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Extracorporeal membrane oxygenation is increasingly being used to support patients with hypoxemic respiratory failure and cardiogenic shock. During the COVID‐19 pandemic, consensus guidance recommended extracorporeal life support for patients with COVID‐19‐related cardiopulmonary disease refractory to optimal conventional therapy, prompting a substantial expansion in the use of this support modality. Extracorporeal membrane oxygenation was particularly integral to the bridging of COVID‐19 patients to heart or lung transplantation. Limited human and physical resources precluded widespread utilization of mechanical support during the COVID‐19 pandemic, necessitating careful patient selection and optimal management by expert healthcare teams for judicious extracorporeal membrane oxygenation use. This review outlines the evidence supporting the use of extracorporeal life support in COVID‐19, describes the practice and outcomes of extracorporeal membrane oxygenation for COVID‐19‐related respiratory failure and cardiogenic shock, and proposes lessons learned for the implementation of extracorporeal membrane oxygenation as a bridge to transplantation in future public health emergencies. [ABSTRACT FROM AUTHOR]

Animals sense chemical cues such as nutritious and noxious stimuli through the chemosensory system and adapt their behavior, physiology, and developmental schedule to the environment. In the Drosophila central nervous system, chemosensory interneurons that produce neuropeptides called Hugin (Hug) peptides receive signals from gustatory receptor neurons and regulate feeding behavior. Because Hug neurons project their axons to the higher brain region within the protocerebrum where dendrites of multiple neurons producing developmentally important neuropeptides are extended, it has been postulated that Hug neurons regulate development through the neuroendocrine system. In this study, we show that Hug neurons interact with a subset of protocerebrum neurons that produce prothoracicotropic hormone (PTTH) and regulate the onset of metamorphosis and systemic growth. Loss of the hug gene and silencing of Hug neurons caused a delay in larval‐to‐prepupal transition and an increase in final body size. Furthermore, deletion of Hug receptor‐encoding genes also caused developmental delay and body size increase, and the phenotype was restored by expressing Hug receptors in PTTH‐producing neurons. These results indicate that Hug neurons regulate developmental timing and body size via PTTH‐producing neurons. This study provides a basis for understanding how chemosensation is converted into neuroendocrine signaling to control insect growth and development. [ABSTRACT FROM AUTHOR]

Uncovering slow collective variables (CVs) of self-assembly dynamics is important to elucidate its numerous kinetic assembly pathways and drive the design of novel structures for advanced materials through the bottom-up approach. However, identifying the CVs for self-assembly presents several challenges. First, self-assembly systems often consist of identical monomers, and the feature representations should be invariant to permutations and rotational symmetries. Physical coordinates, such as aggregate size, lack high-resolution detail, while common geometric coordinates like pairwise distances are hindered by the permutation and rotational symmetry challenges. Second, self-assembly is usually a downhill process, and the trajectories often suffer from insufficient sampling of backward transitions that correspond to the dissociation of self-assembled structures. Popular dimensionality reduction methods, such as time-structure independent component analysis, impose detailed balance constraints, potentially obscuring the true dynamics of self-assembly. In this work, we employ GraphVAMPnets, which combines graph neural networks with a variational approach for Markovian process (VAMP) theory to identify the slow CVs of the self-assembly processes. First, GraphVAMPnets bears the advantages of graph neural networks, in which the graph embeddings can represent self-assembly structures in high-resolution while being invariant to permutations and rotational symmetries. Second, it is built upon VAMP theory, which studies Markov processes without forcing detailed balance constraints, which addresses the out-of-equilibrium challenge in the self-assembly process. We demonstrate GraphVAMPnets for identifying slow CVs of self-assembly kinetics in two systems: the aggregation of two hydrophobic molecules and the self-assembly of patchy particles. We expect that our GraphVAMPnets can be widely applied to molecular self-assembly. [ABSTRACT FROM AUTHOR]

