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Nicola Wearne,1 Kajiru Kilonzo,2 Emmanuel Effa,3 Bianca Davidson,1 Peter Nourse,4 Udeme Ekrikpo,1,5 Ikechi G Okpechi1 1Division of Nephrology and Hypertension, University of Cape Town, Cape Town, South Africa; 2Department of Medicine, Kilimanjaro Christian Medical College, Moshi, Tanzania; 3Department of Medicine, University of Calabar, Calabar, Nigeria; 4Division of Paediatric Nephrology, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa; 5Department of Internal Medicine, University of Uyo, Uyo, Nigeria Abstract: Chronic kidney disease is a major public health problem that continues to show an unrelenting global increase in prevalence. The prevalence of chronic kidney disease has been predicted to grow the fastest in low- to middle-income countries (LMICs). There is evidence that people living in LMICs have the highest need for renal replacement therapy (RRT) despite the lowest access to various modalities of treatment. As continuous ambulatory peritoneal dialysis (CAPD) does not require advanced technologies, much infrastructure, or need for dialysis staff support, it should be an ideal form of RRT in LMICs, particularly for those living in remote areas. However, CAPD is scarcely available in many LMICs, and even where available, there are several hurdles to be confronted regarding patient selection for this modality. High cost of CAPD due to unavailability of fluids, low patient education and motivation, low remuneration for nephrologists, lack of expertise/experience for catheter insertion and management of complications, presence of associated comorbid diseases, and various socio-demographic factors contribute significantly toward reduced patient selection for CAPD. Cost of CAPD fluids seems to be a major constraint given that many countries do not have the capacity to manufacture fluids but instead rely heavily on fluids imported from developed countries. There is need to invest in fluid manufacturing (either nationally or regionally) in LMICs to improve uptake of patients treated with CAPD. Workforce training and retraining will be necessary to ensure that there is coordination of CAPD programs and increase the use of protocols designed to improve CAPD outcomes such as insertion of catheters, treatment of peritonitis, and treatment of complications associated with CAPD. Training of nephrology workforce in CAPD will increase workforce experience and make CAPD a more acceptable RRT modality with improved outcomes. Keywords: dialysis cost, dialysis fluid, peritoneal dialysis, peritonitis, nephrology workforce

Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Abstract Electron-electron interactions in materials lead to exotic many-body quantum phenomena, including Mott metal-insulator transitions (MITs), magnetism, quantum spin liquids, and superconductivity. These phases depend on electronic band occupation and can be controlled via the chemical potential. Flat bands in two-dimensional (2D) and layered materials with a kagome lattice enhance electronic correlations. Although theoretically predicted, correlated-electron Mott insulating phases in monolayer 2D metal-organic frameworks (MOFs) with a kagome structure have not yet been realised experimentally. Here, we synthesise a 2D kagome MOF on a 2D insulator. Scanning tunnelling microscopy (STM) and spectroscopy reveal a MOF electronic energy gap of ∼200 meV, consistent with dynamical mean-field theory predictions of a Mott insulator. Combining template-induced (via work function variations of the substrate) and STM probe-induced gating, we locally tune the electron population of the MOF kagome bands and induce Mott MITs. These findings enable technologies based on electrostatic control of many-body quantum phases in 2D MOFs.

Mechanical forces and tissue mechanics influence the morphology of the developing brain, but the underlying molecular mechanisms have been elusive. Here, we examine the role of mechanotransduction in brain development by focusing on Piezo1, a mechanically activated ion channel. We find that Piezo1 deletion results in a thinner neuroepithelial layer, disrupts pseudostratification, and reduces neurogenesis in E10.5 mouse embryos. Proliferation and differentiation of Piezo1 knockout (KO) mouse neural stem cells (NSCs) isolated from E10.5 embryos are reduced in vitro compared to littermate WT NSCs. Transcriptome analysis of E10.5 Piezo1 KO brains reveals downregulation of the cholesterol biosynthesis superpathway, in which 16 genes, including Hmgcr, the gene encoding the rate-limiting enzyme of the cholesterol biosynthesis pathway, are downregulated by 1.5-fold or more. Consistent with this finding, membrane lipid composition is altered, and the cholesterol levels are reduced in Piezo1 KO NSCs. Cholesterol supplementation of Piezo1 KO NSCs partially rescues the phenotype in vitro. These findings demonstrate a role for Piezo1 in the neurodevelopmental process that modulates the quantity, quality, and organization of cells by influencing cellular cholesterol metabolism. Our study establishes a direct link in NSCs between PIEZO1, intracellular cholesterol levels, and neural development.

