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33,583,347 |
The effects of the activation of hostile and non-hostile schemas on intent attribution processes in non-aggressive individuals: An ERP study.
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We investigated the influences of hostile and non-hostile schemas activations in non-aggressive individuals on their intent attribution processes in various social contexts. 38 non-aggressive participants were randomly assigned to one of two groups, one primed with negative words, to be conditioned as temporarily hostile (TH), and the other with positive words, be conditioned as temporarily non-hostile (TNH). They were asked to read social scenarios composed of positive or negative behaviors of others whose intentions are ambiguous followed by a disambiguation of others' real intentions (hostile vs non-hostile) behind their behaviors. Neural activity related to spontaneous intent attribution processes was measured using electroencephalography (EEG). The results showed that when non-hostile intentions were revealed following ambiguous-negative behaviors of others, the N400 effect was observed only in the TH group. Similarly, when hostile intentions were revealed following ambiguous-positive behaviors of others, the N400 effect was observed only in the TNH group. In other words, non-aggressive individuals were led to attribute either hostile or non-hostile intentions to the same ambiguous behaviors of others depending on which concepts or thoughts (hostile vs non hostile) were activated and accessible in memory by priming at the time of social interactions.
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Social neuroscience
| 2,021 | 4 | 0 | 0 |
30,243,037 |
Sensitivity to pain expectations: A Bayesian model of individual differences.
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The thoughts and feelings people have about pain (referred to as 'pain expectations') are known to alter the perception of pain. However little is known about the cognitive processes that underpin pain expectations, or what drives the differing effect that pain expectations have between individuals. This paper details the testing of a model of pain perception which formalises the response to pain in terms of a Bayesian prior-to-posterior updating process. Using data acquired from a short and deception-free predictive cue task, it was found that this Bayesian model predicted ratings of pain better than other, simpler models. At the group level, the results confirmed two core predictions of predictive coding; that expectation alters perception, and that increased uncertainty in the expectation reduces its impact on perception. The addition of parameters relating to trait differences in pain expectation improved the fit of the model, suggesting that such traits play a significant role in perception above and beyond the influence of expectations triggered by predictive cues. When the model parameters were allowed to vary by participant, the model's fit improved further. This final model produced a characterisation of each individual's sensitivity to pain expectations. This model is relevant for the understanding of the cognitive basis of pain expectations and could potentially act as a useful tool for guiding patient stratification and clinical experimentation.
|
Cognition
| 2,019 | 1 | 0 | 0 |
32,622,019 |
Spatiotemporally tracking of nano-biofilaments inside the nuclear pore complex core.
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Nuclear pore complex (NPC) is a gating nanomachine with a central selective barrier composed mainly of Nups, which contain intrinsically disordered (non-structured) regions (IDRs) with phenylalanine-glycine (FG) motifs (FG-NUPs). The NPC central FG network dynamics is poorly understood, as FG-NUPs liquid-liquid phase separation (LLPS) have evaded structural characterization. Moreover, the working mechanism of single FG-NUP-biofilaments residing at the central lumen is unknown. In general, flexible biofilaments are expected to be tangled and knotted during their motion and interaction. However, filament knotting visualization in real-time and space has yet to be visualized at the nanoscale. Here, we report a spatiotemporally tracking method for FG-NUP organization with nanoscale resolution, unveiling FG-NUP conformation in NPCs of colorectal cells and organoids at timescales of ~150 ms using high-speed atomic force microscopy (HS-AFM). Tracking of FG-NUP single filaments revealed that single filaments have a heterogeneous thickness in normal and cancer models which in turn affected the filament rotation and motion. Notably, FG-NUPs are overexpressed in various cancers. Using the FG-NUP inhibitor, trans-1,2-cyclohexanediol, we found that central plug size was significantly reduced and incompletely reversible back to filamentous structures in aggressive colon cancer cells and organoids. These data showed a model of FG-NUPs reversible self-assembly devolving into the central plug partial biogenesis. Taken together, HS-AFM enabled the tracking and manipulation of single filaments of native FG-NUPs which has remained evasive for decades.
|
Biomaterials
| 2,020 | 10 | 0 | 0 |
32,891,686 |
Role of orexin receptors within the dentate gyrus in antinociception induced by chemical stimulation of the lateral hypothalamus in an animal model of inflammatory pain.
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Pain is a complex experience consisting of sensory, affective-motivational, and cognitive dimensions. Hence, identifying the multiple neural pathways subserving these functional aspects is a valuable task. The role of dentate gyrus (DG) as a relay station of neocortical afferents in the hippocampal formation (HF) in persistent pain is still controversial. The lateral hypothalamus (LH)-HF neural circuits are involved in numerous situations such as anxiety-like behavior, reward processing, feeding, orofacial as well as acute pain. Nonetheless, to our knowledge, the involvement of the LH-DG neural circuit in persistent pain has already remained unexplored. Adult male Wistar rats weighing 220-250 g were undergone stereotaxic surgery for unilateral implantation of two separate cannulae into the LH and DG. Intra-DG administration of the orexin-1 (OX1) and orexin-2 (OX2) receptor antagonists, SB334867 and TCS OX2 29, respectively, was performed 5 min before intra-LH microinjection of carbachol. Animals were then undergone the formalin test using 50 μl formalin injection (2.5%) into the plantar surface of the hind paw. Microinjection of SB334867 or TCS OX2 29 into the DG region attenuated the antinociceptive effect produced by carbachol microinjection into the LH. The preventive effect of SB334867 and TCS OX2 29 on intra-LH carbachol-induced antinociception was approximately equal in both early and late phases of formalin nociception. The results suggest a neural pathway from the LH to the DG, which contributes to the modulation of formalin-induced inflammatory pain through the recruitment of OX1 and OX2 receptors within the DG.
|
Peptides
| 2,020 | 12 | 0 | 0 |
32,657,247 |
Arterial spin labeling-MR may be an alternative to SPECT for evaluating cerebral perfusion in patients with unilateral middle cerebral artery stenosis.
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Cerebral blood flow (CBF) mapping of single-photon emission tomography (SPECT) is considered a gold standard for evaluating cerebral perfusion. However, invasiveness, high costs and strict technical requirements can limit its clinical use. We aimed to evaluate the concordance of CBF maps obtained from SPECT and pseudo-continuous arterial spin labeling magnetic resonance (PCASL-MR) imaging for evaluating cerebral perfusion.
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Neurological research
| 2,020 | 8 | 0 | 0 |
33,245,766 |
BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis.
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Ribosome biogenesis is a fundamental process required for cell proliferation. Although evolutionally conserved, the mammalian ribosome assembly system is more complex than in yeasts. BCCIP was originally identified as a BRCA2 and p21 interacting protein. A partial loss of BCCIP function was sufficient to trigger genomic instability and tumorigenesis. However, a complete deletion of BCCIP arrested cell growth and was lethal in mice. Here, we report that a fraction of mammalian BCCIP localizes in the nucleolus and regulates 60S ribosome biogenesis. Both abrogation of BCCIP nucleolar localization and impaired BCCIP-eIF6 interaction can compromise eIF6 recruitment to the nucleolus and 60S ribosome biogenesis. BCCIP is vital for a pre-rRNA processing step that produces 12S pre-rRNA, a precursor to the 5.8S rRNA. However, a heterozygous Bccip loss was insufficient to impair 60S biogenesis in mouse embryo fibroblasts, but a profound reduction of BCCIP was required to abrogate its function in 60S biogenesis. These results suggest that BCCIP is a critical factor for mammalian pre-rRNA processing and 60S generation and offer an explanation as to why a subtle dysfunction of BCCIP can be tumorigenic but a complete depletion of BCCIP is lethal.
|
Nucleic acids research
| 2,020 | 12 | 0 | 0 |
33,582,524 |
Reward and Punishment Sensitivity are Associated with Cross-disorder Traits.
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Reversal learning deficits following reward and punishment processing are observed across disruptive behaviors (DB) and attention-deficit/hyperactivity disorder (ADHD), and have been associated with callous-unemotional (CU) traits. However, it remains unknown to what extent these altered reinforcement sensitivities are linked to the co-occurrence of oppositional traits, ADHD symptoms, and CU traits. Reward and punishment sensitivity and perseverative behavior were therefore derived from a probabilistic reversal learning task to investigate reinforcement sensitivity in participants with DB (n=183, ODD=62, CD=10, combined=57, age-range 8-18), ADHD (n=144, age-range 11-28), and controls (n=191, age-range 8-26). The SNAP-IV and Conners rating scales were used to assess oppositional and ADHD traits. The Inventory of CU traits was used to assess CU traits. Decreased reward sensitivity was associated with ADHD symptom severity (p=0.018) if corrected for oppositional symptoms. ADHD symptomatology interacted with oppositional behavior on perseveration (p=0.019), with the former aggravating the effect of oppositional behavior on perseveration and vice versa. Within a pooled sample, reversal learning alterations were associated with the severity of ADHD symptoms, underpinned by hyposensitivity to reward and increased perseveration. These results show ADHD traits, as opposed to oppositional behavior and CU traits, is associated with decreased reward-based learning in adolescents and adults.
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Psychiatry research
| 2,021 | 4 | 0 | 0 |
32,827,666 |
Nutritional implications of ginger: chemistry, biological activities and signaling pathways.
|
Ginger (Zingiber officinale Roscoe) has been used as a food, spice, supplement and flavoring agent and in traditional medicines due to its beneficial characteristics such as pungency, aroma, nutrients and pharmacological activity. Ginger and ginger extracts were reported to have numerous effects, such as those on diabetes and metabolic syndrome, cholesterol levels and lipid metabolism, and inflammation, revealed by epidemiological studies. To understand the beneficial characteristics of ginger, especially its physiological and pharmacological activities at the molecular level, the biological effects of ginger constituents, such as monoterpenes (cineole, citral, limonene and α/β-pinenes), sesquiterpenes (β-elemene, farnesene and zerumbone), phenolics (gingerols, [6]-shogaol, [6]-paradol and zingerone) and diarylheptanoids (curcumin), and the associated signaling pathways are summarized. Ginger constituents are involved in biological activities, such as apoptosis, cell cycle/DNA damage, chromatin/epigenetic regulation, cytoskeletal regulation and adhesion, immunology and inflammation, and neuroscience, and exert their effects through specific signaling pathways associated with cell functions/mechanisms such as autophagy, cellular metabolism, mitogen-activated protein kinase and other signaling, and development/differentiation. Estrogens, such as phytoestrogens, are one of the most important bioactive materials in nature, and the molecular mechanisms of estrogen actions and the assays to detect them have been discussed. The molecular mechanisms of estrogen actions induced by ginger constituents and related applications, such as the chemoprevention of cancers, and the improvement of menopausal syndromes, osteoporosis, endometriosis, prostatic hyperplasia, polycystic ovary syndrome and Alzheimer's disease, were summarized by a comprehensive search of references to understand more about their health benefits and associated health risks.
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The Journal of nutritional biochemistry
| 2,020 | 12 | 0 | 0 |
32,949,450 |
Expanding Data Collection for the MDSGene Database: X-linked Dystonia-Parkinsonism as Use Case Example.
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MDSGene is an online database on movement disorders that collates genetic and clinical knowledge using a standardized published literature abstraction strategy. This review is dedicated to X-linked dystonia-parkinsonism (XDP). We screened 233 citations and curated phenotypic and genotypic data for 414 cases. To reduce data missingness, we (1) contacted authors and engaged the research community to provide additional clinical and genetic information, and (2) revisited previously unpublished data from a cohort of XDP patients seen at our institution. Using these approaches, we expanded the cohort to 577 cases and increased information available for important clinical and genetic features such as age at onset, initial manifestation, predominant motor symptoms, functional impairments, and repeat size information. We established the use of mining unpublished data to expand the MDSGene workflow and present an up-to-date description of the phenomenology of XDP using an extensive collection of previously reported and unreported data. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Movement disorders : official journal of the Movement Disorder Society
| 2,020 | 11 | 0 | 0 |
29,746,088 |
Structure-Activity Studies Reveal the Molecular Basis for GABA
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α-Conotoxins are disulfide-bonded peptides from cone snail venoms and are characterized by their affinity for nicotinic acetylcholine receptors (nAChR). Several α-conotoxins with distinct selectivity for nAChR subtypes have been identified as potent analgesics in animal models of chronic pain. However, a number of α-conotoxins have been shown to inhibit N-type calcium channel currents in rodent dissociated dorsal root ganglion (DRG) neurons via activation of G protein-coupled GABA
|
ACS chemical biology
| 2,018 | 6 | 0 | 0 |
33,135,781 |
Autophagy in white matter disorders of the CNS: mechanisms and therapeutic opportunities.
