Blast-related traumatic brain injury (TBI) is a common cause of injury in the military operations in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. The aim ...of the present study was to examine whether blast exposure affects the cerebral vasculature in a rodent model. We analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Rats were sacrificed 24 hours or between 6 and 10 months after exposure. Blast-induced cerebral vascular pathology was examined by a combination of light microscopy, immunohistochemistry, and electron microscopy.
We describe a selective vascular pathology that is present acutely at 24 hours after injury. The vascular pathology is found at the margins of focal shear-related injuries that, as we previously showed, typically follow the patterns of penetrating cortical vessels. However, changes in the microvasculature extend beyond the margins of such lesions. Electron microscopy revealed that microvascular pathology is found in regions of the brain with an otherwise normal neuropil. This initial injury leads to chronic changes in the microvasculature that are still evident many months after the initial blast exposure.
These studies suggest that vascular pathology may be a central mechanism in the induction of chronic blast-related injury.
We describe the prediction, design, execution and calibration of stellar and solar occultation observations of Saturn's rings by the Visual and Infrared Mapping Spectrometer (VIMS) instrument on the ...Cassini spacecraft. Particular attention is paid to the technique developed for onboard acquisition of the stellar target and to the geometric and photometric calibration of the data. Examples of both stellar and solar occultation data are presented, highlighting several aspects of the data as well as the different occultation geometries encountered during Cassini's 13-year orbital tour. Complete catalogs of ring stellar and solar occultations observed by Cassini-VIMS are presented, as a guide to the standard data sets which have been delivered to the Planetary Data System's Ring Moon Systems Node (Hedman and Nicholson, 2019b).
•The Cassini VIMS instrument observed 190 stellar occultations by Saturn's rings.•We describe their prediction, design, execution and calibration.•The radial resolution of the data ranges from 50 m to 500 m.•The minimum detectable optical depth is < 3 × 10−4 at 10 km resolution.•The maximum detectable optical depth is ∼5.5 at 10 km resolution.
Blast exposure is common in military personnel during training and combat operations, yet biological mechanisms related to cell survival and function that coordinate recovery remain poorly ...understood. This study explored how moderate blast exposure influences gene expression; specifically, gene-network changes following moderate blast exposure. On day 1 (baseline) of a 10-day military training program, blood samples were drawn, and health and demographic information collected. Helmets equipped with bilateral sensors worn throughout training measured overpressure in pounds per square inch (psi). On day 7, some participants experienced moderate blast exposure (peak pressure ≥5 psi). On day 10, 3 days post-exposure, blood was collected and compared to baseline with RNA-sequencing to establish gene expression changes. Based on dysregulation data from RNA-sequencing, followed by top gene networks identified with Ingenuity Pathway Analysis, a subset of genes was validated (NanoString). Five gene networks were dysregulated; specifically, two highly significant networks: (1) Cell Death and Survival (score: 42), including 70 genes, with 50 downregulated and (2) Cell Structure, Function, and Metabolism (score: 41), including 69 genes, with 41 downregulated. Genes related to ubiquitination, including neuronal development and repair: UPF1, RNA Helicase and ATPase (
) was upregulated while UPF3 Regulator of Nonsense Transcripts Homolog B (
) was downregulated. Genes related to inflammation were upregulated, including AKT serine/threonine kinase 1 (
), a gene coordinating cellular recovery following TBIs. Moderate blast exposure induced significant gene expression changes including gene networks involved in (1) cell death and survival and (2) cellular development and function. The present findings may have implications for understanding blast exposure pathology and subsequent recovery efforts.
