Challenges and Successes in Introducing Coronary CT Angiography in an Emergency Medicine-Run Observation Unit.

This study was designed to analyze the departmental changes in transitioning the Emergency Department (ED)-run Observation Medicine Unit's routine noninvasive cardiac evaluation from the traditional standard-of-care procedures to coronary computed tomography angiography (CCTA).  While the routine use of CCTA for the evaluation of chest pain has been deemed feasible and safe, provider confidence appears apprehensive, and ordering patterns appear reluctant to change.  We conducted a retrospective analysis of data from two risk-matched cohorts of ED patients who presented with symptoms suggestive of acute coronary syndrome (ACS) but without ischemic electrocardiogram (ECG) changes or positive troponin. Endpoints included length of stay, major adverse cardiovascular event (MACE) rates at 28 days, recidivism rate, and downstream findings on coronary catheterization.  The adoption of CCTA led to a significant reduction in the length of stay for patients in the ED-run Observation Medicine Unit. Provider and nursing education initiatives were crucial in overcoming initial resistance and improving the implementation of CCTA. Post-education, there was a marked increase in the volume of CCTA performed and a decrease in the length of stay, enhancing overall departmental throughput.  The results suggest that CCTA offers a reliable and efficient diagnostic alternative to traditional noninvasive tests, with high diagnostic accuracy contributing to faster decision-making and reduced need for invasive procedures. Continuous education for providers and nursing staff was essential to ensure adherence to the new protocol and improve clinical outcomes.  Transitioning to CCTA for routine noninvasive cardiac evaluation in the ED-run Observation Medicine Unit demonstrated significant efficiency and diagnostic accuracy benefits. Successful implementation requires targeted educational efforts to ensure competency and confidence among healthcare providers. The findings support the integration of CCTA into standard clinical practice for the evaluation of chest pain in the emergency setting, with future research needed to validate these results in broader patient populations and assess long-term outcomes.

The Impact of Sociodemographic Variables on Functional Recovery Following Lower Extremity Amputation.

OBJECTIVE: We hypothesize that sociodemographic variables, particularly disadvantaged financial environments, impact both rate of prosthetic utilization and the achievement of ambulation post major amputation. METHODS: All cases in the Vascular Quality Initiative (VQI) amputation module were queried between April 2013 and January 2024. Inclusion was limited to patients who underwent below knee, through knee, and above knee amputation. Two primary outcomes were investigated : Non-ambulatory status after amputation (minimum of 120 days follow up); and, not having obtained a prosthetic limb (minimum of 90 days follow up). The ambulation status and prosthetic status analyses had 6984 and 6793 patients meet inclusion respectively. Multivariable binary logistic regression analysis was performed utilizing variables which achieved univariable significance (P<.05) for the outcomes. RESULTS: Mean follow up for those meeting inclusion was 432 days. Amongst all patients meeting inclusion, 46.7% of patients did not acquire a prosthetic limb and 44.1% were non-ambulatory. Sociodemographic factors with significant multivariable association for the outcome of no prosthetic limb acquisition in follow up were : advancing age (aOR 1.011/year (1.006-1.016), P<.001); female sex (aOR 1.43 (1.28-1.61), P<.001); top 20% ADI representing highest deprivation (aOR 1.24 (1.09-1.41) P=.001); race (P=.002) Insurance status (P=.028) with protective status for commercial insurance (39% rate of no prosthetic) and non US insurance (33%) versus Medicare (51%), Medicaid (48%), VA insurance (49%), Self Pay (42%) and Medicare Advantage (51%). There were numerous co-morbidities which also had association with lack of prosthetic limb acquisition. Sociodemographic variables which achieved multivariable significance (P<.05) for the outcome of non-ambulatory status after major amputation were : female sex (aOR 1.37 (1.23-1.54), P<.001); Medicare insurance (P=.016); advancing age (aOR 1.009/year (1.004-1.014), P<.001); CHF (aOR 1.15 (1.02-1.31), P=.028); and, not living at home in follow up (aOR (3.53 (2.99-4.17) P<.001). Physical therapy at any point after surgery (aOR .742 (.662-.832), P<.001) and commercial insurance (aOR .839 (.737-.956), P=.008) were protective. There were numerous co-morbidities which also had association with non-ambulatory status in follow up. CONCLUSIONS: Living within the most financially disadvantaged areas and race both have a significant independent association with lack of prosthetic limb acquisition following major amputation. Black, Native American and Pacific Islander demographic patients experience lack of acquisition at a higher rate than White and Asian patients independent of co-morbidities and socioeconomic co-variables. Female patients obtain a prosthetic limb and ambulate less frequently than males after major amputation, largely due to a higher rate of above knee amputation. Co-morbidities, and not socioeconomic variables are the leading drivers of non-ambulation.