Mutations in protein phosphatase 2A (PP2A) are connected to intellectual disability and cancer. It has been hypothesized that these mutations might disrupt the autoinhibition and phosphorylation-induced activation of PP2A. Since they are located far from both the active and substrate binding sites, it is unclear how they exert their effect. We performed allosteric pathway analysis based on molecular dynamics simulations and combined it with biochemical experiments to investigate the autoinhibition of PP2A. In the wild type (WT), the C-arm of the regulatory subunit B56δ obstructs the active and substrate binding sites exerting a dual autoinhibition effect. We find that the disease mutant, E198K, severely weakens the allosteric pathways that stabilize the C-arm in the WT. Instead, the strongest allosteric pathways in E198K take a different route that promotes exposure of the substrate binding site. To facilitate the allosteric pathway analysis, we introduce a path clustering algorithm for lumping pathways into channels. We reveal remarkable similarities between the allosteric channels of E198K and those in phosphorylation-activated WT, suggesting that the autoinhibition can be alleviated through a conserved mechanism. In contrast, we find that another disease mutant, E200K, which is in spatial proximity of E198, does not repartition the allosteric pathways leading to the substrate binding site; however, it may still induce exposure of the active site. This finding agrees with our biochemical data, allowing us to predict the activity of PP2A with the phosphorylated B56δ and provide insight into how disease mutations in spatial proximity alter the enzymatic activity in surprisingly different mechanisms. [ABSTRACT FROM AUTHOR]

Clinical relevance: Findings from this study examining Australian optometrists' insights into ocular stem cell (SC) therapies have capacity to inform continuing professional development (CPD) about these interventions. Background: This study investigated Australian optometrists' knowledge, views, experiences, and preferred education sources regarding ocular SC therapies. Methods: An online survey was distributed to optometrists via Optometry Australia, Mivision magazine, professional groups, and social media from August 2020 to March 2021. Data were collected on demographics, and SC knowledge, awareness and experience. Results: Of 81 optometrists who completed the survey, many were metropolitan-based (85%), worked in independent practice (47%), female (56%) and >46 years of age (45%). Approximately one-fifth indicated awareness of ocular SC therapies used in standard practice; one-third had knowledge of SC clinical trials. The most noted SC therapies were for corneal disease in the United States [US] (72%) and Australia (44%). Respondents identified the availability of SC therapies for dry eye disease in Australia and the US (39% and 44% respectively), despite no regulatory-approved treatments for this indication. Clinical trials investigating inherited retinal and corneal diseases in Australia were the most commonly identified (44% and 36%, respectively). Half the respondents felt 'unsure' about the quality of evidence for treating eye conditions using SCs. One-fifth indicated concerns with these therapies; of these, most mentioned efficacy (82%), safety (76%) and/or cost (71%). About one-fifth reported being asked for advice about SCs by patients. Two-thirds felt neutral, uncomfortable, or very uncomfortable providing this advice, due to lack of knowledge or the topic being beyond their expertise. Over half (57%) were unsure if clinical management should change if patients received SC therapies. Respondents were receptive to face-to-face education. Conclusion: Some optometrists responding to this survey were aware of ocular SC therapies and/or clinical trials. CPD programs may assist with maintaining currency in this evolving field. [ABSTRACT FROM AUTHOR]

The article discusses the limitations of evidence-based medicine in the critical care environment and the need for personalized medicine. It highlights the challenges faced by critical care physicians in making decisions based on available evidence, such as the vast amount of literature, outdated information, and the difficulty in conducting high-quality trials. The article also emphasizes the importance of expert judgment and experience in making ad-hoc decisions when evidence is lacking. It suggests that a deeper understanding of disease mechanisms and the development of more targeted therapies may lead to more effective personalized medicine in the future. [Extracted from the article]

In Australia, acute inpatient units within public mental health services have become the last resort for mental health care. This research explored barriers and facilitators to safe, person‐centred, recovery‐oriented mental health care in these settings. It utilised participant observations conducted by mental health nurses in acute inpatient units. These units were located in three distinct facilities, each serving different areas: a large metropolitan suburban area in a State capital, a mid‐sized regional city, and a small city with a large rural catchment area. Our findings highlighted that, in the three inpatient settings, nurses tended to avoid common areas they shared with consumers, except for brief, task‐related visits. The prioritisation of administrative tasks seemed to arise in a situation where nurses lacked awareness of alternative practices and activities. Consumers spent prolonged periods of the day sitting in communal areas, where the main distraction was watching television. Boredom was a common issue across these environments. The nursing team structure in the inpatient units provided a mechanism for promoting a sense of psychological safety for staff and were a key element in how safety culture was sustained. [ABSTRACT FROM AUTHOR]

