Background and Purpose
Olcegepant (BIBN4096BS) is a selective non‐peptide CGRP receptor antagonist with acute antimigraine properties. Since systemic vascular tone is modulated by perivascular ...(primary sensory CGRPergic and sympathetic) nerves, this randomized study investigated in pithed rats the effect of acute i.v. treatment with olcegepant on the neurogenic and non‐neurogenic: (i) CGRPergic vasodepressor responses; and (ii) noradrenergic vasopressor responses. The pithed rat is an experimental model predictive of systemic (cardio) vascular side effects.
Experimental Approach
Seventy‐five male Wistar rats (divided into 15 groups, n = 5 each) were pithed, artificially ventilated and prepared for: (i) spinal stimulation (T9–T12; 0.56–5.6 Hz) of the sensory CGRPergic vasodepressor outflow or i.v. bolus injections (0.1–1 μg·kg−1) of α‐CGRP, substance P or acetylcholine, which induced frequency‐dependent or dose‐dependent vasodepressor responses; or (ii) spinal stimulation (T7–T9; 0.03–3 Hz) of the sympathetic vasopressor outflow or i.v. bolus injections (0.03–3 μg·kg−1) of noradrenaline, which produced frequency‐dependent or dose‐dependent vasopressor responses.
Key Results
Olcegepant (1000 and 3000 μg·kg−1, i.v.) dose‐dependently blocked the vasodepressor responses to sensory nerve stimulation or i.v. α‐CGRP, without affecting those to substance P or acetylcholine. Whereas it potentiated the vasopressor responses to sympathetic nerve stimulation or i.v. noradrenaline.
Conclusions and Implications
Olcegepant (i.v.) selectively blocked the neurogenic and non‐neurogenic CGRPergic vasodepressor responses. This blockade by olcegepant potentiated the neurogenic and non‐neurogenic noradrenergic vasopressor responses in pithed rats, an effect that might result in an increased vascular resistance and, consequently, in a prohypertensive action.
BACKGROUNDin Colombia, oral cancer is the eighth most common type of cancer, with an estimated survival rate of 52%. Lack of knowledge about oral cancer and its risk factors is associated with late ...detection.MATERIAL AND METHODSa descriptive cross-sectional study was carried out on 268 patients attending the School of Dentistry of the University of Antioquia clinics, to whom a validated 47-question questionnaire was applied by phone during the COVID-19 pandemic (2020 and 2021). Data were analyzed using the SPSS software.RESULTSthe mean age was 58.9. 58.6% of the participants had heard of oral cancer, 42% acquire knowledge from the media, and 96.7% considered screening necessary. Most of the patients expressed not feeling worried (54.5%), fearful (59.7%), or anxious (56.3%) in the case of being submitted to an examination for early detection of oral cancer. A correlation between low socioeconomic status and educational level with less knowledge of oral cancer was found. The dimensions of experience and attitude towards screening were not associated with sociodemographic variables.CONCLUSIONSThere is little knowledge about oral cancer, especially in low socioeconomic and educational status, although this does not occur in the dimensions of attitude and experience toward screening. In contrast, patients participating in this study presented high knowledge about oral cancer risk. This population recognizes the situations most related to the development of cancer. This level of knowledge was similar for the demographic conditions except for people with no education, who presented less knowledge of the risks. The need for educational campaigns on oral cancer knowledge is reaffirmed, especially in socially disadvantaged groups, considering that there would be no barriers related to screening.
We use kappa distributions to model thousands of ion and electron flux spectra along the plasma sheet and analyze the variation of the spectral index κ and the temperature T in this region. We find ...that κ distributions are ubiquitous and fit well ion and electron flux spectra during quiet times, and during the expansion and recovery phases of substorms. Near Earth, and up to ∼12 RE, the κ indices are different than the rest of the plasma sheet, both for ions (κi) and electrons (κe). There is a significant dawn‐dusk asymmetry in κi toward the tail, which is enhanced during substorms. The ions also exhibit a permanent temperature asymmetry, determined by a colder dawnside. The whole tail becomes hotter during substorms, but it appears that most of the energy is deposited near Earth.