Aoife Moore,1 Bridget Freyne,2 Clare Nourse3 1Department of General Paediatrics, Children’s Health Queensland, Brisbane, QLD, Australia; 2Department of Paediatric Infectious Diseases, Children’s Health Ireland, Dublin, Ireland; 3Department of Paediatric Infectious Diseases, Children’s Health Queensland, Brisbane, QLD, AustraliaCorrespondence: Aoife Moore, Queensland Children’s Hospital, South Brisbane, QLD, 4101, Tel +61 403 400 190, Email aoife.moore@bigpond.comAbstract: Congenital syphilis (CS), previously considered by many paediatricians as a “historical disease”, has re-emerged as a significant preventable neonatal infection. While low-income countries have the highest burden of disease globally, notifications have increased in many high-income countries (HIC) in recent years. This literature report provides an overview of the current strategies for testing and treating syphilis in pregnancy (SIP) and CS and describes the changing global epidemiology of SIP. National SIP guidelines are reviewed with reference to testing in pregnancy and treatment of CS. The report highlights that there is an ongoing crisis of CS in HICs worldwide and a disproportionate burden is being experienced by vulnerable populations in these countries. Action is needed to address this crisis, and interventions aimed at overcoming social and structural barriers to antenatal care access for vulnerable populations should be prioritised.Keywords: syphilis, pregnancy, congenital, epidemiology

BackgroundGlobally, heart failure (HF) affects more than 64 million people, and attempts to reduce its social and economic burden are a public health priority. Interventions to support people with HF to self-manage have been shown to reduce hospitalizations, improve quality of life, and reduce mortality rates. Understanding how people self-manage is imperative to improve future interventions; however, most approaches to date, have used self-report methods to achieve this. Wearable cameras provide a unique tool to understand the lived experiences of people with HF and the daily activities they undertake, which could lead to more effective interventions. However, their potential for understanding chronic conditions such as HF is unclear. ObjectiveThis study aimed to determine the potential utility of wearable cameras to better understand the activities of daily living in people living with HF. MethodsThe “Seeing is Believing (SIB)” study involved 30 patients with HF who wore wearable cameras for a maximum of 30 days. We used the E-Myscéal web-based lifelog retrieval system to process and analyze the wearable camera image data set. Search terms for 7 daily activities (physical activity, gardening, shopping, screen time, drinking, eating, and medication intake) were developed and used for image retrieval. Sensitivity analysis was conducted to compare the number of images retrieved using different search terms. Temporal patterns in daily activities were examined, and differences before and after hospitalization were assessed. ResultsE-Myscéal exhibited sensitivity to specific search terms, leading to significant variations in the number of images retrieved for each activity. The highest number of images returned were related to eating and drinking, with fewer images for physical activity, screen time, and taking medication. The majority of captured activities occurred before midday. Notably, temporal differences in daily activity patterns were observed for participants hospitalized during this study. The number of medication images increased after hospital discharge, while screen time images decreased. ConclusionsWearable cameras offer valuable insights into daily activities and self-management in people living with HF. E-Myscéal efficiently retrieves relevant images, but search term sensitivity underscores the need for careful selection.

Recent estimates show nearly 90% of school districts nationwide offer some form of online credit recovery. Despite its widespread adoption, there is a dearth of research surrounding the suitability of online credit recovery for students. This study examined potential success factors of students enrolled in virtual recovery courses in a school district in the midAtlantic region of the United States. Descriptive statistics, chi-square analysis, and binary logistic regression modeling was used for data analysis to account for the influence of student characteristics on credit recovery outcome. Findings revealed that grade-level, IEP status, and middle school End-of-Grade Test results could be linked to achievement in online credit recovery courses. Implications of these findings for educators are discussed.

The effective management of chronic conditions requires an approach that promotes a shift in care from the clinic to the home, improves the efficiency of health care systems, and benefits all users irrespective of their needs and preferences. Digital health can provide a solution to this challenge, and in this paper, we provide our vision for a smart health ecosystem. A smart health ecosystem leverages the interoperability of digital health technologies and advancements in big data and artificial intelligence for data collection and analysis and the provision of support. We envisage that this approach will allow a comprehensive picture of health, personalization, and tailoring of behavioral and clinical support; drive theoretical advancements; and empower people to manage their own health with support from health care professionals. We illustrate the concept with 2 use cases and discuss topics for further consideration and research, concluding with a message to encourage people with chronic conditions, their caregivers, health care professionals, policy and decision makers, and technology experts to join their efforts and work toward adopting a smart health ecosystem.

