Innovation, conservation, and repurposing of gene function in root cell type development.

Plant species have evolved myriads of solutions, including complex cell type development and regulation, to adapt to dynamic environments. To understand this cellular diversity, we profiled tomato root cell type translatomes. Using xylem differentiation in tomato, examples of functional innovation, repurposing, and conservation of transcription factors are described, relative to the model plant Arabidopsis. Repurposing and innovation of genes are further observed within an exodermis regulatory network and illustrate its function. Comparative translatome analyses of rice, tomato, and Arabidopsis cell populations suggest increased expression conservation of root meristems compared with other homologous populations. In addition, the functions of constitutively expressed genes are more conserved than those of cell type/tissue-enriched genes. These observations suggest that higher order properties of cell type and pan-cell type regulation are evolutionarily conserved between plants and animals.

Information theory and machine learning illuminate large-scale metabolomic responses of Brachypodium distachyon to environmental change.

Plant responses to environmental change are mediated via changes in cellular metabolomes. However, <5% of signals obtained from liquid chromatography tandem mass spectrometry (LC-MS/MS) can be identified, limiting our understanding of how metabolomes change under biotic/abiotic stress. To address this challenge, we performed untargeted LC-MS/MS of leaves, roots, and other organs of Brachypodium distachyon (Poaceae) under 17 organ-condition combinations, including copper deficiency, heat stress, low phosphate, and arbuscular mycorrhizal symbiosis. We found that both leaf and root metabolomes were significantly affected by the growth medium. Leaf metabolomes were more diverse than root metabolomes, but the latter were more specialized and more responsive to environmental change. We found that 1 week of copper deficiency shielded the root, but not the leaf metabolome, from perturbation due to heat stress. Machine learning (ML)-based analysis annotated approximately 81% of the fragmented peaks versus approximately 6% using spectral matches alone. We performed one of the most extensive validations of ML-based peak annotations in plants using thousands of authentic standards, and analyzed approximately 37% of the annotated peaks based on these assessments. Analyzing responsiveness of each predicted metabolite class to environmental change revealed significant perturbations of glycerophospholipids, sphingolipids, and flavonoids. Co-accumulation analysis further identified condition-specific biomarkers. To make these results accessible, we developed a visualization platform on the Bio-Analytic Resource for Plant Biology website (https://bar.utoronto.ca/efp_brachypodium_metabolites/cgi-bin/efpWeb.cgi), where perturbed metabolite classes can be readily visualized. Overall, our study illustrates how emerging chemoinformatic methods can be applied to reveal novel insights into the dynamic plant metabolome and stress adaptation.

The Impact of Point-of-Care Ultrasound-Guided Resuscitation on Clinical Outcomes in Patients With Shock: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the impact of point-of-care ultrasound (POCUS)-guided resuscitation on clinical outcomes in adult patients with shock. DATA SOURCE: We searched MEDLINE, Embase, and unpublished sources from inception to December 2023. STUDY SELECTION: We included randomized controlled trials (RCTs) that examined the use of POCUS to guide resuscitation in patients with shock. DATA EXTRACTION: We collected data regarding study and patient characteristics, POCUS protocol, control group interventions, and outcomes. DATA SYNTHESIS: We identified 18 eligible RCTs. POCUS slightly influences physicians' plans for IV fluid (IVF) and vasoactive medication prescription (moderate certainty), but results in little to no changes in the administration of IVF (low to high certainty) or inotropes (high certainty). POCUS may result in no change in the number of CT scans performed (low certainty) but probably reduces the number of diagnostic echocardiograms performed (moderate certainty). POCUS-guided resuscitation probably reduces 28-day mortality (relative risk [RR] 0.88; 95% CI, 0.78-0.99), the duration of vasoactive medication (mean difference -0.73 d; 95% CI, -1.16 to -0.30), and the need for renal replacement therapy (RRT) (RR 0.80; 95% CI, 0.63-1.02) (low to moderate certainty evidence), and lactate clearance (high certainty evidence). POCUS-guided resuscitation may results in little to no difference in ICU or hospital admissions, ICU and hospital length of stay, and the need for mechanical ventilation (MV) (low to moderate certainty evidence). There is an uncertain effect on the risk of acute kidney injury and the duration of MV or RRT (very low certainty evidence). CONCLUSIONS: POCUS-guided resuscitation in shock may yield important patient and health system benefits. Due to lack of sufficient evidence, we were unable to explore how the thresholds of operator competency, frequency, and timing of POCUS scans impact patient outcomes.