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Autophagy is a constitutive process that degrades, recycles and clears damaged proteins or organelles, yet, despite activation of this pathway, abnormal proteins accumulate in neurons in neurodegenerative diseases and in oligodendrocytes in white matter disorders. Here, we discuss the role of autophagy in white matter disorders, including neurotropic infections, inflammatory diseases such as multiple sclerosis, and in hereditary metabolic disorders and acquired toxic-metabolic disorders. Once triggered due to cell stress, autophagy can enhance cell survival or cell death that may contribute to oligodendrocyte damage and myelin loss in white matter diseases. For some disorders, the mechanisms leading to myelin loss are clear, whereas the aetiological agent and pathological mechanisms are unknown for other myelin disorders, although emerging studies indicate that a common mechanism underlying these disorders is dysregulation of autophagic pathways. In this review we discuss the alterations in the autophagic process in white matter disorders and the potential use of autophagy-modulating agents as therapeutic approaches in these pathological conditions. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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The Journal of pathology
| 2,021 | 2 | 0 | 0 |
29,621,488 |
Protected by a Fox.
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Cell-specific regulation of gene expression is important for maintaining cortical excitatory/inhibitory balance. In this issue of Neuron, Vuong et al. (2018) reveal an unlikely role for a broadly expressed RNA binding protein, Rbfox1, in protecting inhibitory transmission in the hippocampus.
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Neuron
| 2,018 | 4 | 0 | 0 |
33,109,133 |
Risk factors for incident delirium among urological patients: a systematic review and meta-analysis with GRADE summary of findings.
|
Post-operative delirium is an important, yet under-researched complication of surgery. Patients undergoing urological surgery may be at especially high risk of POD, as they are often older, and interventions can be associated with conditions that trigger delirium. The main aim of this systematic review was to evaluate the available evidence for risk factors in this patient group.
|
BMC urology
| 2,020 | 10 | 0 | 0 |
29,745,268 |
First treatment and retreatment of medically refractive trigeminal neuralgia by stereotactic radiosurgery versus microvascular decompression: a systematic review and Meta-analysis.
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Procedures to treat medically refractory trigeminal neuralgia (MRTN) include stereotactic radiosurgery (SRS) and microvascular decompression (MVD). The aim of this study was to compare outcomes of SRS versus MVD in the treatment of MRTN, with a subgroup focus on those being treated for the first time.
|
British journal of neurosurgery
| 2,018 | 8 | 0 | 0 |
32,763,585 |
Plasma MCP-1 levels in bipolar depression during cyclooxygenase-2 inhibitor combination treatment.
|
Neuroinflammation plays a role in the pathophysiology of Bipolar Disorder Depression (BDD) and altered levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1, aka CCL2) have been reported. This study reports specifically on MCP-1 levels, as a potential marker of BDD and/or treatment response in patients receiving combination treatment with the cyclooxygenase-2 inhibitor, celecoxib (CBX).
|
Journal of psychiatric research
| 2,020 | 10 | 0 | 0 |
33,046,553 |
MeCP2 Levels Regulate the 3D Structure of Heterochromatic Foci in Mouse Neurons.
|
Methyl-CpG binding protein 2 (MeCP2) is a nuclear protein critical for normal brain function, and both depletion and overexpression of MeCP2 lead to severe neurodevelopmental disease, Rett syndrome (RTT) and
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,020 | 11 | 0 | 0 |
32,594,235 |
The two-way relationship between nicotine and cortical activity: a systematic review of neurobiological and treatment aspects.
|
Nicotine intake and cortical activity are closely related, as they can influence each other. Nicotine is implicated in the induction and modification of cortical plasticity and excitability, whereas a change on cortical plasticity and excitability can also lead to a modification of the smoking behaviour of an individual. The aim of this systematic review was, on the one hand, to evaluate the effects of nicotinergic modulation on cortical excitability and plasticity, and, on the other hand, to assess if modifying the brain's excitability and plasticity could influence one's smoking behaviour. Two systematic literature searches in the PubMed/MEDLINE and PsycINFO databases were conducted. Studies focusing either on the impact of nicotinergic modulation on cortical activity or the treatment effect of non-invasive brain stimulation techniques (NIBS) on smoking behaviour were included. A total of 22 studies for the first systematic search and 35 studies for the second one were included after full-text screening. Nicotine's effect on cortical activity appeared to depend on smoking status of the individual. While deprived smokers seem to generally profit from nicotine consumption in terms of cortical excitability and plasticity, the contrary was true for non-smokers. Regarding the questions of how changes in cortical excitability can influence smoking behaviour, a trend points towards NIBS being a potential intervention technique for smoking cessation.
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European archives of psychiatry and clinical neuroscience
| 2,021 | 2 | 0 | 0 |
18,937,116 |
Endogenous glucocorticoids participate in retinal degeneration during continuous illumination.
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Continuous illumination (CI) induces an oxidative stress of the retina which is involved in light-induced retinal degeneration (LIRD). As the increase of glucocorticoids (GC) could also collaborate in the damage, adrenalectomized (ADX) and sham-operated rats (control, CTL) were submitted to CI, and their eyes were studied at light and electron microscopic levels. After CI, ADX retinas were significantly thicker than CTL retinas. Retinal alterations appeared earlier and were severer in CTL than in ADX retinas. Corticosterone levels increased gradually in the sera of CTL rats along CI. These results suggest that adrenalectomy attenuates LIRD, supporting the hypothesis.
|
The International journal of neuroscience
| 2,008 | 12 | 0 | 0 |
33,454,403 |
Arcuate fasciculus architecture is associated with individual differences in pre-attentive detection of unpredicted music changes.
|
The mismatch negativity (MMN) is an event related brain potential (ERP) elicited by unpredicted sounds presented in a sequence of repeated auditory stimuli. The neural sources of the MMN have been previously attributed to a fronto-temporo-parietal network which crucially overlaps with the so-called auditory dorsal stream, involving inferior and middle frontal, inferior parietal, and superior and middle temporal regions. These cortical areas are structurally connected by the arcuate fasciculus (AF), a three-branch pathway supporting the feedback-feedforward loop involved in auditory-motor integration, auditory working memory, storage of acoustic templates, as well as comparison and update of those templates. Here, we characterized the individual differences in the white-matter macrostructural properties of the AF and explored their link to the electrophysiological marker of passive change detection gathered in a melodic multifeature MMN-EEG paradigm in 26 healthy young adults without musical training. Our results show that left fronto-temporal white-matter connectivity plays an important role in the pre-attentive detection of rhythm modulations within a melody. Previous studies have shown that this AF segment is also critical for language processing and learning. This strong coupling between structure and function in auditory change detection might be related to life-time linguistic (and possibly musical) exposure and experiences, as well as to timing processing specialization of the left auditory cortex. To the best of our knowledge, this is the first time in which the relationship between neurophysiological (EEG) and brain white-matter connectivity indexes using DTI-tractography are studied together. Thus, the present results, although still exploratory, add to the existing evidence on the importance of studying the constraints imposed on cognitive functions by the underlying structural connectivity.
|
NeuroImage
| 2,021 | 4 | 0 | 0 |
32,725,358 |
Embodying melody through a conducting baton: a pilot comparison between musicians and non-musicians.
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Finger-tapping tasks have been widely adopted to investigate auditory-motor synchronization, i.e., the coupling of movement with an external auditory rhythm. However, the discrete nature of these movements usually limits their application to the study of beat perception in the context of isochronous rhythms. The purpose of the present pilot study was to test an innovative task that allows investigating bodily responses to complex, non-isochronous rhythms. A conductor's baton was provided to 16 healthy subjects, divided into 2 different groups depending on the years of musical training they had received (musicians or non-musicians). Ad hoc-created melodies, including notes of different durations, were played to the subjects. Each subject was asked to move the baton up and down according to the changes in pitch contour. Software for video analysis and modelling (Tracker
|
Experimental brain research
| 2,020 | 10 | 0 | 0 |
32,939,646 |
Association of probable REM sleep behavior disorder with pathology and years of contact sports play in chronic traumatic encephalopathy.
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Probable rapid eye movement (REM) sleep behavior disorder (pRBD) is a synucleinopathy-associated parasomnia in which loss of REM sleep muscle atonia results in motor behavior during REM sleep, including dream enactment. Traumatic brain injury is independently associated with increased risk of pRBD and Lewy body disease, and both pRBD and Lewy body disease are often observed in chronic traumatic encephalopathy (CTE). However, the frequency and pathological substrate of pRBD in CTE have not been formally studied and remain unknown. Of the total sample of 247 men, age at death of 63.1 ± 18.8 years (mean ± SD), 80 [32%] were determined by informant report to have symptoms of pRBD. These participants had played more years of contact sports (18.3 ± 11.4) than those without pRBD (15.1 ± 6.5; P = 0.02) and had an increased frequency of Lewy body disease (26/80 [33%] vs 28/167 [17%], P = 0.005). Of the 80 participants with pRBD, 54 [68%] did not have Lewy body disease; these participants were more likely to have neurofibrillary tangles and pretangles in the dorsal and median raphe (41 of 49 [84%] non-LBD participants with pRBD symptoms vs 90 of 136 [66%] non-LBD participants without pRBD symptoms, P = 0.02), brainstem nuclei with sleep regulatory function. Binary logistic regression modeling in the total study sample showed that pRBD in CTE was associated with dorsal and median raphe nuclei neurofibrillary tangles (OR = 3.96, 95% CI [1.43, 10.96], P = 0.008), Lewy body pathology (OR = 2.36, 95% CI [1.18, 4.72], P = 0.02), and years of contact sports participation (OR = 1.04, 95% CI [1.00, 1.08], P = 0.04). Overall, pRBD in CTE is associated with increased years of contact sports participation and may be attributable to Lewy body and brainstem tau pathologies.
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Acta neuropathologica
| 2,020 | 12 | 0 | 0 |
29,766,414 |
Oral health and oral health risk behaviour in children with and without externalising behaviour problems.
|
This was to study children with early detected externalising behaviour problems compared to matched controls regarding oral health, oral health risk behaviour and the parental evaluation of the child's oral health and dental care.
|
European archives of paediatric dentistry : official journal of the European Academy of Paediatric Dentistry
| 2,018 | 6 | 0 | 0 |
31,438,171 |
Ontology-Driven Real World Evidence Extraction from Clinical Narratives.
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Unstructured clinical notes contain a huge amount of information. We investigated the possibility of harvesting such information through an NLP-based approach. A manually curated ontology is the only resource required to handle all the steps of the process leading from clinical narrative to a structured data warehouse (i2b2). We have tested our approach at the Papa Giovanni XXIII hospital in Bergamo (Italy) on pathology reports collected since 2008.
|
Studies in health technology and informatics
| 2,019 | 8 | 0 | 0 |
33,212,216 |
Lesion of Serotonergic Afferents to the Retrotrapezoid Nucleus Impairs the Tachypneic Response to Hypercapnia in Unanesthetized Animals.