Parkinson's is primarily a non-familial, age-related disorder caused by α-synuclein accumulation and the progressive loss of dopamine neurons in the substantia nigra pars compacta (SNc). G ...protein-coupled receptor (GPCR)-cAMP signaling has been linked to a reduction in human Parkinson's incidence and α-synuclein expression. Neuronal cAMP levels are controlled by GPCRs coupled to Gs or Gi/o, which increase or decrease cAMP, respectively. Regulator of G protein signaling 6 (RGS6) powerfully inhibits Gi/o signaling. Therefore, we hypothesized that RGS6 suppresses D2 autoreceptor- Gi/o signaling in SNc dopamine neurons promoting neuronal survival and reducing α-synuclein expression. Here we provide novel evidence that RGS6 critically suppresses late-age-onset SNc dopamine neuron loss and α-synuclein accumulation. RGS6 is restrictively expressed in human SNc dopamine neurons and, despite their loss in Parkinson's, all surviving neurons express RGS6. RGS6-/- mice exhibit hyperactive D2 autoreceptors with reduced cAMP signaling in SNc dopamine neurons. Importantly, RGS6-/- mice recapitulate key sporadic Parkinson's hallmarks, including: SNc dopamine neuron loss, reduced nigrostriatal dopamine, motor deficits, and α-synuclein accumulation. To our knowledge, Rgs6 is the only gene whose loss phenocopies these features of human Parkinson's. Therefore, RGS6 is a key regulator of D2R-Gi/o signaling in SNc dopamine neurons, protecting against Parkinson's neurodegeneration and α-synuclein accumulation.
Background To determine the effects in adult offspring of maternal exposure to stress and alcohol during pregnancy, we imaged striatal and midbrain dopamine transporter (DAT) binding by positron ...emission tomography in rhesus monkeys ( Macaca mulatta ). We also evaluated the relationship between DAT binding and behavioral responses previously found to relate to dopamine D2 receptor density (responsivity to tactile stimuli, performance on a learning task, and behavior during a learning task). Methods Subjects were adult offspring derived from a 2 × 2 experiment in which pregnant monkeys were randomly assigned to control, daily mild stress exposure (acoustic startle), voluntary consumption of moderate-level alcohol, or both daily stress and alcohol. Adult offspring ( n = 38) were imaged by positron emission tomography with the DAT ligand 18 F2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (18 FFECNT). Results Results showed that prenatal stress yielded an overall increase of 15% in 18 FFECNT binding in the striatum ( p = .016), 17% greater binding in the putamen ( p = .012), and 13% greater binding in the head of the caudate ( p = .028) relative to animals not exposed to prenatal stress. Striatal 18 FFECNT binding correlated negatively with habituation to repeated tactile stimulation and positively with tactile responsivity. There were no significant effects of prenatal alcohol exposure on 18 FFECNT binding. Conclusions Maternal exposure to mild daily stress during pregnancy yielded increases in striatal DAT availability that were apparent in adult offspring and were associated with behavioral characteristics reflecting tactile hyperresponsivity, a condition associated with problem behaviors in children.
Highlights • Rhesus monkeys chronically self-administered (drank) alcohol over 12 months. • PET 5-HT1A binding was measured before and after 9–12 months alcohol drinking. • Global increases in 5-HT1A ...binding were observed during chronic alcohol drinking. • Raphe Nuclei 5-HT1A binding positively correlated with average alcohol drinking.
To evaluate the impact of baseline retinal capillary nonperfusion (RNP) and macular retinal capillary nonperfusion (MNP) status on outcomes at week 24 (W24).
Post hoc analyses of 2 phase 3, ...randomized, double-masked, multicenter, sham-controlled studies.
Three hundred sixty-six patients with macular edema secondary to central retinal vein occlusion randomized in COPERNICUS and GALILEO.
We randomized patients 3:2 to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until W24. RNP and MNP were assessed by a masked independent reading center.
Proportion of patients with 10 disc areas (DA) or more of RNP and any degree of MNP at W24, relative risks of 10 DA or more of RNP or any degree of MNP at W24 developing, change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by baseline RNP and MNP status, and relationship between baseline RNP and MNP status.
At baseline, 24.6% of patients showed 10 DA or more of RNP and 72.6% showed MNP, regardless of baseline RNP status. At W24, the pooled proportions of patients in the intravitreal aflibercept and sham groups with 10 DA or more of RNP were 11.6% and 29.0%, respectively (P = 0.0001); the respective proportions with any degree of MNP were 61.2% and 79.5% (P = 0.0008). Relative risks and 95% confidence intervals for intravitreal aflibercept versus sham were 0.4 (0.25–0.62) for 10 DA or more of RNP and 0.8 (0.68–0.90) for MNP, indicating a lower risk for these outcomes with intravitreal aflibercept than with sham. Mean BCVA change was greater in intravitreal aflibercept- versus sham-treated eyes, with less than 10 DA and 10 DA or more of RNP at baseline (+17.5 vs. +0.8 letters and +18.3 vs. −4.1 letters, respectively) and with and without baseline MNP (+15.7 vs. +0.3 letters and +17.1 vs. +0.4 letters, respectively). Agreement between baseline RNP and MNP status was low (κ = 0.12). The proportions of patients with 1 or more ocular serious adverse event in the intravitreal aflibercept- and sham-treated groups, respectively, were 3.2% and 11.3%.
