The vertebrate stress response (SR) is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and contributes to generating context appropriate physiological and behavioral changes. Although the ...HPA axis plays vital roles both in stressful and basal conditions, research has focused on the response under stress. To understand broader roles of the HPA axis in a changing environment, we characterized an adaptive behavior of larval zebrafish during ambient illumination changes. Genetic abrogation of glucocorticoid receptor (nr3c1) decreased basal locomotor activity in light and darkness. Some key HPI axis receptors (mc2r ACTH receptor, nr3c1), but not nr3c2 (mineralocorticoid receptor), were required to adapt to light more efficiently but became dispensable when longer illumination was provided. Such light adaptation was more efficient in dimmer light. Our findings show that the HPI axis contributes to the SR, facilitating the phasic response and maintaining an adapted basal state, and that certain adaptations occur without HPI axis activity.
RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated ...proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.
ABSTRACT Stellar evolution calculations have had great success reproducing the observed atmospheric properties of different classes of stars. Recent detections of g-mode pulsations in evolved He ...burning stars allow a rare comparison of their internal structure with stellar models. Asteroseismology of subdwarf B (sdB) stars suggests convective cores of 0.22-0.28 M , 45% of the total stellar mass. Previous studies found significantly smaller convective core masses ( 0.19 M ) at a comparable evolutionary stage. We evolved stellar models with Modules for Experiments in Stellar Astrophysics (MESA) to explore how well the interior structures inferred from asteroseismology can be reproduced by standard algorithms. Our qualitative evolutionary paths, position in the diagram, and model timescales are consistent with previous results. The sdB masses from our full evolutionary sequences fall within the range of the empirical sdB mass distribution, but are nearly always lower than the median. Using standard MLT with atomic diffusion we find convective core masses of ∼0.17-0.18 M , averaged over the entire sdB lifetime. We can increase the convective core sizes to be as large as those inferred from asteroseismology, but only for extreme values of the overshoot parameter (overshoot gives numerically unstable and physically unrealistic behavior at the boundary). High resolution three-dimensional simulations of turbulent convection in stars suggest that the Schwarzschild criterion for convective mixing systematically underestimates the actual extent of mixing because a boundary layer forms. Accounting for this would decrease the errors in both sdB total and convective core masses.
BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures, and lead to constitutive activation of the ...mitogen-activated protein (MAP) kinase pathway. However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown. Here we report frequent somatic mutations in the heterotrimeric G protein -subunit, GNAQ, in blue naevi (83%) and ocular melanoma of the uvea (46%). The mutations occur exclusively in codon 209 in the Ras-like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention.
Economic review of point-of-care EEG Green, Adam; Wegman, M Elizabeth; Ney, John P
Journal of medical economics,
12/2024, Letnik:
27, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Point-of-care electroencephalogram (POC-EEG) is an acute care bedside screening tool for the identification of nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE). The objective ...of this narrative review is to describe the economic themes related to POC-EEG in the United States (US).
We examined peer-reviewed, published manuscripts on the economic findings of POC-EEG for bedside use in US hospitals, which included those found through targeted searches on PubMed and Google Scholar. Conference abstracts, gray literature offerings, frank advertisements, white papers, and studies conducted outside the US were excluded.
Twelve manuscripts were identified and reviewed; results were then grouped into four categories of economic evidence. First, POC-EEG usage was associated with clinical management amendments and antiseizure medication reductions. Second, POC-EEG was correlated with fewer unnecessary transfers to other facilities for monitoring and reduced hospital length of stay (LOS). Third, when identifying NCS or NCSE onsite, POC-EEG was associated with greater reimbursement in Medical Severity-Diagnosis Related Group coding. Fourth, POC-EEG may lower labor costs
decreasing after-hours requests to EEG technologists for conventional EEG (convEEG).
We conducted a narrative review, not a systematic review. The studies were observational and utilized one rapid circumferential headband system, which limited generalizability of the findings and indicated publication bias. Some sample sizes were small and hospital characteristics may not represent all US hospitals. POC-EEG studies in pediatric populations were also lacking. Ultimately, further research is justified.
