The relative clinical efficacy of 4-factor prothrombin complex concentrate (4F-PCC) in oral anticoagulant-associated intracranial hemorrhage is unknown, especially for factor Xa-inhibiting ...anticoagulants. We report short-term outcomes of patients with oral anticoagulant-associated intracranial hemorrhage on vitamin K antagonists and factor Xa inhibitors who were treated with 4F-PCC. This multicenter, observational study involved patients presenting to the emergency department in nine hospitals in an integrated health care delivery system in Texas between July 2013 and December 2015. Forty-two patients diagnosed with oral anticoagulant-associated intracranial hemorrhage-24 taking a vitamin K antagonist and 14 taking a factor Xa inhibitor-were treated with 4F-PCC as part of usual care. Study patients had similar baseline demographics, with the exception of suspected etiology of hemorrhage. Outcomes of the vitamin K antagonist group were similar to those of the factor Xa inhibitor group, with no significant differences in overall in-hospital mortality (32.1% vs 14.2%, respectively), length of stay, or rates of hemorrhagic expansion, thromboembolism, or discharge to home. In conclusion, this small sample of patients with oral factor Xa inhibitor and vitamin K antagonist-associated intracranial hemorrhage treated with 4F-PCC had similar mortality and neurological outcomes, with no venous thromboembolic events.
Taurine is an endogenous ligand acting on glycine receptors in many brain regions, including the hippocampus, prefrontal cortex, and nucleus accumbens (nAcc). These areas also contain low ...concentrations of zinc, which is known to potentiate glycine receptor responses. Despite an increasing awareness of the role of the glycine receptor in the rewarding properties of drugs of abuse, the possible interactions of these compounds with zinc has not been thoroughly addressed. Two-electrode voltage-clamp electrophysiological experiments were performed on α1, α2 α1β and α2β glycine receptors expressed in Xenopus laevis oocytes. The effects of zinc alone, and zinc in combination with other positive modulators on the glycine receptor, were investigated when activated by the full agonist glycine versus the partial agonist taurine. Low concentrations of zinc enhanced responses of maximally-effective concentrations of taurine but not glycine. Likewise, chelation of zinc from buffers decreased responses of taurine- but not glycine-mediated currents. Potentiating concentrations of zinc decreased ethanol, isoflurane, and toluene enhancement of maximal taurine currents with no effects on maximal glycine currents. Our findings suggest that the concurrence of high concentrations of taurine and low concentrations of zinc attenuate the effects of additional modulators on the glycine receptor, and that these conditions are more representative of in vivo functioning than effects seen when these modulators are applied in isolation.
•Glycine receptor function is modulated by many allosteric modulators.•Tricine decreases the effects of maximally-effective concentrations of taurine.•Allosteric modulators potentiate maximally-effective concentrations of taurine.•Allosteric modulators do not enhance maximally-effective concentrations of glycine.•Zinc decreases allosteric modulator potentiation of taurine-activated receptors.
Abstract
Background. Intraosseous (IO) needle insertion is often utilized in the adult population for critical resuscitation purposes. Standard insertion sites include the proximal humerus and ...proximal tibia, for which limited comparison data are available. Objective. This study compared the frequencies of IO first-attempt success between humeral and tibial sites in out-of-hospital cardiac arrest. Methods. This observational study was conducted in an urban setting between August 28, 2009, and October 31, 2009, and included all medical cardiac arrest patients for whom resuscitative efforts were performed. Cardiac arrest protocols stipulate that paramedics insert an IO line for initial vascular access. During the first month of the study, the proximal humerus was the preferred primary insertion site, whereas the tibia was preferred throughout the second month. The primary outcome was first-attempt success, defined as secure IO needle position in the marrow cavity and normal fluid flow. Any needle dislodgment during resuscitation was also recorded. The association between first-attempt IO success and initial IO insertion location was analyzed using a test of independent proportions and 95% confidence intervals (CIs) for the difference in proportions. Results. There were 88 cardiac arrest patients receiving IO placement, with 58 (65.9%) patients receiving their initial IO attempt in the tibia. The rate of first-time IO success at the tibia was significantly higher than that observed at the humerus (89.7% vs. 60.0%; p < 0.01). There were 18 initial successes at the humerus; for six (33.3%) of these, the needle became dislodged during resuscitation, compared with 52 initial successes at the tibia, with three (5.8%) dislodgments. The rate of total success for initial IO placements was significantly lower for the humerus (40.0%) compared with that for the tibia (84.5%; p < 0.01) during resuscitation efforts. Conclusions. In this subset of patients, tibial IO needle placement appeared to be a more effective insertion site than the proximal humerus. Success rates were higher with a lower incidence of needle dislodgments. Further randomized studies are required in order to validate these results.