At W24, visual and anatomic improvements, including perfusion status, were greater in eyes treated with intravitreal aflibercept than in eyes treated with sham, regardless of baseline RNP or MNP status.
In this paper we explore the scientific synergies between
Athena
and some of the key multi-messenger facilities that should be operative concurrently with
Athena
. These facilities include LIGO A+, ...Advanced Virgo+ and future detectors for ground-based observation of gravitational waves (GW), LISA for space-based observations of GW, IceCube and KM3NeT for neutrino observations, and CTA for very high energy observations. These science themes encompass pressing issues in astrophysics, cosmology and fundamental physics such as: the central engine and jet physics in compact binary mergers, accretion processes and jet physics in Super-Massive Binary Black Holes (SMBBHs) and in compact stellar binaries, the equation of state of neutron stars, cosmic accelerators and the origin of Cosmic Rays (CRs), the origin of intermediate and high-Z elements in the Universe, the Cosmic distance scale and tests of General Relativity and the Standard Model. Observational strategies for implementing the identified science topics are also discussed. A significant part of the sources targeted by multi-messenger facilities is of transient nature. We have thus also discussed the synergy of
Athena
with wide-field high-energy facilities, taking THESEUS as a case study for transient discovery. This discussion covers all the
Athena
science goals that rely on follow-up observations of high-energy transients identified by external observatories, and includes also topics that are not based on multi-messenger observations, such as the search for missing baryons or the observation of early star populations and metal enrichment at the cosmic dawn with Gamma-Ray Bursts (GRBs).
Adherence to childhood immunization schedules is a function of various factors. Given the increased use of technology as a strategy to increase immunization coverage, it is important to investigate ...how parents perceive different forms of communication, including traditional means and text-message reminders.
To examine current forms of communication about immunization information, parents' satisfaction levels with these communication modes, perceived barriers and benefits to using text messaging, and the ideal content of text messages for immunization reminders.
Structured interviews were developed and approved by two Institutional Review Boards. A convenience sample of 50 parents was recruited from two local pediatric clinics. The study included a demographics questionnaire, the shortened form of the Test of Functional Health Literacy for Adults (S-TOFHLA), questions regarding benefits and barriers of text communication from immunization providers, and preferred content for immunization reminders. Content analyses were performed on responses to barriers, benefits, and preferred content (all Cohen's kappas > 0.70).
Respondents were mostly female (45/50, 90%), white non-Hispanic (31/50, 62%), between 20-41 years (mean = 29, SD 5), with one or two children (range 1-9). Nearly all (48/50, 96%) had an S-TOFHLA score in the "adequate" range. All parents (50/50, 100%) engaged in face-to-face contact with their child's physician at appointments, 74% (37/50) had contact via telephone, and none of the parents (0/50, 0%) used email or text messages. Most parents were satisfied with the face-to-face (48/50, 96%) and telephone (28/50, 75%) communication. Forty-nine of the 50 participants (98%) were interested in receiving immunization reminders by text message, and all parents (50/50, 100%) were willing to receive general appointment reminders by text message. Parents made 200 comments regarding text-message reminders. Benefits accounted for 63.5% of comments (127/200). The remaining 37.5% (73/200) regarded barriers; however, no barriers could be identified by 26% of participants (13/50). Parents made 172 comments regarding preferred content of text-message immunization reminders. The most frequently discussed topics were date due (50/172, 29%), general reminder (26/172, 26%), and child's name (21/172, 12%).
Most parents were satisfied with traditional communication; however, few had experienced any alternative forms of communication regarding immunizations. Benefits of receiving text messages for immunization reminders far outweighed the barriers identified by parents. Few barriers identified were text specific. Those that were, centered on cost if parents did not have unlimited texting plans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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