Association between patient-reported onset-to-door time and mortality in patients hospitalized with COVID-19 disease.

INTRODUCTION: Timely hospital presentation and treatment are critical for recovery from coronavirus disease (COVID-19). However, the relationship between symptom onset-to-door time and key clinical outcomes, such as inpatient mortality, has been poorly understood due to the difficulty of retrospectively measuring symptom onset in observational data. This study examines the association between patient-reported symptom onset-to-door time (ODT) and mortality among patients hospitalized and treated for COVID-19 disease. METHODS: We conducted a retrospective cohort study of emergency department (ED) encounters of patients with COVID-19 disease who were hospitalized and received remdesivir and/or dexamethasone between March 1, 2020, and March 1, 2022. The exposure was patient-reported ODT in days. The outcome of interest was inpatient mortality, including referral to hospice care. We used multivariable logistic regression to examine the association between ODT and mortality while adjusting for patient characteristics, hospital sites, and seasonality. We tested whether severe illness on hospital presentation modified the association between ODT and mortality. Severe illness was defined by Emergency Severity Index triage level 1 or 2 and hypoxia (SpO2 < 94%). RESULTS: Of the 3451 ED hospitalizations included, 439 (12.7%) resulted in mortality, and 1693 (49.1%) involved patients with severe illness on hospital presentation. Greater ODT was significantly associated with lower odds of inpatient mortality (adjusted odds ratio (AOR) = 0.96, 95% CI = 0.93-1.00, P = 0.023). There was a statistically significant interaction between ODT and severe illness at hospital arrival on mortality, suggesting the negative association between ODT and mortality specifically pertained to patients who were not severely ill upon ED presentation (AOR = 0.93, 95% CI = 0.87-1.00, P = 0.035). The adjusted probability of mortality was significantly lower for non-severely ill, hospitalized patients who presented on days 8-14 (5.2%-3.3%) versus days 0-3 (9.4%-7.5%) after symptom onset. CONCLUSION: More days between symptom onset and hospital arrival were associated with lower mortality among hospitalized patients treated for COVID-19 disease, particularly if they did not have severe illness at ED presentation. However, onset-to-door time was not associated with mortality among hospitalized patients with severe illness at ED presentation. Collectively, these results suggest that non-severely ill COVID-19 patients who require hospitalization are less likely to decompensate with each passing day without severe illness. These findings may continue to guide clinical care delivery for hospitalized COVID-19 patients.

Characterizing the impact of thermoregulation in patients after cardiac arrest: a retrospective cohort study.

PURPOSE: Core body temperature has been extensively investigated as a thereuptic target in care after cardiac arrest. Nevertheless, the integrity of thermoregulation in patients after cardiac arrest has not been well studied. We sought to evaluate whether low spontaneous body temperature after cardiac arrest is associated with increased death and a worse neurologic outcome, and whether patients with low spontaneous body temperature exhibit features suggestive of impaired thermoregulation. METHODS: We conducted a single-centre retrospective cohort study. We included all adult patients who underwent temperature control with hypothermia after cardiac arrest between 1 January 2014 and 30 June 2020. The primary exposure was low spontaneous core body temperature (< 35 °C) at initiation of hypothermia therapy. The primary outcome was in-hospital death and the secondary outcome was poor neurologic outcomes at discharge. RESULTS: Five hundred and ninety-seven adult patients, comprising both in- and out-of-hospital cardiac arrests, were included. Patients with low spontaneous body temperature also had slightly lower average temperature, and more frequent transient but controlled breakthrough fever episodes in the first 24 hr. In the multivariable logistic regression analysis, low spontaneous body temperature was associated with higher odds of in-hospital death (odds ratio, 2.9; 95% confidence interval, 1.9 to 4.2; P < 0.001). CONCLUSION: In this single-centre retrospective cohort study, low spontaneous core body temperature was associated with poor outcomes in patients after cardiac arrest. Patients with low spontaneous body temperature also exhibited features suggestive of impaired thermoregulation. Further research is needed to determine whether body temperature upon presentation reflects the robustness of the patient's underlying physiology and severity of brain insult after a cardiac arrest.

