (H2L) featuring alcoholic and phenolic groups has been synthesised starting from 2‐hydroxy‐3‐(hydroxymethyl)‐5‐methylbenzaldehyde (A). Using this ligand, three 2p–4 f binuclear complexes have been obtained and crystallographically characterized: [Ln2(HL)2(hfac)4], (Ln=Gd 1, Tb 2, Dy 3). Apart from the desired compounds, two by‐products have been isolated as a molecular alloy containing an intermediate bearing hydroxylamino and N‐oxide groups, i. e. (1‐hydroxy‐2‐(2‐hydroxy‐3‐(hydroxymethyl)‐5‐methylphenyl)‐4,4,5,5‐tetramethyl‐4,5‐dihydro‐1H‐imidazole 3‐oxide, B, and the imino‐nitroxide derivative, C. This system was characterized by single crystal X‐ray diffraction, UV‐VIS and EPR spectroscopy. During the synthesis of compounds 1–3, two other complexes have been obtained and characterized: [Ln(C)(hfac)3] (4, Ln=Tb) and [Ln2(A−H)2(hfac)4] (5, Ln=Tb), where (A−H) results from the deprotonation of the phenolic group in A. The synthetic procedure was optimized in order to obtain pure 1–3 complexes. The cryomagnetic properties of compounds 1–3 have been investigated. Continuous‐wave (CW) electron paramagnetic resonance (EPR) measurements were carried out at X‐ and Q‐band for compound 1. Time‐dependent experiments were performed at three magnetic fields. Phase memory times, Tm, were found to be about 1000 ns at 6 K. [ABSTRACT FROM AUTHOR]

Abstract: Chronic pain is a highly debilitating and difficult to treat condition, which affects the structure of the brain. Although the development of chronic pain is moderately heritable, how disease-related alterations at the microscopic genetic architecture drive macroscopic brain abnormalities is currently largely unknown. Here, we examined alterations in morphometric similarity (MS) and applied an integrative imaging transcriptomics approach to identify transcriptional and cellular correlates of these MS changes, in 3 independent small cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain, and fibromyalgia) and age-matched and sex-matched pain-free controls. We uncover a novel pattern of cortical MS remodelling involving mostly small-to-medium MS increases in the insula and limbic cortex (none of these changes survived stringent false discovery rate correction for the number of regions tested). This pattern of changes is different from that observed in patients with major depression and cuts across the boundaries of specific pain syndromes. By leveraging transcriptomic data from Allen Human Brain Atlas, we show that cortical MS remodelling in chronic pain spatially correlates with the brain-wide expression of genes related to pain and broadly involved in the glial immune response and neuronal plasticity. Our findings bridge levels to connect genes, cell classes, and biological pathways to in vivo imaging correlates of chronic pain. Although correlational, our data suggest that cortical remodelling in chronic pain might be shaped by multiple elements of the cellular architecture of the brain and identifies several pathways that could be prioritized in future genetic association or drug development studies. [ABSTRACT FROM AUTHOR]

Diverse GABAergic interneuron networks orchestrate information processing in the brain. Understanding the principles underlying the organisation of this system in the human brain, and whether these principles are reflected by available non-invasive in vivo neuroimaging methods, is crucial for the study of GABAergic neurotransmission. Here, we use human gene expression data and state-of-the-art imaging transcriptomics to uncover co-expression patterns between genes encoding GABAA receptor subunits and inhibitory interneuron subtype-specific markers, and their association with binding patterns of the gold-standard GABA PET radiotracers [11C]Ro15-4513 and [11C]flumazenil. We found that the inhibitory interneuron marker somatostatin covaries with GABAA receptor-subunit genes GABRA5 and GABRA2, and that their distribution followed [11C]Ro15-4513 binding. In contrast, the inhibitory interneuron marker parvalbumin covaried with GABAA receptor-subunit genes GABRA1, GABRB2 and GABRG2, and their distribution tracked [11C]flumazenil binding. Our findings indicate that existing PET radiotracers may provide complementary information about key components of the GABAergic system. Molecular origin of GABA receptor PET tracer signal is probed by performing correlation studies using regional PET signal and gene expression levels of GABA receptors and inhibitory interneuron markers. The results provide insight in the application and interpretation of these GABA receptor PET tracers in clinical populations. [ABSTRACT FROM AUTHOR]

Intranasal oxytocin (OT) has been suggested as a putative adjunctive treatment for patients with schizophrenia and autism spectrum disorders (ASD). Here, we examine available evidence from trials investigating the effects of repeated administrations of intranasal OT on the core symptoms of patients with schizophrenia and ASD, focusing on its therapeutic efficacy and heterogeneity of response (meta‐ANOVA). Repeated administration of intranasal OT does not improve most of the core symptoms of schizophrenia and ASD, beyond a small tentative effect on schizophrenia general symptoms. However, we found significant moderator effects for dose in schizophrenia total psychopathology and positive symptoms, and percentage of included men and duration of treatment in schizophrenia general symptoms. We found evidence of heterogeneity (increased variance) in the response of schizophrenia negative symptoms to intranasal OT compared with placebo, suggesting that subgroups of responsive and non‐responsive patients might coexist. For other core symptoms of schizophrenia, or any of the core symptom dimensions in ASD, the response to repeated treatment with intranasal OT did not show evidence of heterogeneity. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc [ABSTRACT FROM AUTHOR]

In this paper we investigate the deeply virtual Compton scattering (DVCS) process in electron–ion collisions at the Electron–Ion Collider (EIC) and Large Hadron Electron Collider (LHeC). The coherent and incoherent DVCS cross sections and differential distributions are estimated considering the possible states of nucleon configurations in the nuclear wave function and taking into account of the nonlinear corrections to the QCD dynamics. The impact of the nonlinear (saturation) effects is estimated. Our results indicate that a future experimental analysis of these processes can shed light on the description of the QCD dynamics at high energies. [ABSTRACT FROM AUTHOR]

