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The purpose of this study was to examine the differences in braking and propulsion force-time characteristics and barbell velocity between traditional (TRAD) and accentuated eccentric loaded (AEL) back squats using various load combinations. Sixteen resistance-trained men participated in four separate testing sessions which included a one repetition maximum (1RM) back squat during the first session and three squat testing sessions. During the squat testing sessions, participants either performed sets of three repetitions of TRAD back squats each with 50, 60, 70, and 80% 1RM or performed the same loads with the addition of weight releasers that increased the total eccentric weight of the first repetition of each set to either 100 (AEL-MAX) or 110% 1RM (AEL-SUPRA). Braking and propulsion mean force, duration, and impulse as well as mean and peak barbell velocity were compared between each condition and load. Significantly greater braking impulses were produced during the AEL-MAX and AEL-SUPRA conditions compared to TRAD (p < 0.03) with small-moderate effect sizes favoring AEL-SUPRA. No other significant differences existed among conditions for other braking, propulsion, or barbell velocity variables. AEL-MAX and AEL-SUPRA back squats may provide a greater braking stimulus compared to TRAD squats; however, the propulsion phase of the movement does not appear to be impacted. From a loading standpoint, larger and smaller load spreads may favor rapid and maximal force production characteristics, respectively. Further research on this topic is needed as a large portion of the braking stimulus experienced during AEL back squats may be influenced by relative strength., Competing Interests: The authors declare no conflict of interest., (Copyright: © Academy of Physical Education in Katowice.)

β-Hairpin peptides with RNA-binding sequences mimicking the central two β-strands of the RNA recognition motif (RRM) protein domain have been observed to bind in a 2:1 fashion to a series of RNA homooligonucleotides in aqueous solution (PBS buffer, pH 7.40) with binding energies (-27 to -35 kJ mol -1 ) similar to those of full-size protein RRMs. The peptides display mild selectivities with respect to the binding of the different homooligomers. Binding studies in 500 mM magnesium chloride suggest that the complex formation is not predominantly driven by Coulombic attraction. These peptides represent a starting point for further studies of non-Coulombic binding of RNA by peptides and proteins, which is important in the context of contemporary biology, potential therapeutic applications, and prebiotic peptide-RNA interactions.

We report the co-polymerization of glycol nucleic acid (GNA) monomers with unsubstituted and substituted dicarboxylic acid linkers under plausible early Earth aqueous dry-down conditions. Both linear and branched co-polymers are produced. Mechanistic aspects of the reaction and potential roles of these polymers in prebiotic chemistry are discussed.

Background: Creating the capacity and capability for meaningful improvement in healthcare quality is a challenge many organizations face. Before 2012, Children's Mercy sponsored 20 leaders to obtain advanced improvement training from peer organizations. Recognizing an opportunity to build upon this momentum, we developed an organization-wide curriculum for teaching continuous improvement., Methods: A steering committee was created in 2011 to define, advise, and oversee education in improvement science. We agreed upon a framework for improvement, a program name [Continuous Quality and Practice Improvement (CQPI)], and a phased curriculum development approach, beginning with a project/experiential learning based course (Team CQPI). Course evaluation for Team CQPI consisted of a standard evaluation of objectives, pre- and post-course assessment, qualitative feedback, and serial assessment of project progress using the Team Assessment Score (TAS). The curriculum committee monitored improvement., Results: From 2012 to 2017, 297 people participated in the project-based course, completing a total of 83 projects. TAS improved throughout the 4-month project-based course, from an average starting score of 1 ("forming a team") to 2.7 ("changes tested"). The average TAS at 12 months following completion of the Team CQPI course was 3.5 ("improvement") out of 5., Conclusions: Development of a comprehensive curriculum for driving continuous improvement has resulted in a measurable change in TAS scores representative of local improvement efforts.

