Mitochondrial ATP generation is more proteome efficient than glycolysis.

Metabolic efficiency profoundly influences organismal fitness. Nonphotosynthetic organisms, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. Although respiration is more energy efficient, some cells favor glycolysis even when oxygen is available (aerobic glycolysis, Warburg effect). A leading explanation is that glycolysis is more efficient in terms of ATP production per unit mass of protein (that is, faster). Through quantitative flux analysis and proteomics, we find, however, that mitochondrial respiration is actually more proteome efficient than aerobic glycolysis. This is shown across yeast strains, T cells, cancer cells, and tissues and tumors in vivo. Instead of aerobic glycolysis being valuable for fast ATP production, it correlates with high glycolytic protein expression, which promotes hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth but outgrow respiratory cells during oxygen limitation. We accordingly propose that aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.

Treatment of Postoperative Instability Following Total Knee Arthroplasty in Patients With Parkinson's Disease.

Acute postoperative posterior total knee arthroplasty (TKA) dislocation is rare in primary surgery but has been associated with Parkinson's disease (PD). We present a 77-year-old woman with knee arthritis and PD who sustained an acute, recurrent TKA posterior dislocation, recalcitrant to polyethylene upsizing. Transient stability was obtained for a period of 1 year after postoperative hamstring injection with botulinum toxin A and short-term immobilization. Spontaneous instability recurred after 1 year, and stability was obtained with revision to a more constrained construct and has been monitored over a period of 2 years. This is the first report demonstrating the use of botulinum toxin A for acute posterior TKA instability associated with PD. We endorse the necessity of increased constraint to maintain long-term stability in patients with Parkinson's disease.

Iatrogenic Injury During Intraoperative Transesophageal Echocardiography: Implications for Medical Equipment Storage.

BACKGROUND: Medical equipment failure is an underappreciated source of iatrogenesis. The authors report a successful root cause analysis and action (RCA2) to improve compliance and decrease risks to patients during cardiac anesthesia care. METHODS: A quality and safety team of five content experts performed an RCA2 after an iatrogenic injury with transesophageal echocardiogram (TEE) probe insertion. The team used a fishbone diagram to identify causes and performed a Gemba walk to discuss probability of the different causes with key stakeholders. The team reviewed hospital policies and procedures as well as manufacturer manuals regarding best practices for maintenance and storage of TEE probes. The team created a corrective action plan centered on purchasing larger TEE storage cabinets, education of those who handle TEE probes, and implementing standard operating procedures. Effectiveness of the intervention was evaluated by analyzing frequency of TEE probe maintenance. RESULTS: The study period ranged from July 2016 to June 2021. TEE probes required maintenance 51 times, of which 40 (78.4%) occurred prior to the larger storage cabinet purchase, and 11 (21.6%) afterward. The number of TEE probes requiring maintenance per quarter was 4.4 (standard deviation [SD] 2.5) during the preintervention period and 1.0 (SD 1.0) during the postintervention period (mean difference 3.4, 95% confidence interval 1.0-5.9, p = 0.0006). CONCLUSION: An extensive RCA2 resulting in a corrective action plan centered on compliance with manufacturer recommendations for storage of TEE probes resulted in fewer maintenance requests, which decreased the risk of iatrogenic patient injury from TEE probe failure during cardiac anesthesia care.

Comparative study of two Saccharomyces cerevisiae strains with kinetic models at genome-scale.

The parameterization of kinetic models requires measurement of fluxes and/or metabolite levels for a base strain and a few genetic perturbations thereof. Unlike stoichiometric models that are mostly invariant to the specific strain, it remains unclear whether kinetic models constructed for different strains of the same species have similar or significantly different kinetic parameters. This important question underpins the applicability range and prediction limits of kinetic reconstructions. To this end, herein we parameterize two separate large-scale kinetic models using K-FIT with genome-wide coverage corresponding to two distinct strains of Saccharomyces cerevisiae: CEN.PK 113-7D strain (model k-sacce306-CENPK), and growth-deficient BY4741 (isogenic to S288c; model k-sacce306-BY4741). The metabolic network for each model contains 306 reactions, 230 metabolites, and 119 substrate-level regulatory interactions. The two models (for CEN.PK and BY4741) recapitulate, within one standard deviation, 77% and 75% of the fitted dataset fluxes, respectively, determined by 13C metabolic flux analysis for wild-type and eight single-gene knockout mutants of each strain. Strain-specific kinetic parameterization results indicate that key enzymes in the TCA cycle, glycolysis, and arginine and proline metabolism drive the metabolic differences between these two strains of S. cerevisiae. Our results suggest that although kinetic models cannot be readily used across strains as stoichiometric models, they can capture species-specific information through the kinetic parameterization process.