Factors contributing to health care worker turnover in intensive care units during the COVID-19 pandemic in Alberta, Canada: a qualitative descriptive interview study.

PURPOSE: The COVID-19 pandemic has resulted in increased job vacancies in Canadian intensive care units (ICUs). We aimed to identify, explore, and describe factors contributing to the decisions of health care workers to leave, or strongly consider leaving their ICU positions during the peri-COVID-19 pandemic era. METHODS: We undertook a qualitative descriptive study between June and August 2022. We conducted semistructured interviews with 19 registered nurses and one respiratory therapist from a single ICU in Alberta, Canada who had left, or had strongly considered leaving their ICU position since the beginning of the pandemic. We used Braun and Clarke's thematic analysis to generate themes from these interviews. RESULTS: We identified five themes to describe the factors that contributed to participants' decisions to leave, or strongly consider leaving, their ICU positions. These were: 1) toxic workplace, 2) inadequate staffing, 3) distress from providing nonbeneficial care, 4) caring for patients with COVID-19 and their families, and 5) paradoxical responses to COVID-19 outside of the ICU. Some of these factors existed before the pandemic and were exacerbated by it, while others were novel to COVID-19. CONCLUSIONS: Participants described as key factors in their decision or desire to leave their ICU positions the impacts of the COVID-19 pandemic on workplace culture, staffing, and patient interactions, as well as the discourse surrounding COVID-19 outside of work. Strategies that target workplace culture and ensure adequate staffing should be prioritized to promote staff retention following the pandemic.

RéSUMé: OBJECTIF: La pandémie de COVID-19 a entraîné une augmentation du nombre de postes vacants dans les unités de soins intensifs (USI) canadiennes. Notre objectif était d'identifier, d'explorer et de décrire les facteurs qui ont contribué à la décision des travailleuses et travailleurs de la santé de quitter ou d'envisager fortement de quitter leur poste aux soins intensifs pendant la période péri-pandémie de COVID-19. MéTHODE: Nous avons réalisé une étude descriptive qualitative entre juin et août 2022. Nous avons mené des entrevues semi-structurées auprès de 19 membres du personnel infirmier autorisé et d'un·e inhalothérapeute d'une seule unité de soins intensifs en Alberta, au Canada, qui avaient quitté ou fortement envisagé de quitter leur poste aux soins intensifs depuis le début de la pandémie. Nous avons utilisé l'analyse thématique de Braun et Clarke pour générer des thèmes à partir de ces entretiens. RéSULTATS: Nous avons cerné cinq thèmes pour décrire les facteurs qui ont contribué à la décision des participant·es de quitter ou d'envisager fortement de quitter leur poste aux soins intensifs : 1) un lieu de travail toxique, 2) un personnel inadéquat, 3) la détresse liée à la fourniture de soins non bénéfiques, 4) la prise en charge des personnes atteintes de COVID-19 et de leurs familles, et 5) les réponses paradoxales à la COVID-19 en dehors de l'unité de soins intensifs. Certains de ces facteurs existaient avant la pandémie et ont été exacerbés par celle-ci, tandis que d'autres étaient nouveaux et liés à la COVID-19. CONCLUSION: Les participant·es ont décrit comme des facteurs clés dans leur décision ou leur désir de quitter leur poste aux soins intensifs les répercussions de la pandémie de COVID-19 sur la culture du lieu de travail, la dotation et les interactions avec la patientèle, ainsi que le discours entourant la COVID-19 en dehors du travail. Les stratégies qui ciblent la culture du milieu de travail et assurent une dotation adéquate devraient être priorisées afin de favoriser le maintien en poste du personnel après la pandémie.