RéSUMé: OBJECTIF: La température corporelle centrale a fait l'objet d'études approfondies en tant que cible thérapeutique dans les soins après un arrêt cardiaque. Néanmoins, l'intégrité de la thermorégulation après un arrêt cardiaque n'a pas été bien étudiée. Nous avons cherché à évaluer si une température corporelle spontanément basse après un arrêt cardiaque était associée à une augmentation de la mortalité et à une issue neurologique plus grave, et si les individus ayant une température corporelle spontanément basse présentaient des caractéristiques suggérant une altération de la thermorégulation. MéTHODE: Nous avons mené une étude de cohorte rétrospective monocentrique. Nous avons inclus tou·tes les patient·es adultes ayant bénéficié d'un contrôle de température lors d'une hypothermie après un arrêt cardiaque entre le 1er janvier 2014 et le 30 juin 2020. L'exposition principale était une température corporelle centrale spontanément basse (< 35 °C) au début du traitement de l'hypothermie. Le critère d'évaluation principal était le décès à l'hôpital, et le critère d'évaluation secondaire était de mauvaises issues neurologiques à la sortie de l'hôpital. RéSULTATS: Cinq cent quatre-vingt-dix-sept patient·es adultes, ayant subi des arrêts cardiaques à l'hôpital ou hors de l'hôpital, ont été inclus·es. Les patient·es ayant une température corporelle spontanément basse avaient également une température moyenne légèrement plus basse et des épisodes de fièvre paroxystique transitoires mais contrôlés plus fréquents au cours des premières 24 heures. Dans l'analyse de régression logistique multivariée, une température corporelle spontanément basse était associée à une probabilité plus élevée de décès à l'hôpital (rapport de cotes, 2,9; intervalle de confiance à 95 %, 1,9 à 4,2; P < 0,001). CONCLUSION: Dans cette étude de cohorte rétrospective monocentrique, une température corporelle centrale spontanément basse a été associée à de mauvais devenirs après un arrêt cardiaque. Les patient·es présentant une température corporelle spontanément basse présentaient également des caractéristiques suggérant une altération de la thermorégulation. D'autres recherches sont nécessaires pour déterminer si la température corporelle lors de la présentation reflète la robustesse de la physiologie sous-jacente des patient·es et la gravité de la lésion cérébrale après un arrêt cardiaque.

Collaborative Team Training in Virtual Reality is Superior to Individual Learning For Performing Complex Open Surgery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether multiplayer immersive Virtual Reality (iVR) training was superior to single-player training for the acquisition of both technical and nontechnical skills in learning complex surgery. BACKGROUND: Superior teamwork in the operating room (OR) is associated with improved technical performance and clinical outcomes. iVR can successfully train OR staff individually; however, iVR team training has yet to be investigated. METHODS: Forty participants were randomized to individual or team iVR training. Individually trained participants practiced alongside virtual avatar counterparts, whereas teams trained live in pairs. Both groups underwent 5 iVR training sessions over 6 weeks. Subsequently, they completed a real-life assessment in which they performed anterior approach total hip arthroplasty surgery on a high-fidelity model with real equipment in a simulated OR. Teams performed together, and individually trained participants were randomly paired up. Videos were marked by 2 blinded assessors recording the 'Non-Operative Technical Skills for Surgeons, Oxford NOn-TECHnical Skills II and Scrub Practitioners' List of Intraoperative Non-Technical Skills' scores. Secondary outcomes were procedure duration and the number of technical errors. RESULTS: Teams outperformed individually trained participants for nontechnical skills in the real-world assessment (Non-Operative Technical Skills for Surgeons: 13.1±1.5 vs 10.6±1.6, P = 0.002, Non-TECHnical Skills II score: 51.7 ± 5.5 vs 42.3 ± 5.6, P = 0.001 and Scrub Practitioners' List of Intraoperative Non-Technical Skills: 10 ± 1.2 vs 7.9 ± 1.6, P = 0.004). They completed the assessment 33% faster (28.2 minutes ± 5.5 vs 41.8 ± 8.9, P < 0.001), and made fewer than half the number of technical errors (10.4 ± 6.1 vs 22.6 ± 5.4, P < 0.001). CONCLUSIONS: Multiplayer training leads to faster surgery with fewer technical errors and the development of superior nontechnical skills.

