Here we present an 83-year-old woman with truncal pain, hypoxemia, and nausea after a Hymenoptera sting. Due to progressive truncal pain, emergent computed tomography angiography was ordered and ...confirmed an acute Stanford type A aortic dissection extending from the aortic root and terminating in the left common iliac artery. She was emergently transferred to a quaternary care center and managed surgically. This case highlights anaphylaxis as a unique potential trigger of aortic dissection and the need for a high index of suspicion for early diagnosis.
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.
Benzodiazepines are positive allosteric modulators of the GABAA receptor (GABAAR), acting at the α–γ subunit interface to enhance GABAAR function. GABA or benzodiazepine binding induces distinct ...conformational changes in the GABAAR. The molecular rearrangements in the GABAAR following benzodiazepine binding remain to be fully elucidated. Using two molecular models of the GABAAR, we identified electrostatic interactions between specific amino acids at the α–γ subunit interface that were broken by, or formed after, benzodiazepine binding. Using two-electrode voltage clamp electrophysiology in Xenopus laevis oocytes, we investigated these interactions by substituting one or both amino acids of each potential pair. We found that Lys104 in the α1 subunit forms an electrostatic bond with Asp75 of the γ2 subunit after benzodiazepine binding and that this bond stabilizes the positively modified state of the receptor. Substitution of these two residues to cysteine and subsequent covalent linkage between them increased the receptor's sensitivity to low GABA concentrations and decreased its response to benzodiazepines, producing a GABAAR that resembles a benzodiazepine-bound WT GABAAR. Breaking this bond restored sensitivity to GABA to WT levels and increased the receptor's response to benzodiazepines. The α1 Lys104 and γ2 Asp75 interaction did not play a role in ethanol or neurosteroid modulation of GABAAR, suggesting that different modulators induce different conformational changes in the receptor. These findings may help explain the additive or synergistic effects of modulators acting at the GABAAR.
Previously called Secondary Traumatic Stress (STS), secondary exposure to trauma is now considered a valid DSM-5 Criterion A stressor for posttraumatic stress disorder (PTSD). Previous studies have ...found high rates of STS in clinicians who treat traumatically injured patients. However, little research has examined STS among Emergency Medicine (EM) physicians and advanced practice providers (APPs). The current study enrolled EM providers (N = 118) working in one of 10 hospitals to examine risk factors, protective factors, and the prevalence of STS in this understudied population. Most of the participants were physicians (72.9%), Caucasian (85.6%), and male (70.3%) with mean age of 39.7 (SD = 8.9). Overall, 12.7% of the sample screened positive for STS with clinical levels of intrusion, arousal, and avoidance symptom clusters, and 33.9% had at least one symptom cluster at clinical levels. Low resilience and a history of personal trauma were positively associated with positive STS screens and STS severity scores. Borderline significance suggested that female gender and spending ≥10% of one's time with trauma patients could be additional risk factors. Findings suggest that resilience-building interventions may be beneficial.
The glycine receptor is a member of the Cys-loop receptor superfamily of ligand-gated ion channels and is implicated as a possible therapeutic target for the treatment of diseases such as alcoholism ...and inflammatory pain. In humans, four glycine receptor subtypes (α1, α2, α3, and β) co-assemble to form pentameric channel proteins as either α homomers or αβ heteromers. To date, few agents have been identified that can selectively modulate the glycine receptor, especially those possessing subtype specificity. We used a cell-based method of phage display panning, coupled with two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes, to identify novel heptapeptide modulators of the α1β glycine receptor. This involved a panning procedure in which the phage library initially underwent subtractive panning against Human Embryonic Kidney (HEK) 293 cells expressing alternative glycine receptor subtypes before panning the remaining library over HEK 293 cells expressing the target, the α1β glycine receptor. Peptides were identified that act with selectivity on α1β and α3β, compared to α2β, glycine receptors. In addition, peptide activity at the glycine receptor decreased when zinc was chelated by tricine, similar to previous observations of a decrease in ethanol's enhancing actions at the receptor in the absence of zinc. Comparisons of the amino acid sequences of heptapeptides capable of potentiating glycine receptor function revealed several consensus sequences that may be predictive of a peptide's enhancing ability.
No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic ...acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI.
Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3-12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later.
Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only.
While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo.
Diagnostic test, level III.
Quantitative resuscitation consists of structured cardiovascular intervention targeting predefined hemodynamic end points. We sought to measure the treatment effect of quantitative resuscitation on ...mortality from sepsis.
We conducted a systematic review of the Cochrane Library, MEDLINE, EMBASE, CINAHL, conference proceedings, clinical practice guidelines, and other sources using a comprehensive strategy.