Modelling the potential increase in eligible participants in clinical trials with inclusion of community intensive care unit patients in Alberta, Canada: a decision tree analysis.

PURPOSE: Critical care research in Canada is conducted primarily in academically affiliated intensive care units (ICUs) with established research infrastructure. Efforts are made to engage community hospital ICUs in research, although the impacts of their inclusion in clinical research have never been explicitly quantified. We therefore sought to determine the number of additional eligible patients that could be recruited into critical care trials and the change in time to study completion if community ICUs were included in clinical research. METHODS: We conducted a decision tree analysis using 2018 Alberta Health Services data. Patient demographics and clinical characteristics for all ICU patients were compared against eligibility criteria from ten landmark, randomized, multicentre critical care trials. Individual patients from academic and community ICUs were assessed for eligibility in each of the ten studies, and decision tree analysis models were built based on prior inclusion and exclusion criteria from those trials. RESULTS: The number of potentially eligible patients for the ten trials ranged from 2,082 to 10,157. Potentially eligible participants from community ICUs accounted for 40.0% of total potentially eligible participants. The recruitment of community ICU patients in trials would have increased potential enrolment by an average of 64.0%. The inclusion of community ICU patients was predicted to decrease time to trial completion by a mean of 14 months (43% reduction). CONCLUSION: Inclusion of community ICU patients in critical care research trials has the potential to substantially increase enrolment and decrease time to trial completion.

RéSUMé: OBJECTIF: La recherche en soins intensifs au Canada est principalement réalisée dans des unités de soins intensifs affiliées à des centres universitaires jouissant d'infrastructures de recherche bien établies. Des efforts ont été déployés pour engager les unités de soins intensifs des hôpitaux communautaires en recherche, mais les impacts de leur participation à la recherche clinique n'ont jamais été explicitement quantifiés. Nous avons conséquemment cherché à déterminer le nombre de patient·es additionnel·les pouvant être recruté·es dans des études de soins critiques ainsi que la variation du temps nécessaire pour compléter les études si la patientèle issue d'unités de soins intensifs d'hôpitaux communautaires participait à la recherche clinique. MéTHODE: Une analyse par arbre de décision a été réalisée à partir de données provenant des Alberta Health Services pour l'année 2018. Les données démographiques et les caractéristiques cliniques de tou·tes les patient·es admis·es aux soins intensifs ont été comparées avec les critères d'éligibilité de dix importantes études multicentriques, randomisées, contrôlées en soins intensifs. Les patient·es des unités de soins intensifs universitaires et communautaires ont tou·tes été évalué·es pour leur éligibilité à chacune des dix études, et des modèles d'arbres décisionnels ont été construits en se basant sur les critères originaux d'inclusion et d'exclusion. RéSULTATS: Le nombre de personnes potentiellement éligibles pour les dix études s'est situé entre 2082 et 10 157. Les patient·es potentiellement admissibles en provenance d'unités de soins intensifs communautaires ont représenté 40,0 % de toutes les personnes potentiellement admissibles. Le recrutement de patient·es en provenance d'unités de soins intensifs communautaires aurait permis une hausse moyenne du recrutement potentiel de 64,0 %. L'inclusion de patient·es des unités de soins intensifs communautaires pourrait également réduire le temps nécessaire à la complétion des études de 14 mois en moyenne (réduction de 43 %). CONCLUSION: L'inclusion de patient·es en provenance d'unités de soins intensifs d'hôpitaux communautaires dans la recherche clinique en soins critiques a le potentiel d'augmenter substantiellement le recrutement et de diminuer le temps nécessaire à la complétion des études.