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Hypercapnia promotes an increase in pulmonary ventilation due to the stimulation of brainstem chemosensory cells that are connected to the respiratory network. Among these cells are the raphe serotonergic neurons which widely send projections to distinct central respiratory compartments. Nevertheless, the physiological role of specific raphe serotonergic projections to other chemosensitive sites on the emergence of hypercapnia ventilatory response in vivo still remains to be elucidated. Here we investigated whether the ventilatory response to hypercapnia requires serotonergic inputs to the chemosensitive cells of the retrotrapezoid nucleus (RTN) in the ventrolateral medulla. To test this, pulmonary ventilation was evaluated under baseline conditions and during hypercapnia (7% CO
|
Neuroscience
| 2,021 | 1 | 0 | 0 |
21,887,175 |
Hydrocephalic holoprosencephaly: An oxymoron? Insights into etiology and management.
|
Holoprosencephaly is usually associated with microcephaly, although macrocephaly is not uncommonly seen. However, the cause of hydrocephalus in holoprosencephaly remains ill-defined. Here, the authors report a case of CSF ascites following ventriculoperitoneal shunt placement in a five month-old child with alobar holoprosencephaly, and hypothesize that the excessive CSF production which occurs in this condition may be responsible for the formation of CSF ascites. Further research is required to assess whether the gene responsible for holoprosencephaly is also responsible for upregulating CSF production in patients with concomitant hydrocephalus.
|
Journal of pediatric neurosciences
| 2,009 | 1 | 0 | 0 |
37,284,623 |
Neurodegeneration: 2021 update.
|
This article reviews a collection of manuscripts in the field of neurodegenerative disease chosen from what are considered by the author to be among the 10 most important and potentially impactful topics or research trends of 2020 relevant to the field of experimental and diagnostic neuropathology. A deliberate effort was made to provide balance among disease categories covered. The result is a varied selection that includes not just individual papers but also research topics and trends. The association of COVID-19 with longer-term neurological symptoms has launched a research trend fueled by speculation that the SARS-CoV-2 might trigger neurodegenerative changes. The onslaught of transcriptomic studies has begun to give way to proteomics, with three transformative studies published examining glial contributions to Alzheimer disease, cerebral atherosclerosis in cognitive decline, and the complex sequence of post-translational modifications of the tau protein. Plasma biomarkers for Alzheimer disease have continued to make rapid advances, especially around highly sensitive assays capable of detecting different forms of abnormal hyperphosphorylated tau in peripheral blood. Two studies using cryo-electron microscopy showed the power of the approach by continuing to elucidate the diversity of filamentous tau inclusions, and a third study gave the first glimpse of α-synuclein aggregates at near atomic resolution. Another study continued to delineate how different α-synuclein conformers ("strains") target specific brain regions and lead to neurodegeneration. In Huntington's disease, we saw compelling molecular data showing how cells adapt to endoplasmic reticulum stress through the unfolded protein response. Finally, the role of astrocytes in chronic traumatic encephalopathy has emerged as a critical area of interest.
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Free neuropathology
| 2,021 | 1 | 0 | 0 |
32,563,075 |
Pseudo-continuous arterial spin labeling MRI study of patients with obsessive-compulsive disorder.
|
Arterial spin labeling (ASL) magnetic resonance imaging is a novel technique that can measure regional cerebral blood flow (rCBF). Here we used pseudo-continuous ASL (pCASL) to examine the structural and functional imaging data in patients with obsessive-compulsive disorder (OCD). We estimated the gray matter volume imaging and pCASL imaging data by means of a voxel-by-voxel statistical analysis. We evaluated the differences of rCBF and gray matter volume between the OCD patients and healthy subjects. We detected a significant rCBF reduction in OCD patients in the right posterior cingulate extending to the lingual gyrus, thalamus, and hippocampus, and a significant increase in the left temporal gyrus and left frontal white matter region, compared with healthy subjects. We also observed a significant reduction in gray matter volume of OCD patients in the right hippocampus. We also estimated the correlation between the clinical severity of OCD and the rCBF and gray matter volumes, and found significant negative correlations between the severity of illness and the regional gray matter volume in the bilateral anterior cingulate corti. Our study demonstrated significant changes of rCBF in the cortico-striato-thalamo-cortical pathway around the hippocampus in OCD patients. These findings may help to elucidate the pathogenesis of OCD.
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Psychiatry research. Neuroimaging
| 2,020 | 9 | 0 | 0 |
30,507,652 |
Effect of Titanium Particles on the Voltage-Gated Potassium Channel Currents in Trigeminal Root Ganglion Neurons.
|
Titanium (Ti) is the key material used in dental implants because of its excellent biocompatibility. But wear and corrosion Ti particles had been widely reported to induce inflammation and promote bone absorption. However, little information is known about the damage of Ti particles on neurons.
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Implant dentistry
| 2,019 | 2 | 0 | 0 |
33,753,814 |
Social categorization based on permanent versus transient visual traits in neurotypical children and children with autism spectrum disorder.
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The present study was designed to test the relative weight of different types of category markers in children's representations of social and biological kinds. We reasoned that in order to efficiently navigate through the mesh network of overlapping social categories, the representational system dedicated to processing information about social groups should be prepared to flexibly switch between potential ways of categorizing fellow humans. Thus, we hypothesized that children would assign more relevance to transient but symbolic features, such as shirt colour, when categorizing humans than other animal species. Across two experiments, we investigated whether typically developing children as well as children diagnosed with Autism Spectrum Disorder would categorize drawings of humans and dogs along a transient or a biologically set, permanent marker. The results show that both groups of children overwhelmingly selected the permanent feature to categorize dogs, however, they were more likely to categorize fellow humans based on transient features. We suggest that this tendency lays the ground for humans' ability to efficiently represent the complex structure of societies.
|
Scientific reports
| 2,021 | 3 | 0 | 0 |
33,008,094 |
Astaxanthin Suppresses PM2.5-Induced Neuroinflammation by Regulating Akt Phosphorylation in BV-2 Microglial Cells.
|
Air pollution has become one of the most serious issues for human health and has been shown to be particularly concerning for neural and cognitive health. Recent studies suggest that fine particulate matter of less than 2.5 (PM2.5), common in air pollution, can reach the brain, potentially resulting in the development and acceleration of various neurological disorders including Alzheimer's disease, Parkinson's disease, and other forms of dementia, but the underlying pathological mechanisms are not clear. Astaxanthin is a red-colored phytonutrient carotenoid that has been known for anti-inflammatory and neuroprotective effects. In this study, we demonstrated that exposure to PM2.5 increases the neuroinflammation, the expression of proinflammatory M1, and disease-associated microglia (DAM) signature markers in microglial cells, and that treatment with astaxanthin can prevent the neurotoxic effects of this exposure through anti-inflammatory properties. Diesel particulate matter (Sigma-Aldrich) was used as a fine particulate matter 2.5 in the present study. Cultured rat glial cells and BV-2 microglial cells were treated with various concentrations of PM2.5, and then the expression of various inflammatory mediators and signaling pathways were measured using qRT-PCR and Western blot. Astaxanthin was then added and assayed as above to evaluate its effects on microglial changes, inflammation, and toxicity induced by PM2.5. PM2.5 increased the production of nitric oxide and reactive oxygen species and upregulated the transcription of various proinflammatory markers including Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor necrosis factor α (TNFα), inducible nitric oxide synthase (iNOS), triggering receptor expressed on myeloid cells 2 (TREM2), Toll-like receptor 2/4 (TLR2/4), and cyclooxygenase-2 (COX-2) in BV-2 microglial cells. However, the mRNA expression of IL-10 and arginase-1 decreased following PM2.5 treatment. PM2.5 treatment increased c-Jun N-terminal kinases (JNK) phosphorylation and decreased Akt phosphorylation. Astaxanthin attenuated these PM2.5-induced responses, reducing transcription of the proinflammatory markers iNOS and heme oxygenase-1 (HO-1), which prevented neuronal cell death. Our results indicate that PM2.5 exposure reformulates microglia via proinflammatory M1 and DAM phenotype, leading to neurotoxicity, and the fact that astaxanthin treatment can prevent neurotoxicity by inhibiting transition to the proinflammatory M1 and DAM phenotypes. These results demonstrate that PM2.5 exposure can induce brain damage through the change of proinflammatory M1 and DAM signatures in the microglial cells, as well as the fact that astaxanthin can have a potential beneficial effect on PM2.5 exposure of the brain.
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International journal of molecular sciences
| 2,020 | 9 | 0 | 0 |
32,992,526 |
A Fluorescence Polarization-Based High-Throughput Screen to Identify the First Small-Molecule Modulators of the Human Adenylyltransferase HYPE/FICD.
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The covalent transfer of the AMP portion of ATP onto a target protein-termed adenylylation or AMPylation-by the human Fic protein HYPE/FICD has recently garnered attention as a key regulatory mechanism in endoplasmic reticulum homeostasis, neurodegeneration, and neurogenesis. As a central player in such critical cellular events, high-throughput screening (HTS) efforts targeting HYPE-mediated AMPylation warrant investigation. Herein, we present a dual HTS assay for the simultaneous identification of small-molecule activators and inhibitors of HYPE AMPylation. Employing the fluorescence polarization of an ATP analog fluorophore-Fl-ATP-we developed and optimized an efficient, robust assay that monitors HYPE autoAMPylation and is amenable to automated, high-throughput processing of diverse chemical libraries. Challenging our pilot screen with compounds from the LOPAC, Spectrum, MEGx, and NATx libraries yielded 0.3% and 1% hit rates for HYPE activators and inhibitors, respectively. Further, these hits were assessed for dose-dependency and validated via orthogonal biochemical AMPylation assays. We thus present a high-quality HTS assay suitable for tracking HYPE's enzymatic activity, and the resultant first small-molecule manipulators of HYPE-promoted autoAMPylation.
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International journal of molecular sciences
| 2,020 | 9 | 0 | 0 |
31,183,125 |
The analysis of glutamate and glutamine frequencies in human proteins as marker of tissue oxygenation.
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In this study, we investigated whether the relative abundance of glutamate and glutamine in human proteins reflects the availability of these amino acids (AAs) dictated by the cellular context. In particular, because hypoxia increases the conversion of glutamate to glutamine, we hypothesized that the ratio glutamate/glutamine could be related to tissue oxygenation. By histological, biochemical and genetic evaluation, we identified proteins expressed selectively by distinct cellular populations that are exposed in the same tissue to high or low oxygenation, or proteins codified by different chromosomal loci. Our biochemical assessment was implemented by software tools that calculated the absolute and the relative frequencies of all AAs contained in the proteins. Moreover, an agglomerative hierarchical cluster analysis was performed. In the skin model that has a strictly local metabolism, we demonstrated that the ratio glutamate/glutamine of the selected proteins was directly proportional to oxygenation. Accordingly, the proteins codified by the epidermal differentiation complex in the region 1q21.3 and by the lipase clustering region 10q23.31 showed a significantly lower ratio glutamate/glutamine compared with the nearby regions of the same chromosome. Overall, our results demonstrate that the estimation of glutamate/glutamine ratio can give information on tissue oxygenation and could be exploited as marker of hypoxia, a condition common to several pathologies.
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Royal Society open science
| 2,019 | 4 | 0 | 0 |
23,100,874 |
Utility of serum lysosomal enzyme assay in the detection of cerebral sphingolipidoses in patients with progressive neurologic dysfunction.
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The cerebral sphingolipidoses which form part of a larger group of lysosomal disorders can be detected and conclusively confirmed by the demonstration of the relevent enzyme deficiency in easily available tissue samples like serum. We have assayed acid β-galactosidase, β-hexosaminidase and its isozymes hexosaminidase A and B, and arylsulfatase A in the serum of patients with progressive cerebral dysfunction and detected 18 patients with enzyme defects, thereby confirming the diagnosis of a specific type of cerebral lipidosis in these patients. The assay of serum lysosomal enzymes was of immense diagnostic use as it obviated the need for highly invasive techniques like a brain biopsy.