Chalcopyrite bioleaching efficacy by extremely thermoacidophilic archaea leverages balanced iron and sulfur biooxidation.

Factors that contribute to optimal chalcopyrite bioleaching by extremely thermoacidophilic archaea were examined for ten species belonging to the order Sulfolobales from the genera Acidianus (A. brierleyi), Metallosphaera (M. hakonensis, M. sedula, M. prunae), Sulfuracidifex (S. metallicus, S. tepriarius), Sulfolobus (S. acidocaldarius), Saccharlobus (S. solfataricus) and Sulfurisphaera (S. ohwakuensis, S. tokodaii). Only A. brierleyi, M. sedula, S. metallicus, S. tepriarius, S. ohwakuensis, and S. tokodai exhibited significant amounts of bioleaching and were investigated further. At 70-75 °C, Chalcopyrite loadings of 10 g/l were leached for 21 days during which pH, redox potential, planktonic cell density, iron concentrations and sulfate levels were monitored, in addition to copper mobilization. S. ohwakuensis proved to be the most prolific bioleacher. This was attributed to balanced iron and sulfur oxidation, thereby reducing by-product (e.g., jarosites) formation and minimizing surface passivation. Comparative genomics suggest markers for bioleaching potential, but the results here point to the need for experimental verification.

Retinoic acid signalling regulates branchiomeric neck muscle development at the head trunk interface.

Skeletal muscles of the head and trunk originate in distinct lineages with divergent regulatory programs converging on activation of myogenic determination factors. Branchiomeric head and neck muscles share a common origin with cardiac progenitor cells in cardiopharyngeal mesoderm (CPM). The retinoic acid (RA) signalling pathway is required during a defined early time window for normal deployment of cells from posterior CPM to the heart. Here we show that blocking RA signalling in the early mouse embryo also results in selective loss of the trapezius neck muscle, without affecting other skeletal muscles. RA signalling is required for robust expression of myogenic determination factors in posterior CPM and subsequent expansion of the trapezius primordium. Lineage specific activation of a dominant negative RA receptor reveals that trapezius development is not regulated by direct RA signalling to myogenic progenitor cells in CPM, or through neural crest cells, but indirectly through the somitic lineage, closely apposed with posterior CPM in the early embryo. These findings suggest that trapezius development is dependent on precise spatiotemporal interactions between cranial and somitic mesoderm at the head/trunk interface.

Correction: Late date of human arrival to North America: Continental scale differences in stratigraphic integrity of pre-13,000 BP archaeological sites.

[This corrects the article DOI: 10.1371/journal.pone.0264092.].

Transient formation of collaterals contributes to the restoration of the arterial tree during cardiac regeneration in neonatal mice.