Background: Absent "organic" disease, dyspeptic symptoms may arise from abnormal gastric sensation, accommodation, motility or emptying (GE). Extensive gastric sensorimotor evaluation is rarely undertaken because testing is prolonged, invasive, poorly tolerated or unavailable. Aims: To investigate whether gastric antral motor function, evaluated with scintigraphy, predicts GE. To explore whether motor testing with symptom recording predicts day‐to‐day symptoms in patients with dyspepsia. Methods: GE was determined using a scintigraphic solid‐meal protocol (296 kcal, 35% fat). Antral motility was estimated from 10 min of scintigraphic time‐activity curves acquired 40 min after meal consumption. An antral motility index (MI) was derived from contraction amplitude and frequency. Intra‐gastric distribution of the meal on scintograms at 1 h (IGD1) was determined. Meal‐induced symptoms were evaluated by questionnaire. Patients completed the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI‐DD) for 14 days. Results: Twelve healthy participants and 23 prospectively recruited patients completed the study. Nine patients had delayed, and 2 had rapid, GE. In univariate analysis MI explained 42% of GE half‐time. In multivariate analysis MI and GE half‐time explained 25% of the variance in meal‐induced symptoms. While scintigraphic evaluation of gastric motor function with symptom recording explained 80% of the variance in the GCSI‐DD, meal‐induced symptoms were the only significant predictor. However, among patients with delayed GE, MI, GE half‐time, IGD1, and meal‐induced symptoms all significantly predicted GCSI‐DD. Conclusions: Antral motility predicts GE. In exploratory analyses, only meal‐induced symptoms predicted daily symptoms among patients with dyspepsia. However, motor function also predicted symptoms in patients with delayed GE. [ABSTRACT FROM AUTHOR]

In Drosophila coordinated proliferation of two neural stem cells, neuroblasts (NB) and neuroepithelial (NE) cells, is pivotal for proper larval brain growth that ultimately determines the final size and performance of an adult brain. The larval brain growth displays two phases based on behaviors of NB and NEs: the first one in early larval stages, influenced by nutritional status and the second one in the last larval stage, promoted by ecdysone signaling after critical weight checkpoint. Mutations of the baboon (babo) gene that produces three isoforms (BaboA-C), all acting as type-I receptors of Activin-type transforming growth factor β (TGF-β) signaling, cause a small brain phenotype due to severely reduced proliferation of the neural stem cells. In this study we show that loss of babo function severely affects proliferation of NBs and NEs as well as conversion of NEs from both phases. By analyzing babo-null and newly generated isoform-specific mutants by CRISPR mutagenesis as well as isoform-specific RNAi knockdowns in a cell- and stage-specific manner, our data support differential contributions of the isoforms for these cellular events with BaboA playing the major role. Stage-specific expression of EcR-B1 in the brain is also regulated primarily by BaboA along with function of the other isoforms. Blocking EcR function in both neural stem cells results in a small brain phenotype that is more severe than baboA-knockdown alone. In summary, our study proposes that the Babo-mediated signaling promotes proper behaviors of the neural stem cells in both phases and achieves this by acting upstream of EcR-B1 expression in the second phase. [ABSTRACT FROM AUTHOR]

Molecular breast imaging (MBI) is one of several options available to patients seeking supplemental screening due to mammographically dense breasts. Patient experience during MBI may influence willingness to undergo the test but has yet to be formally assessed. We aimed to assess patient comfort level during MBI, to compare MBI comfort with mammography comfort, to identify factors associated with MBI discomfort, and to evaluate patients' willingness to return for future MBI. Methods: A 10-question survey was sent by e-mail to patients undergoing MBI between August and December 2022 to obtain quantitative assessments and qualitative opinions about MBI. Results: Of 561 invited patients, 209 (37%) completed the survey and provided study consent. Their average age was 60.1 y (range, 40–81 y). Of the 209 responders, 202 (97%) were presenting for screening MBI, 195 (94%) had dense breasts, and 46 (22%) had a personal history of breast cancer. The average rating of MBI comfort was 2.9 (SD, 1.5; median, 3.0) on a 7-point scale (1 indicating extremely comfortable and 7 indicating extremely uncomfortable). The rating distribution was as follows: 140 (67%) comfortable (rating, 1–3); 24 (12%) neither comfortable nor uncomfortable (rating, 4); and 45 (22%) uncomfortable (rating, 5 or 6). No responders gave a 7 rating. The most frequently mentioned sources of discomfort included breast compression (n = 16), back or neck discomfort (n = 14), and maintaining position during the examination (n = 14). MBI comfort was associated with responder age (74% ≥55 y old were comfortable, versus 53% <55 y old [P = 0.003]) and history of MBI (71% with prior MBI were comfortable, versus 61% having a first MBI [P = 0.006]). Of 208 responders with a prior mammogram, 148 (71%) said MBI is more comfortable than mammography (a significant majority [P < 0.001]). Of 202 responders to the question of whether they were willing to return for a future MBI, 196 (97%) were willing. A notable factor in positive patient experience was interaction with the MBI nuclear medicine technologist. Conclusion: Most responders thought MBI to be a comfortable examination and more comfortable than mammography. Patient experience during MBI may be improved by ensuring back support and soliciting patient feedback at the time of positioning and throughout the examination. Methods under study to reduce imaging time may be most important for improving patient experience. [ABSTRACT FROM AUTHOR]