Nonsteroidal anti-inflammatory drugs for analgesia in intensive care units: a survey of Canadian critical care physicians.

PURPOSE: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs). METHODS: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing. RESULTS: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care. CONCLUSIONS: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients.

RéSUMé: OBJECTIF: Les opioïdes restent le pilier de l'analgésie pour les patient·es gravement malades, mais l'exposition à ces agents est associée à des effets négatifs, notamment à leur utilisation persistante après le congé de l'hôpital. Les anti-inflammatoires non stéroïdiens (AINS) pourraient constituer une alternative efficace aux opioïdes avec moins d'effets indésirables. Nous avons cherché à décrire les croyances et les attitudes à l'égard de l'utilisation des AINS dans les unités de soins intensifs (USI) pour adultes. MéTHODE: Notre sondage auprès des médecins intensivistes au Canada a été mené à l'aide d'une plateforme Web et distribué aux personnes sur la liste de distribution électronique de la Société canadienne de soins intensifs (SCSI). Nous avons utilisé une méthodologie d'élaboration d'enquêtes décrite précédemment, y compris la génération et la réduction de questions, les tests préalables, la sensibilité clinique et les tests pilotes. RéSULTATS: Nous avons reçu 115 sondages remplis par 321 membres de la SCSI (36 %). L'utilisation d'anti-inflammatoires non stéroïdiens a été décrite comme « rare ¼ (59 répondant·es, 51 %), la principale préoccupation étant les événements indésirables (insuffisance rénale aiguë [108 répondant·es, 94 %] et saignements gastro-intestinaux [92 répondant·es, 80 %]). Le principal analgésique préféré était l'acétaminophène (75 répondant·es, 65 %), suivi des opioïdes (40 répondant·es, 35 %). La plupart des répondant·es (91 répondant·es, 80 %) seraient prêt·es à participer à une étude randomisée contrôlée examinant l'utilisation des AINS en soins intensifs. CONCLUSION: Dans notre sondage, les médecins intensivistes au Canada n'ont pas mentionné l'utilisation courante d'AINS, principalement en raison de préoccupations concernant leurs effets indésirables. Néanmoins, les répondant·es étaient intéressé·es à étudier plus avant le kétorolac, un AINS couramment utilisé en dehors des soins intensifs, chez les patient·es gravement malades.

Green Seaweed Caulerpa racemosa as a Novel Non-Small Cell Lung Cancer Inhibitor in Overcoming Tyrosine Kinase Inhibitor Resistance: An Analysis Employing Network Pharmacology, Molecular Docking, and In Vitro Research.

The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is Caulerpa racemosa, a type of green algae known as green seaweed, seagrapes, or green caviar. This organism stands out because it has great promise for use in medicine, especially in the study of cancer. Through the utilization of computational modeling (in silico) and cellular laboratory experiments (in vitro), the chemical components included in the green seaweed C. racemosa were effectively analyzed, uncovering its capability to treat non-small cell lung cancer (NSCLC). The study specifically emphasized blocking SRC, STAT3, PIK3CA, MAPK1, EGFR, and JAK1 using molecular docking and in vitro. These proteins play a crucial role in the EGFR Tyrosine Kinase Inhibitor Resistance pathway in NSCLC. The chemical Caulersin (C2) included in C. racemosa extract (CRE) has been identified as a potent and effective agent in fighting against non-small cell lung cancer (NSCLC), both in silico and in vitro. CRE and C2 showed a level of inhibition similar to that of osimertinib (positive control/NSCLC drug).

Heterogeneous Catalyst as a Functional Substrate Governing the Shape of Electrochemical Precipitates in Oxygen-Fueled Rechargeable Batteries.