Revascularization of ischemic myocardium following cardiac damage is an important step in cardiac regeneration. However, the mechanism of arteriogenesis has not been well described during cardiac regeneration. Here we investigated coronary artery remodeling and collateral growth during cardiac regeneration. Neonatal MI was induced by ligature of the left descending artery (LAD) in postnatal day (P) 1 or P7 pups from the Cx40-GFP mouse line and the arterial tree was reconstructed in 3D from images of cleared hearts collected at 1, 2, 4, 7 and 14 days after infarction. We show a rapid remodeling of the left coronary arterial tree induced by neonatal MI and the formation of numerous collateral arteries, which are transient in regenerating hearts after MI at P1 and persistent in non-regenerating hearts after MI at P7. This difference is accompanied by restoration of a perfused or a non-perfused LAD following MI at P1 or P7 respectively. Interestingly, collaterals ameliorate cardiac perfusion and drive LAD repair, and lineage tracing analysis demonstrates that the restoration of the LAD occurs by remodeling of pre-existing arterial cells independently of whether they originate in large arteries or arterioles. These results demonstrate that the restoration of the LAD artery during cardiac regeneration occurs by pruning as the rapidly forming collaterals that support perfusion of the disconnected lower LAD subsequently disappear on restoration of a unique LAD. These results highlight a rapid phase of arterial remodeling that plays an important role in vascular repair during cardiac regeneration.

Phenotype-driven assessment of the ancestral trajectory of sulfur biooxidation in the thermoacidophilic archaea Sulfolobaceae.

Certain members of the family Sulfolobaceae represent the only archaea known to oxidize elemental sulfur, and their evolutionary history provides a framework to understand the development of chemolithotrophic growth by sulfur oxidation. Here, we evaluate the sulfur oxidation phenotype of Sulfolobaceae species and leverage comparative genomic and transcriptomic analysis to identify the key genes linked to sulfur oxidation. Metabolic engineering of the obligate heterotroph Sulfolobus acidocaldarius revealed that the known cytoplasmic components of sulfur oxidation alone are not sufficient to drive prolific sulfur oxidation. Imaging analysis showed that Sulfolobaceae species maintain proximity to the sulfur surface but do not necessarily contact the substrate directly. This indicates that a soluble form of sulfur must be transported to initiate cytoplasmic sulfur oxidation. Conservation patterns and transcriptomic response implicate an extracellular tetrathionate hydrolase and putative thiosulfate transporter in a newly proposed mechanism of sulfur acquisition in the Sulfolobaceae.IMPORTANCESulfur is one of the most abundant elements on earth (2.9% by mass), so it makes sense that the earliest biology found a way to use sulfur to create and sustain life. However, beyond evolutionary significance, sulfur and the molecules it comprises have important technological significance, not only in chemicals such as sulfuric acid and in pyritic ores containing critical metals but also as a waste product from oil and gas production. The thermoacidophilic Sulfolobaceae are unique among the archaea as sulfur oxidizers. The trajectory for how sulfur biooxidation arose and evolved can be traced using experimental and bioinformatic analyses of the available genomic data set. Such analysis can also inform the process by which extracellular sulfur is acquired and transported by thermoacidophilic archaea, a phenomenon that is critical to these microorganisms but has yet to be elucidated.

Cardiac Development and Animal Models of Congenital Heart Defects.

The major events of cardiac development, including early heart formation, chamber morphogenesis and septation, and conduction system and coronary artery development, are briefly reviewed together with a short introduction to the animal species commonly used to study heart development and model congenital heart defects (CHDs).

Molecular Pathways and Animal Models of Tetralogy of Fallot and Double Outlet Right Ventricle.

Tetralogy of Fallot and double-outlet right ventricle are outflow tract (OFT) alignment defects situated on a continuous disease spectrum. A myriad of upstream causes can impact on ventriculoarterial alignment that can be summarized as defects in either i) OFT elongation during looping morphogenesis or ii) OFT remodeling during cardiac septation. Embryological processes underlying these two developmental steps include deployment of second heart field cardiac progenitor cells, establishment and transmission of embryonic left/right information driving OFT rotation and OFT cushion and valve morphogenesis. The formation and remodeling of pulmonary trunk infundibular myocardium is a critical component of both steps. Defects in myocardial, endocardial, or neural crest cell lineages can result in alignment defects, reflecting the complex intercellular signaling events that coordinate arterial pole development. Importantly, however, OFT alignment is mechanistically distinct from neural crest-driven OFT septation, although neural crest cells impact indirectly on alignment through their role in modulating signaling during SHF development. As yet poorly understood nongenetic causes of alignment defects that impact the above processes include hemodynamic changes, maternal exposure to environmental teratogens, and stochastic events. The heterogeneity of causes converging on alignment defects characterizes the OFT as a hotspot of congenital heart defects.