While sexual boundary violations by doctors (SBVs) are viewed with utmost seriousness by disciplinary bodies and tribunals, complaints of SBVs in Australia continue to increase. In 2023, the Australian Health Practitioner Regulation Agency (Ahpra) outlined a "blueprint" to protect patients better from sexual misconduct in healthcare: reform being considered in 2024, by Australian health ministers. Few analyses or studies have offered an overview of the prevalence, effects, and causes of SBVs, nor the duties, liabilities, possible disciplinary action against, and potential treatment of, doctors who commit them. This column offers such an overview, and considers, additionally, whether doctors who may have psychiatric disorders associated with their boundary violations would be suitable candidates for treatment. Ultimately, we contend that a purely "responsive" approach is inadequate, and preventive measures such as screening and more effective education should be considered in medical schools as a way of reducing the incidence of SBVs. [ABSTRACT FROM AUTHOR]

We present OrbNet Denali, a machine learning model for an electronic structure that is designed as a drop-in replacement for ground-state density functional theory (DFT) energy calculations. The model is a message-passing graph neural network that uses symmetry-adapted atomic orbital features from a low-cost quantum calculation to predict the energy of a molecule. OrbNet Denali is trained on a vast dataset of 2.3 × 106 DFT calculations on molecules and geometries. This dataset covers the most common elements in biochemistry and organic chemistry (H, Li, B, C, N, O, F, Na, Mg, Si, P, S, Cl, K, Ca, Br, and I) and charged molecules. OrbNet Denali is demonstrated on several well-established benchmark datasets, and we find that it provides accuracy that is on par with modern DFT methods while offering a speedup of up to three orders of magnitude. For the GMTKN55 benchmark set, OrbNet Denali achieves WTMAD-1 and WTMAD-2 scores of 7.19 and 9.84, on par with modern DFT functionals. For several GMTKN55 subsets, which contain chemical problems that are not present in the training set, OrbNet Denali produces a mean absolute error comparable to those of DFT methods. For the Hutchison conformer benchmark set, OrbNet Denali has a median correlation coefficient of R2 = 0.90 compared to the reference DLPNO-CCSD(T) calculation and R2 = 0.97 compared to the method used to generate the training data (ωB97X-D3/def2-TZVP), exceeding the performance of any other method with a similar cost. Similarly, the model reaches chemical accuracy for non-covalent interactions in the S66x10 dataset. For torsional profiles, OrbNet Denali reproduces the torsion profiles of ωB97X-D3/def2-TZVP with an average mean absolute error of 0.12 kcal/mol for the potential energy surfaces of the diverse fragments in the TorsionNet500 dataset. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is defined as pain lasting longer than 3 months. This often causes persistent emotional distress and functional disability that is refractory to conventional treatments. Emerging evidence suggests that oral Ketamine therapy may have a specific role in managing treatment-resistant chronic pain. This study aimed to assess the effectiveness of oral ketaminewithin a tertiary chronic painmanagement clinic. Methods: This study was a clinic-based retrospective descriptive study of 79 patients with a broad range of chronic pain diagnoses and treated with oral ketamine over a period up to 12 years. Changes in pain, mood and quality of life (QoL) were assessed using a numerical pain severity score, the Brief Pain Inventory (BPI), the Public Health Questionnaire (PHQ-9) and American Chronic Pain Association Quality of Life (QoL) scale. Results: 73 patients were accessible for follow-up (mean daily dose and treatment duration were 193.84 mg and 22.6 months respectively). Pain scores decreased (p < 0.0001) on both numerical scores (41.6% decrease) and BPI scoring (mean decrease 2.61). Mood improved (p < 0.0001) across both PHQ-9 and BPI measurements. Patients also reported less difficulty with daily activities and improved QoL. The most common adverse reaction was drowsiness (21.9%), with 30.1% reporting no adverse reactions from Ketamine. Discussion: This work adds to the growing body of evidence that under the supervision of a pain specialist, oral ketamine therapy may be a safe, tolerable and effective treatment for chronic pain conditions which have not responded to other management options. Further research is required to produce a more accurate understanding of its chronic use. Key message: This real-world study shows that patients being treated with oral ketamine for chronic pain report decreased severity of pain, improved mood and increased quality of life across all conditions. [ABSTRACT FROM AUTHOR]