POC-EEG is a rapid screening tool for NCS and NCSE in critical care and emergency medicine with potential financial benefits through refining clinical management, reducing unnecessary patient transfers and hospital LOS, improving reimbursement, and mitigating burdens on healthcare staff and hospitals. Since POC-EEG has limitations (i.e. no video component and reduced montage), the studies asserted that it did not replace convEEG.
Introduction
The input from practitioners in developmental assessment test revision is a crucial and leading component of the project. This paper highlights six key phases of the Griffiths III ...revision process and the value of having a guiding plan that includes test practitioner input.
Methods
The revision of the Griffiths III consisted of six separate phases that were supported by practitioner and user input and feedback. These six phases and practitioner views ensured that the necessary core constructs and new areas for item development were included in the revised version. These processes also underscored the construct development and task review, item design, piloting and standardization of the revised version, as well as its production, release and subsequent training methods.
Results
The six guiding phases provided a methodologically robust frame to the revision process. Practitioners valued an overall developmental measure with discrete data about and within the ‘avenues of learning’ allowing them to analyse a child's strengths and weaknesses. Communication with practitioners across the world demonstrated the wide disparity of culture and environments that the Griffiths Scales are deployed in. It is not possible to design a revised scale that is appropriate for all areas of use, so in this revision process, it was decided to design the scales as culturally fair as possible and support practitioners in other countries to translate and validate the scales for use.
Conclusions
The revision of the Griffiths III found test users to be valuable sources of information on the basis of their experiences with the test and professional knowledge. Creating a continuous feedback mechanism within a phased process provided opportunities for the revision team to engage meaningfully with the data being obtained as well as test users to advance the scope and quality of the test. Revision teams are encouraged to consider the process and engagement methods explored in this study during their projects.
Lack of behavioral suppression typifies substance use disorders, yet the neural circuit underpinnings of drug-induced behavioral disinhibition remain unclear. Here, we employ deep-brain two-photon ...calcium imaging in heroin self-administering mice, longitudinally tracking adaptations within a paraventricular thalamus to nucleus accumbens behavioral inhibition circuit from the onset of heroin use to reinstatement. We find that select thalamo-accumbal neuronal ensembles become profoundly hypoactive across the development of heroin seeking and use. Electrophysiological experiments further reveal persistent adaptations at thalamo-accumbal parvalbumin interneuronal synapses, whereas functional rescue of these synapses prevents multiple triggers from initiating reinstatement of heroin seeking. Finally, we find an enrichment of μ-opioid receptors in output- and cell-type-specific paraventricular thalamic neurons, which provide a mechanism for heroin-induced synaptic plasticity and behavioral disinhibition. These findings reveal key circuit adaptations that underlie behavioral disinhibition in opioid dependence and further suggest that recovery of this system would reduce relapse susceptibility.
Display omitted
•Heroin use and seeking are predicted by inhibition of PVT→NAc neuronal ensembles•Heroin also weakens PVT→NAcPV-IN synapses, collectively inducing behavioral disinhibition•Behavioral inhibition is restored by rescuing activity at PVT→NAcPV-IN synapses•Heroin-induced synaptic adaptations and behavioral disinhibition rely on PVT μ-ORs
Behavioral disinhibition is the cardinal feature of substance use disorders, enabling drug use and relapse despite significant consequences. Paniccia, Vollmer, Green, and colleagues discover that heroin use induces behavioral disinhibition through maladaptive plasticity in a thalamus-nucleus accumbens circuit, whereas restoration of this circuit prevents heroin seeking in mice.