Lithium-oxygen batteries have the potential to become the most eminent solution for future energy storage with their theoretical energy density exceeding all existing batteries. However, the insulating and insoluble discharge product (lithium peroxide; Li2O2) impairs practical application. Conventional catalyst designs based on the electronic structure and interfacial charge transfer descriptors have not been able to overcome these limitations due to Li2O2. Herein, we revisit the role of heterogeneous catalysts as substrates to regulate Li2O2 growth and the formation of solid/solid reaction interfaces. We demonstrate that controlled solid/solid interfacial structure design is a critical performance parameter beyond the inherent electronic structure. In particular, the Cu2O substrate in this study induces a homogeneous deposition of Pd atoms, which leads to well-controlled growth of Li2O2 resolving mass and charge transport limits (i.e., the bottleneck of oxygen reduction/evolution reactions), thus improving reversibility, capacity, and durability of the cells by dissipating electrochemical and mechanical stress. We thus verified the essential role of solid/solid interfaces to regulate the nucleation and growth process of Li2O2 in lithium-oxygen batteries.

Safety Outcomes of Direct Discharge Home From ICUs: An Updated Systematic Review and Meta-Analysis (Direct From ICU Sent Home Study).

OBJECTIVE: To evaluate the impact of direct discharge home (DDH) from ICUs compared with ward transfer on safety outcomes of readmissions, emergency department (ED) visits, and mortality. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature from inception until March 28, 2022. STUDY SELECTION: Randomized and nonrandomized studies of DDH patients compared with ward transfer were eligible. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the Newcastle-Ottawa Scale for observational studies. A random-effects meta-analysis model and heterogeneity assessment was performed using pooled data (inverse variance) for propensity-matched and unadjusted cohorts. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: Of 10,228 citations identified, we included six studies. Of these, three high-quality studies, which enrolled 49,376 patients in propensity-matched cohorts, could be pooled using meta-analysis. For DDH from ICU, compared with ward transfers, there was no difference in the risk of ED visits at 30-day (22.4% vs 22.7%; relative risk [RR], 0.99; 95% CI, 0.95-1.02; p = 0.39; low certainty); hospital readmissions at 30-day (9.8% vs 9.6%; RR, 1.02; 95% CI, 0.91-1.15; p = 0.71; very low-to-low certainty); or 90-day mortality (2.8% vs 2.6%; RR, 1.06; 95% CI, 0.95-1.18; p = 0.29; very low-to-low certainty). There were no important differences in the unmatched cohorts or across subgroup analyses. CONCLUSIONS: Very low-to-low certainty evidence from observational studies suggests that DDH from ICU may have no difference in safety outcomes compared with ward transfer of selected ICU patients. In the future, this research question could be further examined by randomized control trials to provide higher certainty data.

Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Di-fluoro azepane HBV capsid assembly modulators.

The protein that forms the inner shell of the HBV virus, known as the capsid core protein, plays a crucial role in allowing chronic HBV infections to persist. Studies have shown that disrupting the assembly of the capsid can effectively combat the virus, and small molecule drugs that target the HBV capsid assembly modulator (CAM) process have been successful in clinical trials. Herein is described a distinct series of di-fluoro azepane CAMs with exceptional potency, pharmacokinetic, and solubility properties.

Prevalence and Readmission Rates of Discharge Directly Home From the PICU: A Systematic Review.

OBJECTIVES: Critically ill patients are increasingly being discharged directly home from PICU as opposed to discharged home, via the ward. The objective was to assess the prevalence, safety, and satisfaction of discharge directly home from PICUs. DATA SOURCES: We searched PubMed, Medline, EMBASE, PsycINFO, and CINAHL for studies published between January 1991 and June 2021. STUDY SELECTION: We included observational or randomized studies, of children up to 18 years old, that reported on the prevalence, safety, or satisfaction of discharge directly home from the PICU, compared with the ward. Safety outcomes included readmission, unplanned visits to hospital, and any adverse events. We excluded case series, reviews, and studies discharging patients to other facilities. DATA EXTRACTION: Two independent reviewers evaluated 88 full-text articles; five studies met eligibility (362,868 patients). Only one study had discharge directly home as a primary outcome. DATA SYNTHESIS: Prevalence of discharge directly to home from the PICU ranged from less than 1% to 23% (random effects proportion 7.7 [95% CI, 1.3-18.6]). Readmissions to the PICU (only safety outcome) were significantly lower in the discharge directly home group compared with the ward group, in two of three studies (p < 0.0001). No studies reported on patient or family satisfaction. CONCLUSIONS: The prevalence of discharge directly home from the PICU ranges from 1% to 23%. PICU readmission rates do not appear to increase after discharge directly home. Caution is needed in the interpretation of the results, given the significant heterogeneity of the included studies. Further high-quality studies are needed to evaluate the safety of discharge directly home from the PICU and support families in this transition.