This study investigated PhD candidate feedback on research and employability skills training, delivered via workintegrated learning (WIL) within an alternative doctoral training model. Voluntary feedback was received using a mixed-methods survey consisting of 10 quantitative statements reflecting on learning, and qualitative feedback comprising best aspects and needs improvement comments. The results indicate candidates highly valued the WIL-based assessments, teacher interactions, workload, research-relevant problem-solving frameworks, workrelated knowledge and skills, and confidence-building. The qualitative analysis also revealed some PhD candidates desired more peer interactions early in candidature. The study reinforces four emerging design principles for WIL in doctoral programs and provides a contemporary evidence-base for improving alternative doctoral training programs. Areas for further research include: understanding training motivation and needs including content complexity, internships, and culturally and linguistically diverse (CALD) candidate needs; benchmarking engagement with doctoral WIL; increasing doctoral peer interactions; WIL for new technologies; and communicating the value of doctoral WIL. [ABSTRACT FROM AUTHOR]

The ability to understand and engineer molecular structures relies on having accurate descriptions of the energy as a function of atomic coordinates. Here, we outline a new paradigm for deriving energy functions of hyperdimensional molecular systems, which involves generating data for low-dimensional systems in virtual reality (VR) to then efficiently train atomic neural networks (ANNs). This generates high-quality data for specific areas of interest within the hyperdimensional space that characterizes a molecule's potential energy surface (PES). We demonstrate the utility of this approach by gathering data within VR to train ANNs on chemical reactions involving fewer than eight heavy atoms. This strategy enables us to predict the energies of much higher-dimensional systems, e.g., containing nearly 100 atoms. Training on datasets containing only 15k geometries, this approach generates mean absolute errors around 2 kcal mol−1. This represents one of the first times that an ANN-PES for a large reactive radical has been generated using such a small dataset. Our results suggest that VR enables the intelligent curation of high-quality data, which accelerates the learning process. [ABSTRACT FROM AUTHOR]

An updated position paper on critical care pharmacy services recommends the development of new clinical programs. However, proposed pragmatic strategies for critical care pharmacy practice advancement are lacking. The purpose of this position paper is to develop consensus recommendations aimed at direct patient care activities for the advancement of critical care pharmacy practice. A 24‐member task force of critical care pharmacists, physicians, and nurses participated in a Recommendation Development Phase and Consensus‐building Phase (using a Delphi method) to produce the final critical care practice advancement recommendations. Proposed recommendations of pragmatic medication management opportunities with an advanced scope of practice involving pharmacist prescriptive authority for initiating, modifying, or discontinuing drug therapy and medication monitoring were developed. Task force participants anonymously voted on each proposed recommendation using a five‐point Likert scale (1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, and 5 = strongly disagree). Recommendations failing to achieve consensus (≥70% agreement on "strongly agree"/"agree" votes) were revised for subsequent voting. Task force response rates during the first and second voting rounds were 71% (n = 17) and 79% (n = 19), respectively. A total of 57 (93.4%) of the 61 proposed practice advancement recommendations achieved consensus of which 88.5% (n = 54) met consensus after the first round. Consensus recommendations involved the critical care pharmacist initiating (n = 15), modifying (n = 22), or discontinuing (n = 9) drug therapy, and ordering relevant laboratory values or tests to optimize drug therapy (n = 11). One recommendation failing consensus was not revised for additional voting given the impracticality of achieving agreement. Fifty‐seven of the proposed 61 recommendation statements (93%) achieved the consensus threshold after two rounds of voting by an interprofessional expert panel. These recommendations provide a conceptual framework for promoting novel critical care pharmacist prescriptive authority over specific aspects of direct patient care. Implementation challenges and barriers, further described in this paper, must be explored at the institutional level for acceptance. [ABSTRACT FROM AUTHOR]

Heart and lung transplant recipients require care provided by clinicians from multiple different specialties, each contributing unique expertise and perspective. The period the patient spends in the intensive care unit is one of the most critical times in the perioperative trajectory. Various organizational models of intensive care exist, including those led by intensivists, surgeons, transplant cardiologists, and pulmonologists. Coordinating timely efficient intensive care is an essential and logistically difficult goal. The present work product of the American Society of Transplantation's Thoracic and Critical Care Community of Practice, Critical Care Task Force outlines operational guidelines and principles that may be applied in different organizational models to optimize the delivery of intensive care for the cardiothoracic organ recipient. [ABSTRACT FROM AUTHOR]