An Improved Recombineering Toolset for Plants.

Gene functional studies often rely on the expression of a gene of interest as transcriptional and translational fusions with specialized tags. Ideally, this is done in the native chromosomal contexts to avoid potential misexpression artifacts. Although recent improvements in genome editing have made it possible to directly modify the target genes in their native chromosomal locations, classical transgenesis is still the preferred experimental approach chosen in most gene tagging studies because of its time efficiency and accessibility. We have developed a recombineering-based tagging system that brings together the convenience of the classical transgenic approaches and the high degree of confidence in the results obtained by direct chromosomal tagging using genome-editing strategies. These simple, scalable, customizable recombineering toolsets and protocols allow a variety of genetic modifications to be generated. In addition, we developed a highly efficient recombinase-mediated cassette exchange system to facilitate the transfer of the desired sequences from a bacterial artificial chromosome clone to a transformation-compatible binary vector, expanding the use of the recombineering approaches beyond Arabidopsis (Arabidopsis thaliana). We demonstrated the utility of this system by generating more than 250 whole-gene translational fusions and 123 Arabidopsis transgenic lines corresponding to 62 auxin-related genes and characterizing the translational reporter expression patterns for 14 auxin biosynthesis genes.

Ultrasound-guided joint interventions of the lower extremity.

The purpose of this article is to better understand the role ultrasound plays in lower extremity joint interventions. Ultrasound is an important and reliable tool diagnostically and therapeutically. Real-time feedback, lack of ionizing radiation, and dynamic maneuverability make ultrasound an important tool in the proceduralist's armament. This article will touch upon the important anatomic considerations, clinical indications, and technical step-by-step details for lower extremity ultrasound interventions. Specifically, we will look at interventions involving the hip, knee, ankle, and foot. In addition, this article will discuss the roles corticosteroid and platelet-rich plasma may play in certain interventions.

Incorporating ultrasound training into undergraduate medical education in a faculty-limited setting.

BACKGROUND: Point of care ultrasound (POCUS) is becoming a major extension of patient care. From diagnostic efficacy to its widespread accessibility, POCUS has expanded beyond emergency departments to be a tool utilized by many specialties. With the expansion of its use, medical education has begun to implement ultrasound education earlier in curricula. However, at institutions without a formal ultrasound fellowship or curriculum, these students lack the fundamental knowledge of ultrasound. At our institution, we set out to incorporate an ultrasound curriculum, into undergraduate medical education utilizing a single faculty member and minimal curricular time. METHODS: Our stepwise implementation began with the development of a 3-hour fourth-year (M4) Emergency Medicine clerkship ultrasound teaching session, which included pre- and post-tests as well as a survey. The success with this session progressed to the development of a designated fourth-year ultrasound elective, which was evaluated with narrative feedback. Finally, we developed six 1-hour ultrasound sessions that correlated with first-year (M1) gross anatomy and physiology. A single faculty member was responsible for this curriculum and other instructors included residents, M4 students, and second-year (M2) near-peer tutors. These sessions also included pre- and post-tests and a survey. Due to curricular time limitations, all but the M4 Emergency Medicine clerkship session were optional. RESULTS: 87 students participated in the emergency medicine clerkship ultrasound session and 166 M1 students participated in the voluntary anatomy and physiology ultrasound sessions. All participants agreed or strongly agreed that they would like more ultrasound training, that ultrasound training should be integrated into all four years of undergraduate medical education. Students were in strong agreement that the ultrasound sessions helped increase understanding of anatomy and anatomical identification with ultrasound. CONCLUSION: We describe the stepwise addition of ultrasound into the undergraduate medical education curriculum of an institution with limited faculty and curricular time.

The impact of music, play, and pet therapies in managing pain and anxiety in paediatric patients in hospital: a rapid systematic review.