Plain Language Summary
Ions and electrons in space plasmas rarely experience collisions and the only way they exchange energy is via electromagnetic interactions. It is said that these plasmas are out of thermal equilibrium, which is the ground state of most systems, and can be compared to the balance of temperatures observed when two bodies are in contact. In the Earth's magnetosphere, plasmas are constantly energized by geomagnetic storms and substorms. Because of all this, and contrary to most materials on Earth, particles outside the Earth are always out of thermal equilibrium and their energy budgets are difficult to describe. We have studied ions and electrons in the magnetotail of the Earth's magnetosphere using data taken by the Time History of Events and Macroscale Interactions during Substorms satellites. We confirmed that particles are out thermal equilibrium and found that their behavior is not entirely random, but somewhat organized, even during substorms. They follow the so called kappa functions. This means that particles somehow have an efficient way to organize themselves. We think our findings can provide scientist with better ways to characterize particles in this area of the magnetosphere and build more reliable models.
Key Points
Study of ion and electron energy spectra along the plasma sheet using THEMIS data
Kappa distribution fits of 624‐eV to 93‐keV electrons, and 1.75‐ to 210‐keV ions
Kappa indices exhibit dawn‐dusk asymmetry and depend on substorm activity
Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor (GPCR) expressed in several mammalian brain areas and activated by “trace amines” (TAs). TAs role is unknown; however, ...discovery of their receptors provided an opportunity to investigate their functions. In vivo evidence has indicated an inhibitory influence of TAAR1 on dopamine (DA) neurotransmission, presumably via modulation of dopamine transporter (DAT) or interaction with the D2 DA receptor and/or activation of inwardly rectifying K+ channels. To elucidate the mechanisms of TAAR1-dependent modulation, we used TAAR1 knockout mice (TAAR1-KO), a TAAR1 agonist (RO5166017) and a TAAR1 antagonist (EPPTB) in a set of neurochemical experiments. Analysis of the tissue content of TAAR1-KO revealed increased level of the DA metabolite homovanillic acid (HVA), and in vivo microdialysis showed increased extracellular DA in the nucleus accumbens (NAcc) of TAAR1-KO. In fast scan cyclic voltammetry (FSCV) experiments, the evoked DA release was higher in the TAAR1-KO NAcc. Furthermore, the agonist RO5166017 induced a decrease in the DA release in wild-type that could be prevented by the application of the TAAR1 antagonist EPPTB. No alterations in DA clearance, which are mediated by the DAT, were observed. To evaluate the interaction between TAAR1 and D2 autoreceptors, we tested the autoreceptor-mediated dynamics. Only in wild type mice, the TAAR1 agonist was able to potentiate quinpirole-induced inhibitory effect on DA release. Furthermore, the short-term plasticity of DA release following paired pulses was decreased in TAAR1-KO, indicating less autoinhibition of D2 autoreceptors. These observations suggest a close interaction between TAAR1 and the D2 autoreceptor regulation.
•TAAR1 is a GPCR expressed in several brain areas.•In vivo evidence showed inhibitory influence of TAAR1 on dopamine neurotransmission.•Fast scan cyclic voltammetry experiments showed higher DA release in TAAR1-KO NAcc.•TAAR1 agonist was able to potentiate quinpirole effect on DA release.•These studies suggest an interaction between TAAR1 and the D2 autoreceptor regulation.
This article presents the dental restoration of a young female patient complaining of erosive dental wear using a three-step restorative technique, an alternative approach with some novel ...adjustments.
For successful tooth wear treatment, determining the etiological systemic and local factors is the main priority before deciding on effective and long-term preventive and/or therapeutic restorative approaches. In addition to professional intervention, achieving optimal outcomes requires patients to control their diet and/or gastric issues, thus minimizing the wear process. However, continuous wear constitutes the most challenging scenario, mainly when it affects young patients' dentitions. This article describes the dental restoration of posterior teeth with reestablishment of occlusal vertical dimension before treating the anterior teeth, while educating the patient and providing medical monitoring. The three-step restorative technique seems to be properly applicable in cases of significant dental compromise due mainly to erosive wear and is based on direct procedures, which can assure a reliable and feasible approach.
We report the detection of pulsed gamma-ray emission from the fast millisecond pulsars (MSPs) B1937+21 (also known as J1939+2134) and B1957+20 (J1959+2048) using 18 months of survey data recorded by ...the Fermi Large Area Telescope and timing solutions based on radio observations conducted at the Westerbork and Nancay radio telescopes. In addition, we analyzed archival Rossi X-ray Timing Explorer and XMM-Newton X-ray data for the two MSPs, confirming the X-ray emission properties of PSR B1937+21 and finding evidence (~4 Delta *s) for pulsed emission from PSR B1957+20 for the first time. In both cases the gamma-ray emission profile is characterized by two peaks separated by half a rotation and are in close alignment with components observed in radio and X-rays. These two pulsars join PSRs J0034--0534 and J2214+3000 to form an emerging class of gamma-ray MSPs with phase-aligned peaks in different energy bands. The modeling of the radio and gamma-ray emission profiles suggests co-located emission regions in the outer magnetosphere.