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Indian journal of clinical biochemistry : IJCB
| 1,997 | 7 | 0 | 0 |
33,256,444 |
Association of Missense Mutation in FOLH1 With Decreased NAAG Levels and Impaired Working Memory Circuitry and Cognition.
|
Altering the metabotropic glutamate receptor 3 (mGluR3) by pharmacology or genetics is associated with differences in learning and memory in animals and humans. GRM3 (the gene coding for mGluR3) is also genome-wide associated with risk for schizophrenia. The neurotransmitter
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The American journal of psychiatry
| 2,020 | 12 | 0 | 0 |
31,647,892 |
Dynamics of Neuronal Activity in the Cortical Column during Behavior: Both Neuron Type and Layers Matter.
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In this issue of Neuron, Yu et al. (2019) reveal the activity of excitatory cells and GABAergic inhibitory interneurons throughout the neocortical column during active sensation. The authors utilized a combination of spike waveform analysis and genetic tools to identify cell types, demonstrating their distinct patterns of recruitment during behavior.
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Neuron
| 2,019 | 10 | 0 | 0 |
33,066,894 |
Impact of the Coronavirus Disease Pandemic on the Number of Strokes and Mechanical Thrombectomies: A Systematic Review and Meta-Analysis.
|
This systematic review and meta-analysis aimed to evaluate the impact of the coronavirus disease (COVID-19) pandemic on stroke care, including the number of stroke alerts/codes, number of reperfusions, and number of thrombectomies during the pandemic compared to those during the pre-pandemic period.
|
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
| 2,020 | 11 | 0 | 0 |
33,542,082 |
Nonhuman Primates Satisfy Utility Maximization in Compliance with the Continuity Axiom of Expected Utility Theory.
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Expected Utility Theory (EUT), the first axiomatic theory of risky choice, describes choices as a utility maximization process: decision makers assign a subjective value (utility) to each choice option and choose the one with the highest utility. The continuity axiom, central to Expected Utility Theory and its modifications, is a necessary and sufficient condition for the definition of numerical utilities. The axiom requires decision makers to be indifferent between a gamble and a specific probabilistic combination of a more preferred and a less preferred gamble. While previous studies demonstrated that monkeys choose according to combinations of objective reward magnitude and probability, a concept-driven experimental approach for assessing the axiomatically defined conditions for maximizing utility by animals is missing. We experimentally tested the continuity axiom for a broad class of gamble types in 4 male rhesus macaque monkeys, showing that their choice behavior complied with the existence of a numerical utility measure as defined by the economic theory. We used the numerical quantity specified in the continuity axiom to characterize subjective preferences in a magnitude-probability space. This mapping highlighted a trade-off relation between reward magnitudes and probabilities, compatible with the existence of a utility function underlying subjective value computation. These results support the existence of a numerical utility function able to describe choices, allowing for the investigation of the neuronal substrates responsible for coding such rigorously defined quantity.
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The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,021 | 3 | 0 | 0 |
32,533,744 |
Neural networks of different species, brain areas and states can be characterized by the probability polling state.
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Cortical networks are complex systems of a great many interconnected neurons that operate from collective dynamical states. To understand how cortical neural networks function, it is important to identify their common dynamical operating states from the probabilistic viewpoint. Probabilistic characteristics of these operating states often underlie network functions. Here, using multi-electrode data from three separate experiments, we identify and characterize a cortical operating state (the "probability polling" or "p-polling" state), common across mouse and monkey with different behaviors. If the interaction among neurons is weak, the p-polling state provides a quantitative understanding of how the high dimensional probability distribution of firing patterns can be obtained by the low-order maximum entropy formulation, effectively utilizing a low dimensional stimulus-coding structure. These results show evidence for generality of the p-polling state and in certain situations its advantage of providing a mathematical validation for the low-order maximum entropy principle as a coding strategy.
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The European journal of neuroscience
| 2,020 | 10 | 0 | 0 |
32,860,323 |
Trial-to-Trial Variability in Electrodermal Activity to Odor in Autism.
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Abnormal trial-to-trial variability (TTV) has been identified as a key feature of neural processing that is related to increased symptom severity in autism. The majority of studies evaluating TTV have focused on cortical processing. However, identifying whether similar atypicalities are evident in the peripheral nervous system will help isolate perturbed mechanisms in autism. The current study focuses on TTV in responses from the peripheral nervous system, specifically from electrodermal activity (EDA). We analyzed previously collected EDA data from 17 adults with autism and 19 neurotypical controls who viewed faces while being simultaneously exposed to fear (fear-induced sweat) and neutral odors. Average EDA peaks were significantly smaller and TTV was reduced in the autism group compared to controls, particularly during the fear odor condition. Amplitude and TTV were positively correlated in both groups, but the relationship was stronger in the control group. In addition, TTV was reduced in those with higher Autism Quotient scores but only for the individuals with autism. These findings confirm the existing results that atypical TTV is a key feature of autism and that it reflects symptom severity, although the smaller TTV in EDA contrasts with the previous findings of greater TTV in cortical responses. Identifying the relationship between cortical and peripheral TTV in autism is key for furthering our understanding of autism physiology. LAY SUMMARY: We compared the changes in electrodermal activity (EDA) to emotional faces over the course of repeated faces in adults with autism and their matched controls. The faces were accompanied by smelling fear-inducing odors. We found smaller and less variable responses to the faces in autism when smelling fear odors, suggesting that the peripheral nervous system may be more rigid. These findings were exaggerated in those who had more severe autism-related symptoms.
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Autism research : official journal of the International Society for Autism Research
| 2,020 | 12 | 0 | 0 |
32,464,148 |
The effect of 3-nitropropionic acid on behavioral dysfunction, neuron loss and gliosis in the brain of adult male rats: The case of prefrontal cortex, hippocampus and the cerebellum.
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3-nitropropionic acid (3-NP) is a mycotoxin widely used to produce a rat model of Huntington's disease. While there are numerous studies on the effect of this neurotoxin, still further investigation is required to understand the influence of this toxin on different regions of the brain. In the present study, there are two groups of rats of which one is treated with 3-NP. Behavioral, stereological and immunohistochemical analyses were conducted. The results show that locomotor activity is largely affected and anxiety is induced up to a certain level, but there is no gross manifestation of deficit in memory. Microscopic observations illustrate damages in the hippocampus and other parts of the brain. Astrogliosis and glial scars were another finding of this study. In conclusion, although 3-NP can be used as a model of Huntington's disease, it exerts a disseminated effect on different regions of the brain.
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Toxicon : official journal of the International Society on Toxinology
| 2,020 | 8 | 0 | 0 |
33,858,527 |
Efficacy of an integrative approach for bipolar disorder: preliminary results from a randomized controlled trial.
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Bipolar disorder (BD) represents one of the most therapeutically complex psychiatric disorders. The development of a feasible comprehensive psychological approach to complement pharmacotherapy to improve its clinical management is required. The main objective of the present randomized controlled trial (RCT) was to test the efficacy of a novel adjunctive treatment entitled integrative approach in patients with BD, including: psychoeducation, mindfulness training, and functional remediation.
|
Psychological medicine
| 2,021 | 4 | 0 | 0 |
32,935,147 |
Potential of zebrafish as a model to characterise MicroRNA profiles in mechanically mediated joint degeneration.
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Mechanically mediated joint degeneration and cartilage dyshomeostasis is implicated in highly prevalent diseases such as osteoarthritis. Increasingly, MicroRNAs are being associated with maintaining the normal state of cartilage, making them an exciting and potentially key contributor to joint health and disease onset. Here, we present a summary of current in vitro and in vivo models which can be used to study the role of mechanical load and MicroRNAs in joint degeneration, including: non-invasive murine models of PTOA, surgical models which involve ligament transection, and unloading models based around immobilisation of joints or removal of load from the joint through suspension. We also discuss how zebrafish could be used to advance this field, namely through the availability of transgenic lines relevant to cartilage homeostasis and the ability to accurately map strain through the cartilage, enabling the response of downstream MicroRNA targets to be followed dynamically at a cellular level in areas of high and low strain.
|
Histochemistry and cell biology
| 2,020 | 11 | 0 | 0 |
33,027,630 |
Residential greenness and indicators of stress and mental well-being in a Canadian national-level survey.
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Residential proximity to greenness in urban areas has been shown to confer a number of health benefits, including improved mental health. We investigated whether greenness was associated with self-reported stress, distress, and mental health among adult participants of multiple cycles of a national Canadian health survey, and whether these associations varied by sex, age, income, and neighbourhood characteristics.
|
Environmental research
| 2,021 | 1 | 0 | 0 |
31,430,230 |
Observing Erotic Videos with Heterosexual Content Induces Different Cerebral Responses in Homosexual and Heterosexual Men.
|
To determine the cerebral functionality associated with the perception and processing of erotic stimuli in men with different sexual orientation, this work evaluated the electroencephalographic activity (EEG) from several cortical areas, as well as subjective arousal in homosexual and heterosexual men during observation of an erotic film with heterosexual content. The heterosexual men rated the erotic video with higher general and sexual arousal than the homosexual participants. During observation of the neutral and erotic videos, both groups showed a decreased amplitude of the alpha band in prefrontal and parietal cortices, indicating increased attention. When watching the erotic video, the homosexual men showed an increased amplitude of the theta and fast bands only in the prefrontal cortex, which could be related to the cognitive processing of the erotic stimulus. These EEG results should broaden our knowledge of the cortical mechanisms related to the different perception and processing of erotic stimuli in men with different sexual orientations.
|
Journal of homosexuality
| 2,021 | 1 | 0 | 0 |
22,946,114 |
Giuseppe Ferrario and the epidemiology of apoplexy during the 19th century.
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To analyze the pioneering research of Giuseppe Ferrario (1802-1870) on the epidemiology of apoplexy. To our knowledge, his work might have been the first to systematically investigate the epidemiology of cerebrovascular accidents, with the aim of shedding light on the underlying causes.
|
Neurology
| 2,012 | 9 | 0 | 0 |
32,951,262 |
Subthalamic Nucleus Deep Brain Stimulation Modulates 2 Distinct Neurocircuits.
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Current understanding of the neuromodulatory effects of deep brain stimulation (DBS) on large-scale brain networks remains elusive, largely due to the lack of techniques that can reveal DBS-induced activity at the whole-brain level. Using a novel 3T magnetic resonance imaging (MRI)-compatible stimulator, we investigated whole-brain effects of subthalamic nucleus (STN) stimulation in patients with Parkinson disease.
|
Annals of neurology
| 2,020 | 12 | 0 | 0 |
31,372,434 |
MEG data representing a gamma oscillatory response during the hold/release paradigm.
|
The article presents magnetoencephalography (MEG) data from healthy participants while undergoing the Hold/Release paradigm. During the paradigm, participants visually perceived a sequence of two letter strings which either assembled into real words (Hold condition) or pseudowords (Release condition). If the first letter string was morphologically valid, they held their attention (and/or held the item in working-memory) to wait for the second string, whereas if it were invalid, they could release it, respectively. We present data on high-frequency neuronal oscillations of the Hold condition compared to the Release condition. Making this information publicly available could allow other researchers to perform analyses and contribute to understanding the cognitive processes such as language, mnemonic or attentional processes.
|
Data in brief
| 2,019 | 4 | 0 | 0 |
32,873,532 |
Sexual Orientation-Related Differences in Sexual Satisfaction and Sexual Problems-A Population-Based Study in Sweden.
|
Human sexuality is a natural and important part of peoples' life and well-being. The underlying interactions affecting sexual satisfaction are complex, and sexual orientation differences partly remain to be identified as well as explained.
|
The journal of sexual medicine
| 2,020 | 12 | 0 | 0 |
32,951,934 |
Genetic investigation of amyotrophic lateral sclerosis patients in south Italy: a two-decade analysis.