Associations between GoSmart Channel, health literacy and health behaviours in adolescents: A population-based study.

BACKGROUND: Health literacy is essential in the promotion of healthy lifestyle habits and chronic disease prevention. OBJECTIVE: To assess the health literacy level among Hong Kong adolescents; to evaluate the association between access of an online health information platform (GoSmart Channel) and health literacy level; and to examine the association between health literacy level and various unhealthy behaviours. DESIGN: This study recruited students from 10 local secondary schools in Hong Kong to assess the health literacy level among adolescents. SETTINGS AND PARTICIPANTS: Participants were required to complete a self-administered questionnaire on health behaviours and health literacy using the Health Literacy Measure for Adolescents (HELMA). MAIN OUTCOME MEASURE: Data were analysed using descriptive statistics and multivariate regression modelling. RESULTS: A total of 777 responses were collected. Overall, most (74.4%) of the adolescents in Hong Kong have limited health literacy (HELMA score <66). The majority (63.7%) of adolescents relied on their parents for health information, while 11.4% of the respondents sought information from the GoSmart Channel. The intervention of GoSmart Channel was significantly associated with better health literacy in almost all aspects among adolescents. Desired levels of health literacy were significantly associated with better perceived health (adjusted odds ratio: 2.04, p = .001) and negatively associated with a range of unhealthy and risky behaviours including unhealthy dietary habits, poor hygienic measures and physical inactivity. DISCUSSION AND CONCLUSION: This study highlights the importance of improving health literacy among Hong Kong adolescents and the potential of technology-based interventions. The findings suggest the need for continued efforts to promote health literacy and healthy behaviours among adolescents, especially given the limited health literacy levels observed in the study. PATIENT OR PUBLIC CONTRIBUTION: Members of the GoSmart.Net Built-on Project patient and public involvement and engagement group advised about survey development.

Regulating Pseudo-Jahn-Teller Effect and Superstructure in Layered Cathode Materials for Reversible Alkali-Ion Intercalation.

The Jahn-Teller effect (JTE) is one of the most important determinators of how much stress layered cathode materials undergo during charge and discharge; however, many reports have shown that traces of superstructure exist in pristine layered materials and irreversible phase transitions occur even after eliminating the JTE. A careful consideration of the energy of cationic distortion using a Taylor expansion indicated that second-order JTE (pseudo-JTE) is more widespread than the aforementioned JTE because of the various bonding states that occur between bonding and antibonding molecular orbitals in transition-metal octahedra. As a model case, a P2-type Mn-rich cathode (Na3/4MnO2) was investigated in detail. MnO6 octahedra are well known to undergo either elongation or contraction in a specific direction due to JTE. Here, the substitution of Li for Mn (Na3/4(Li1/4Mn3/4)O2) helped to oxidize Mn3+ to Mn4+ suppressing JTE; however, the MnO6 octahedra remained asymmetric with a clear trace of the superstructure. With various advanced analyses, we disclose the pseudo-JTE as a general reason for the asymmetric distortions of the MnO6 octahedra. These distortions lead to the significant electrochemical degradation of Na3/4Li1/4Mn3/4O2. The suppression of the pseudo-JTE modulates phase transition behaviors during Na intercalation/deintercalation and thereby improves all of the electrochemical properties. The insight obtained by coupling a theoretical background for the pseudo-JTE with verified layered cathode material lattice changes implies that many previous approaches can be rationalized by regulating pseudo-JTE. This suggests that the pseudo-JTE should be thought more important than the well-known JTE for layered cathode materials.