The short-term results of a randomized trial testing a brief feedback and motivational intervention for substance use among homeless adolescents are presented. Homeless adolescents ages 14-19 (
N
= ...285) recruited from drop-in centers at agencies and from street intercept were randomly assigned to either a brief motivational enhancement (ME) group or 1 of 2 control groups. The 1-session motivational intervention presented personal feedback about patterns of risks related to alcohol or substance use in a style consistent with motivational interviewing. Follow-up interviews were conducted at 1 and 3 months postintervention. Youths who received the motivational intervention reported reduced illicit drug use other than marijuana at 1-month follow-up compared with youths in the control groups. Treatment effects were not found with respect to alcohol or marijuana. Post hoc analyses within the ME group suggested that those who were rated as more engaged and more likely to benefit showed greater drug use reduction than did those rated as less engaged. Limitations of the study are discussed as are implications for development of future substance use interventions for this high-risk group.
The emergence of conductive 2D and less commonly 3D coordination polymers (CPs) and metal–organic frameworks (MOFs) promises novel applications in many fields. However, the synthetic parameters for ...these electronically complex materials are not thoroughly understood. Here we report a new 3D semiconducting CP Fe5(C6O6)3, which is a fusion of 2D Fe‐semiquinoid materials and 3D cubic Fex(C6O6)y materials, by using a different initial redox‐state of the C6O6 linker. The material displays high electrical conductivity (0.02 S cm−1), broad electronic transitions, promising thermoelectric behavior (S2σ=7.0×10−9 W m−1 K−2), and strong antiferromagnetic interactions at room temperature. This material illustrates how controlling the oxidation states of redox‐active components in conducting CPs/MOFs can be a “pre‐synthetic” strategy to carefully tune material topologies and properties in contrast to more commonly encountered post‐synthetic modifications.
A novel 3D semiconducting coordination polymer Fe5(C6O6)3 is reported with high conductivity, broad electronic transitions and interesting thermoelectric/magnetic properties. The unique structure and properties of this material illustrate that controlling the oxidation states of redox‐active components in conducting metal‐organic materials can be a “pre‐synthetic” strategy to carefully tune material topologies, properties, and functionalities.
Introduction. The relative age effect (RAE) refers to performance advantage of youth born in the first quarter of the birth year when auditioning for select, age-restricted sports. This advantage ...conferred to the older athlete is a result of being more physically and emotionally mature, therefore, assumed to be a more advanced player. We hypothesize an RAE exists in Olympic athletes, and this extends across selected categories of athletes (by gender), such as team versus individual sports, winter versus summer athletes, and sports using a ball versus those not using a ball. Methods. We extended the exploration of an RAE beyond specific sports by examining the birth quarter of more than 44 000 Olympic athlete’s birthdates, born between 1964-1996. The data were summarized by birth quarter (January 1 to March 31, etc) and presented as percentages and 95% confidence intervals. Results. The fractions of births in the first versus the fourth quarter were significantly different ( P < .001) from each other for the summer and winter Olympians, ball and nonball sports, and team as well as individual sports. Conclusions. The general presence of an RAE in Olympic athletes exists regardless of global classification.