Context.
The characteristic age of PSR J1734−3333 estimated from its current spin down rate implies that it is a young pulsar (
τ
c
= 8.1 kyr). However, the time derivative of its spin-down rate ...differs markedly from that assumed for normal radio pulsars, meaning its actual age is uncertain. G354.8−0.8 is a supernova remnant (SNR) whose centre is located 21′ away from the pulsar, and which has a morphology that suggests an association with the pulsar.
Aims.
We aim to assess the likelihood of the association between PSR J1734−3333 and G354.8−0.8 or other nearby SNRs quantitatively, with the objective of shedding light on the real age of this pulsar.
Methods.
Observations with the Karl G. Jansky Very Large Array were carried out in 2015 and 2019 that allow precise astrometric measurements and consequently a proper motion estimate for the pulsar.
Results.
The proper motion was found to be
μ
α
= 10 ± 10 mas yr
−1
and
μ
δ
= −29 ± 11 mas yr
−1
(error bars are 1-
σ
). Though marginal, this detection rules out the association with G354.8−0.8 because it means the pulsar is not moving away from the centre of the SNR. No SNR consistent with the measured proper motion and an age
τ
c
could be found. We also present the first measurement of the spectral index for this pulsar,
α
= −1.1 ± 0.3, measured between 1.5 and 3.0 GHz.
Conclusions.
The SNR produced by the birth supernova of PSR J1734−3333 could have already faded to undetectable brightness, estimates of which suggest timescales of 10 − 100 kyr. This and other considerations lead us to conclude that the pulsar is possibly older than 45 − 100 kyr. PSR J1734−3333 is a pulsar with rotational properties that place it between standard radio pulsars and magnetars, and we interpret our result in the context of a possible future life as a magnetar for this pulsar.
This study aimed to examine the factors associated with low sugar-sweetened beverage (SSB) consumption and intention to avoid these products as well as investigate the role of different types of ...social norms in the adoption of this behaviour.
This study reports the results of a secondary data analysis from a cross-sectional telephone survey.
A total of 1000 adults were randomly recruited in the province of Québec, Canada, using a random-digit dialling procedure. Eligibility criteria were to be aged between 18 and 64 years; able to answer a questionnaire in French or English; and to reside in the province of Québec. SSB consumption, social norms and variables from the theory of planned behaviour were assessed by means of a questionnaire. Logistic regression analyses were conducted to examine factors associated with behaviour and intention.
Consuming <1 SSB per day was significantly associated with intention, perceived behavioural control, and risk perception about tooth decay. Descriptive (perceived prevalence in the close surroundings of one person) and perceived societal norms (perceived broad societal approval/disapproval of the behaviour) were associated with behaviour. All theory of planned behaviour variables (including injunctive norm) and risk perception pertaining to chronic diseases predicted intention to avoid the consumption of ≥1 SSB per day. Sex, age, income, and risk perception pertaining to chronic diseases were associated with perceived societal disapproval of SSB consumption.
This study confirms the importance of social norms in the prediction of SSB consumption but also highlights the need to address motivation and capacities in public health interventions to reduce SSB consumption.
ABSTRACT
A striking feature of the Vela pulsar (PSR J0835−4510) is that it undergoes sudden increases in its spin frequency, known as glitches, with a fractional amplitude of the order of 10−6 ...approximately every 900 d. Glitches of smaller magnitudes are also known to occur in Vela. Their distribution in both time and amplitude is less well constrained but equally important for understanding the physical process underpinning these events. In order to better understand these small glitches in Vela, an analysis of high-cadence observations from the Mount Pleasant Observatory is presented. A hidden Markov model (HMM) is used to search for small, previously undetected glitches across 24 yr of observations covering MJD 44929 to MJD 53647. One previously unknown glitch is detected around MJD 48636 (1992 January 15), with fractional frequency jump Δf/f = (8.19 ± 0.04) × 10−10 and frequency derivative jump $\Delta \dot{f}/\dot{f} = (2.98 \pm 0.01) \times 10^{-4}$ . Two previously reported small glitches are also confidently redetected, and independent estimates of their parameters are reported. Excluding these events, 90 per cent confidence frequentist upper limits on the sizes of missed glitches are also set, with a median upper limit of $\Delta f^{90~{{\% }}}/f = 1.35 \times 10^{-9}$. Upper limits of this kind are enabled by the semi-automated and computationally efficient nature of the HMM, and are crucial to informing studies that are sensitive to the lower end of the glitch size distribution.
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