Neonatal anoxia is a well‐known world health problem that results in neurodevelopmental deficits, such as sensory alterations that are observed in patients with cerebral palsy and autism disorder, for which oxygen deprivation is a risk factor. Nociceptive response, as part of the sensory system, has been reported as altered in these patients. To determine whether neonatal oxygen deprivation alters nociceptive sensitivity and promotes medium‐ and long‐term inflammatory feedback in the central nervous system, Wistar rats of around 30 h old were submitted to anoxia (100% nitrogen flux for 25 min) and evaluated on PND23 (postpartum day) and PND90. The nociceptive response was assessed by mechanical, thermal, and tactile tests in the early postnatal and adulthood periods. The lumbar spinal cord (SC, L4–L6) motor neurons (MNs) and the posterior insular cortex neurons were counted and compared with their respective controls after anoxia. In addition, we evaluated the possible effect of anoxia on the expression of astrocytes in the SC at adulthood. The results showed increased nociceptive responses in both males and females submitted to anoxia, although these responses were different according to the nociceptive stimulus. A decrease in MNs in adult anoxiated females and an upregulation of GFAP expression in the SC were observed. In the insular cortex, a decrease in the number of cells of anoxiated males was observed in the neonatal period. Our findings suggest that oxygen‐deprived nervous systems in rats may affect their response at the sensorimotor pathways and respective controlling centers with sex differences, which were related to the used stimulus. [ABSTRACT FROM AUTHOR]

• Vagal dysfunction is present in fibromyalgia. • Fibromyalgia is a stress-related disorder. • Psychosocial factors can play an important role in fibromyalgia. • Stress systems alter neurotransmitters in fibromyalgia. Fibromyalgia (FM) syndrome is a common illness characterized by chronic widespread pain, sleep problems, fatigue, and cognitive difficulties. Dysfunctional neurotransmitter systems that influence the body's endogenous stress response systems are thought to underlie many of the major FM-related symptoms. A model of FM pathogenesis suggests biological and psychosocial variables interact to influence the genetic predisposition, but the precise mechanisms remain unclear. The Polyvagal Theory provides a theoretical framework from which to investigate potential biological mechanisms. The vagus nerve (VN) has anti-inflammatory properties via its afferent and efferent fibers. A low vagal tone (as assessed by low heart rate variability), has been observed in painful and inflammatory diseases, including FM, while the ventral branch of the VN is linked to emotional expression and social engagement. These anti-inflammatory and psychological (limbic system) properties of the VN may possess therapeutic potential in treating FM. This review paper summarizes the scientific literature regarding the potential role of the VN in transducing and/or therapeutically managing FM signs and symptoms. [ABSTRACT FROM AUTHOR]

Advanced methods such as REACT have allowed the integration of fMRI with the brain's receptor landscape, providing novel insights transcending the multiscale organisation of the brain. Similarly, normative modelling has allowed translational neuroscience to move beyond group-average differences and characterise deviations from health at an individual level. Here, we bring these methods together for the first time. We used REACT to create functional networks enriched with the main modulatory, inhibitory, and excitatory neurotransmitter systems and generated normative models of these networks to capture functional connectivity deviations in patients with schizophrenia, bipolar disorder (BPD), and ADHD. Substantial overlap was seen in symptomatology and deviations from normality across groups, but these could be mapped into a common space linking constellations of symptoms through to underlying neurobiology transdiagnostically. This work provides impetus for developing novel biomarkers that characterise molecular- and systems-level dysfunction at the individual level, facilitating the transition towards mechanistically targeted treatments. A study combining fMRI data with molecular templates through REACT defines models of brain function and links deviations from normality in psychiatric populations to transdiagnostic symptomatology. [ABSTRACT FROM AUTHOR]

Substituted phenethylamines including 2C (2,5-dimethoxyphenethylamines) and NBOMe (N-(2-methoxybenzyl)phenethylamines) drugs are potent psychoactive substances with little to no knowledge available on their toxicity. In the present in vitro study, we explored the mechanisms underlying the neurotoxicity of six substituted phenethylamines: 2C-T-2, 2C-T-4, 2C-T-7 and their corresponding NBOMes. These drugs were synthesized and chemically characterized, and their cytotoxicity (0–1000 μM) was evaluated in differentiated SH-SY5Y cells and primary rat cortical cultures, by the NR uptake and MTT reduction assays. In differentiated SH-SY5Y cells, mitochondrial membrane potential, intracellular ATP and calcium levels, reactive oxygen species production, and intracellular total glutathione levels were also evaluated. All the tested drugs exhibited concentration-dependent cytotoxic effects towards differentiated SH-SY5Y cells and primary rat cortical cultures. The NBOMe drugs presented higher cytotoxicity than their counterparts, which correlates with the drug's lipophilicity. These cytotoxic effects were associated with mitochondrial dysfunction, evident through mitochondrial membrane depolarization and lowered intracellular ATP levels. Intracellular calcium imbalance was observed for 2C-T-7 and 25T7-NBOMe, implying a disrupted calcium regulation. Although reactive species levels remained unchanged, a reduction in intracellular total GSH content was observed. Overall, these findings contribute to a deeper understanding of these drugs, shedding light on the mechanisms underpinning their neurotoxicity. [ABSTRACT FROM AUTHOR]

The coherent and incoherent J / Ψ photoproduction in P b - P b collisions are investigated by considering the possible states of nucleon configurations in the nuclear wave function and of the non-linear corrections to the QCD dynamics. The cross sections and the differential rapidity and transverse momentum distributions are estimated for the energies of the future runs of the LHC, High-Energy LHC and Future Circular Collider. Our results indicate that a future experimental analysis of these processes will be useful to discriminate between different approaches for the QCD dynamics as well to improve our description of the gluon saturation effects. [ABSTRACT FROM AUTHOR]