We identified randomized control trials comparing quantitative resuscitation with standard resuscitation in adult patients who were diagnosed with sepsis using standard criteria. The primary outcome variable was mortality.
Three authors independently extracted data and assessed study quality using standardized instruments; consensus was reached by conference. Preplanned subgroup analysis required studies to be categorized based on early (at the time of diagnosis) vs. late resuscitation implementation. We used the chi-square test and I to assess for statistical heterogeneity (p < 0.10, I > 25%). The primary analysis was based on the random effects model to produce pooled odds ratios with 95% confidence intervals.
The search yielded 29 potential publications; nine studies were included in the final analysis, providing a sample of 1001 patients. The combined results demonstrate a decrease in mortality (odds ratio 0.64, 95% confidence interval 0.43-0.96); however, there was statistically significant heterogeneity (p = 0.07, I = 45%). Among the early quantitative resuscitation studies (n = 6) there was minimal heterogeneity (p = 0.40, I = 2.4%) and a significant decrease in mortality (odds ratio 0.50, 95% confidence interval 0.37-0.69). The late quantitative resuscitation studies (n = 3) demonstrated no significant effect on mortality (odds ratio 1.16, 95% confidence interval 0.60-2.22).
This meta-analysis found that applying an early quantitative resuscitation strategy to patients with sepsis imparts a significant reduction in mortality.
In the United States (U.S.), Hispanics experience breast cancer disparities. Breast cancer is the leading cause of cancer-related death among Hispanic women, and Hispanic women receive mammography ...screening at lower rates than some other ethnic groups. This low rate of screening mammography is associated with increased risk for possible late-stage diagnosis and lower survival rates. Educational interventions could play a role in increasing screening mammography rates among Hispanic women. This systematic review synthesized the current literature on educational interventions to increase mammography screening among Hispanic women. The review included studies published between May 2003 and September 2017 with experimental and quasi-experimental interventions to increase mammography screening among Hispanics in the U.S. Five studies out of an initial 269 studies met inclusion criteria for the review. All studies employed an interpersonal intervention strategy with community health workers, or promotoras, to deliver the mammography screening intervention. For each study, odds ratios (OR) were calculated to estimate intervention effectiveness based on similar follow-up time periods. The study ORs resulted in a narrow range between 1.02 and 2.18, indicating a low to moderate intervention effect for these types of interpersonal cancer education interventions. The summary OR for the random effects model was 1.67 (CI 1.24–2.26). Hispanics exhibit lower levels of adherence to screening mammography than non-Hispanic whites. Interpersonal cancer education interventions such as the use of promotoras may help to mediate the impact of barriers to receiving a mammogram such as low health literacy, deficits in knowledge about the benefits of screening, and low awareness of the availability of screening services.
1. Increasing habitat availability (i.e. habitat suitable for occupancy) is often assumed to elevate the abundance or production of mobile consumers; however, this relationship is often nonlinear ...(threshold or unimodal). Identifying the mechanisms underlying these nonlinearities is essential for predicting the ecological impacts of habitat change, yet the functional forms and ultimate causation of consumerhabitat relationships are often poorly understood. 2. Nonlinear effects of habitat on animal abundance may manifest through physical constraints on foraging that restrict consumers from accessing their resources. Subsequent spatial incongruence between consumers and resources should lead to unimodal or saturating effects of habitat availability on consumer production if increasing the area of habitat suitable for consumer occupancy comes at the expense of habitats that generate resources. However, the shape of this relationship could be sensitive to cross-ecosystem prey subsidies, which may be unrelated to recipient habitat structure and result in more linear habitat effects on consumer production. 3. We investigated habitat-production relationships for juveniles of stream-rearing Pacific salmon and trout (Oncorhynchus spp.), which typically forage in low-velocity pool habitats, while their prey (drifting benthic invertebrates) are produced upstream in high-velocity riffles. However, juvenile salmonids also consume subsidies of terrestrial invertebrates that may be independent of pool-riffle structure. 4. We measured salmonid biomass production in 13 experimental enclosures each containing a downstream pool and upstream riffle, spanning a gradient of relative pool area (14%-80% pool). Increasing pool relative to riffle habitat area decreased prey abundance, leading to a nonlinear saturating effect on fish production. We then used bioenergetics model simulations to examine how the relationship between pool area and salmonid biomass is affected by varying levels of terrestrial subsidy. Simulations indicated that increasing terrestrial prey inputs linearized the effect of habitat availability on salmonid biomass, while decreasing terrestrial inputs exaggerated a "hump-shaped" effect. 5. Our results imply that nonlinear effects of habitat availability on consumer production can arise from trade-offs between habitat suitable for consumer occupancy and habitat that generates prey. However, cross-ecosystem prey subsidies can effectively decouple this trade-off and modify consumer-habitat relationships in recipient systems.
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