Background: Hospitalized children face pain and anxiety associated with the environment and procedures. Objective: This review aimed to assess the impact of music, play, pet and art therapies on pain and anxiety in hospitalized paediatric patients. RCTs assessing the impact of music, play, pet, and/or art therapies on pain and/or anxiety in hospitalized paediatric patients were eligible. Methods: Database searching and citation screening was completed to identify studies. A narrative synthesis was used to summarize study findings and certainty of evidence was assessed using GRADE. Of the 761 documents identified, 29 were included spanning music (n = 15), play (n = 12), and pet (n = 3) therapies. Results: A high certainty of evidence supported play in reducing pain and moderate certainty for music and pet. A moderate certainty of evidence supported music and play in reducing anxiety. Conclusion: Complementary therapies utilized alongside conventional medical treatment may mitigate pain and anxiety in hospitalized paediatric patients.

Increased Peripheral Blood Neutrophil Activation Phenotypes and Neutrophil Extracellular Trap Formation in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series and Review of the Literature.

BACKGROUND: Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. METHODS: Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. RESULTS: Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1ß, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. CONCLUSIONS: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.

Inflammatory phenotype modulation in the respiratory tract and systemic circulation of e-cigarette users: a pilot study.

Over 40 million people use e-cigarettes worldwide, but the impact of chronic e-cigarette use on health has not been adequately defined. In particular, effects of e-cigarette aerosol inhalation on inflammation and host defenses across the body are not fully understood. We conducted a longitudinal cohort pilot study to explore changes in the inflammatory state and monocyte function of e-cigarette users (n = 20) versus healthy controls (n = 13) and to evaluate effects of e-cigarette use reduction on the same. Saliva, sputum, and blood were obtained from e-cigarette users at baseline and after a 2-wk intervention of decreased e-cigarette use. Overall, across 38 proteins quantified by multiplex, airway samples from e-cigarette users tended to have decreased levels of immunomodulatory proteins relative to healthy controls, whereas levels of cytokines, chemokines, and growth factors in the circulation tended to be elevated. Specifically, e-cigarette users had lower levels of IL-1 receptor antagonist (IL-1Ra) in saliva (P < 0.0001), with higher IL-1Ra and growth-regulated oncogene (GRO) levels in sputum (P < 0.01 and P < 0.05, respectively), and higher levels of both TNFß (P < 0.0001) and VEGF (P < 0.0001) in plasma. Circulating monocytes from e-cigarette users had alterations in their inflammatory phenotype in response to reduced e-cigarette use, with blunted IL-8 and IL-6 release upon challenge with bacterial lipopolysaccharide (P < 0.001 and P < 0.05, respectively), suggesting a decreased ability to appropriately respond to bacterial infection. Based on these findings, chronic inhalation of e-cigarette aerosols alters the inflammatory state of the airways and systemic circulation, raising concern for the development of both inflammatory and infectious diseases in chronic users of e-cigarettes.

Immersive virtual reality enables technical skill acquisition for scrub nurses in complex revision total knee arthroplasty.

INTRODUCTION: Immersive Virtual Reality (iVR) is a novel technology which can enhance surgical training in a virtual environment without supervision. However, it is untested for the training to select, assemble and deliver instrumentation in orthopaedic surgery-typically performed by scrub nurses. This study investigates the impact of an iVR curriculum on this facet of the technically demanding revision total knee arthroplasty. MATERIALS AND METHODS: Ten scrub nurses completed training in four iVR sessions over a 4-week period. Initially, nurses completed a baseline real-world assessment, performing their role with real equipment in a simulated operation assessment. Each subsequent iVR session involved a guided mode, where the software taught participants the procedural choreography and assembly of instrumentation in a simulated operating room. In the latter three sessions, nurses also undertook an assessment in iVR. Outcome measures were related to procedural sequence, duration of surgery and efficiency of movement. Transfer of skills from iVR to the real world was assessed in a post-training simulated operation assessment. A pre- and post-training questionnaire assessed the participants knowledge, confidence and anxiety. RESULTS: Operative time reduced by an average of 47% across the 3 unguided sessions (mean 55.5 ± 17.6 min to 29.3 ± 12.1 min, p > 0.001). Assistive prompts reduced by 75% (34.1 ± 16.8 to 8.6 ± 8.8, p < 0.001), dominant hand motion by 28% (881.3 ± 178.5 m to 643.3 ± 119.8 m, p < 0.001) and head motion by 36% (459.9 ± 99.7 m to 292.6 ± 85.3 m, p < 0.001). Real-world skill improved from 11% prior to iVR training to 84% correct post-training. Participants reported increased confidence and reduced anxiety in scrubbing for rTKA procedures (p < 0.001). CONCLUSIONS: For scrub nurses, unfamiliarity with complex surgical procedures or equipment is common. Immersive VR training improved their understanding, technical skills and efficiency. These iVR-learnt skills transferred into the real world.