Localisation of sound sources on vibrating structures is a critical part of the design in many engineering applications. In structures with stiffeners, so-called Bloch–Floquet waves are generated due to the interaction between the flexural waves in the host structure and the flexural/torsional waves of the stiffeners. It is known that the Bloch–Floquet waves have a significant contribution to the radiated sound. However, it is not understood which area of the vibrating stiffened structures contributes significantly to the radiation in the far-field. Non-negative intensity (NNI) is a powerful tool developed recently to locate the surface regions on structures that can contribute to the radiated sound power. Although NNI has been used for several distinct structures under different excitations, it has not been considered for analysing structures with stiffeners. In this work, NNI is evaluated for an infinite fluid-loaded stiffened plate subjected to a point force to localise the sources of sound and to shed light on the mechanism involved in the far-field radiation. An analytical model formulated in the wavenumber domain is presented to carry out fast calculations of the plate vibroacoustic responses and the NNI maps. A parametric study is then performed by comparing the vibroacoustic responses with the NNI maps to highlight the capability of NNI for sound source localisation. This is achieved by analysing the results for stiffened/unstiffened structures with excitation on/between the stiffeners, and at frequencies either in a passband or in a stopband. Moreover, the NNI maps are further explained and interpreted using identified Bloch–Floquet radiating bands. • Vibroacoustics of a heavy fluid-loaded stiffened plate is studied. • Analytical model of the non-negative intensity in the wavenumber domain is proposed. • NNI is used to identify the areas on the stiffened plate contributing to the radiated sound power. • Propagation of Bloch–Floquet waves is visualised using the NNI maps. [ABSTRACT FROM AUTHOR]

Oxytocin has recently received remarkable attention for its role as a modulator of human behaviour. Here, we aimed to expand our knowledge of the neural circuits engaged by oxytocin by investigating the effects of intranasal and intravenous oxytocin on the functional connectome at rest in 16 healthy men. Oxytocin modulates the functional connectome within discrete neural systems, but does not affect the global capacity for information transfer. These local effects encompass key hubs of the oxytocin system (e.g. amygdala) but also regions overlooked in previous hypothesis-driven research (i.e. the visual circuits, temporal lobe and cerebellum). Increases in levels of oxytocin in systemic circulation induce broad effects on the functional connectome, yet we provide indirect evidence supporting the involvement of nose-to-brain pathways in at least some of the observed changes after intranasal oxytocin. Together, our results suggest that oxytocin effects on human behaviour entail modulation of multiple levels of brain processing distributed across different systems. Martins et al. examine the effects of different routes of administration of oxytocin on functional connections in the brain of healthy males at rest. They observe local effects in key-hubs of brain's oxytocin system (i.e. amygdala) as well as wider-spread effects. This demonstrates that oxytocin likely affects human behaviour by modulating multiple levels of brain processing across different systems. [ABSTRACT FROM AUTHOR]

Single measurements of salivary and plasmatic oxytocin are used as indicators of the physiology of the oxytocin system. However, questions remain about whether they are sufficiently stable to provide valid trait markers of the physiology of the oxytocin system, and whether salivary oxytocin can accurately index its plasmatic concentrations. Using radioimmunoassay, we measured baseline plasmatic and/or salivary oxytocin from two independent datasets. We also administered exogenous oxytocin intravenously and intranasally in a triple dummy, within-subject, placebo- controlled design and compared baseline levels and the effects of routes of administration. Our findings question the use of single measurements of baseline oxytocin concentrations in saliva and plasma as valid trait markers of the physiology of the oxytocin system in humans. Salivary oxytocin is a weak surrogate for plasmatic oxytocin. The increases in salivary oxytocin observed after intranasal oxytocin most likely reflect unabsorbed peptide and should not be used to predict treatment effects. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a chronic pain syndrome, characterised by several symptoms. One of the most prevalent symptoms in FM is balance impairment that compromise the autonomy, function and performance status of patients. Purpose: The main objective of the present study was to evaluate the effect of sensory stimulation provided by the use of a low additional thickness of 0.8 mm placed under the great toes bilaterally on the centre of pressure (CoP) measures in patients with FM. It was hypothesised that postural ability would change with a low focal additional thickness used to compute these measures. Materials and Method: Twenty-four patients with FM voluntarily participated in this study. Postural performance during quiet standing was investigated through the CoP displacements recorded using a force-plate. Sensory stimulation was provided by a small additional thickness of 0.8 mm placed under the great toe bilaterally and two conditions were compared: additional thickness 0 (control) and 0.8 mm. Results: An improvement of body balance through spatial parameters with sensory cutaneous stimulation applied under the great toe bilaterally were observed in patients with FM. Our results showed a significant decrease of surface area and mean speed of CoP, associated to a significant decrease of variance of speed. An additional observation is that sagittal (Y) mean position of the CoP gets more anterior (+ 5 mm) relative to control condition. Conclusion: These findings brings new clinical perspectives in the development of intervention strategies in the management of patients with FM and balance disorders, completing validated therapeutic strategies. [ABSTRACT FROM AUTHOR]