Background: The purpose of this study was to evaluate the effect of paramedic-administered neuromuscular blocking agents as part of a rapid-sequence intubation (RSI) protocol on successful intubation of severely head-injured patients in a large, urban prehospital system., Methods: Adult head-injured patients were prospectively enrolled over 1 year using these inclusion criteria: Glasgow Coma Scale (GCS) score of 3 to 8, transport time > 10 minutes, and inability to intubate without RSI. Midazolam and succinylcholine were administered before laryngoscopy; rocuronium was given after tube placement was confirmed using capnometry, syringe aspiration, and pulse oximetry. The Combitube was used as a salvage airway device. All adult trauma victims with a GCS score of 3 to 8 were identified during the first 12 months of the study as the trial cohort and from the preceding 12 months as the control cohort. The trial and control cohorts were compared with regard to demographic data, mechanism of injury, initial vital signs, and GCS scores. The primary outcome measure was intubation success, defined as insertion of either an endotracheal tube or a Combitube, with patients stratified by GCS score., Results: The trial cohort (n = 249) and control cohort (n = 189) were similar with regard to demographic data, mechanism of injury, and initial vital signs and GCS scores. Intubation success rates increased significantly during the trial period for all patients and when stratified into GCS score of 3 and GCS score of 4 to 8. The percentage of patients intubated without neuromuscular blocking agents actually increased during the trial period. Although the number of intubations by helicopter flight crews decreased during the trial, the overall use of aeromedical resources did not change., Conclusion: Paramedic-administered neuromuscular blockade as part of an RSI protocol improves intubation success in a large, urban prehospital system.

Objective: To evaluate the effect of paramedic rapid sequence intubation (RSI) on outcome in patients with severe traumatic brain injury., Methods: Adult major trauma victims were prospectively enrolled over two years using the following inclusion criteria: Glasgow Coma Scale (GCS) 3-8, suspected head injury by mechanism or physical examination, transport time > 10," and inability to intubate without RSI. Midazolam and succinylcholine were administered before laryngoscopy; rocuronium was given after tube placement was confirmed using physical examination, capnometry, syringe aspiration, and pulse oximetry. The Combitube was used as a salvage airway device. For this analysis, trial patients were excluded for absence of a head injury (Head/Neck AIS score < 2), failure to fulfill major trauma outcome study criteria, unsuccessful intubation or Combitube insertion, or death in the field or in the resuscitation suite within 30" of arrival. Each study patient was hand matched to three nonintubated historical controls from our trauma registry using the following parameters: age, sex, mechanism of injury, trauma center, and AIS score for each body system. Controls were excluded for Head/Neck AIS defined by a c-spine injury or death in the field or in the resuscitation suite within 30" of arrival. chi 2, odds ratios, and logistic regression were used to investigate the impact of RSI on the primary outcome measures of mortality and incidence of a "good outcome," defined as discharge to home, rehabilitation, psychiatric facility, jail, or signing out against medical advice., Results: A total of 209 trial patients were hand matched to 627 controls. The groups were similar with regard to all matching parameters, admission vital signs, frequency of specific head injury diagnoses, and incidence of invasive procedures. Mortality was significantly increased in the trial cohort versus controls for all patients (33.0% versus 24.2%, p < 0.05) and in those with Head/Neck AIS scores of 3 or greater (41.1% versus 30.3%, p < 0.05). The incidence of a "good outcome" was lower in the trial cohort versus controls (45.5% versus 57.9%, p < 0.01). Factors that may have contributed to the increase in mortality include transient hypoxia, inadvertent hyperventilation, and longer scene times associated with the RSI procedure., Conclusion: Paramedic RSI protocols to facilitate intubation of head-injured patients were associated with an increase in mortality and decrease in good outcomes versus matched historical controls.