Multiphoton microscopy is one of several new technologies providing unprecedented insight into the activity dynamics and function of neural circuits. Unfortunately, some of these technologies require ...experimentation in head-restrained animals, limiting the behavioral repertoire that can be integrated and studied. This issue is especially evident in drug addiction research, as no laboratories have coupled multiphoton microscopy with simultaneous intravenous drug self-administration, a behavioral paradigm that has predictive validity for treatment outcomes and abuse liability. Here, we describe a new experimental assay wherein head-restrained mice will press an active lever, but not inactive lever, for intravenous delivery of heroin or cocaine. Similar to freely moving animals, we find that lever pressing is suppressed through daily extinction training and subsequently reinstated through the presentation of relapse-provoking triggers (drug-associative cues, the drug itself, and stressors). Finally, we show that head-restrained mice will show similar patterns of behavior for oral delivery of a sucrose reward, a common control used for drug self-administration experiments. Overall, these data demonstrate the feasibility of combining drug self-administration experiments with technologies that require head-restraint, such as multiphoton imaging. The assay described could be replicated by interested labs with readily available materials to aid in identifying the neural underpinnings of substance use disorder.
BACKGROUND Mortality associated with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) is higher than mortality due to carbapenem-sensitive pathogens. OBJECTIVE To examine the ...association between mortality from bacteremia caused by carbapenem-resistant (CRKP) and carbapenem-sensitive Klebsiella pneumoniae (CSKP) and to assess the impact of appropriate initial antibiotic therapy (IAT) on mortality. DESIGN Systematic review and meta-analysis METHODS We searched MEDLINE, EMBASE, CINAHL, and Wiley Cochrane databases through August 31, 2016, for observational studies reporting mortality among adult patients with CRKP and CSKP bacteremia. Search terms were related to Klebsiella, carbapenem-resistance, and infection. Studies including fewer than 10 patients per group were excluded. A random-effects model and meta-regression were used to assess the relationship between carbapenem-resistance, appropriateness of IAT, and mortality. RESULTS Mortality was higher in patients who had CRKP bacteremia than in patients with CSKP bacteremia (15 studies; 1,019 CRKP and 1,148 CSKP patients; unadjusted odds ratio OR, 2.2; 95% confidence interval CI, 1.8-2.6; I2=0). Mortality was lower in patients with appropriate IAT than in those without appropriate IAT (7 studies; 658 patients; unadjusted OR, 0.5; 95% CI, 0.3-0.8; I2=36%). CRKP patients (11 studies; 1,326 patients; 8-year period) were consistently less likely to receive appropriate IAT (unadjusted OR, 0.5; 95% CI, 0.3-0.7; I2=43%). Our meta-regression analysis identified a significant association between the difference in appropriate IAT and mortality (OR per 10% difference in IAT, 1.3; 95% CI, 1.0-1.6). CONCLUSIONS Appropriateness of IAT is an important contributor to the observed difference in mortality between patients with CRKP bacteremia and patients with CSKP bacteremia. Infect Control Hosp Epidemiol 2017;38:1319-1328.
Abstract
We confirm the planetary nature of two gas giants discovered by the Transiting Exoplanet Survey Satellite to transit M dwarfs. TOI-3714 (
V
= 15.24,
J
= 11.74) is an M2 dwarf hosting a hot ...Jupiter (
M
p
= 0.70 ± 0.03
M
J
and
R
p
= 1.01 ± 0.03
R
J
) on an orbital period of 2.154849 ± 0.000001 days with a resolved white dwarf companion. TOI-3629 (
V
= 14.63,
J
= 11.42) is an M1 dwarf hosting a hot Jupiter (
M
p
= 0.26 ± 0.02
M
J
and
R
p
=0.74 ± 0.02
R
J
) on an orbital period of
3.936551
−
0.000006
+
0.000005
days. We characterize each transiting companion using a combination of ground-based and space-based photometry, speckle imaging, and high-precision velocimetry from the Habitable-zone Planet Finder and the NEID spectrographs. With the discovery of these two systems, there are now nine M dwarfs known to host transiting hot Jupiters. Among this population, TOI-3714 b (
T
eq
= 750 ± 20 K and TSM = 98 ± 7) and TOI-3629 b (
T
eq
= 690 ± 20 K and TSM = 80 ± 9) are warm gas giants amenable to additional characterization with transmission spectroscopy to probe atmospheric chemistry and, for TOI-3714, obliquity measurements to probe formation scenarios.
PDF