Thymosin ß4 coated nanofiber scaffolds for the repair of damaged cardiac tissue.

After a cardiac event, proper treatment and care of the damaged tissue is crucial in restoring optimal cardiac function and preventing future cardiac events. Recently, thymosin ß4 has been found to play a vital role in cardiac cell health and development by regulating angiogenesis, inflammatory responses, and wound healing. We proposed that defined poly(ϵ-caprolactone) (PCL) nanoscaffolds coated with thymosin ß4 could efficiently differentiate murine-derived cardiomyocytes into functioning cardiac tissue. PCL nanoscaffolds were developed through electrospinning technology, and subsequently coated with a thymosin ß4 solution. Cardiomyocytes were seeded on coated and uncoated nanoscaffolds and observed for six days via fluorescent and electron microscopy. Our results demonstrated a robust growth and differentiation of cardiomyocytes on coated nanoscaffolds compared with uncoated, showing potential for nanoscaffold-mediated cardiac cell replacement in vivo after an MI or other cardiac event.

Exploring the experiences of Canadian medical students with a background in the arts and humanities.

Background: Arts and Humanities (A/H) training is a powerful strategy to help medical students develop key competencies which align with the CanMEDS roles that Canadian physicians are expected to embody. Students with backgrounds in A/H may enter medical school with the skills and dispositions that A/H training provides. This paper explores the varied experiences of medical students with prior A/H backgrounds, with an emphasis on how they navigate relationships with their student cohorts and participate in undergraduate medical training environments. Methods: Descriptive qualitative research methodology was used to conduct and analyze semi-structured interviews exploring the perspectives of Canadian medical students with either a A/H degree or training in A/H (n = 13). Domains such as identity, integration of interests, and challenges in maintaining A/H interests during medical training were explored. Results: Participants described their A/H identity as intertwined with their identity as medical trainees and described their sense of interconnection between the disciplines. Challenges included imposter syndrome and difficulties in relating with peers from science backgrounds. Participants described returning to their A/H interests as a tool for wellness amidst medical training. Conclusions: Medical students with a background in A/H training describe this background as offering both affordances and challenges for their sense of identity, belonging, and wellness. These students offer an untapped resource: they come with dispositions of value to medicine, and they perceive a positive, hidden A/H curriculum that supports their maintenance of these dispositions during training. Understanding more about these hidden treasures could help foster the development of well-rounded and humanistic physicians in the entire medical class.