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Amyotrophic lateral sclerosis (ALS) is a multifactorial disease characterized by the interplay of genetic and environmental factors. In the majority of cases, ALS is sporadic, whereas familial forms occur in less than 10% of patients. Herein, we present the results of molecular analyses performed in a large cohort of Italian ALS patients, focusing on novel and already described variations in ALS-linked genes. Our analysis revealed that more than 10% of tested patients carried a mutation in one of the major ALS genes, with C9orf72 hexanucleotide expansion being the most common mutation. In addition, our study confirmed a significant association between ALS patients carrying the ATNX-1 intermediate repeat and the pathological C9orf72 expansion, supporting the involvement of this risk factor in neuronal degeneration. Overall, our study broadens the known mutational spectrum in ALS and provides new insights for a more accurate view of the genetic pattern of the disease.
|
Neurobiology of aging
| 2,021 | 3 | 0 | 0 |
32,951,009 |
Metformin effectively restores the HPA axis function in diet-induced obese rats.
|
The hypothalamo-pituitary-adrenal (HPA) axis is perturbed in obesity. We previously reported presence of leptin resistance in the brainstem and uncoupling between central noradrenergic tone and the HPA axis in obesity-prone (DIO) rats. Metformin is shown to lower body weight and adiposity, but the underlying mechanism is unclear. We hypothesized that this is associated with restored HPA axis function.
|
International journal of obesity (2005)
| 2,021 | 2 | 0 | 0 |
32,180,220 |
GTP-binding inhibitors increase LRRK2-linked ubiquitination and Lewy body-like inclusions.
|
Parkinson's disease (PD) is one of the most common movement disorders with loss of dopaminergic neurons and the presence of Lewy bodies in certain brain areas. However, it is not clear how Lewy body (inclusion with protein aggregation) formation occurs. Mutations in leucine-rich repeat kinase 2 (LRRK2) can cause a genetic form of PD and contribute to sporadic PD with the typical Lewy body pathology. Here, we used our recently identified LRRK2 GTP-binding inhibitors as pharmacological probes to study the LRRK2-linked ubiquitination and protein aggregation. Pharmacological inhibition of GTP-binding by GTP-binding inhibitors (68 and Fx2149) increased LRRK2-linked ubiquitination predominantly via K27 linkage. Compound 68- or Fx2149 increased G2019S-LRRK2-linked ubiquitinated aggregates, which occurred through the atypical linkage types K27 and K63. Coexpression of K27R and K63R, which prevented ubiquitination via K27 and K63 linkages, reversed the effects of 68 and Fx2149. Moreover, 68 and Fx2149 also promoted G2019S-LRRK2-linked aggresome (Lewy body-like inclusion) formation via K27 and K63 linkages. These findings demonstrate that LRRK2 GTP-binding activity is critical in LRRK2-linked ubiquitination and aggregation formation. These studies provide novel insight into the LRRK2-linked Lewy body-like inclusion formation underlying PD pathogenesis.
|
Journal of cellular physiology
| 2,020 | 10 | 0 | 0 |
29,956,574 |
The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder.
|
To create a gene expression signature (GES) to represent the biological effects of a combination of known drugs for bipolar disorder (BD) on cultured human neuronal cells (NT2-N) and rat brains, which also has evidence of differential expression in individuals with BD. To use the GES to identify new drugs for BD using Connectivity Map (CMap).
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The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
| 2,020 | 12 | 0 | 0 |
32,667,229 |
Physiological characterization of a rare subpopulation of doublet-spiking neurons in the ferret lateral geniculate nucleus.
|
Interest in exploring homologies in the early visual pathways of rodents, carnivores, and primates has recently grown. Retinas of these species contain morphologically and physiologically heterogeneous retinal ganglion cells that form the basis for parallel visual information processing streams. Whether rare retinal ganglion cells with unusual visual response properties in carnivores and primates project to the visual thalamus and drive unusual visual responses among thalamic relay neurons is poorly understood. We surveyed neurophysiological responses among hundreds of lateral geniculate nucleus (LGN) neurons in ferrets and observed a novel subpopulation of LGN neurons displaying doublet-spiking waveforms. Some visual response properties of doublet-spiking LGN neurons, like contrast and temporal frequency tuning, were intermediate to those of X and Y LGN neurons. Interestingly, most doublet-spiking LGN neurons were tuned for orientation and displayed direction selectivity for horizontal motion. Spatiotemporal receptive fields of doublet-spiking neurons were diverse and included center/surround organization, On/Off responses, and elongated separate On and Off subregions. Optogenetic activation of corticogeniculate feedback did not alter the tuning or spatiotemporal receptive fields of doublet-spiking neurons, suggesting that their unusual tuning properties were inherited from retinal inputs. The doublet-spiking LGN neurons were found throughout the depth of LGN recording penetrations. Together these findings suggest that while extremely rare (<2% of recorded LGN neurons), unique subpopulations of LGN neurons in carnivores receive retinal inputs that confer them with nonstandard visual response properties like direction selectivity. These results suggest that neuronal circuits for nonstandard visual computations are common across a variety of species, even though their proportions vary.
|
Journal of neurophysiology
| 2,020 | 8 | 0 | 0 |
32,833,279 |
Sleep Disruption in Epilepsy: Ictal and Interictal Epileptic Activity Matter.
|
Disturbed sleep is common in epilepsy. The direct influence of nocturnal epileptic activity on sleep fragmentation remains poorly understood. Stereo-electroencephalography paired with polysomnography is the ideal tool to study this relationship. We investigated whether sleep-related epileptic activity is associated with sleep disruption.
|
Annals of neurology
| 2,020 | 11 | 0 | 0 |
32,607,739 |
Prevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years.
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This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P < 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity. Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.
|
Neuroscience bulletin
| 2,020 | 9 | 0 | 0 |
33,588,002 |
Divergent Alterations of Structural-Functional Connectivity Couplings in First-episode and Chronic Schizophrenia Patients.
|
Emerging evidence suggests that the coupling relating the structural connectivity (SC) of the brain to its functional connectivity (FC) exhibits remarkable changes during development, normal aging, and diseases. Although altered structural-functional connectivity couplings (SC-FC couplings) have been previously reported in schizophrenia patients, the alterations in SC-FC couplings of different illness stages of schizophrenia (SZ) remain largely unknown. In this study, we collected structural and resting-state functional MRI data from 73 normal controls (NCs), 61 first-episode (FeSZ) and 78 chronic (CSZ) schizophrenia patients. Positive and negative syndrome scale (PANSS) scores were assessed for all patients. Structural and functional brain networks were constructed using gray matter volume (GMV) and resting-state magnetic resonance imaging (rs-fMRI) time series measurements. At the connectivity level, the CSZ patients showed significantly increased SC-FC coupling strength compared with the FeSZ patients. At the node strength level, significant decreased SC-FC coupling strength was observed in the FeSZ patients compared to that of the NCs, and the coupling strength was positively correlated with negative PANSS scores. These results demonstrated divergent alterations of SC-FC couplings in FeSZ and CSZ patients. Our findings provide new insight into the neuropathological mechanisms underlying the developmental course of SZ.
|
Neuroscience
| 2,021 | 4 | 0 | 0 |
36,132,572 |
Controllable self-patterning behaviours of flexible self-assembling peptide nanofibers.
|
In recent years, fabricating flexible one-dimensional nanofibers with a high aspect ratio and controlling their two-dimensional patterns on a certain surface have attracted more and more attention. Although molecular self-assembly as a useful strategy has been widely used to obtain nanofibers from soft materials such as peptides and polymers, extremely long nanofibers with high flexibility were rarely reported, and it's even more challenging to organize these organic nanofibers into ordered patterns in a controllable manner. In this study, we designed a flat-wedge-shaped bolaamphiphilic peptide which could self-assemble into ultra-flexible long nanofibers. These nanofibers were deposited on a mica surface by long-term incubation and exhibited various self-patterning behaviours as controlled by intended treatment. By changing the incubation time on the mica surface, vapour pH in the incubation device, and the peptide concentration, various patterns including nanofiber coils, parallel or single straight long nanofibers, and a network of hexagonally aligned short nanofibers could be obtained. These results indicated that not only the nanostructure formed by self-assembling peptides, but also the higher-order patterning behaviour of the nanostructures could be rationally controlled, providing a promising strategy for fabricating complicated nanoscale architectures with various potential applications.
|
Nanoscale advances
| 2,021 | 3 | 0 | 0 |
31,434,784 |
Mixed methods implementation research of cognitive stimulation therapy (CST) for dementia in low and middle-income countries: study protocol for Brazil, India and Tanzania (CST-International).
|
In low/middle-income countries (LMICs), the prevalence of people diagnosed with dementia is expected to increase substantially and treatment options are limited, with acetylcholinesterase inhibitors not used as frequently as in high-income countries (HICs). Cognitive stimulation therapy (CST) is a group-based, brief, non-pharmacological intervention for people with dementia that significantly improves cognition and quality of life in clinical trials and is cost-effective in HIC. However, its implementation in other countries is less researched. This protocol describes CST-International; an implementation research study of CST. The aim of this research is to develop, test, refine and disseminate implementation strategies for CST for people with mild to moderate dementia in three LMICs: Brazil (upper middle-income), India (lower middle-income) and Tanzania (low-income).
|
BMJ open
| 2,019 | 8 | 0 | 0 |
34,284,987 |
The regulatory mechanisms of behavioral and cognitive aging.
|
With the increase of life expectancy, the world's population is aging rapidly. Previous work in the field of aging greatly increases our understanding of biological mechanisms underlying longevity. Researchers have unraveled a number of longevity pathways conserved from yeast to mammals. However, recent evidence shows that mechanisms regulating the life span and those regulating age-related behavioral decline could be dissociated. The regulatory mechanisms underlying behavioral and cognitive aging is largely unknown. Previous work has described a significant age-related decline in cognitive behaviors including episodic memory, working memory, processing speed, as well as motor function deterioration and circadian dysfunction. With the advance of neuroscience and technology, more and more studies have focused on the age-related changes in structure and function of the brain. In this review, we briefly describe the deterioration of cognitive function and other behaviors in the aging process, and survey the role of age-related changes in brain structure and network, neuron morphology and function, transcriptome in brain and some conserved biological pathways on age-related cognitive and behavioral decline. Further studies on the mechanisms underpinning age-related cognitive and behavioral decline may provide clues not only for improving the quality of life for the ageing population, but also for developing intervention approaches for neurodegenerative diseases.
|
Yi chuan = Hereditas
| 2,021 | 6 | 0 | 0 |
33,476,680 |
Concurrent E-cigarette and marijuana use and health-risk behaviors among U.S. high school students.
|
The use of electronic cigarettes (e-cigarettes) and marijuana remain prevalent problems among adolescents nationwide. We assessed current (past 30-day) exclusive e-cigarette use, exclusive marijuana use, and concurrent use with unintentional injury and violent behaviors, alcohol and other drug use behaviors, and sexual behaviors among U.S. high school students. We analyzed 2017 Youth Risk Behavior Survey data including 12,578 high school students nationwide. Multivariable logistic regression models were performed to compare these health-risk behaviors among exclusive e-cigarette users, exclusive marijuana users, and concurrent users with non-users among the overall sample, and then to compare exclusive e-cigarette users and exclusive marijuana users with concurrent users among current users only. All models adjusted for adolescent sex, grade, and race/ethnicity, and other tobacco product use. Approximately 77% of students were non-users, 5.2% were exclusive e-cigarette users, 9.9% were exclusive marijuana users, and 7.8% were concurrent users. Compared to non-users, exclusive e-cigarette users and exclusive marijuana users were more likely to engage in most negative health-risk behaviors associated with unintentional injuries and violence, alcohol and other drug use, and sexual behaviors. Among current users only, exclusive e-cigarette users and exclusive marijuana users were at reduced odds of engaging in most of these health-risk behaviors when compared to concurrent users of both substances. The relationship between exclusive and concurrent e-cigarette and marijuana use and health-risk behaviors highlights the importance of comprehensive educational efforts during high school. Findings suggest need for more studies on influence of e-cigarette and marijuana use on injury and violence risk among youth.
|
Preventive medicine
| 2,021 | 4 | 0 | 0 |
33,972,904 |
Cadaveric Evidence of Complete Transection of the Lumbar Sympathetic Trunk After Extreme Lateral Transpsoas Approach to the Lumbar Spine: A Word of Caution.