This study analyzed the effects of photobiomodulation (PBM) with low-level laser therapy on nociceptive behavior and neuronal activity in the trigeminal nucleus after experimental unilateral temporomandibular joint (TMJ) disc injury. The animals were divided into 4 groups (n = 10 each): group 1, surgical injury of the articular disc and PBM; group 2, sham-operated subjected to PBM; group 3, surgical injury of the articular disc; and group 4, control (Naïve). Ten sessions of PBM were performed using GaAs laser with a wavelength of 904 nm, power of 75 W pico, average power of 0.043 W, area of the beam of 0.13 cm2, duration of the pulses of 60 nseg (in the frequency of 9500 Hz), energy density of 5.95 J/cm2, energy per point of 0.7 J, and power density of 333.8 mW/cm2, and the irradiation was done for 18 s per point. Neuropathic symptoms were evaluated using the von Frey test. Trigeminal ganglion samples underwent immunoblotting to examine the expression of substance P, vanilloid transient potential receptor of subtype-1 (TRPV-1), and peptide related to the calcitonin gene (CGRP). There was a total decrease in pain sensitivity after the second session of PBM in operated animals, and this decrease remains until the last session. There was a significant decrease in the expression of SP, TRPV-1, and CGRP after PBM. Photobiomodulation therapy was effective in reducing nociceptive behavior and trigeminal nucleus neuronal activity after TMJ disc injury. [ABSTRACT FROM AUTHOR]

Objective of the study: We aim to perform a Systematic Literature Review (SLR) to clarify how Social Media (SM) are used to develop and strengthen Knowledge Management (KM) in organizations. Methodology/approach: We made a SLR supported by meta-analyses using the technique conceptualized by Kitchenham (2004). In this study, we selected all articles in the SciELO website that directly mentioned any of the names among the eight SM sites researched, then followed the steps described by Kitchenham (2004) from planning to execution and presentation of the results. Originality/Relevance: We made a review of all national researches published in Portuguese that addresses the use of SM in organizational environments, responsible for synthesizing the knowledge of the area. Main results: We observed an incipient presence of studies on SM associated with KM. However, there is a gradual increase in the number of publications over the years. We also found a concentration of published papers in the CAPES evaluation fields Interdisciplinary and Languages, with a predominance of qualitative research. Most of the studies found portray Facebook as the main SM used for KM, with the improvement of organizational communication, corporate education, and access to information as the major objective. Theoretical/methodological contributions: We present the empirical research on KM and SM already published in Portuguese in the journals of greatest national impact. We achieve a methodological application of the procedures suggested by Kitchenham (2004). Social/management contributions: We synthesize the KM practices used by organizations within the environment of SM, enabling the construction of a future research agenda. [ABSTRACT FROM AUTHOR]

This research aims to identify variables of the Visionary Theory of Filion that further a greater influence on the entrepreneurial intention of students of the Administration and Civil Engineering courses of Public and Private Higher Education Institutions (IES) of the city of Teresina, state of Piauí, Brazil. The methodological approach used was quantitative, using statistical techniques of descriptive and multivariate analysis of the data from the application of logistic regression, with the aid of the Software Statistical Package for Social (SPSS) for the processing of data collected through online questionnaires sent to the universe of 1,664 students from public and private higher education institutions in the city of Teresina, state of Piauí. After the research, It has been diagnosed that the dimensions of the Filion theory that exert major influences on entrepreneurial intent are individual perception and energy. [ABSTRACT FROM AUTHOR]

Background: Drug checking services are being implemented in recreational settings across the world, however these projects are frequently accused of a lack of evidence concerning their impact on people who use drugs. This paper describes the implementation of a drug checking service at the Boom Festival 2016 and explores the impact of this service on its users' behavioural intentions.Methods: 753 drug samples were submitted to the drug checking service for chemical analysis. All drug checking users were invited to fill a pre-analysis and a post-analysis questionnaire. 310 pre- and post-analysis questionnaires answered by users of the service were successfully matched.Results: When the test results were "unexpected" (N = 86), 94.3% of the service users reported that they would not to take the drug. When the test result indicated the sample contained "the expected substance plus adulterants" (N = 41) 32% of users stated they would not take it. When the test result was "only the expected substance" (N = 370), as anticipated, 98% of the participants reported they would take it. There was a statistically significant association between users' behavioural intentions and drug-checking result (χ2(2) = 350,042, p < .001).Conclusions: These results support the hypothesis that providing drug checking services in large-scale festivals helps users to better manage their drug use and deal with drug adulteration. The data corroborates the supposition that when provided with objective information about the content of their drugs, some users consider health protecting behaviours. Additionally, these results can contribute to the design of tailored harm reduction interventions that take into consideration clients' characteristics, profiles and motivations. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether quantitative computed tomography (CT) measurements can predict microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Materials and Methods: This was a retrospective analysis of 200 cases of surgically proven HCCs in 125 consecutive patients evaluated between March 2010 and November 2017. We quantitatively measured regions of interest in lesions and adjacent areas of the liver on unenhanced CT scans, as well as in the arterial, portal venous, and equilibrium phases on contrast-enhanced CT scans. Enhancement profiles were analyzed and compared with histopathological references of MVI. Univariate and multivariate logistic regression analyses were used in order to evaluate CT parameters as potential predictors of MVI. Results: Of the 200 HCCs, 77 (38.5%) showed evidence of MVI on histopathological analysis. There was no statistical difference between HCCs with MVI and those without, in terms of the percentage attenuation ratio in the portal venous phase (114.7 vs. 115.8) and equilibrium phase (126.7 vs. 128.2), as well as in terms of the relative washout ratio, also in the portal venous and equilibrium phases (15.0 vs. 8.2 and 31.4 vs. 26.3, respectively). Conclusion: Quantitative dynamic CT parameters measured in the preoperative period do not appear to correlate with MVI in HCC. [ABSTRACT FROM AUTHOR]

Background: Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown. Methods: Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses. Results: Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo. Conclusions: These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population. [ABSTRACT FROM AUTHOR]