Many attempts at providing a single-scale exponent and mechanism to explain metabolic rate assert a monolithic selective mechanism for allometries, characterized by a universal allometric scale power (usually chosen to be 0.75). To test for the deviations from universal allometric scaling, we gathered data from previously published metabolic measurements on 903 bird species and performed regressions of log(basal metabolic rate) and log(body mass) for (1) all birds and (2) 20 monophyletic clades within birds. We constructed two Bayesian linear mixed models—one included ecological variables and the other included data for mammals from Sieg et al. (2009). Overall allometric patterns differed significantly among clades of birds, and some clades were not consistent with the 0.75 scale power. We were unable to find apparent physiological, morphological, phylogenetic, or ecological characteristics among clades, predicting a difference in allometry or consistency with any previously proposed universal allometry. The Bayesian analysis illuminated novel bivariate, clade-specific differences in scaling slope-intercept space, separating large groups of birds and mammals. While significantly related to basal metabolic rate, feeding guild and migratory tendency had small effects compared to clade and body mass. We propose that allometric hypotheses, in general, must extend beyond simple overarching mechanisms to allow for conflicting and interacting influences that produce allometric patterns at narrower taxonomic scales—perhaps including other processes whose optimization may interfere with that of the system proposed by the metabolic theory of ecology. [ABSTRACT FROM AUTHOR]

As molecular scientists have made progress in their ability to engineer nanoscale molecular structure, we face new challenges in our ability to engineer molecular dynamics (MD) and flexibility. Dynamics at the molecular scale differs from the familiar mechanics of everyday objects because it involves a complicated, highly correlated, and three-dimensional many-body dynamical choreography which is often nonintuitive even for highly trained researchers. We recently described how interactive molecular dynamics in virtual reality (iMD-VR) can help to meet this challenge, enabling researchers to manipulate real-time MD simulations of flexible structures in 3D. In this article, we outline various efforts to extend immersive technologies to the molecular sciences, and we introduce "Narupa," a flexible, open-source, multiperson iMD-VR software framework which enables groups of researchers to simultaneously cohabit real-time simulation environments to interactively visualize and manipulate the dynamics of molecular structures with atomic-level precision. We outline several application domains where iMD-VR is facilitating research, communication, and creative approaches within the molecular sciences, including training machines to learn potential energy functions, biomolecular conformational sampling, protein-ligand binding, reaction discovery using "on-the-fly" quantum chemistry, and transport dynamics in materials. We touch on iMD-VR's various cognitive and perceptual affordances and outline how these provide research insight for molecular systems. By synergistically combining human spatial reasoning and design insight with computational automation, technologies such as iMD-VR have the potential to improve our ability to understand, engineer, and communicate microscopic dynamical behavior, offering the potential to usher in a new paradigm for engineering molecules and nano-architectures. [ABSTRACT FROM AUTHOR]

The article discusses strategies to eliminate developmental writing and reading courses and shifting to an all-inclusive, no-placement-necessary, integrated reading and writing course without lowering student success rates. Topics include ongoing changes at Onondaga Community College, an open-admission, public community college, Accelerated Learning Program (ALP) pioneered by Community College of Baltimore County (CCBC), and mental health services for students.

Despite significant recent changes to the doctoral training environment, particularly provision of employability skills during candidature, there is a paucity of research investigating best practice in this area. This paper describes a case study in how various pedagogical theories, curriculum co-creation, lifelong learner, adult learning, cognitive load, spiral learning, reflective practice, and community of practice theories, were applied at an Australian university to develop and implement a Graduate Certificate aimed at increasing work readiness by delivering research and employability skills training to PhD candidates. Outlined are the rationale, student interest and theoretical basis underpinning this program, and its integrated suite of work-integrated learning (WIL) activities. Comparison against an emerging framework for high quality WIL demonstrated key alignments between the program and the quality WIL framework. These alignments highlight important considerations for comprehensive training of PhD candidates, together with recommendations for future research into WIL and employability training for PhD candidates. [ABSTRACT FROM AUTHOR]