|
Lateral transpsoas approaches to the lumbar spine are believed to entail less risk of injury to the lumbar sympathetic trunk and plexus than anterior approaches. However, even the lateral approach can occasionally injure the sympathetic trunk. We report a literature review and cadaveric case of complete resection of the left sympathetic trunk at L3 following lateral transpsoas approach performed by a well-trained spine surgeon. A left lateral approach to the lumbar spine for a two-level total discectomy at L3-L4 and L4-L5 was undertaken on a fresh-frozen cadaver by an experienced spinal surgeon. The procedure followed standard spinal technique under fluoroscopy guidance. The cadaver was placed in a right lateral position and an operative corridor to the lateral aspect of the psoas major muscle was developed. Blunt dissection was carried through the muscle and standard total discectomy was completed at the target levels. Following the procedure, the lumbar spine and adjacent structures were anatomically dissected. It was found that the sympathetic trunk had been completely transected at the L3 level during the surgical procedure. Other major structures such as the femoral nerve, obturator nerve, and roots of the lumbar spinal nerves had not been injured. The above case highlights the proximity of the sympathetic trunk to lateral transpsoas approaches and the possibility of injury to it. We review the literature on postoperative cases of lumbar sympathetic dysfunction (SD) following such procedures and posit that some of these are due to direct iatrogenic injury.
|
Cureus
| 2,021 | 4 | 0 | 0 |
33,688,075 |
A single-plasmid approach for genome editing coupled with long-term lineage analysis in chick embryos.
|
An important strategy for establishing mechanisms of gene function during development is through mutation of individual genes and analysis of subsequent effects on cell behavior. Here, we present a single-plasmid approach for genome editing in chick embryos to study experimentally perturbed cells in an otherwise normal embryonic environment. To achieve this, we have engineered a plasmid that encodes Cas9 protein, gene-specific guide RNA (gRNA), and a fluorescent marker within the same construct. Using transfection- and electroporation-based approaches, we show that this construct can be used to perturb gene function in early embryos as well as human cell lines. Importantly, insertion of this cistronic construct into replication-incompetent avian retroviruses allowed us to couple gene knockouts with long-term lineage analysis. We demonstrate the application of our newly engineered constructs and viruses by perturbing β-catenin in vitro and Sox10, Pax6 and Pax7 in the neural crest, retina, and neural tube and segmental plate in vivo, respectively. Together, this approach enables genes of interest to be knocked out in identifiable cells in living embryos and can be broadly applied to numerous genes in different embryonic tissues.
|
Development (Cambridge, England)
| 2,021 | 4 | 0 | 0 |
33,520,147 |
Effects of a vibrational proprioceptive stimulation on recovery phase after maximal incremental cycle test.
|
Global Proprioceptive Resonance (GPR) is a recently developed approach conceived to solicit the various cutaneous mechanoreceptors, through application of mechanical multifocal vibration at low amplitude and at definite body sites, limiting the stimulation of the profound structures. This interventional study evaluated the effects of GPR on cardiorespiratory function during the post-exertional recovery period. A group of volunteers involved in Triathlon (a multisport discipline consisting of sequential swim, cycle, and run disciplines higly demanding in terms of metabolic engagment), underwent two maximal incremental exercise tests until exhaustion followed alternatively to (a) a 13 minutes section of GPR or (b) a standard low intensity exercise acute trend of the same duration. These effects of these two approaches were compared in terms of recovery of: heart rate (HR), respiratory rate (RR), peripheral oxygen saturation (SpO2) and venous lactate concentration (Lac). The physiological parameters (HR, RR, SpO2 and Lac) recorded in the pre-exertion session showed similar values between the 40 volunteers while several differences were recorded in the post-exertion phase. After 6 min of GPR recovery it was recorded a drop in RR below baseline (19.4±4.15 min-1 vs. 12.2± 0.4 min-1; p<0.001) coupled with an increase in peripheral oxygen saturation above the baseline (GPR: 99.0%±0.16% vs. 96.6%±0.77%, p<0.001). Moreover, the most striking result was the drop in lactate concentration measured after 13 min of GPR recovery: 84.5±3.5% in GPR vs 2.9±7.6% reduction in standard recovery (p<0.001). Notably no differences were recorded recovery of heart rate. GPR has promising effects on post-exercise recovery on RR, SpO2 and lactate level on young athletes.
|
European journal of translational myology
| 2,020 | 12 | 0 | 0 |
31,826,789 |
Nonhuman sequence learning findings argue against Hoerl and McCormack's two systems of temporal cognition.
|
Hoerl & McCormack propose that animals learn sequences through an entrainment-like process, rather than tracking the temporal addresses of each event in a given sequence. However, past research suggests that animals form "temporal maps" of sequential events and also comprehend the concept of ordinal position. These findings suggest that a clarification or qualification of the authors' hypothesis is needed.
|
The Behavioral and brain sciences
| 2,019 | 12 | 0 | 0 |
30,189,987 |
Sleep and Orofacial Pain.
|
Sleep and pain share a bidirectional relationship. Therefore, it is important for practitioners managing patients experiencing either sleep and/or pain issues to recognize and understand this complex association from a neurobiological perspective involving neuroanatomic and neurochemical processes. Accounting for the influence of pain on the various aspects of sleep and understanding its impact on various orofacial pain disorders assists in developing a prudent management approach. Screening for sleep disorders benefits practitioners in identifying these individuals. Instituting evidence-based multidisciplinary management strategies using both behavioral and pharmacologic strategies enhances the delivery of appropriate care.
|
Dental clinics of North America
| 2,018 | 10 | 0 | 0 |
32,965,057 |
Protocol for a single patient therapy plan: A randomised, double-blind, placebo-controlled N-of-1 trial to assess the efficacy of cannabidiol in patients with intractable epilepsy.
|
This paper describes the use of the single patient therapy plan (SPTP). The SPTP has been designed to assess the efficacy at an individual level of a commercially available cannabinoid product, cannabidiol, in reducing seizure frequency in paediatric patients with intractable epilepsy.
|
Journal of paediatrics and child health
| 2,020 | 12 | 0 | 0 |
28,471,950 |
Comparison of Sleep Latency and Number of SOREMPs in the Home and Hospital With a Modified Multiple Sleep Latency Test: A Randomized Crossover Study.
|
Comparison of mean sleep latencies and number of sleep-onset rapid eye movement periods (SOREMPs) between modified multiple sleep latency test (MSLT) performed in the unattended home and in-hospital laboratory setting.
|
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society
| 2,017 | 5 | 0 | 0 |
32,388,740 |
Prognostic Impact of Preoperative Nutritional Risk in Patients Who Undergo Surgery for Pancreatic Adenocarcinoma.
|
Nutritional derangements are common hallmarks of pancreatic cancer (PC). Their early detection and management are usually overlooked in routine practice. This study aimed to explore preoperative nutritional status and its prognostic value in patients undergoing surgery for PC.
|
Annals of surgical oncology
| 2,020 | 12 | 0 | 0 |
32,369,706 |
Physical activity perceptions, experiences, and beliefs of older adults with mild cognitive impairment or Alzheimer's disease and their care partners.
|
Physical activity (PA) participation provides functional and social benefits for persons with mild cognitive impairment (MCI) and Alzheimer's disease (AD), but PA participation in these populations is low. To support health promotion initiatives for cognitively impaired older adults, this study explored the perceptions, experiences, and beliefs of older adults with cognitive impairment and their caregivers concerning PA. Ten care dyads (community-dwelling adult aged ≥65 years diagnosed with MCI or mild-to-moderate AD and their care partner) participated in semi-structured interviews informed by the Theoretical Domains Framework about their PA perceptions, experiences, and beliefs. Interpretive phenomenological analysis of interview transcripts yielded 4 emergent themes: (1) PA as a meaningful activity, (2) experience versus evidence as motivating, (3) participation is possible despite dementia, and (4) care partners as enablers. Findings from this study address a research gap concerning the PA perceptions, experiences, and beliefs of cognitively impaired older adults and their care partners.
|
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
| 2,020 | 11 | 0 | 0 |
31,173,309 |
The future of transcranial magnetic stimulation in neuroscience and neurology in the Middle East.
|
Transcranial magnetic stimulation (TMS) is a noninvasive technique for brain stimulation often used as a diagnostic and therapeutic therapy in neuroscience and psychiatry for different diseases including epilepsy, stroke, multiple sclerosis, and treatment-resistant major depressive disorders, such as autism and schizophrenia.
|
European review for medical and pharmacological sciences
| 2,019 | 5 | 0 | 0 |
33,578,220 |
Early life factors and COVID-19 infection in England: A prospective analysis of UK Biobank participants.
|
This study aims to examine whether maternal smoking, birth weight, birth month and breastfeeding are associated with COVID-19 infection and hospitalisation. Maternal smoking was positively associated with COVID-19 infection. Breastfeeding was negatively associated with COVID-19 infection. The odds of being hospitalised due to COVID-19 were higher among those who had lower birthweight and mothers who were smoking during pregnancy.
|
Early human development
| 2,021 | 4 | 0 | 0 |
29,632,276 |
[Pathomechanism of Autoantibody Production in the Nervous System Diseases].
|
Antibodies to different brain and peripheral nerve proteins have recently been found to be associated with several different autoimmune diseases. They can bind to either neuronal or non-neuronal antigens and may have a pathogenic role by themselves or in synergy with other inflammatory mediators after penetrating the blood-brain barrier or the blood-nerve barrier. In this review, we will describe the association with the impairment of immune tolerance, innate immunity, and autoantibody production of myasthenia gravis (MG), systemic lupus erythematosus (SLE), and Guillain-Barré syndrome (GBS). Impairment of central tolerance, which is characterized by the repertoire selection of immature T-lymphocytes in the thymus, is seen in patients with MG who are positive for anti-Ach R antibodies. Impairment of peripheral tolerance due to activation of autoreactive T-cells and suppression of regulatory T-cells is seen in SLE. In addition, molecular mimicry between the lipooligosaccharides of Campylobacter jejuni and gangliosides of the peripheral nerves results in the production of anti-gangliosides antibodies in GBS. Next, we will describe the antibody-mediated pathology in neuromyelitis optica and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. The binding of anti-aquaporin-4 antibodies or anti-NMDAR antibodies to their respective targets initiates target internalization and complement- or antibody-dependent cellular cytotoxicity of the target cells. Further understanding of antibody-mediated pathology may suggest novel therapeutic strategies.
|
Brain and nerve = Shinkei kenkyu no shinpo
| 2,018 | 4 | 0 | 0 |
33,045,245 |
Sex differences in behavioral and metabolic effects of gene inactivation: The neuropeptide Y and Y receptors in the brain.
|
Brain and gonadal hormones interplay controls metabolic and behavioral functions in a sex-related manner. However, most translational neuroscience research related to animal models of endocrine and psychiatric disorders are often carried out in male animals only. The Neuropeptide Y (NPY) system shows sex-dependent differences and is sensitive to gonadal steroids. Based on published data from our and other laboratories, in this review we will discuss the sex related differences of NPY action on energy balance, bone homeostasis and behavior in rodents with the genetic manipulation of genes encoding NPY and its Y1, Y2 and Y5 cognate receptors. Comparative analyses of the phenotype of transgenic and knockout NPY and Y receptor rodents unravels sex dependent differences in the functions of this neurotransmission system, potentially helping to develop therapeutics for a variety of sex-related disorders including metabolic syndrome, osteoporosis and ethanol addiction.
|
Neuroscience and biobehavioral reviews
| 2,020 | 12 | 0 | 0 |
32,598,299 |
Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department.
|
Objectives The diagnosis of sepsis in the Emergency Department (ED) is challenging and a reliable biomarker is needed. The current study aimed to evaluate the diagnostic accuracy of monocyte distribution width (MDW) for the early identification of sepsis in the ED. Methods We performed a large observational study including consecutive adult patients (≥18 years of age) presenting to the ED between September and November 2019, with an order for complete blood count (CBC) evaluation. A total of 2,215 patients were enrolled and classified based on Sepsis-2 criteria as the control group (1,855), infection group (172), Systemic Inflammatory Response Syndrome (SIRS) group (100), and sepsis group (88). Results MDW levels were higher in patients with sepsis than in all other groups (p<0.001). ROC curve analysis showed an optimal diagnostic accuracy of MDW for sepsis prediction at a cut-off point of 23.5, with an AUC of 0.964, sensitivity and specificity of 0.920 and 0.929, respectively. Conclusions Our findings encourage further investigation to validate the use of MDW as a screening tool for the early identification of patients at risk of sepsis in the ED.
