Retinopathy of prematurity (ROP) causes 100,000 new cases of childhood blindness each year. ROP is initiated by oxygen supplementation necessary to prevent neonatal death. We used organ systems ...pharmacology to define the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, ROP model) by hypoxia-inducible factor (HIF) stabilization via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarate analog dimethyloxalylglycine (DMOG). Although both molecules conferred a protective phenotype, gene expression analysis by RNA sequencing found that Roxadustat can prevent OIR by two pathways: direct retinal HIF stabilization and induction of aerobic glycolysis or indirect hepatic HIF-1 stabilization and increased serum angiokines. As predicted by pathway analysis, Roxadustat rescued the hepatic HIF-1 knockout mouse from retinal oxygen toxicity, whereas DMOG could not. The simplicity of systemic treatment that targets both the liver and the eye provides a rationale for protecting the severely premature infant from oxygen toxicity.
The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, ...were being evaluated in terms of the ability to affect hemostasis.
Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation.
The lethal dose of radiation to 50% of the population (LD50) of the ferrets was established at ∼ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days.
Data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.
Abstract
Purpose: To determine the mechanism of proton radiation- induced coagulopathy.
Material and methods: Ferrets were exposed to either solar particle event (SPE)-like proton radiation at a ...predetermined dose rate of 0.5 Gray (Gy) per hour (h) for a total dose of 0 or 1 Gy. Blood was collected pre- and post-irradiation for a complete blood cell count or a soluble fibrin concentration analysis, to determine whether coagulation activation had occurred. Tissue was stained with an anti-fibrinogen antibody to confirm the presence of fibrin in blood vessels.
Results: SPE-like proton radiation exposure resulted in coagulation cascade activation, as determined by increased soluble fibrin concentration in blood from 0.7-2.4 at 3 h, and 9.9 soluble fibrin units (p < 0.05) at 24 h post-irradiation and fibrin clots in blood vessels of livers, lungs and kidneys from irradiated ferrets. In combination with this increase in fibrin clots, ferrets had increased prothrombin time and partial thromboplastin time values post-irradiation, which are representative of the extrinsic/intrinsic coagulation pathways. Platelet counts remained at pre-irradiation values over the course of 7 days, indicating that the observed effects were not platelet-related, but instead likely to be due to radiation-induced effects on secondary hemostasis. White blood cell (WBC) counts were reduced in a statistically significant manner from 24 h through the course of the seven-day experiment.
Conclusions: SPE-like proton radiation results in significant decreases in all WBC counts as well as activates secondary hemostasis; together, these data suggest severe risks to astronaut health from exposure to SPE radiation.
The sex-based differences in the structure and rules of boys' and girls' lacrosse result in very different styles of play, which may have significant implications for the rates and patterns of ...injuries.
To compare the epidemiology of injuries sustained by boys' and girls' lacrosse players.
Descriptive epidemiology study.
Web-based online surveillance system.
The High School Reporting Information Online database was used to analyze injuries reported by certified athletic trainers from 2008-2009 through 2015-2016.
Practice and competition injury rates, body site, diagnosis, and mechanism.
Boys had a higher injury rate than girls (20.9 versus 15.7 per 10 000 athlete-exposures, respectively; rate ratio = 1.3, 95% confidence interval = 1.2, 1.4). The most commonly injured body sites for boys and girls, respectively, were the lower extremities (38.0%, 56.4%) and the head/neck (28.3%, 29.8%). More specifically, the most frequently diagnosed injuries for both boys and girls, respectively, in competitions were concussions (23.1%, 25.6%), ankle ligament sprains (7.8%, 15.3%), upper leg strains (4.8%, 6.7%), and knee ligament sprains (4.2%, 6.7%). The most cited mechanism of injury overall was contact with another player (22.0%); among boys, it was contact with a stick (14.8%) and among girls, the most frequent mechanisms were overuse (25.0%) and contact with a stick (14.7%).
Injury rates and mechanisms of injuries differed between high school boys' and girls' lacrosse players. Boys had a higher rate of injury, with the most common mechanism of injury being contact with another player compared with overuse in girls. However, similarities were seen between sexes for the most frequently injured body sites and injury diagnoses. Future authors should continue to compare differences in injury rates, equipment upgrades, and rule changes in boys' and girls' lacrosse.
To identify research and practice gaps to establish future research priorities to advance the detection of cognitive impairment and dementia in the emergency department (ED).
Literature review and ...consensus-based rankings by a transdisciplinary, stakeholder task force of experts, persons living with dementia, and care partners.
Scoping reviews focused on adult ED patients.
Two systematic scoping reviews of 7 medical research databases focusing on best tools and approaches for detecting cognitive impairment and dementia in the ED in terms of (1) most accurate and (2) most pragmatic to implement. The results were screened, reviewed, and abstracted for relevant information and presented at the stakeholder consensus conference for discussion and ranked prioritization.
We identified a total of 1464 publications and included 45 to review for accurate tools and approaches for detecting cognitive impairment and dementia. Twenty-seven different assessments and instruments have been studied in the ED setting to evaluate cognitive impairment and dementia, with many focusing on sensitivity and specificity of instruments to screen for cognitive impairment. For pragmatic tools, we identified a total of 2166 publications and included 66 in the review. Most extensively studied tools included the Ottawa 3DY and Six-Item Screener (SIS). The SIS was the shortest to administer (1 minute). Instruments with the highest negative predictive value were the SIS (vs MMSE) and the 4 A's Test (vs expert diagnosis). The GEAR 2.0 Advancing Dementia Care Consensus conference ranked research priorities that included the need for more approaches to recognize more effectively and efficiently persons who may be at risk for cognitive impairment and dementia, while balancing the importance of equitable screening, purpose, and consequences of differentiating various forms of cognitive impairment.
The scoping review and consensus process identified gaps in clinical care that should be prioritized for research efforts to detect cognitive impairment and dementia in the ED setting. These gaps will be addressed as future GEAR 2.0 research funding priorities.
The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we ...demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell-mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.
Changes in intracranial pressure (ICP) during space flight have stimulated an area of research in space medicine. It is widely speculated that elevations in ICP contribute to structural and ...functional ocular changes, including deterioration in vision, which is also observed during space flight. The aim of this study was to investigate changes in opening pressure (OP) occurring as a result of ionizing radiation exposure (at doses and dose-rates relevant to solar particle event radiation). We used a large animal model, the Yucatan mini-pig, and were able to obtain measurements over a 90 day period. This is the first investigation to show long term recordings of ICP in a large animal model without an invasive craniotomy procedure. Further, this is the first investigation reporting increased ICP after radiation exposure.
•Intracranial pressure measurements were recorded in a large animal model without an invasive craniotomy procedure.•Intracranial pressure was measured in the minipig model over an extended period of 90 days.•Solar particle event-like radiation induces increased intracranial pressure.
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