In a multivariate analysis of 30 574 blood culture (BC) results, BC contamination was associated with only a small increase in antibiotic length of therapy compared to no-growth BCs (difference, 0.36 days [95% confidence interval,.05–.67]; P =.02). Stewardship processes at our institution appear to be effective in reducing the impact of BC contamination. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction plays a central role in the pathogenesis of sepsismediated multiple organ failure. Several clinical and experimental studies have suggested that the glycocalyx is an early target of endothelial injury during an infection. Colivelin, a synthetic derivative of the mitochondrial peptide humanin, has displayed cytoprotective effects in oxidative conditions. In the current study, we aimed to determine the potential therapeutic effects of colivelin in endothelial dysfunction and outcomes of sepsis in vivo. Male C57BL/6 mice were subjected to a clinically relevant model of polymicrobial sepsis by cecal ligation and puncture (CLP) and were treated with vehicle or colivelin (100-200 µg/kg) intraperitoneally at 1 h after CLP. We observed that vehicle-treated mice had early elevation of plasma levels of the adhesion molecules ICAM-1 and P-selectin, the angiogenetic factor endoglin and the glycocalyx syndecan-1 at 6 h after CLP when compared to control mice, while levels of angiopoietin-2, a mediator of microvascular disintegration, and the proprotein convertase subtilisin/kexin type 9, an enzyme implicated in clearance of endotoxins, raised at 18 h after CLP. The early elevation of these endothelial and glycocalyx damage biomarkers coincided with lung histological injury and neutrophil inflammation in lung, liver, and kidneys. At transmission electron microscopy analysis, thoracic aortas of septic mice showed increased glycocalyx breakdown and shedding, and damaged mitochondria in endothelial and smooth muscle cells. Treatment with colivelin ameliorated lung architecture, reduced organ neutrophil infiltration, and attenuated plasma levels of syndecan-1, tumor necrosis factor-a, macrophage inflammatory protein-1a and interleukin-10. These therapeutic effects of colivelin were associated with amelioration of glycocalyx density and mitochondrial structure in the aorta. At molecular analysis, colivelin treatment was associated with inhibition of the signal transducer and activator of transcription 3 and activation of the AMP-activated protein kinase in the aorta and lung. In long-term outcomes studies up to 7 days, co-treatment of colivelin with antimicrobial agents significantly reduced the disease severity score when compared to treatment with antibiotics alone. In conclusion, our data support that damage of the glycocalyx is an early pathogenetic event during sepsis and that colivelin may have therapeutic potential for the treatment of sepsisassociated endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Airborne spread of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains a significant risk for healthcare workers. Understanding transmission of SARS‐CoV‐2 in the hospital could help minimize nosocomial infection. The objective of this pilot study was to measure aerosolization of SARS‐CoV‐2 in the hospital rooms of COVID‐19 patients. Methods: Two air samplers (Inspirotec) were placed 1 and 4 m away from adults with SARS‐CoV‐2 infection hospitalized at an urban, academic tertiary care center from June to October 2020. Airborne SARS‐CoV‐2 concentration was measured by quantitative reverse transcription polymerase chain reaction and analyzed by clinical parameters and patient demographics. Results: Thirteen patients with COVID‐19 (eight females [61.5%], median age: 57 years old, range 25–82) presented with shortness of breath (100%), cough (38.5%) and fever (15.4%). Respiratory therapy during air sampling varied: mechanical ventilation via endotracheal tube (n = 3), high flow nasal cannula (n = 4), nasal cannula (n = 4), respiratory helmet (n = 1), and room air (n = 1). SARS‐CoV‐2 RNA was identified in rooms of three out of three intubated patients compared with one out of 10 of the non‐intubated patients (p =.014). Airborne SARS‐CoV‐2 tended to decrease with distance (1 vs. 4 m) in rooms of intubated patients. Conclusions: Hospital rooms of intubated patients had higher levels of aerosolized SARS‐CoV‐2, consistent with increased aerosolization of virus in patients with severe disease or treatment with positive pressure ventilation through an endotracheal tube. While preliminary, these data have safety implications for health care workers and design of protective measures in the hospital. Level of Evidence: 2 [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal (GI) motility disorders affect millions of people worldwide, yet they remain poorly treated in part due to insufficient knowledge of the molecular networks controlling GI motility. Interstitial cells of Cajal (ICC) are critical GI pacemaker cells, and abnormalities in ICC are implicated in GI motility disorders. Two cell surface proteins, KIT and ANO1, are used for identifying ICC. However, difficulties accessing human tissue and the low frequency of ICC in GI tissues have meant human ICC are insufficiently characterized. Here, a range of characterization assays including single‐cell RNA sequencing (scRNA‐seq) was performed using KIT+CD45−CD11B− primary human gastric ICC to better understand networks controlling human ICC biology. Methods: Excess sleeve gastrectomy tissues were dissected; ICC were analyzed by immunofluorescence, fluorescence‐activated cell sorting (FACSorting), real‐time PCR, mass spectrometry, and scRNA‐seq. Key Results: Immunofluorescence identified ANO1+/KIT+ cells throughout the gastric muscle. Compared to the FACSorted negative cells, PCR showed the KIT+CD45−CD11B− ICC were enriched 28‐fold in ANO1 expression (p < 0.01). scRNA‐seq analysis of the KIT−CD45+CD11B+ and KIT+CD45−CD11B− ICC revealed separate clusters of immune cells and ICC (respectively); cells in the ICC cluster expressed critical GI motility genes (eg, CAV1 and PRKG1). The scRNA‐seq data for these two cell clusters predicted protein interaction networks consistent with immune cell and ICC biology, respectively. Conclusions & Inferences: The single‐cell transcriptome of purified KIT+CD45−CD11B− human gastric ICC presented here provides new molecular insights and hypotheses into evolving models of GI motility. This knowledge will provide an improved framework to investigate targeted therapies for GI motility disorders. [ABSTRACT FROM AUTHOR]