We studied a mouse doubly homozygous for mutations in the genes encoding malic enzyme (EC 1.1.1.40) and cytosolic glycerol phosphate dehydrogenase (EC 1.1.1.8) (cGPD). This mouse, which we call the mmgg mouse and which is the product of intercrosses between the Mod-1 mouse and the BALB/cHeA mouse, lacks activity of both enzymes. Like both parental strains the mmgg mouse is completely normal in appearance. cGPD is one of the two enzymes that catalyze the reactions of the glycerol phosphate shuttle. The activity of the other enzyme of the glycerol phosphate shuttle, mitochondrial glycerol phosphate dehydrogenase (EC 1.1.99.5) (mGPD), is abundant in tissues, such as brain, skeletal muscle and the pancreatic islet, suggesting that the glycerol phosphate shuttle is important in these tissues which rapidly metabolize glucose. Cytosolic malic enzyme activity is important for shuttles which transport NADPH equivalents from mitochondria to the cytosol. The major finding of the study was a highly abnormal metabolite pattern in tissues of the mmgg mouse suggesting a block in the glycerol phosphate shuttle due to cGPD deficiency. The metabolite pattern did not suggest that malic enzyme deficiency caused an abnormality. Tissue levels of glycerol phosphate (low) and dihydroxyacetone phosphate (high) were only abnormal in skeletal muscle. Glycolytic intermediates, situated at or before the triose phosphates in the pathway, such as fructose bisphosphate and glyceraldehyde phosphate were increased depending on the tissue. Taken together with previous extensive data on the mouse deficient only in cGPD, this suggests a block in glycolysis at the step catalyzed by glyceraldehyde phosphate dehydrogenase caused by an abnormally low NAD/NADH ratio resulting from a nonfunctional glycerol phosphate shuttle. Consistent with this idea the lactate/pyruvate ratio was high in skeletal muscle signifying a low cytosolic NAD/NADH ratio. The mmgg mouse was normal in all other factors studied including blood glucose and serum insulin levels, pancreatic islet mass, insulin release from isolated pancreatic islets, as well as the activities of five metabolic enzymes, including mGPD, in liver, kidney, skeletal muscle and pancreatic islets. cGPD enzyme activity was undetectable in pancreatic islets, 0.5% of normal in liver, and 2.1% of normal in kidney and skeletal muscle. Malic enzyme activity was undetectable in these same tissues.

We surveyed the BALB/cHeA mouse, which lacks cytosolic glycerol phosphate dehydrogenase an enzyme that catalyzes a reaction in the glycerol phosphate shuttle. The other enzyme of this shuttle, mitochondrial glycerol phosphate dehydrogenase, is abundant in skeletal muscle and pancreatic islets suggesting that the shuttle's activity is high in these tissues. Levels of glycerol phosphate (low) and dihydroxyacetone phosphate (high) were very abnormal in nonislet tissue, especially in skeletal muscle. Intermediates situated before the triose phosphates in the glycolysis pathway were increased and those after the triose phosphates were generally low, depending on the tissue. The lactate/pyruvate ratio in muscle was low signifying a low cytosolic NAD/NADH ratio. This suggests that a nonfunctional glycerol phosphate shuttle caused a block in glycolysis at the step catalyzed by glyceraldehyde phosphate dehydrogenase. When exercised, mice were unable to maintain normal ATP levels in skeletal muscle. Blood glucose, serum insulin levels, and pancreatic islet mass were normal. In isolated pancreatic islets insulin release, glucose metabolism and ATP levels were normal, but lactate levels and lactate/pyruvate ratios with a glucose load were slightly abnormal. The BALB/cHeA mouse can maintain NAD/ NADH ratios sufficient to function normally under most conditions, but the redox state is not normal. Glycerol phosphate is apparently formed at a slow rate. Skeletal muscle is severely affected probably because it is dependent on the glycerol phosphate shuttle more than other tissues. It most likely utilizes glycerol phosphate rapidly and, due to the absence of glycerol kinase in muscle, is unable to rapidly form glycerol phosphate from glycerol. Glycerol kinase is also absent in the pancreatic insulin cell, but this cell's function is essentially normal probably because of redundancy of NAD(H) shuttles.