Cardiac Progenitor Cells of the First and Second Heart Fields.

The heart forms from the first and second heart fields, which contribute to distinct regions of the myocardium. This is supported by clonal analyses, which identify corresponding first and second cardiac cell lineages in the heart. Progenitor cells of the second heart field and its sub-domains are controlled by a gene regulatory network and signaling pathways, which determine their behavior. Multipotent cells in this field can also contribute cardiac endothelial and smooth muscle cells. Furthermore, the skeletal muscles of the head and neck are clonally related to myocardial cells that form the arterial and venous poles of the heart. These lineage relationships, together with the genes that regulate the heart fields, have major implications for congenital heart disease.

A Comparison of Brain-State Representations of Binary Neuroimaging Connectivity Data. Comment on Samantaray et al. Unique Brain Network Identification Number for Parkinson's and Healthy Individuals Using Structural MRI. Brain Sci. 2023, 13, 1297.

Samantaray et al [...].

On the involvement of the second heart field in congenital heart defects.

Congenital heart defects (CHD) affect 1 in 100 live births and result from defects in cardiac development. Growth of the early heart tube occurs by the progressive addition of second heart field (SHF) progenitor cells to the cardiac poles. The SHF gives rise to ventricular septal, right ventricular and outflow tract myocardium at the arterial pole, and atrial, including atrial septal myocardium, at the venous pole. SHF deployment creates the template for subsequent cardiac septation and has been implicated in cardiac looping and in orchestrating outflow tract development with neural crest cells. Genetic or environmental perturbation of SHF deployment thus underlies a spectrum of common forms of CHD affecting conotruncal and septal morphogenesis. Here we review the major properties of SHF cells as well as recent insights into the developmental programs that drive normal cardiac progenitor cell addition and the origins of CHD.

Les malformations cardiaques congénitales touchent 1 naissance sur 100 et résultent d'anomalies du développement cardiaque. La croissance du tube cardiaque précoce se produit par l'ajout progressif de cellules progénitrices du second champ cardiaque (SHF) aux pôles cardiaques. Le SHF contribue au myocarde septal ventriculaire, au myocarde ventriculaire droit et au myocarde de la voie de sortie au pôle artériel, et au myocarde auriculaire, y compris le myocarde septal auriculaire, au pôle veineux. Le déploiement du SHF est essentiel pour la septation cardiaque et a été impliqué dans la formation du boucle cardiaque et, avec les cellules de la crête neurale, dans l'orchestration du développement de la voie efférente. Perturbation génétique ou environnementale du déploiement du SHF est donc à l'origine d'un spectre de formes communes de maladies cardiaques congénitales affectant la morphogenèse conotroncale et septale. Ici, nous passons en revue les principales propriétés des cellules du SHF ainsi que les découvertes récentes sur les programmes de développement qui contrôlent l'ajout de cellules progénitrices cardiaques ainsi que les origines des malformations cardiaques congénitales.

Complete genome sequence for the thermoacidophilic archaeon Metallosphaera sedula (DSM:5348).

The complete genome sequence of the thermoacidophilic archaeon Metallosphaera sedula (DSM 5348) is reported here. M. sedula, originally isolated from a volcanic field in Italy, is a prolific iron-oxidizing archaeon with applications in bioleaching of sulfide minerals.

Use of hare bone for the manufacture of a Clovis bead.