Changes in Elective and Urgent Surgery Among TRICARE Beneficiaries During the COVID-19 Pandemic.

BACKGROUND: COVID-19 is known to have altered the capacity to perform surgical procedures in numerous health care settings. The impact of this change within the direct and private-sector settings of the Military Health System has not been effectively explored, particularly as it pertains to disparities in surgical access and shifting of services between sectors. We sought to characterize how the COVID-19 pandemic influenced access to care for surgical procedures within the direct and private-sector settings of the Military Health System. METHODS: We retrospectively evaluated claims for patients receiving urgent and elective surgical procedures in March-September 2017, 2019, and 2020. The pre-COVID period consisted of 2017 and 2019 and was compared to 2020. We adjusted for sociodemographic characteristics, medical comorbidities, and region of care using multivariable Poisson regression. Subanalyses considered the impact of race and sponsor rank as a proxy for socioeconomic status. RESULTS: During the period of the COVID-19 pandemic, there was no significant difference in the adjusted rate of urgent surgical procedures in direct (risk ratio, 1.00; 95% CI, 0.97-1.03) or private-sector (risk ratio, 0.99; 95% CI, 0.97-1.02) care. This was also true for elective surgeries in both settings. No significant disparities were identified in any of the racial subgroups or proxies for socioeconomic status we considered in direct or private-sector care. CONCLUSIONS: We found a similar performance of elective and urgent surgeries in both the private sector and direct care during the first 6 months of the COVID-19 pandemic. Importantly, no racial disparities were identified in either care setting.

Multiple transcriptome mining coupled with tissue specific molecular cloning and mass spectrometry provide insights into agatoxin-like peptide conservation in decapod crustaceans.

Over the past decade, in silico genome and transcriptome mining has led to the identification of many new crustacean peptide families, including the agatoxin-like peptides (ALPs), a group named for their structural similarity to agatoxin, a spider venom component. Here, analysis of publicly accessible transcriptomes was used to expand our understanding of crustacean ALPs. Specifically, transcriptome mining was used to investigate the phylogenetic/structural conservation, tissue localization, and putative functions of ALPs in decapod species. Transcripts encoding putative ALP precursors were identified from one or more members of the Penaeoidea (penaeid shrimp), Sergestoidea (sergestid shrimps), Caridea (caridean shrimp), Astacidea (clawed lobsters and freshwater crayfish), Achelata (spiny/slipper lobsters), and Brachyura (true crabs), suggesting a broad, and perhaps ubiquitous, conservation of ALPs in decapods. Comparison of the predicted mature structures of decapod ALPs revealed high levels of amino acid conservation, including eight identically conserved cysteine residues that presumably allow for the formation of four identically positioned disulfide bridges. All decapod ALPs are predicted to have amidated carboxyl-terminals. Two isoforms of ALP appear to be present in most decapod species, one 44 amino acids long and the other 42 amino acids in length, both likely generated by alternative splicing of a single gene. In carideans, a gene or terminal exon duplication appears to have occurred, with alternative splicing producing four ALPs, two 44 and two 42 amino acid isoforms. The identification of ALP precursor-encoding transcripts in nervous system-specific transcriptomes (e.g., Homarus americanus brain, eyestalk ganglia, and cardiac ganglion assemblies, finding confirmed using RT-PCR) suggests that members of this peptide family may serve as locally-released and/or hormonally-delivered neuromodulators in decapods. Their detection in testis- and hepatopancreas-specific transcriptomes suggests that members of the ALP family may also play roles in male reproduction and innate immunity/detoxification.