|
Clinical chemistry and laboratory medicine
| 2,020 | 10 | 0 | 0 |
33,217,696 |
Prevalence and incidence of multiple sclerosis in Ardabil, Northwest of Iran.
|
Multiple sclerosis (MS) epidemiology is studies in many populations; however, studying populations with unique characteristics could provide opportunities to deepen the understanding of the underlying reason of the disease. In this regard, we aimed to study the epidemiology of MS in Ardabil, a province in northwest Iran, where the majority are of Iranian Azerbaijanis.
|
Multiple sclerosis and related disorders
| 2,021 | 1 | 0 | 0 |
33,393,967 |
Finite Element Model of Ocular Adduction by Active Extraocular Muscle Contraction.
|
In order to clarify the role of the optic nerve (ON) as a load on ocular rotation, we developed a finite element model (FEM) of incremental adduction induced by active contractility of extraocular muscles (EOMs), with and without tethering by the ON.
|
Investigative ophthalmology & visual science
| 2,021 | 1 | 0 | 0 |
33,554,140 |
Protocol for quantitative assessment of social cooperation in mice.
|
Social cooperation in rodents was recently validated in rats, and we recently successfully applied a modified automated analysis to mice. Here, we describe a detailed procedure for using this paradigm in mice that relies on reward-based mutual communication that is automatically detected by a software algorithm embedded in the custom-made equipment. We also describe exemplary results of analyses in mice as a guide to broader neuroscience research applications employing transgenic knockout mice modeling neuropsychiatric disorders and mice of various ages. For complete details on the use and execution of this protocol, please refer to Han et al. (2020).
|
STAR protocols
| 2,021 | 3 | 0 | 0 |
33,007,971 |
Heteromerization of Endogenous Mu and Delta Opioid Receptors Induces Ligand-Selective Co-Targeting to Lysosomes.
|
Increasing evidence indicates that native mu and delta opioid receptors can associate to form heteromers in discrete brain neuronal circuits. However, little is known about their signaling and trafficking. Using double-fluorescent knock-in mice, we investigated the impact of neuronal co-expression on the internalization profile of mu and delta opioid receptors in primary hippocampal cultures. We established ligand selective mu-delta co-internalization upon activation by 1-[[4-(acetylamino)phenyl]methyl]-4-(2-phenylethyl)-4-piperidinecarboxylic acid, ethyl ester (CYM51010), [d-Ala2, NMe-Phe4, Gly-ol5]enkephalin (DAMGO), and deltorphin II, but not (+)-4-[(α
|
Molecules (Basel, Switzerland)
| 2,020 | 9 | 0 | 0 |
31,567,268 |
Helmet CPAP as a Bridge From a Rapid Response Activation for Hypoxia Through Awake Tracheostomy in the Operating Room in a Patient With a Difficult Airway: A Case Report.
|
Continuous positive airway pressure (CPAP) has been used in multiple clinical settings with increasing frequency. However, its use in improving blood oxygenation for difficult airways has never been a specific consideration. Here, we present a rapid response team (RRT) intervention in a patient with severe hypoxia requiring emergent surgical tracheostomy. To restore an adequate level of blood oxygen saturation, helmet CPAP was used during transportation and surgical tracheostomy. In selected cases involving difficult airways, helmet CPAP may have some advantages. Additional studies are warranted to assess the benefits of introducing this device to RRT equipment.
|
A&A practice
| 2,019 | 11 | 0 | 0 |
23,296,199 |
Luminance contrast has little influence on the spread of object-based attention.
|
We direct our attention to those visual stimuli that are relevant to our behavioral goals. Some of the visual stimuli that surround us are represented more strongly, because they have a higher luminance contrast. However, selective attention also boosts the representation of visual stimuli. It is not yet well understood how attention and contrast interact. Some previous theories proposed that attentional effects are strongest at low contrast, others that they are strongest at high contrast and yet others that the effects of selective attention are largely independent of contrast. In the present study, we investigated the interaction between selective attention and luminance contrast with a contour-grouping task that provides a sensitive measure of the spread of object-based attention, with delays of several hundreds of milliseconds. We find that the spread of object-based attention is largely independent of contrast, and that subjects experience little difficulty in grouping low-contrast contour elements in the presence of other contour elements with a much higher contrast. The results imply that object-based attention and contrast have largely independent effects on visual processing.
|
Vision research
| 2,013 | 6 | 0 | 0 |
19,755,129 |
A flexible system for hands-free intracranial microinjection.
|
Neuroscience research projects often use intracranial (IC) microinfusions to target drug delivery to specific brain areas during behavioral testing. These experiments require accurate and precisely-timed delivery of small volumes. We present here a stepper motor-powered micropump assembly for such delivery. This system is hands-free, does not use a potentially leaky fluid swivel or use long delivery tubes that are subject to peristaltic forces during animal movements, and has been applied in combination with other paradigms. This micropump system reliably delivers a wide range of fluid volumes (e.g. 50 nL to 1 microL in tissue or greater for intraventricular injections) bilaterally from two independent, commercially available microsyringes through standard surgically implanted guide cannulae. It is easy to build and disassemble for cleaning or changing microsyringes. This system can also be used for a variety of purposes, e.g. intracranial self-administration, place conditioning, and many more, with the advantage that it provides a way to gather important data in the seconds and minutes following IC microinfusion without disruption of the animal's behavior by handling.
|
Journal of neuroscience methods
| 2,009 | 12 | 0 | 0 |
33,654,818 |
Protocol for Measuring Compulsive-like Feeding Behavior in Mice.
|
Obesity is an important health problem with a strong environmental component that is acquiring pandemic proportion. The high availability of caloric dense foods promotes overeating potentially causing obesity. Animal models are key to validate novel therapeutic strategies, but researchers must carefully select the appropriate model to draw the right conclusions. Obesity is defined by an increased body mass index greater than 30 and characterized by an excess of adipose tissue. However, the regulation of food intake involves a close interrelationship between homeostatic and non-homeostatic factors. Studies in animal models have shown that intermittent access to sweetened or calorie-dense foods induces changes in feeding behavior. However, these studies are focused mainly on the final outcome (obesity) rather than on the primary dysfunction underlying the overeating of palatable foods. We describe a protocol to study overeating in mice using diet-induced obesity (DIO). This method can be applied to free choice between palatable food and a standard rodent chow or to forced intake of calorie-dense and/or palatable diets. Exposure to such diets is sufficient to promote changes in meal pattern that we register and analyze during the period of weight gain allowing the longitudinal characterization of feeding behavior in mice. Abnormal eating behaviors such as binge eating or snacking, behavioral alterations commonly observed in obese humans, can be detected using our protocol. In the free-choice procedure, mice develop a preference for the rewarding palatable food showing the reinforcing effect of this diet. Compulsive components of feeding are reflected by maintenance of feeding despite an adverse bitter taste caused by adulteration with quinine and by the negligence of standard chow when access to palatable food is ceased or temporally limited. Our strategy also enables to identify compulsive overeating in mice under a high-caloric regime by using limited food access and finally, we propose complementary behavioral tests to confirm the non-homeostatic food-taking triggered by these foods. Finally, we describe how to computationally explore large longitudinal behavioral datasets.
|
Bio-protocol
| 2,019 | 7 | 0 | 0 |
26,796,246 |
The implications of the new approach to classification: Adults with an intellectual disability.
|
The new ILAE classification offers the potential for clarity and improved translation of the understanding of the nature of epilepsy in people with an intellectual disability. This is particularly true in the use of the term genetic epilepsy and the removal of the term cryptogenic. However, the definition of the "dyscognitive" nature of seizures needs greater definition in those with coexistent cognitive impairment. This is of particular importance when ameliorating risk associated with impaired consciousness. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy".
|
Epilepsy & behavior : E&B
| 2,016 | 11 | 0 | 0 |
33,432,877 |
Real world prognosis in MS: does early versus late diagnosis matter?
|
Multiple sclerosis (MS) often presents soon after the onset of a recognized clinically isolated syndrome (CIS). In order to interpret data from CIS trials, it is important to know whether patients presenting as classical CIS provide group data representative of RRMS.
|
Neurological research
| 2,021 | 6 | 0 | 0 |
33,200,103 |
COVID-19 and stroke: Red flags for secondary movement disorders?
|
•Hypercoagulability may predispose COVID-19 patients to thromboembolic complications.•Movement disorders may develop as complications of vascular events and infections.•Health professionals should be vigilant for abnormal movements in COVID-19 patients.
|
eNeurologicalSci
| 2,020 | 12 | 0 | 0 |
32,795,554 |
Covariation between Childhood-Trauma Related Resting-State Functional Connectivity and Affective Temperaments is Impaired in Individuals with Major Depressive Disorder.
|
Affective temperaments and childhood-trauma experiences are associated with major depressive disorder (MDD). So far, how the covariation between distinct affective temperaments and childhood-trauma insulted brain functional connectivities (FCs) contribute to MDD remains unclear. Here, we aimed to investigate whether certain brain FC patterns are related to certain affective temperaments and whether the FCs contribute to depressive symptom dimensions of MDD patients. Twenty-nine medication-free MDD patients and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Two multivariate analyses of partial least squares (PLS) regression were used to explore the associations among childhood-trauma related resting-state FCs, affective temperaments and depressive symptom dimensions. In all participants, a linear combination of 81 FCs (involving parahippocampus, amygdala, cingulate cortex, insula, frontal-temporal-parietal-occipital cortex, pallidum, and cerebellum) were associated with a linear combination of increased depressive, irritable, anxious, and cyclothymic temperaments. Moreover, the covariation between the PLS FC profile and the PLS affective-temperament profile were enhanced in the MDD patients compared to healthy controls. In MDD participants alone, the affective-temperament modulated FC profile (mainly of the lingual and temporal cortex) was associated with the somatization symptom dimension when age, sex, ill-duration, age-of-onset, and HARS scores were adjusted. The findings imply possible neural correlates of affective temperaments and may find applications in intervention of the somatization-depression symptoms by stimulation of the related neural correlates.
|
Neuroscience
| 2,021 | 1 | 0 | 0 |
33,638,793 |
Part I: The Complex Spikes as One of the Cerebellar Secrets.
|
The olivocerebellar tract has unique morphological, physiological, and developmental properties. Olivocerebellar axons are the source of multiple climbing fibers (CFs). The synapse between CFs and the Purkinje neuron is one of the most powerful excitatory in the central nervous system. Complex spikes are composed of an initial large amplitude spike followed by spikelets. The spatiotemporal patterns of complex/simple spikes complement the rate coding to enhance the accuracy of motor and cognitive processing, and to improve predictions related to internal models. Understanding the role of complex spikes is essential in clarifying how the cerebellar cortex contributes to learning, motor control, cognitive tasks, and the processing of emotions. This Cerebellar Classic is devoted to the pioneering work of Eccles, Llinás, and Sasaki on complex spikes using intracellular recordings from Purkinje neurons.
|
Cerebellum (London, England)
| 2,021 | 6 | 0 | 0 |
32,559,304 |
Environmental Complexity and Research Outcomes.
|
Environmental complexity is an experimental paradigm as well as a potential part of animals' everyday housing experiences. In experimental uses, researchers add complexity to stimulate brain development, delay degenerative brain changes, elicit more naturalistic behaviors, and test learning and memory. Complexity can exacerbate or mitigate behavioral problems, give animals a sense of control, and allow for expression of highly driven, species-typical behaviors that can improve animal welfare. Complex environments should be designed thoughtfully with the animal's natural behaviors in mind, reported faithfully in the literature, and evaluated carefully for unexpected effects.