A tubular bone bead dating to ~ 12,940 BP was recovered from a hearth-centered activity area at the La Prele Mammoth site in Converse County, Wyoming, USA. This is the oldest known bead from the Western Hemisphere. To determine the taxonomic origin of the bead, we extracted collagen for zooarchaeology by mass spectrometry (ZooMS). We also used micro-CT scanning for morphological analysis to determine likely skeletal elements used for its production. We conclude that the bead was made from a metapodial or proximal phalanx of a hare (Lepus sp.). This find represents the first secure evidence for the use of hares during the Clovis period. While the use of hare bone for the manufacture of beads was a common practice in western North America during the Holocene, its origins can now be traced back to at least the terminal Pleistocene.

Complete genome sequence for the extremely thermophilic bacterium Anaerocellum danielii (DSM:8977).

The complete genome sequence of the extremely thermophilic bacterium Anaerocellum (f. Caldicellulosiruptor) danielii (DSM:8977) is reported here. A. danielii is a fermentative anaerobe and capable of lignocellulose degradation with potential applications in biomass degradation and production of chemicals and fuels from renewable feedstocks.

Bony encasement of the ulnar nerve secondary to heterotopic ossification of the elbow: an evaluation of long-term outcomes.

BACKGROUND: Ulnar neuropathy at the elbow caused by heterotopic ossification (HO) is a rare condition. This retrospective study aims to report on 32 consecutive cases of ulnar nerve encasement caused by elbow HO and evaluate long-term outcomes of operative management and a standardized postoperative rehabilitation regimen. METHODS: A retrospective case series was conducted on 32 elbows (27 patients) that underwent operative management of bony ulnar nerve encasement. All procedures were performed in the inpatient setting at an Academic Level 1 Trauma Center from September 1999 to July 2021 by one of 3 fellowship-trained shoulder and elbow. Postoperatively, all patients received formal physical therapy, HO prophylaxis (30 received indomethacin, 2 received radiation), and a structured continuous passive motion machine regimen. Patient demographics, age, gender, type of injury, history of tobacco use, and medical comorbidities were obtained to include in the analysis. Long-term follow-up examinations were performed to evaluate elbow flexion-extension arc of motion, Mayo Elbow Performance Score, and visual analog scale pain scores. RESULTS: Thirty-two elbows with complete bony ulnar nerve encasement secondary to HO were identified (14 from burns, 15 from trauma, 3 closed head injuries). Following surgery, the mean flexion-extension arc of motion improved significantly, increasing from 21° to 100° at long-term follow-up (average 8.7 years, range 2-17 years), with statistically significant improvements in preoperative vs. long-term postoperative elbow extension (P < .001), flexion (P < .001), and total arc of motion (P < .001). There was a statistically significant improvement in pre- vs. postprocedure ulnar nerve function, as demonstrated by a decrease in average McGowan grade (1.2-0.7; P = .002). Additionally, 63% of patients with preoperative ulnar neuropathy symptoms (20/32) had either complete resolution or subjective improvement after surgery. The mean time from injury to surgery was 518 days (range 65-943 days). Age, gender, time to surgery, and medical comorbidities were not associated with outcomes. The complication rate was 9% (3/32). Patients had an average flexion-extension arc of motion of 97° and average Mayo Elbow Performance Score of 80 ("good") at long-term follow-up. CONCLUSIONS: The combination of operative management, postoperative HO prophylaxis, and a regimented rehabilitation program has proven to be a durable solution for treating and ensuring good long-term functional outcomes for patients with elbow HO and bony ulnar nerve encasement. This treatment approach leads to superior range of motion, improved or resolved ulnar neuropathy, and good to excellent long-term functional outcomes.

Assessing the impact of environmental enrichment on behavior in understudied armadillo species: A case study.