Inferior alveolar nerve (IAN) injuries may occur during various dental routine procedures, especially in the removal of impacted lower third molars, and nerve recovery in these cases is a great challenge in dentistry. Here, the IAN crush injury model was used to assess the efficacy of photobiomodulation (PBM) in the recovery of the IAN in rats following crushing injury (a partial lesion). Rats were divided into four experimental groups: without any procedure, IAN crush injury, and IAN crush injury with PBM and sham group with PBM. Treatment was started 2 days after surgery, above the site of injury, and was performed every other day, totaling 10 sessions. Rats were irradiated with GaAs Laser (Gallium Arsenide, Laserpulse, Ibramed Brazil) emitting a wavelength of 904 nm, an output power of 70 mWpk, beam spot size at target ∼0.1 cm2, a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6 J/cm2. Nerve recovery was investigated by measuring the morphometric data of the IAN using TEM and by the expression of laminin, neurofilaments (NFs), and myelin protein zero (MPZ) using Western blot analysis. We found that IAN-injured rats which received PBM had a significant improvement of IAN morphometry when compared to IAN-injured rats without PBM. In parallel, all MPZ, laminin, and NFs exhibited a decrease after PBM. The results of this study indicate that the correlation between the peripheral nerve ultrastructure and the associated protein expression shows the beneficial effects of PBM. [ABSTRACT FROM AUTHOR]

Of the renewable energy sources, which are less polluting and with the same efficiency of petroleum products, we highlight biodiesel, a renewable and promising source of clean energy, which is now being added in small quantities to commercial diesel used in diesel cycle engine. However, it is necessary to evaluate several factors, so that the amount of biodiesel in the diesel is increased, among them the physicochemical properties of the biodiesel and its mixtures with the commercial diesel, so that they are according to specification of the National Petroleum Agency (ANP) besides the corrosion that it can cause to the constituents of the motor, when in contact. Thus, this work had as main objective to verify the existence of a corrosive process in diesel engine piston when in contact with commercial diesel, biodiesel, and its mixtures, in different proportions and temperatures. For this, initially accomplished the biodiesel synthesis and the characterizations physiochemical of the same. Posteriorly, got it fortyfour samples, which were immersed in the pure biodiesel (B100) and its mixtures with commercial diesel in the proportions of 7, 10, 20, 30, 40, 50, 60, 70, 80, and 90% in different temperatures, after the immersion tests, it was calculated the corrosion rate present and analysis of the samples with the help of the scanning electron microscopy (SEMA), that were analyzed through of the ImageJ program. After analysis, it can be concluded that the biodiesel synthesized had the properties within the limits established by the ANP, that the corrosion in the material that compose the engine piston in the studied period was low for all the mixtures used. Therefore, it is suggested that the biodiesel obtained in this work and itis respective mixtures are viable as alternative renewable sources to be applied as fuel in engines. [ABSTRACT FROM AUTHOR]

Background: Testicular adrenal rest tumors (TART) can cause infertility in congenital adrenal hyperplasia (CAH) males. Aims: To determine TART prevalence in patients with CAH due to 21-hydroxylase deficiency (21-OHD) and evaluate possible factors associated with its development. Methods: This is a descriptive and analytical cross-sectional study evaluating males with the classical form of 21-OHD through testicular ultrasonography and serum inhibin B dosages. Data on prescribed glucocorticoid dose and serum levels of 17- hydroxyprogesterone (17-OHP), androstenedione (Andro), ACTH, renin, and LH were obtained from medical records. Results: Thirty-eight males were evaluated. The mean age on ultrasonography was 15.2 ± 6.7 (3–27) years. Nine patients (23.7%) had TART, 4 of them were prepubertal and the youngest was 5 years old. No association was found between TART and 21-OHD phenotype, glucocorticoid dose, or 17-OHP, ACTH, LH, renin, and inhibin B levels measured in the 6 preceding years. However, 50% of the patients who presented increased Andro 2 years prior to the evaluation had TART (p = 0.018, OR = 8.00 [95% CI: 1.42–44.92]), whereas in the normal Andro group only 16.7% had tumors. Conclusion: This study showed that TART can occur in prepubertal patients and that disease control could be a factor associated with its development. Therefore, we suggest investigating TART development early in childhood, mainly in poorly controlled 21-OHD patients. [ABSTRACT FROM AUTHOR]

• Consciousness emerges from complex interactions across organisational hierarchies. • The dopaminergic network shows cognition-related modulation under anaesthesia. • GABAergic and noradrenergic circuits undergo functional changes during sedation. • Multimodal imaging offers new insight into the complex mechanisms of consciousness. Placing a patient in a state of anaesthesia is crucial for modern surgical practice. However, the mechanisms by which anaesthetic drugs, such as propofol, impart their effects on consciousness remain poorly understood. Propofol potentiates GABAergic transmission, which purportedly has direct actions on cortex as well as indirect actions via ascending neuromodulatory systems. Functional imaging studies to date have been limited in their ability to unravel how these effects on neurotransmission impact the system-level dynamics of the brain. Here, we leveraged advances in multi-modal imaging, Receptor-Enriched Analysis of functional Connectivity by Targets (REACT), to investigate how different levels of propofol-induced sedation alter neurotransmission-related functional connectivity (FC), both at rest and when individuals are exposed to naturalistic auditory stimulation. Propofol increased GABA-A- and noradrenaline transporter-enriched FC within occipital and somatosensory regions respectively. Additionally, during auditory stimulation, the network related to the dopamine transporter showed reduced FC within bilateral regions of temporal and mid/posterior cingulate cortices, with the right temporal cluster showing an interaction between auditory stimulation and level of consciousness. In bringing together these micro- and macro-scale systems, we provide support for both direct GABAergic and indirect noradrenergic and dopaminergic-related network changes under propofol sedation. Further, we delineate a cognition-related reconfiguration of the dopaminergic network, highlighting the utility of REACT to explore the molecular substrates of consciousness and cognition. [ABSTRACT FROM AUTHOR]

