Analysis of fibrinolytic shutdown in trauma patients with traumatic brain injury.

BACKGROUND: Coagulation profiles following major trauma vary depending on injury pattern and degree of shock. The physiologic mechanisms involved in coagulation function at any given time are varied and remain poorly understood. Thromboelastography (TEG) has been used evaluate coagulation profiles in the trauma population with some reports demonstrating a spectrum of fibrinolysis to fibrinolytic shutdown on initial presentation. The objective of this study was to evaluate the fibrinolytic profile of patients with TBI using thromboelastography (TEG). We hypothesized that patients with TBI would demonstrate low fibrinolytic activity. METHODS: All trauma activations at an ACS-verified level 1 trauma center received a TEG analysis upon arrival from December 2019 to June 2021. A retrospective review of the results and outcomes was conducted, and TBI patients were compared to patients without TBI. Linear regression was used to evaluate the effect of patient and injury factors on fibrinolysis. Hyperfibrinolysis was defined as LY30 â€‹> â€‹7.7%, physiologic fibrinolysis as LY30 0.6-7.7%, and fibrinolytic shutdown as LY30 â€‹< â€‹0.6%. RESULTS: A total of 1369 patients received an admission TEG analysis. Patients with TBI had a significantly higher median ISS (16 vs. 8, p â€‹< â€‹0.001), lower median admission Glasgow Coma Scale (14 vs. 15, p â€‹< â€‹0.001), longer intensive care unit length of stay (3 vs. 2 days, p â€‹< â€‹0.0001), increased ventilator days (216 vs. 183, p â€‹< â€‹0.001), higher mortality (14.6% vs. 5.1%, p â€‹< â€‹0.001), but lower shock index (0.6 vs. 0.7, p â€‹< â€‹0.0001) compared to those without TBI. Median LY30 was found to be decreased in the TBI group (0.1 vs. 0.2, p â€‹= â€‹0.0006). Patients with TBI were found to have a higher rate of fibrinolytic shutdown compared those without TBI (68.7% vs. 63.5%, p â€‹= â€‹0.054). ISS, sex, and shock index were found to be predictive of LY30 on linear regression, but TBI was not (Β: 0.09, SE: 0.277, p â€‹= â€‹0.745). The rate of DVT/PE did not appear to be elevated in patients with TBI (0.8%) and without TBI (1.2%). CONCLUSIONS: Trauma patients with and without TBI were found to have high rates of fibrinolytic shutdown. Although there was a high incidence of fibrinolytic shutdown, it did not appear to have an impact on the rate of thrombotic complications. The clinical significance of these results is unclear and differs significantly from recent reports which demonstrated that TBI is associated with a 25% rate of fibrinolytic shutdown. Further investigation is needed to better define the fibrinolytic pathway in patients with trauma and TBI to develop optimal treatment algorithms.

High-throughput printing of combinatorial materials from aerosols.

The development of new materials and their compositional and microstructural optimization are essential in regard to next-generation technologies such as clean energy and environmental sustainability. However, materials discovery and optimization have been a frustratingly slow process. The Edisonian trial-and-error process is time consuming and resource inefficient, particularly when contrasted with vast materials design spaces1. Whereas traditional combinatorial deposition methods can generate material libraries2,3, these suffer from limited material options and inability to leverage major breakthroughs in nanomaterial synthesis. Here we report a high-throughput combinatorial printing method capable of fabricating materials with compositional gradients at microscale spatial resolution. In situ mixing and printing in the aerosol phase allows instantaneous tuning of the mixing ratio of a broad range of materials on the fly, which is an important feature unobtainable in conventional multimaterials printing using feedstocks in liquid-liquid or solid-solid phases4-6. We demonstrate a variety of high-throughput printing strategies and applications in combinatorial doping, functional grading and chemical reaction, enabling materials exploration of doped chalcogenides and compositionally graded materials with gradient properties. The ability to combine the top-down design freedom of additive manufacturing with bottom-up control over local material compositions promises the development of compositionally complex materials inaccessible via conventional manufacturing approaches.

A plasmid system with tunable copy number.

Plasmids are one of the most commonly used platforms for genetic engineering and recombinant gene expression in bacteria. The range of available copy numbers for cloning vectors is largely restricted to the handful of Origins of Replication (ORIs) that have been isolated from plasmids found in nature. Here, we introduce two systems that allow for the continuous, finely-tuned control of plasmid copy number between 1 and 800 copies per cell: a plasmid with an anhydrotetracycline-controlled copy number, and a parallelized assay that is used to generate a continuous spectrum of 1194 ColE1-based copy number variants. Using these systems, we investigate the effects of plasmid copy number on cellular growth rates, gene expression, biosynthesis, and genetic circuit performance. We perform single-cell timelapse measurements to characterize plasmid loss, runaway plasmid replication, and quantify the impact of plasmid copy number on the variability of gene expression. Using our assay, we find that each plasmid imposes a 0.063% linear metabolic burden on their hosts, hinting at a simple relationship between metabolic burdens and plasmid DNA synthesis. Our systems enable the precise control of gene expression, and our results highlight the importance of tuning plasmid copy number as a powerful tool for the optimization of synthetic biological systems.

A relationship between temperature and aggression in NFL football penalties.

BACKGROUND: Increased ambient temperature has been implicated in increased physical aggression, which has important practical consequences. The present study investigates this established relationship between aggressive behavior and ambient temperature in the highly aggressive context of professional football in the National Football League (NFL). METHODS: Using a publicly available dataset, authors conducted multiple hierarchical regression analyses on game-level data (2326 games). RESULTS: The analysis revealed that temperature positively predicted aggressive penalties in football, and that this relationship was significant for teams playing at home but not for visiting teams. CONCLUSION: These results indicate that even in the aggressive context of football, warmer weather contributes to increased violence. Further, the presence of the heat-aggression relationship for the home team suggests that the characteristics of interacting groups may influence whether heat would have an adverse effect on the outcome of those interactions.