The implementation of environmental enrichment (EE) can be effective in promoting zoo animal welfare by enhancing the performance of natural or species-typical behaviors. Research on the effects of EE is biased towards larger mammalian species, with less charismatic species being overlooked. Armadillos are one such overlooked example. A captive environment that results in inactivity, obesity, and associated poor health can negatively affect armadillo well-being. The aim of this study was to evaluate how the implementation of four physical object-based EEs could positively affect the behaviors of three armadillo species, housed in four similar exhibits. Behavioral data were collected both before (baseline) and during (treatment) EE periods, alongside of visitor number and environmental temperatures. The EE comprised of a plastic ball or a cardboard tube or a cardboard box, or a scatter-feed, and these were rotated each week of study until each exhibit had received them in turn. Despite the presence of different EE types, activity remained low throughout the study. However, results suggest that the plastic ball and cardboard box increased exploratory behaviors in the armadillos, but no overall increase in activity was noted during the scatter feed. Visitor presence had no effect on armadillo activity, and armadillos showed reduced activity with increasing environmental temperature. Overall, the use of physical object-based EE promoted beneficial natural behaviors in zoo-housed armadillos, but environmental conditions (i.e., temperature) also impacted armadillo activity, suggesting a complicated relationship between an enclosure's environmental variable and any behavioral husbandry measures.

Complete genome sequence for the thermoacidophilic archaeon Sulfuracidifex (f. Sulfolobus) metallicus DSM 6482.

Reported here is the complete genome sequence (2,191,724 bp) for the thermoacidophilic archaeon Sulfuracidifex (f. Sulfolobus) metallicus DSM 6482 (Topt 65°C, pHopt 2.0). This obligately chemolithoautotrophic microorganism is a prolific metal and sulfur oxidizer and has application in metal bioleaching operations. A multi-assembly reconciliation approach enabled closure of the genome.

Metabolic engineering of Caldicellulosiruptor bescii for 2,3-butanediol production from unpretreated lignocellulosic biomass and metabolic strategies for improving yields and titers.

The platform chemical 2,3-butanediol (2,3-BDO) is used to derive products, such as 1,3-butadiene and methyl ethyl ketone, for the chemical and fuel production industries. Efficient microbial 2,3-BDO production at industrial scales has not been achieved yet for various reasons, including product inhibition to host organisms, mixed stereospecificity in product formation, and dependence on expensive substrates (i.e., glucose). In this study, we explore engineering of a 2,3-BDO pathway in Caldicellulosiruptor bescii, an extremely thermophilic (optimal growth temperature = 78°C) and anaerobic bacterium that can break down crystalline cellulose and hemicellulose into fermentable C5 and C6 sugars. In addition, C. bescii grows on unpretreated plant biomass, such as switchgrass. Biosynthesis of 2,3-BDO involves three steps: two molecules of pyruvate are condensed into acetolactate; acetolactate is decarboxylated to acetoin, and finally, acetoin is reduced to 2,3-BDO. C. bescii natively produces acetoin; therefore, in order to complete the 2,3-BDO biosynthetic pathway, C. bescii was engineered to produce a secondary alcohol dehydrogenase (sADH) to catalyze the final step. Two previously characterized, thermostable sADH enzymes with high affinity for acetoin, one from a bacterium and one from an archaeon, were tested independently. When either sADH was present in C. bescii, the recombinant strains were able to produce up to 2.5-mM 2,3-BDO from crystalline cellulose and xylan and 0.2-mM 2,3-BDO directly from unpretreated switchgrass. This serves as the basis for higher yields and productivities, and to this end, limiting factors and potential genetic targets for further optimization were assessed using the genome-scale metabolic model of C. bescii.IMPORTANCELignocellulosic plant biomass as the substrate for microbial synthesis of 2,3-butanediol is one of the major keys toward cost-effective bio-based production of this chemical at an industrial scale. However, deconstruction of biomass to release the sugars for microbial growth currently requires expensive thermochemical and enzymatic pretreatments. In this study, the thermo-cellulolytic bacterium Caldicellulosiruptor bescii was successfully engineered to produce 2,3-butanediol from cellulose, xylan, and directly from unpretreated switchgrass. Genome-scale metabolic modeling of C. bescii was applied to adjust carbon and redox fluxes to maximize productivity of 2,3-butanediol, thereby revealing bottlenecks that require genetic modifications.