We report the synthesis of a series of temperature‐sensitive non‐classical early Ln(II) (Ln=lanthanide) complexes, [K(2.2.2‐cryptand)][Ln(Cptt)3] (Cptt=C5H3tBu2‐1,3; 1‐Ln; Ln=La−Nd). Complexes 1‐Ln were typically prepared using Schlenk line techniques rather than more common glove box protocols, by the reduction of the parent Ln(III) complexes [Ln(Cptt)3] (2‐Ln) with KC8 in THF in the presence of 2.2.2‐cryptand at −30 °C. The majority of the 2‐Ln series have been reported previously by the salt metathesis reactions of 3 eq. KCptt with parent LnCl3, and these methods were adapted here to afford 2‐Pr. Complexes 1‐Ln and 2‐Pr were characterized by single crystal XRD, elemental analysis, ATR‐IR and UV‐Vis‐NIR spectroscopy; 1‐La and 2‐Pr were additionally characterized by c.w. EPR spectroscopy, and variable temperature magnetic susceptibility measurements were performed on 2‐Pr. During attempts to synthesize 2‐Nd and 2‐Sm we also obtained small crops of crystals of [Nd(Cptt)2(μ‐I)]2 (3) and [Sm(Cptt)2(μ‐Cl)]2 ⋅ C7H8 (4 ⋅ C7H8), respectively; these complexes were also structurally authenticated, and magnetic data was collected for 4 ⋅ C7H8. The combination of data obtained indicate that the Ln(II) centers in 1‐Ln adopt 4fn5d1 electron configurations, in common with other literature examples of [Ln(CpR)3]− anions (CpR=substituted cyclopentadienyl) for these metals. [ABSTRACT FROM AUTHOR]

This paper presents a study on the equimomental systems of point-masses of planar rigid bodies. In this work, the equimomental systems of three point-masses of planar rigid bodies are investigated using the concept of pseudo-inertia matrix. It is found that given a planar rigid body, it is always possible to determine an equimomental system of three equal masses located at the vertices of an isosceles triangle. A procedure is presented to determine equimomental systems with different masses, guaranteeing that the masses are positive. It is shown that it is always possible to choose an equimomental system of three point-masses located at the vertices of an isosceles triangle with a prescribed position of one mass. The conditions for prescribing the position of two and three point-masses are also investigated. A first idealized example shows the step-by-step procedure for determining an equimomental system of three point-masses of a planar rigid body. The proposed model is applied to a symmetric connecting rod in a second example due to its wide use in combustion engines. A third example shows an equimomental system of an asymmetric bucket of an excavator. [ABSTRACT FROM AUTHOR]

The study of meteorology are based on atmospheric phenomena, your behavior and physical, chemical and dynamic interactions with the other elements of the Earth's surface. The aim of this study was to characterize climatically the municipality of Feira de Santana (BA), as to the availability of water for farming, using data provided by INMET, which were processed through the climatic water balance method, from which he obtained the water index, index of dryness and moisture content, and aid the sort keys of Thornthwaite. The water balance showed that the municipality features an ETP of 1431.7 mm year-1, ETR to 720.7 mm year-1, DEF of 711.0 mm year-1 and EXC equal to zero. The climatic type through the methodology of Köppen's "wing", megatérmico with winter rains and hot summers, whereas Thornthwaite's C1w2A 'a', Sub-humid climate with dry off excess summer, megatérmico and potential evapotranspiration in summer concentration equal to 31.2%. The municipality of Feira de Santana presents a high ETP, influenced by high temperatures. The period of lowest water deficiency is recorded in the months of may, June and July, being suitable for dryland crops. The Thornthwaite climate classification method offers greater detail than the Köppen. [ABSTRACT FROM AUTHOR]

The hypothalamic nonapeptides oxytocin and vasopressin are important modulators of socio-affective behaviours in a wide variety of animal species, including humans. Nevertheless, there is little research addressing their possible roles on socio-affective dimensions of human behaviour across development, during which considerable behavioural and physiological change occurs. Questions still remain about the extent to which findings from adults may directly apply to earlier phases of human development. In this article, we systematically summarize and discuss all existing studies investigating the developmental association of endogenous levels of hypothalamic neuropeptides oxytocin and vasopressin with human social behaviour or on its disruption in paediatric populations. Evidence is sparse insofar as there are still relatively few developmental studies and limited due to correlational research designs and unreliability of methods currently used for neuropeptide measurements in biological fluids. The findings to date generally converge with adult evidence, but also suggest that important differences between age stages may exist. Further studies focusing these differences may prove critical for informing drug development for socio-affective deficits in paediatric populations. [ABSTRACT FROM AUTHOR]

The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg, s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day after injury and until the 18th day by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage. [ABSTRACT FROM AUTHOR]

Hybrid metaheuristics—developed based on the combination of metaheuristics with concepts and techniques from other research areas—represent an important subject in combinatorial optimization research. Data mining techniques have been coupled with metaheuristics in order to obtain patterns of suboptimal solutions, which are used to guide the search for better-cost solutions. In this paper, we incorporate a data mining procedure into a state-of-the-art heuristic for a specific problem in order to give evidences that, when a technique is able to reach an optimal solution, or a near-optimal solution with little chance of improvements, the mined patterns could be used to guide the search for the optimal or near optimal solution in less computational time. We developed a data mining hybrid version of a previously proposed and state-of-the-art multistart heuristic for the classical p-median problem. Computational experiments, conducted on a set of instances from the literature, showed that the new version of the heuristic was able to reach optimal and near-optimal solutions, on average, 27.32 % faster than the original strategy. [ABSTRACT FROM AUTHOR]