Structure and localization of the IGFBP-1 gene and its expression during liver regeneration.

Insulin-like growth factor-binding protein-1s are important modulators of the insulin-like growth factors that may have both positive and negative effects on the ability of insulin-like growth factors to stimulate cell growth. The IGFBP-1 gene is one of the most highly induced immediate-early genes after partial hepatectomy. The IGFBP-1 gene is also expressed at a high level during fetal liver development and in response to nutritional changes and diabetes. Therefore it may have important roles in liver growth and metabolism. To begin to examine the regulation of this gene, we cloned and sequenced the entire mouse IGFBP-1 gene. Its structure is highly similar to that of the human gene, and, in addition to the exonic regions, the two genes are highly conserved in specific regions in the promoter and first intron. Analysis of this conservation allows us to predict important regulatory sites that define the tissue specific and insulin-mediated regulation of the gene and identify potential sites that might be important for the transcriptional induction during liver regeneration. The mouse gene is located on mouse chromosome 11; it is found at the boundary between regions in the mouse genome homologous to human chromosomes 22 and 7. We found IGFBP-1 mRNA in both parenchymal and nonparenchymal RNA after partial hepatectomy. Using in situ hybridization of IGFBP-1 mRNA in regenerating rat liver tissue, we demonstrated IGFBP-1 transcripts in several cell types. We found that IGFBP-1 gene induction after partial hepatectomy is paralleled by protein expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Protective effects of swainsonine on murine survival and bone marrow proliferation during cytotoxic chemotherapy.

We have investigated the ability of swainsonine, an indolizidine alkaloid with pleiotropic in vivo effects, to confer protection against the cytotoxic effects of both cell cycle-specific and cell cycle-nonspecific cytotoxic anticancer agents. The intraperitoneal administration of swainsonine decreased the lethality of methotrexate (MTX), fluorouracil (5-FU), cyclophosphamide (CPM), and doxorubicin (DOX) in non-tumor-bearing C57BL/6 mice. The increased survival rate was found to correlate with stimulation of bone marrow cell proliferation, as measured by increases in 1) bone marrow cellularity, 2) in vivo and in vitro colony-forming activity, and 3) engraftment efficiency. These responses were critically dependent on the dose, sequence, and timing of swainsonine administration. If these results are confirmed in humans, swainsonine may offer promise in future intensive chemotherapy programs, allowing increased dosage and/or frequency of administration of cytotoxic agents without increasing toxic effects in bone marrow.

Surgical repair of coarctation of the aorta in infants less than six months of age: including the question of pulmonary artery banding.

High mortality rates (20% to 60%) have been reported in the repair of coarctation of the aorta in infancy. During a 4 year period, 34 infants less than 6 months of age had coarctation repair (two prior to 1976). Eleven were less than 2 weeks of age, nine were 2 weeks to 1 month, eight were 1 to 2 months, and six were 2 to 6 months. Associated lesions were patent ductus arteriosus (PDA) (82%), ventricular septal defect (VSD) (53%), and other intracardiac lesions (35%). Twenty-three patients (67%) had emergency operations; the other procedures were semielective. The indications for operation included congestive cardiac failure (91%), acidosis (32%), hypertension (29%), cardiogenic shock (26%), and cardiac arrest (18%). There was one operative death (2.9%) in a patient with severe pulmonary valve insufficiency and multiple VSDs. There was one late death a 4 months (Taussig-Bing complex). Primary repair was used in 15, patch-graft angioplasty in 19 (left subclavian artery in nine, left common carotid in one, and Dacron or pericardial patch in nine). Two (6%) required reoperation for recurrent coarctation (follow-up 3 to 36 months with a mean of 25.8). Of 15 patients with a large VSD, six had pulmonary artery banding with two deaths (one operative and one late), two had debanding plus VSD repair, and two are awaiting operation. The remaining nine patients did not have banding (no operative or late deaths), four patients required late VSD closure, two VSDs closed spontaneously, two VSDs became smaller, and one patient is awaiting VSD closure. The infrequent need for pulmonary artery banding may be partly due to "physiological banding" seen at Denver's high altitude. The VSD spontaneously closed or became smaller in 44% of nonbanded patients. The low operative mortality can be ascribed to (1) aggressive medical therapy, (2) emergency catheterization and repair, (3) avoidance of hypothermia, and (4) adequate relief of the coarctation.

Atypical radiographic findings in neonates with absent pulmonary valve and tetralogy of Fallot.

At birth, three infants had typical to-and-fro murmurs and laboratory features suggesting tetralogy of Fallot with absent pulmonary valve. Initial posteroanterior chest x-ray films were atypical for the condition because of the apparent absence of dilation of the proximal pulmonary arterial tree. Lateral chest x-ray films invariably demonstrated a large hilar mass. Radiographic findings on the posteroanterior chest x-ray film considered pathognomonic for the complex lesion may not evolve until later during the first year of life.

The growth of the chick retina after hatching.

In autoradiographs of the retina from two-week old chicks injected with tritiated thymidine during the first week after hatching, the labelled cells were found mainly in the extreme periphery of the retina and the ciliary epithelium of the pars plana. The pattern of labelling in the extreme periphery resembles that observed (Fujita and Horii, '63) in retinae exposed to tritiated thymidine during embryonic development. The mechanisms underlying the histogenesis of retinal cells during growth at the extreme periphery in young stages may be the same as those which operate during embryonic devolopment.