Contexte: Une formation en arts et sciences humaines (A/SH) est une stratégie efficace pour aider les étudiants en médecine à développer des compétences clés qui s'harmonisent aux rôles CanMEDS que les médecins canadiens sont censés incarner. Les étudiants ayant un bagage en A/SH peuvent entrer à la faculté de médecine dotés des compétences et des dispositions qu'une formation en A/SH apporte. Cet article explore les expériences diverses vécues par des étudiants en médecine ayant déjà un bagage en A/SH, en mettant l'accent sur la façon dont ils entretiennent des relations au sein de leurs cohortes d'étudiants et s'intègrent dans des contextes de formation médicale de premier cycle. Méthodes: Une méthodologie de recherche qualitative descriptive a été utilisée pour mener et analyser des entretiens semi-structurés explorant les points de vue d'étudiants en médecine canadiens ayant soit un diplôme en A/SH ou une formation en A/SH (n=13). Des domaines tels que l'identité, la conciliation des champs d'intérêt et les défis liés au maintien de ceux liés aux A/SH pendant la formation médicale ont été explorés. Résultats: Les participants ont décrit leur identité A/SH comme étant intimement liée à celle de médecin en formation et ont décrit leur sentiment d'interconnexion entre les disciplines. Parmi les défis à relever figurent le syndrome de l'imposteur et les difficultés à nouer des relations avec des pairs ayant un bagage scientifique. Les participants ont décrit le fait de revenir à leurs champs d'intérêt liés aux A/SH comme étant un outil de bien-être au courant de la formation médicale. Conclusions: Les étudiants en médecine qui ont un bagage en A/SH le décrivent comme offrant à la fois des possibilités et des défis pour leur sentiment d'identité, d'appartenance et de bien-être. Ces étudiants constituent une ressource inexploitée : ils ont des dispositions recherchées en médecine et ils ont l'impression de profiter d'un curriculum caché A/H positif qui les aide à conserver ces dispositions au cours de leur formation. Mieux comprendre ces trésors cachés pourrait contribuer à favoriser le développement de médecins compétents et humanistes au sein de leur cohorte.

Early Repolarization Syndrome Leading to Recurrent Cardiac Arrest in a Young Active Duty Patient.

A previously healthy, active duty 37-year-old male experienced recurrent cardiac arrests because of ventricular fibrillation and polymorphic ventricular tachycardia. Initial evaluation did not reveal a clear ischemic, structural, toxic, or metabolic cause. Close monitoring of telemetry before his third cardiac arrest revealed the cause to be early repolarization syndrome (ERS). In this case, we review the diagnosis, epidemiology, and prognostic significance of early repolarization pattern as it relates to ERS. We also discuss acute and long-term treatment strategies for patients with ERS.

The hallmarks of a tradeoff in transcriptomes that balances stress and growth functions.

Fast growth phenotypes are achieved through optimal transcriptomic allocation, in which cells must balance tradeoffs in resource allocation between diverse functions. One such balance between stress readiness and unbridled growth in E. coli has been termed the fear versus greed (f/g) tradeoff. Two specific RNA polymerase (RNAP) mutations observed in adaptation to fast growth have been previously shown to affect the f/g tradeoff, suggesting that genetic adaptations may be primed to control f/g resource allocation. Here, we conduct a greatly expanded study of the genetic control of the f/g tradeoff across diverse conditions. We introduced 12 RNA polymerase (RNAP) mutations commonly acquired during adaptive laboratory evolution (ALE) and obtained expression profiles of each. We found that these single RNAP mutation strains resulted in large shifts in the f/g tradeoff primarily in the RpoS regulon and ribosomal genes, likely through modifying RNAP-DNA interactions. Two of these mutations additionally caused condition-specific transcriptional adaptations. While this tradeoff was previously characterized by the RpoS regulon and ribosomal expression, we find that the GAD regulon plays an important role in stress readiness and ppGpp in translation activity, expanding the scope of the tradeoff. A phylogenetic analysis found the greed-related genes of the tradeoff present in numerous bacterial species. The results suggest that the f/g tradeoff represents a general principle of transcriptome allocation in bacteria where small genetic changes can result in large phenotypic adaptations to growth conditions.IMPORTANCETo increase growth, E. coli must raise ribosomal content at the expense of non-growth functions. Previous studies have linked RNAP mutations to this transcriptional shift and increased growth but were focused on only two mutations found in the protein's central region. RNAP mutations, however, commonly occur over a large structural range. To explore RNAP mutations' impact, we have introduced 12 RNAP mutations found in laboratory evolution experiments and obtained expression profiles of each. The mutations nearly universally increased growth rates by adjusting said tradeoff away from non-growth functions. In addition to this shift, a few caused condition-specific adaptations. We explored the prevalence of this tradeoff across phylogeny and found it to be a widespread and conserved trend among bacteria.