Critical care, heart disease, lung disease Keywords: critical care; heart disease; lung disease EN critical care heart disease lung disease 1 3 3 04/13/23 20230401 NES 230401 The ability to promptly recognize and manage complications following cardiac surgery is closely associated with operative mortality,[1] and there has been increasing interest in the impact of intensive care unit (ICU) staffing models on post-operative care.[[2], [4]] Thoracic transplant recipients have particularly complex peri-operative care needs necessitating a multidisciplinary approach, yet there is limited information on existing ICU structure and staffing models for these patients in current practice. In total, 17 (60.7%) respondents were critical care board certified, and 6 (50%) anesthesiologists were dual trained in critical care and cardiac anesthesia. [Extracted from the article]

In polarized epithelial cells, receptor–ligand interactions can be restricted by different spatial distributions of the 2 interacting components, giving rise to an underappreciated layer of regulatory complexity. We explored whether such regulation occurs in the Drosophila wing disc, an epithelial tissue featuring the TGF-β family member Decapentaplegic (Dpp) as a morphogen controlling growth and patterning. Dpp protein has been observed in an extracellular gradient within the columnar cell layer of the disc, but also uniformly in the disc lumen, leading to the question of how graded signaling is achieved in the face of 2 distinctly localized ligand pools. We find the Dpp Type II receptor Punt, but not the Type I receptor Tkv, is enriched at the basolateral membrane and depleted at the junctions and apical surface. Wit, a second Type II receptor, shows a markedly different behavior, with the protein detected on all membrane regions but enriched at the apical side. Mutational studies identified a short juxtamembrane sequence required for basolateral restriction of Punt in both wing discs and mammalian Madin-Darby canine kidney (MDCK) cells. This basolateral targeting (BLT) determinant can dominantly confer basolateral localization on an otherwise apical receptor. Rescue of punt mutants with transgenes altered in the targeting motif showed that flies expressing apicalized Punt due to the lack of a functional BLT displayed developmental defects, female sterility, and significant lethality. We also show that apicalized Punt does not produce an ectopic signal, indicating that the apical pool of Dpp is not a significant signaling source even when presented with Punt. Instead, we find that basolateral presentation of Punt is required for optimal signaling. Finally, we present evidence that the BLT acts through polarized sorting machinery that differs between types of epithelia. This suggests a code whereby each epithelial cell type may differentially traffic common receptors to enable distinctive responses to spatially localized pools of extracellular ligands. Receptor-ligand interactions can be restricted by different spatial distributions of the two interacting components, giving rise to an underappreciated layer of regulatory complexity. This study reveals that an evolutionarily conserved mechanism for polarized delivery of a transmembrane receptor (the Dpp Type II receptor Punt) supports robust morphogen signaling in a model epithelial tissue, the Drosophila wing disc. [ABSTRACT FROM AUTHOR]

How do Catholic schools create inclusive, equitable environments that embrace the identities of their students, including their race, ethnicity, and culture What does Catholic theological spirituality say about diversity, equity, and inclusion to address racism What is the connection between Catholic theological spirituality and equitable school practices to bring about equity in Catholic schools In response to increased diversity of students, educators, communities, and societal challenges, there is a need for a framework for Catholic schools with a culturally diverse student body, or with a student body and staff with different cultures. We synthesize Catholic theological spirituality and research about equity in public and Catholic schools to create a framework for Catholic school educators in their support of students whose cultural identity is different from the faculty and staff. The framework uses Catholic theological spirituality and equitable school practices to promote equity in Catholic schools using equitable school practices. [ABSTRACT FROM AUTHOR]