The aim of the study was to determine the optimal set point for the critical event benchmarks described in stroke guidelines and validate the ability of these goals to predict successful ...administration of intravenous thrombolysis within 60 min of hospital arrival.
This was a retrospective cohort analysis of patients with acute ischemic stroke who received intravenous thrombolysis following presentation to the emergency department. The national benchmarks for time intervals associated with the completion of critical events required to determine candidacy for thrombolysis were evaluated for the ability to predict successful administration of thrombolysis within 60 min of hospital arrival. Optimal time interval cut points were then estimated using regression and receiver-operator characteristic curve analysis and compared to guidelines.
Of the 523 patients included in the analysis, 229 (43.8%) received intravenous thrombolysis within 60 min of hospital arrival. Of the patients who met the critical event interval goals described in guidelines, only 51.6% received thrombolysis within 60 min. The optimized cut points suggested by the regression analysis aligned with the guideline benchmarks with the only substantial difference being a shortened goal of arrival to neuroimaging start time of 19 min. This difference did not impact the overall predictive value.
The critical event benchmarks proposed in this study by logistic regression closely correlate with the critical event benchmarks described in the AHA/ASA acute stroke guidelines.
Signal transducer and activator of transcription 3 (Stat3) is involved in aberrant growth and survival signals in malignant tumor cells and is a validated target for anticancer drug design. We are ...targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. The amino acids of our lead phosphopeptide, Ac-pTyr-Leu-Pro-Gln-Thr-Val-NH2, were replaced with conformationally constrained mimics. Structure−affinity studies led to the peptidomimetic, pCinn-Haic-Gln-NHBn (21), which had an IC50 of 162 nM (fluorescence polarization), compared to 290 nM for the lead phosphopeptide (pCinn = 4-phosphoryloxycinnamate, Haic = (2S,5S)-5-amino-1,2,4,5,6,7-hexahydro-4-oxo-azepino3,2,1-hiindole-2-carboxylic acid). pCinn-Haic-Gln-OH was docked to the SH2 domain (AUTODOCK), and the two highest populated clusters were subjected to molecular dynamics simulations. Both converged to a common peptide conformation. The complex exhibits unique hydrogen bonding between Haic and Gln and Stat3 as well as hydrophobic interactions between the protein and pCinn and Haic.
Abstract Introduction Therapeutic hypothermia has been shown to improve both mortality and neurologic outcomes following pulseless ventricular tachycardia and fibrillation. Animal data suggest ...intra-arrest induction of therapeutic hypothermia (IATH) improves frequency of return of spontaneous circulation (ROSC). Our objective was to evaluate the association between IATH and ROSC. Methods This was a retrospective analysis of individuals experiencing non-traumatic cardiac arrest in a large metropolitan area during a 12-month period. Six months into the study a prehospital IATH protocol was instituted whereby patients received 2000 ml of 4 °C normal saline directly after obtaining IV/IO access. The main outcome variables were prehospital ROSC, survival to admission, and to discharge. A secondary analysis was conducted to assess the relationship between the quantity of cold saline infused and the likelihood of prehospital ROSC. Results 551 patients met inclusion criteria with all the elements available for data analysis. Rates of prehospital ROSC were 36.5% versus 26.9% (OR 1.83; 95% CI 1.19–2.81) in patients who received IATH versus normothermic resuscitation respectively. While the frequency of survival to hospital admission and discharge were increased among those receiving IATH, the differences did not reach statistical significance. The secondary analysis found a linear association between the amount of cold saline infused and the likelihood of prehospital ROSC. Conclusion The infusion of 4 °C normal saline during the intra-arrest period may improve rate of ROSC even at low fluid volumes. Further study is required to determine if intra-arrest cooling has a beneficial effect on rates of ROSC, mortality, and neurologic function.
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