Outcomes After Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis.

OBJECTIVES: To compare health service use and clinical outcomes for patients with and without direct discharge to home (DDH) from ICUs in Ontario. DESIGN: Population-based, observational, cohort study using propensity scoring to match patients who were DDH to those not DDH and a preference-based instrumental variable (IV) analysis using ICU-level DDH rate as the IV. SETTING: ICUs in Ontario. PATIENTS: Patients discharged home from a hospitalization either directly or within 48 hours of care in an ICU between April 1, 2015, and March 31, 2017. INTERVENTION: DDH from ICU. MEASUREMENTS AND MAIN RESULTS: Among 76,737 patients in our cohort, 46,859 (61%) were DDH from the ICU. In the propensity matched cohort, the odds for our primary outcome of hospital readmission or emergency department (ED) visit within 30 days were not significantly different for patients DDH (odds ratio [OR], 1.00; 95% CI, 0.96-1.04), and there was no difference in mortality at 90 days for patients DDH (OR, 1.08; 95% CI, 0.97-1.21). The effect on hospital readmission or ED visits was similar in the subgroup of patients discharged from level 2 (OR, 0.98; 95% CI, 0.92-1.04) and level 3 ICUs (OR, 1.02; 95% CI, 0.96-1.09) and in the subgroups with cardiac conditions (OR, 1.03; 95% CI, 0.96-1.12) and noncardiac conditions (OR, 0.98; 95% CI, 0.94-1.03). Similar results were obtained in the IV analysis (coefficient for hospital readmission or ED visit within 30 d = -0.03 ± 0.03 ( se ); p = 0.3). CONCLUSIONS: There was no difference in outcomes for patients DDH compared with ward transfer prior to discharge when two approaches were used to minimize confounding within a large health systemwide observational cohort. We did not evaluate how patients are selected for DDH. Our results suggest that with careful patient selection, this practice might be feasible for routine implementation to ensure efficient and safe use of limited healthcare resources.

Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To determine the safety and efficacy of probiotics or synbiotics on morbidity and mortality in critically ill adults and children. DATA SOURCES: We searched MEDLINE, EMBASE, CENTRAL, and unpublished sources from inception to May 4, 2021. STUDY SELECTION: We performed a systematic search for randomized controlled trials (RCTs) that compared enteral probiotics or synbiotics to placebo or no treatment in critically ill patients. We screened studies independently and in duplicate. DATA EXTRACTION: Independent reviewers extracted data in duplicate. A random-effects model was used to pool data. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Sixty-five RCTs enrolled 8,483 patients. Probiotics may reduce ventilator-associated pneumonia (VAP) (relative risk [RR], 0.72; 95% CI, 0.59 to 0.89 and risk difference [RD], 6.9% reduction; 95% CI, 2.7-10.2% fewer; low certainty), healthcare-associated pneumonia (HAP) (RR, 0.70; 95% CI, 0.55-0.89; RD, 5.5% reduction; 95% CI, 8.2-2.0% fewer; low certainty), ICU length of stay (LOS) (mean difference [MD], 1.38 days fewer; 95% CI, 0.57-2.19 d fewer; low certainty), hospital LOS (MD, 2.21 d fewer; 95% CI, 1.18-3.24 d fewer; low certainty), and duration of invasive mechanical ventilation (MD, 2.53 d fewer; 95% CI, 1.31-3.74 d fewer; low certainty). Probiotics probably have no effect on mortality (RR, 0.95; 95% CI, 0.87-1.04 and RD, 1.1% reduction; 95% CI, 2.8% reduction to 0.8% increase; moderate certainty). Post hoc sensitivity analyses without high risk of bias studies negated the effect of probiotics on VAP, HAP, and hospital LOS. CONCLUSIONS: Low certainty RCT evidence suggests that probiotics or synbiotics during critical illness may reduce VAP, HAP, ICU and hospital LOS but probably have no effect on mortality.