Background Neuropathic pain is relatively common and occurs in approximately 6–8% of the population. It is associated with allodynia and hyperalgesia. Thus, non-pharmacological treatments, such as transcranial direct current stimulation (tDCS) may be useful for relieving pain. Objectives This study aimed to investigate the antiallodynic effect of tDCS in a mice model of neuropathic pain, and the underlying neurotransmission systems that could drive these effects. Methods Male, Swiss mice, weighing 25–35 g, were subjected to partial sciatic nerve ligation (PSNL). Allodynia was assessed using a Von Frey filament (0.6 g). First, the behavioral time-course of these mice was assessed after 5, 10, 15 and 20 min of tDCS (0.5 mA). Second, the mice that underwent PSNL were assigned to either the tDCS (0.5 mA, 15 min) or tDCS sham group, and further assigned to receive either saline or a drug (i.e., naloxone, yohimbine, a-methyl-p-tyrosine, q-chlorophenylalanine methyl ester, caffeine, 1,3-dipropyl-8-cyclopentylxanthine, AM281, AM630, flumazenil, MK-801, or lidocaine). Results The antiallodynic effect of tDCS lasted 2 h and 4 h, after 10 min and 15 or 20 min of treatment, respectively (P < .001, P < .01, and P < .05, respectively). The antiallodynic effect of tDCS was associated with all the systems that were analyzed, i.e., the opioidergic (P < .01), adenosinergic (P < .001), serotonergic (P < .01), noradrenergic (P < .001), cannabinoid (P < .001), GABAergic, and glutamatergic (P < .001) systems. Lidocaine did not reverse the antiallodynic effect of tDCS (P > .05). Conclusion The antiallodynic effect of tDCS was associated with different neurotransmitters systems; the duration of these after-effects depended on the time exposure to tDCS. [ABSTRACT FROM AUTHOR]

Rewards are appetitive events that elicit approach. Ground-breaking findings from neurophysiological experiments in animals, alongside neuropharmacology and neuroimaging research in human samples have identified dopamine as the main neurochemical messenger of global reward processing in the brain. However, dopamine’s contribution to the different components of reward processing remains to be precisely defined. To facilitate the informed design and interpretation of reward studies in humans, we have systematically reviewed all existing human pharmacological studies investigating how drug manipulation of the dopamine system affects reward-related behaviour and its neural correlates. Pharmacological experiments in humans face methodological challenges in terms of the: 1) specificity and safety of the available drugs for administration in humans, 2) uncertainties about pre- or post-synaptic modes of action, and 3) possible interactions with inter-individual neuropsychological or genotypic variables. In order to circumvent some of these limitations, future research should rely on the combination of different levels of observation, in integrative pharmaco-genetics-neurobehavioral approaches, to more completely characterize dopamine’s role in both general and modality-specific processing of reward. [ABSTRACT FROM AUTHOR]

Purpose: The present study investigates the efficacy of Photobiomodulation (PBM) and Vitamin B Complex (VBC) to relieve pain, both in separately and combined (PBM and VBC). Methods: Rats with chronic constriction injury of the right infraorbital nerve (CCI-IoN) or Sham surgery were used. PBM was administered at a wavelength of 904 nm and energy density of 6.23 J/cm2 and VBC (containing B1, B6 and B12) subcutaneously, both separately and combined. Behavioral tests were performed to assess mechanical and thermal hypersensitivity before and after CCI and after PBM, VBC, or PBM + VBC. The expression of inflammatory proteins in the trigeminal ganglion and the immunohistochemical alterations of Periaqueductal Gray (PAG) astrocytes and microglia were examined following CCI and treatments. Results: All testeds treatments reversed the painful behavior. The decrease in pain was accompanied by a decrease of Glial Fibrillary Acidic Protein (GFAP), a specific astrocytic marker, and Ionized calcium-binding adaptor molecule 1 (Iba-1), a marker of microglia, and decreased expression of Transient Receptor Potential Vanilloid 1 (TRPV1), Substance P, and Calcitonin Gene-Related Peptide (CGRP) induced by CCI-IoN in PAG and Trigeminal ganglion. Furthermore, both treatments showed a higher expression of Cannabinoid-type 1 (CB1) receptor in the trigeminal ganglion compared to CCI-IoN rats. Our results show that no difference was observed between groups. Conclusion: We showed that PBM or VBC regulates neuroinflammation and reduces inflammatory protein expression. However, the combination of PBM and VBC did not enhance the effectiveness of both therapies alone. [ABSTRACT FROM AUTHOR]

Pain is a common non-motor symptom of Parkinson's disease (PD), which often occurs in the early disease stages. Despite the high prevalence, it remains inadequately treated. In a hemi-parkinsonian rat model, we aimed to investigate the neurochemical factors involved in orofacial pain development, with a specific focus on pain-related peptides and cannabinoid receptors. We also evaluated whether treadmill exercise could improve orofacial pain and modulate these mechanisms. Rats were unilaterally injected in the striatum with either 6-hydroxydopamine (6-OHDA) or saline. Fifteen days after stereotactic surgery, the animals were submitted to treadmill exercise (EX), or remained sedentary (SED). Pain assessment was performed before the surgical procedure and prior to each training session. Pain-related peptides, substance P (SP), calcitonin gene-related peptide (CGRP), and transient receptor potential vanilloid type 1 (TRPV1) activation and cannabinoid receptor type 1 (CB1) and type 2 (CB2) were evaluated in the trigeminal nucleus. In order to confirm the possible involvement of cannabinoid receptors, we also injected antagonists of CB1 and CB2 receptors. We confirmed the presence of orofacial pain after unilateral 6-OHDA-injection, which improved after aerobic exercise training. We also observed increased pain-related expression of SP, CGRP and TRPV1 and decreased CB1 and CB2 in the trigeminal ganglion and caudal spinal trigeminal nucleus in animals with PD, which was reversed after aerobic exercise training. In addition, we confirm the involvement of cannabinoid receptors since both antagonists decreased the nociceptive threshold of PD animals. These data suggest that aerobic exercise effectively improved the orofacial pain associated with the PD model, and may be mediated by pain-related neuropeptides and cannabinoid receptors in the trigeminal system. [ABSTRACT FROM AUTHOR]