Factors associated with enteral autonomy after reanastomosis in infants with intestinal failure and ostomy: A descriptive cohort study.

BACKGROUND: To determine variables associated with outcomes in infants with intestinal failure (IF) and ostomy following reanastomosis (RA). METHODS: A single-center, descriptive cohort study of 120 infants with IF and a stoma from January 2011 to December 2020 with subsequent RA during initial hospitalization. The primary outcome was achievement of enteral autonomy (EA) following RA. Other outcomes were duration of hospital stay, and mortality. Penalized logistic regression and linear regression were used for data analysis. RESULTS: The median gestational age was 26 weeks, and the median birth weight was 890 g. Three infants died. The median duration between ostomy creation and RA was 80 days (interquartile range; 62.5, 100.5). For each additional day of discontinuity, the odds of EA decreased by 2% (odds ratio [OR] = 0.980; 95% confidence interval [CI]: 0.962, 0.999; P = 0.038), and death increased by 4.2% (OR = 1.042; 95% CI: 1.010, 1.075; P = 0.009). For each additional mL/kg/day of enteral feeds at RA, the odds of EA increased by 7.5% (OR = 1.075; 95% CI: 1.027, 1.126, P = 0.002) and duration of hospital stay decreased by 0.35 days (slope coefficient = -0.351; 95% CI: -0.540, -0.163; P < 0.001). CONCLUSION: Shorter duration of intestinal discontinuity and enteral nutrition before RA could positively influence EA and duration of stay in infants with IF and ostomy following RA.

Proteome allocation is linked to transcriptional regulation through a modularized transcriptome.

It has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigate whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions can be modularized in the same way to reveal novel relationships between their compositions. We find that; (1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, (2) the modules in the proteome often represent combinations of modules from the transcriptome, (3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and (4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.

Is adiposity associated with white matter microstructural health and intelligence differently in males and females?

OBJECTIVE: The role of vascular risk factors in age-related brain degeneration has long been the subject of intense study, but the role of obesity remains understudied. Given known sex differences in fat storage and usage, this study investigates sex differences in the association between adiposity and white matter microstructural integrity, an important early marker of brain degeneration. METHODS: This study assesses the associations between adiposity (abdominal fat ratio and liver proton density fat fraction) and brain health (measures of intelligence and white matter microstructure using diffusion-tensor imaging [DTI]) in a group of UK Biobank participants. RESULTS: This study finds that intelligence and DTI metrics are indeed associated with adiposity differently in males and females. These sex differences are distinct from those in the associations of DTI metrics with age and blood pressure. CONCLUSIONS: Taken together, these findings suggest that there are inherent sex-driven differences in how brain health is associated with obesity.

The Contractile Response to Oxytocin in Non-pregnant Rat Uteri Is Modified After the First Pregnancy.

During pregnancy, the uterus undergoes several modifications under the influence of hormonal and mechanical stimuli. We hypothesize that while most of these modifications are reverted during involution, some of the physiological properties of the uterus are permanently altered. To investigate this hypothesis, we conducted motility experiments to evaluate the contractility response of uterine tissue samples from non-pregnant virgin and proven breeder female rats to oxytocin (10-10 to 10-5 M). We found that the virgin tissue contracts more robustly than proven breeder tissue in the absence of oxytocin, yet with oxytocin, proven breeder samples displayed a significantly higher increase in activity. These results could depend on a more elevated expression of oxytocin receptor and/or on an alteration in the intracellular pathways affected by the activation of the oxytocin receptors. Here, we explored the impact of some structures involved in the management of intracellular calcium on the dose response to oxytocin recorded from virgin and proven breeder uterine strips. Specifically, we replicated the dose response experiments in low extracellular calcium (10 µM), in the presence of the intracellular calcium channel blocker ruthenium red (10 µM), and in the presence of the sarcoplasmic-endoplasmic reticulum calcium ATP-ase pump inhibitor, cyclopiazonic acid (10 µM). The results of these experiments suggest that also the expression of proteins that control intracellular calcium availability is affected by the experience of pregnancy. Molecular biology experiments will give us more detail on the magnitude of these expression changes.