Diazepinone HBV capsid assembly modulators.

The HBV capsid core protein serves a number of important functions in the viral life cycle enabling chronic HBV infection to persist, and therefore is a promising drug target. Interfering with capsid assembly has shown efficacy in clinical trials with small molecule capsid assembly modulators (CAMs). Herein is described the further optimization of a progressive series of diazepinone HBV CAMs.

Long-term Safety of Directly Discharging Patients Home from the ICU Compared to Ward Transfer.

Purpose: To evaluate the long-term safety of directly discharging intensive care unit (ICU) survivors to their home. Methods: A retrospective observational cohort of 341 ICU survivors who were directly discharged home from the ICU ("direct discharge") or discharged home ≤72 hours after ICU transfer to the ward ("ward transfer") was conducted in Regina, Saskatchewan ICUs between September 1, 2016 and September 30, 2018. The primary outcome was 90-day hospital readmission. Secondary outcomes included 30-day, 90-day, and 365-day emergency department (ED) visits, 30-day and 365-day hospital readmissions, and 365-day mortality. All outcomes were evaluated by multivariable Cox regression after adjustment for demographic and clinical characteristics. Results: Of 341 survivors (25.5% of total ICU visits), 148 (43.4%) patients were direct discharges and 193 (56.6%) were ward transfers. The median age was 46 years (interquartile range, 34-62), 38.4% were female, and 61.8% resided in Regina. Compared to the ward transfer cohort, more patients in the direct discharge cohort had at least one 90-day hospital readmission (30.4% versus 17.1% of patients, adjusted hazard ratio 2.09, 95% confidence interval 1.28-3.40, P = .003), after adjustment. Additionally, there were more 90-day ED visits (P = .045), and 30-day (P = .049) and 365-day hospital readmissions (P = .03), after adjustment. Conclusions: In Saskatchewan, direct discharge compared to ward transfer was associated with an increase in 90-day hospital readmissions, and potentially other clinical outcomes. Further study is necessary.

Needs Assessment Survey Identifying Research Processes Which may be Improved by Automation or Artificial Intelligence: ICU Community Modeling and Artificial Intelligence to Improve Efficiency (ICU-Comma).

BACKGROUND: Critical care research in Canada is conducted primarily in academically-affiliated intensive care units with established research infrastructure, including research coordinators (RCs). Recently, efforts have been made to engage community hospital ICUs in research albeit with barriers. Automation or artificial intelligence (AI) could aid the performance of routine research tasks. It is unclear which research study processes might be improved through AI automation. METHODS: We conducted a cross-sectional survey of Canadian ICU research personnel. The survey contained items characterizing opinions regarding research processes that may be amenable to AI automation. We distributed the questionnaire via email distribution lists of 3 Canadian research societies. Open-ended questions were analyzed using a thematic content analysis approach. RESULTS: A total of 49 survey responses were received (response rate: 8%). Tasks that respondents felt were time-consuming/tedious/tiresome included: screening for potentially eligible patients (74%), inputting data into case report forms (65%), and preparing internal tracking logs (53%). Tasks that respondents felt could be performed by AI automation included: screening for eligible patients (59%), inputting data into case report forms (55%), preparing internal tracking logs (51%), and randomizing patients into studies (45%). Open-ended questions identified enthusiasm for AI automation to improve information accuracy and efficiency while freeing up RCs to perform tasks that require human interaction. This enthusiasm was tempered by the need for proper AI education and oversight. CONCLUSIONS: There were balanced supportive (increased efficiency and re-allocation of tasks) and challenges (informational accuracy and oversight) with regards to AI automation in ICU research.