|
ILAR journal
| 2,020 | 10 | 0 | 0 |
33,038,358 |
Improved functional and histochemical outcomes in l-DOPA plus tolcapone treated VMAT2-deficient mice.
|
Parkinson disease is typically treated with L-3,4-dihydroxyphenylalanine (or levodopa) co-prescribed with concentration stabilizers to prevent undesired motor fluctuations. However, the beneficial role of the chronic combined therapy on disease progression has not been thoroughly explored. We hypothesized that tolcapone, a catechol-O-methyl-transferase inhibitor, co-administered with levodopa may offer beneficial long-term disease-modifying effects through its dopamine stabilization actions. Here, we followed vesicular monoamine transporter 2-deficient and wild-type mice treated twice daily per os with vehicle, levodopa (20 mg/kg), tolcapone (15 mg/kg) or levodopa (12.5 mg/kg) + tolcapone (15 mg/kg) for 17 weeks. We assessed open field, bar test and rotarod performances at baseline and every 4th week thereafter, corresponding to OFF-medication weeks. Finally, we collected coronal sections from the frontal caudate-putamen and determined the reactivity level of dopamine transporter. Vesicular monoamine transporter 2-deficient mice responded positively to chronic levodopa + tolcapone intervention in the bar test during OFF-periods. Neither levodopa nor tolcapone interventions offered significant improvements on their own. Similarly, chronic levodopa + tolcapone intervention was associated with partially rescued dopamine transporter levels, whereas animals treated solely with levodopa or tolcapone did not present this effect. Interestingly, 4-month progression of bar test scores correlated significantly with dopamine-transporter-label density. Overall, we observed a moderate functional and histopathological improvement effect by chronic dopamine replacement when combined with tolcapone in vesicular monoamine transporter 2-deficient mice. Altogether, chronic stabilization of dopamine levels by catechol-O-methyl-transferase inhibition, besides its intended immediate actions, arises as a potential long-term beneficial approach during the progression of Parkinson disease.
|
Neuropharmacology
| 2,020 | 12 | 0 | 0 |
33,465,414 |
Matrix Metalloproteinase-9 Expression is Enhanced by Ischemia and Tissue Plasminogen Activator and Induces Hemorrhage, Disability and Mortality in Experimental Stroke.
|
Matrix metalloproteinase-9 (MMP-9) degrades collagen and other cellular matrix proteins. After acute ischemic stroke, increased MMP-9 levels are correlated with hemorrhage, lack of reperfusion and stroke severity. Nevertheless, definitive data that MMP-9 itself causes poor outcomes in ischemic stroke are limited. In a model of experimental ischemic stroke with reperfusion, we examined whether ischemia and recombinant tissue plasminogen activator (r-tPA) therapy affected MMP-9 expression, and we used specific inhibitors to test if MMP-9 affects brain injury and recovery. After stroke, MMP-9 expression increased significantly in the ischemic vs. non-ischemic hemisphere of the brain (p < 0.001). MMP-9 expression in the ischemic, but not the non-ischemic hemisphere, was further increased by r-tPA treatment (p < 0.001). To determine whether MMP-9 expression contributed to stroke outcomes after r-tPA treatment, we tested three different antibody MMP-9 inhibitors. When compared to treatment with r-tPA and saline, treatment with r-tPA and MMP-9 antibody inhibitors significantly reduced brain hemorrhage by 11.3 to 38.6-fold (p < 0.01), brain swelling by 2.8 to 4.3-fold (p < 0.001) and brain infarction by 2.5 to 3.9-fold (p < 0.0001). Similarly, when compared to treatment with r-tPA and saline, treatment with r-tPA and an MMP-9 antibody inhibitor significantly improved neurobehavioral outcomes (p < 0.001), decreased weight loss (p < 0.001) and prolonged survival (p < 0.01). In summary, both prolonged ischemia and r-tPA selectively enhanced MMP-9 expression in the ischemic hemisphere. When administered with r-tPA, specific MMP-9 inhibitors markedly reduced brain hemorrhage, swelling, infarction, disability and death, which suggests that blocking the deleterious effects of MMP-9 may improve outcomes after ischemic stroke.
|
Neuroscience
| 2,021 | 4 | 0 | 0 |
32,680,963 |
Morphological profiling of tubercle bacilli identifies drug pathways of action.
|
Morphological profiling is a method to classify target pathways of antibacterials based on how bacteria respond to treatment through changes to cellular shape and spatial organization. Here we utilized the cell-to-cell variation in morphological features of
|
Proceedings of the National Academy of Sciences of the United States of America
| 2,020 | 8 | 0 | 0 |
32,707,531 |
Ocrelizumab exposure in the second trimester of pregnancy without neonatal B-cell depletion.
|
Management of multiple sclerosis (MS) before and during pregnancy remains challenging given there are no disease-modifying therapies (DMTs) approved for use during pregnancy, and discontinuation of certain DMTs can lead to rebound relapses. Ocrelizumab is a highly effective therapy for relapsing-remitting MS (RRMS) without reported rebound after discontinuation. However, little is known about the safety of ocrelizumab before or during pregnancy. We report a case of second trimester ocrelizumab exposure in a patient with RRMS transitioning off natalizumab, that resulted in no neonatal B-cell depletion, no infections, and normal infant development, despite suppressed B-cells in the mother at delivery.
|
Multiple sclerosis and related disorders
| 2,020 | 10 | 0 | 0 |
33,271,327 |
HuD regulates SOD1 expression during oxidative stress in differentiated neuroblastoma cells and sporadic ALS motor cortex.
|
The neuronal RNA-binding protein (RBP) HuD plays an important role in brain development, synaptic plasticity and neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's (AD). Bioinformatics analysis of the human SOD1 mRNA 3' untranslated region (3'UTR) demonstrated the presence of HuD binding adenine-uridine (AU)-rich instability-conferring elements (AREs). Using differentiated SH-SY5Y cells along with brain tissues from sporadic amyotrophic lateral sclerosis (sALS) patients, we assessed HuD-dependent regulation of SOD1 mRNA. In vitro binding and mRNA decay assays demonstrate that HuD specifically binds to SOD1 ARE motifs promoting mRNA stabilization. In SH-SY5Y cells, overexpression of full-length HuD increased SOD1 mRNA and protein levels while a dominant negative form of the RBP downregulated its expression. HuD regulation of SOD1 mRNA was also found to be oxidative stress (OS)-dependent, as shown by the increased HuD binding and upregulation of this mRNA after H
|
Neurobiology of disease
| 2,021 | 1 | 0 | 0 |
32,851,476 |
Demographic and clinical determinants of neck pain in idiopathic cervical dystonia.
|
Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain.
|
Journal of neural transmission (Vienna, Austria : 1996)
| 2,020 | 10 | 0 | 0 |
34,336,508 |
Neuropsychiatric Lupus: A Challenging Journey of a Patient With Pulmonary Tuberculosis.
|
Systemic lupus erythematosus (SLE) is a disease that affects multiple systems in the body. Due to its variable manifestations, it can at times pose challenges for physicians to hold SLE as the culprit behind an affected system. This is most true when encountering patients with neuropsychiatric manifestations of SLE. We present a case of a 38-year-old female with known SLE limited to skin involvement and on treatment for active pulmonary tuberculosis (TB), yet otherwise healthy, who presented with acute fever associated with generalized tonic-clonic seizures. She was investigated for meningoencephalitis with a cerebrospinal fluid (CSF) analysis not being fully conclusive and with imaging features suggestive of viral encephalitis. However, despite receiving optimal care for causes of bacterial, viral, and tuberculous meningitis the patient continued to deteriorate and started to develop predominant psychiatric symptoms in the form of confusion and combative behavior requiring pharmacological restraint. Hence a trial of immunosuppressives was given with a presumptive diagnosis of neuropsychiatric lupus with IV methylprednisolone followed by a course of IV cyclophosphamide. However, this treatment proceeded with caution due to the fear of disseminated tuberculosis for which she did not show any sign of in the subsequent weeks. The patient showed modest clinical and radiological improvement and hence the treatment was continued. The case highlights the uncertainty that may precede a diagnosis of neuropsychiatric lupus and the challenges in treating it in patients with active mycobacterial infection.
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Cureus
| 2,021 | 6 | 0 | 0 |
32,448,020 |
Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study.
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22q11.2 deletion syndrome (22q11.2DS) is associated with impaired cognitive functioning. Glutamatergic pathways have been linked with cognition and are hypothesized to be disrupted in 22q11.2DS patients, possibly 'shifting' the excitatory (glutamate)/inhibitory (GABA) balance. Hence, the glutamate/GABA balance may constitute a target for pharmacological treatment. We aimed to examine alterations of glutamate/GABA metabolites in 22q11.2DS
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Journal of psychopharmacology (Oxford, England)
| 2,020 | 8 | 0 | 0 |
33,014,732 |
The clinical utilities of multi-pinhole single photon emission computed tomography.
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Single photon emission computed tomography (SPECT) is an important imaging modality for various applications in nuclear medicine. The use of multi-pinhole (MPH) collimators can provide superior resolution-sensitivity trade-off when imaging small field-of-view compared to conventional parallel-hole and fan-beam collimators. Besides the very successful application in small animal imaging, there has been a resurgence of the use of MPH collimators for clinical cardiac and brain studies, as well as other small field-of-view applications. This article reviews the basic principles of MPH collimators and introduces currently available and proposed clinical MPH SPECT systems.
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Quantitative imaging in medicine and surgery
| 2,020 | 10 | 0 | 0 |
32,944,570 |
I SPY WITH MY LITTLE EYE: WHAT VISUAL SEARCH CAN TELL US ABOUT HOW WE SEE THE WORLD.
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We have all have experienced the frustration of looking for something we want, only to find a seemingly endless series of things we do not want. This process of looking for an object of interest is called visual search. We perform visual search all the time in everyday life, because the objects we want are almost always surrounded by many other objects. But, in some cases, it takes special training to find things, such as when searching for cancers in X-rays, weapons or explosives in airport luggage, or an enemy sniper hidden in the bushes. Understanding how we search for, and find, objects we are looking for is crucial to understanding how ordinary people and experts alike operate in the real world. While much remains to be discovered, what we have learned so far offers a fascinating window into how we see.
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Frontiers for young minds
| 2,019 | 1 | 0 | 0 |
23,883,761 |
The use of non-interactive scenarios in social neuroscience.
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Although we fundamentally agree with Schilbach et al., we argue here that there is still some residual utility for non-interactive scenarios in social neuroscience. They may be useful to quantify individual differences in prosocial inclination that are not influenced by concerns about reputation or social pressure.
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The Behavioral and brain sciences
| 2,013 | 8 | 0 | 0 |
33,291,600 |
Clinical and Pathological Characteristics of Metastatic Renal Cell Carcinoma Patients Needing a Second-Line Therapy: A Systematic Review.
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A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included papers that met the following criteria: original research; English language; human studies; enrolling mRCC patients entering a second-line therapy. Twenty-nine studies enrolling 7650 patients (73.5% male, mean age: 55 to 70 years) were included. Clear cell histology was reported in 74.4% to 100% of cases. Tyrosine kinase inhibitors, immunotherapy, bevacizumab, mTOR inhibitors, and chemotherapy were adopted as first line option in 68.5%, 29.2%, 2.9%, 0.6%, and 0.2% of patients, respectively. Discontinuation of first-line therapy was due to progression and toxicity in 18.4% to 100% and in 17% to 48.8% of patients, respectively. Eastern Cooperative Oncology Group performance status score was 0 or 1 in most cases. Most prevalent prognostic categories according to the International Metastatic RCC Database Consortium and Memorial Sloan-Kettering Cancer Centre score were intermediate and good. About 77.8% of patients harboured ≥2 metastatic sites. In conclusion, patients who enter a second-line therapy are heterogeneous in terms of a clinical-pathological profile. Tailoring of second-line treatment strategies is strongly advocated.
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Cancers
| 2,020 | 12 | 0 | 0 |
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