Objective This paper describes the misrepresentation of LSD at Portugal's Boom Festival 2014 and the prevention of unintentional consumption of DOx and 25x-NBOMe among LSD consumers attending a drug-checking service. Methods Two hundred forty-five drug samples expected to contain LSD were submitted to the drug-checking service for chemical analysis. One hundred ten post-test questionnaires were successfully matched with test results. Results About 67.3% of the alleged LSD samples tested contained only LSD; 0.8% contained LSD combined with adulterants; 24.1% did not contain LSD but did contain another psychoactive substance, including 11.4% that were 2,5-dimethoxyamphetamine derivatives and 9.8% that were N-benzyl-2,5-dimethoxyphenethylamine derivatives; and no psychoactive substance was detected in 7.8%. The majority of service users who received unexpected test results regarding their alleged LSD (74.2%) reported that they did not intend to consume the drug. Following dissemination of alerts on day 2, a larger than expected proportion of all tests conducted were for LSD, when comparing the 2014 festival to 2012, where no such alert was disseminated. Conclusions Although these results support the provision of integrated drug-checking services in party settings, evidence of their utility and effectiveness would be improved through future research incorporating more robust measures of outcomes following provision of drug-checking results. [ABSTRACT FROM AUTHOR]

Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The medicinal plant Pterodon pubescens Benth has been traditionally used for a long time to treat rheumatic diseases due to its anti-inflammatory and analgesic activities. The present study aims to evaluate the antinociceptive effect of ethanolic extract from P. pubescens fruits (EEPp) in a model of neuropathic pain in mice. Materials and methods The phytochemical analysis of EEPp was performed through GC–MS, HPLC and colorimetric analysis. The antinociceptive effects of EEPp (30–300 mg/kg, i.g.) were evaluated on mechanical and thermal (cold or heat) hyperalgesia in neuropathic pain induced by partial sciatic nerve ligation (PSNL) in mice. We also investigated the effects of EEPp on the nociceptive response induced by intrathecal injection (i.t.) of ionotropic (AMPA, NMDA and kainate) and metabotropic (trans-ACPD) glutamate receptor agonists, proinflammatory cytokines such as IL-1β and TNF-α, as well as TRPV1 and TRPA1 agonists. In addition, we also investigated the safety profile of prolonged treatment with EEPp in mice. Results The phytochemical analysis showed a higher amount terpenes, being nine sesquiterpenes and seven diterpenes with vouacapan skeletons, as well as a small amount of phenols and flavonoids. The exact mechanism by which EEPp promotes its antinociceptive effect is not yet fully understood, but its oral administration causes significant inhibition of glutamate-, kainate-, NMDA-, trans-ACPD-induced biting responses, as well as of proinflammatory cytokines (TNF-α and IL-1β) and TRPV1 and TRPA1 channels activators (capsaicin and cinnamaldehyde, respectively). These results may indicate, at least in part, some of the mechanisms that are involved in this effect. In particular, EEPp decreases neuropathic pain and clearly shows, for the first time, a thermal and mechanical hyperalgesia reduction in the model of partial sciatic nerve ligation (PSNL), without inducing tolerance. Furthermore, the prolonged treatment with EEPp (300 mg/kg, i.g.) showed a cumulative effect over 24 h, in the 15th day, after last treatment. In addition, the open-field test showed that doses up to 300 mg/kg in both treatments, acute and/or prolonged, did not affect the motor activity of mice. Also, EEPp showed no toxicity according to the serum levels of the renal and hepatic injury indicators or observed macroscopic organs, after PSNL. Conclusions Taken together, these results provide the first experimental evidence of the significant antinociceptive effect of EEPp on neuropathic pain without causing side effects, such as sedation or locomotor dysfunction. Moreover, these results appear to be mediated, at least in part, by the inhibition of glutamatergic receptors, TRPV1 and TRPA1 channels and proinflammatory cytokines. Thus, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant P. pubescens in the development of phytomedicines for the management of neuropathic pain. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Cedrus atlantica essential oil ( Ca EO) presents analgesic and anti-inflammatory sedative properties. However, it remains unknown whether Ca EO alleviates acute postoperative pain. Materials and methods Here, we investigated the effect of Ca EO on postoperative pain and its mechanisms related to the descending pain control in Swiss males mice induced by a plantar incision surgery (PIS) in the hindpaw. Results Inhalation of Ca EO (5′, 30′ or 60′) markedly reduced mechanical hypersensitivity. This effect was prevented by pre-treatment with naloxone or p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p.)-induced depletion of serotonin. In addition, p -alpha-methyl-para-tyrosin (AMPT, 100 mg/kg, i.p.)-induced depletion of norepinephrine, intraperitoneal injection of the α 2 -adrenergic receptor antagonist yohimbine (0.15 mg/kg, i.p.) or haloperidol (1 mg/kg, i.p.) an antagonist of dopaminergic (D1 and D2) receptors prevented the effect of Ca EO on hypersensitivity. Conclusions These findings suggest that Ca EO alleviates postoperative pain by activating the descending pain modulation pathways on the opioidergic, serotonergic, noradrenergic (α 2 -adrenergic) and dopaminergic (dopamine D1 and D2 receptors) systems. [ABSTRACT FROM AUTHOR]