T lymphocytes encounter complex mechanical cues during an immune response. The mechanosensitive ion channel, Piezo1, drives inflammatory responses to bacterial infections, wound healing, and cancer; however, its role in helper T cell function remains unclear. In an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we found that mice with genetic deletion of Piezo1 in T cells showed diminished disease severity. Unexpectedly, Piezo1 was not essential for lymph node homing, interstitial motility, Ca2+ signaling, T cell proliferation, or differentiation into proinflammatory T helper 1 (TH1) and TH17 subsets. However, Piezo1 deletion in T cells resulted in enhanced transforming growth factor-β (TGFβ) signaling and an expanded pool of regulatory T (Treg) cells. Moreover, mice with deletion of Piezo1 specifically in Treg cells showed significant attenuation of EAE. Our results indicate that Piezo1 selectively restrains Treg cells, without influencing activation events or effector T cell functions.

The Every Student Succeeds Act (ESSA) has created additional opportunities for school librarians to collaborate with classroom teachers, reading specialists, and other educators in support of schools' literacy goals. This potential for expanded collaboration suggests a need for increased focus on reading instruction as part of the school librarian's workload. For a variety of reasons, school librarians may not see this role as a priority within the scope of their many other duties. This convergent mixed-methods study sought to examine the effect of a professional development series emphasizing reading comprehension strategies on school librarians' knowledge and perceptions. Results indicated that participants experienced statistically significant knowledge gains as well as increased acceptance of an enhanced role in literacy instruction.

Abstract Objective To describe a complication associated with the long‐term use of tamoxifen for the treatment of sclerosing encapsulating peritonitis in a dog. Case Summary A 2‐year‐old female spayed poodle cross was evaluated for a stump pyometra. The dog was diagnosed with sclerosing encapsulating peritonitis a year prior and was treated with tamoxifen, an oestrogen receptor antagonist, for treatment of the disease. The dog developed a swollen vulva with vulvar discharge and a stump pyometra was diagnosed on ultrasound. Hormonal testing was submitted to evaluate for an ovarian remnant and the dog underwent an exploratory laparotomy, where the uterine stump was removed. No ovarian remnant tissue was identified intra‐operatively, and hormonal testing (anti‐Müllerian hormone, progesterone, oestradiol) and histopathology were consistent with the absence of ovarian tissue. The tamoxifen was discontinued. The dog recovered uneventfully after surgery. New or Unique Information Provided This report describes a complication of treatment of a rarely described clinical disease. While most cases of stump pyometra involve ovarian remnant syndrome, this case report describes a stump pyometra in a dog without remnant tissue that was undergoing treatment with tamoxifen. Tamoxifen has been reported to cause pyometra in intact female dogs. To the authors’ knowledge, this is the first case report to describe a stump pyometra in a spayed female dog, secondary to the use of tamoxifen.

Abstract Background Insufficient physical activity (PA) is a risk factor for the development of many non-communicable diseases. Electric bicycles (e-bikes) offer considerable potential to support people to be physically active, however, no previous e-bike intervention studies have supported e-bike use with behavioural support. The aim of this study was to co-develop theory-based intervention components which can be used to increase physical activity through e-cycling among people who are overweight or obese and physically inactive. Methods We conducted a mixed-methods study using an online survey and virtual co-design workshops. We utilised the Behaviour Change Wheel (BCW) to inform the development of the behavioural support intervention to facilitate day-to-day e-cycling. Results One hundred participants completed an online survey and seven participated in the online co-design workshops. The development of the intervention identified five intervention functions (enablement, training, environmental restructuring, education, and persuasion) and 16 behaviour change techniques (BCTs) from 11 BCT groups (goals and planning, feedback and monitoring, social support, shaping knowledge, natural consequences, comparison of behaviour, associations, repetition and substitution, comparison of outcomes, antecedents, and self-belief). Conclusion To our knowledge, this is the first study to combine co-design and the BCW to develop a comprehensive behavioural support intervention for e-bike use. Theory based intervention options should be considered when providing e-bikes to individuals to help them increase their habitual PA levels.

Specific cell types and, therefore, organs respond differently during aging. This is also true for the hematopoietic system, where it has been demonstrated that hematopoietic stem cells alter a variety of features, such as their metabolism, and accumulate DNA damage, which can lead to clonal outgrowth over time. In addition, profound changes in the bone marrow microenvironment upon aging lead to senescence in certain cell types such as mesenchymal stem cells and result in increased inflammation. This heterogeneity makes it difficult to pinpoint the molecular drivers of organismal aging gained from bulk approaches, such as RNA sequencing. A better understanding of the heterogeneity underlying the aging process in the hematopoietic compartment is, therefore, needed. With the advances of single-cell technologies in recent years, it is now possible to address fundamental questions of aging. In this review, we discuss how single-cell approaches can and indeed are already being used to understand changes observed during aging in the hematopoietic compartment. We will touch on established and novel methods for flow cytometric detection, single-cell culture approaches, and single-cell omics.

Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration. Studies on Piezo1 have largely focused on transduction of "outside-in" mechanical forces, and its response to internal, cell-generated forces remains poorly understood. Here, using measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that cellular traction forces generate spatially-restricted Piezo1-mediated Ca2+ flickers in the absence of externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched near force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that mobility allows Piezo1 channels to explore a large number of mechanical microdomains and thus respond to a greater diversity of mechanical cues.

Adipocytes function as an energy buffer and undergo significant size and volume changes in response to nutritional cues. This adipocyte plasticity is important for systemic lipid metabolism and insulin sensitivity. Accompanying the adipocyte size and volume changes, the mechanical pressure against cell membrane also changes. However, the role that mechanical pressure plays in lipid metabolism and insulin sensitivity remains to be elucidated. Here we show that Piezo1, a mechanically-activated cation channel stimulated by membrane tension and stretch, was highly expressed in adipocytes. Adipose Piezo1 expression was increased in obese mice. Adipose-specific piezo1 knockout mice (adipose-Piezo1-/-) developed insulin resistance, especially when challenged with a high-fat diet (HFD). Perigonadal white adipose tissue (pgWAT) weight was reduced while pro-inflammatory and lipolysis genes were increased in the pgWAT of HFD-fed adipose-Piezo1-/- mice. The adipose-Piezo1-/- mice also developed hepatic steatosis with elevated expression of fatty acid synthesis genes. In cultured adipocytes, Piezo1 activation decreased, while Piezo1 inhibition elevated pro-inflammatory gene expression. TLR4 antagonist TAK-242 abolished adipocyte inflammation induced by Piezo1 inhibition. Thus, adipose Piezo1 may serve as an adaptive mechanism for adipocyte plasticity restraining pro-inflammatory response in obesity.

Objectives: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration. Methods: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017–2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort. Results: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0–6.2]). Conclusion: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.

Abstract Ozz, a member of the SOCS-box family of proteins, is the substrate-binding component of CRL5Ozz, a muscle-specific Cullin-RING ubiquitin ligase complex composed of Elongin B/C, Cullin 5 and Rbx1. CRL5Ozz targets for proteasomal degradation selected pools of substrates, including sarcolemma-associated β-catenin, sarcomeric MyHCemb and Alix/PDCD6IP, which all interact with the actin cytoskeleton. Ubiquitination and degradation of these substrates are required for the remodeling of the contractile sarcomeric apparatus. However, how CRL5Ozz assembles into an active E3 complex and interacts with its substrates remain unexplored. Here, we applied a baculovirus-based expression system to produce large quantities of two subcomplexes, Ozz–EloBC and Cul5–Rbx1. We show that these subcomplexes mixed in a 1:1 ratio reconstitutes a five-components CRL5Ozz monomer and dimer, but that the reconstituted complex interacts with its substrates only as monomer. The in vitro assembled CRL5Ozz complex maintains the capacity to polyubiquitinate each of its substrates, indicating that the protein production method used in these studies is well-suited to generate large amounts of a functional CRL5Ozz. Our findings highlight a mode of assembly of the CRL5Ozz that differs in presence or absence of its cognate substrates and grant further structural studies.

BackgroundHeart failure (HF) is a common chronic condition that affects over 26 million people worldwide. It is a progressive and debilitating disease with a broad symptom profile, intermittently marked by periods of acute decompensation. People with HF generally do not self-manage their condition well (eg, monitoring symptoms, taking medications regularly, physical activity, etc). A better understanding of self-care activities and what factors may indicate deterioration is warranted. ObjectiveThe aim of this study was to determine the feasibility and acceptability of using wearable cameras to assess self-care activities in people with HF. The study objectives were to (1) explore whether changes in self-care activities could be identified prior to hospitalization and (2) determine the acceptability of wearable cameras to people with HF. MethodsA total of 30 people recently diagnosed with HF wore a camera for a maximum of 30 days; the camera took a photo every 30 seconds in the forward-facing direction. At the end of the study, all 30 participants were presented with 8 statements of acceptability, scored on a 5-point Likert scale. To determine whether camera images could identify changes in self-care activities and lifestyle risk factors before hospitalization, we analyzed images from participants (n=8) who were hospitalized during the 30-day study period. Images from the period immediately prior to hospitalization and a comparison were selected for each participant. Images were manually coded according to 9 different event categories relating to self-care and lifestyle risk factors, and events were compared between the 2 periods. ResultsThe participants reported high acceptability for wearing the cameras, as most strongly agreed or agreed that they were comfortable to wear (28/30, 93%) and easy to use (30/30, 100%). The results of the camera image analysis showed that participants undertook fewer activities of daily living (P=.008) and were more sedentary (P=.02) prior to being hospitalized, compared to a period nonadjacent to hospitalization. ConclusionsAdults with HF were accepting of using a wearable camera for periods within a 30-day time frame. Wearable cameras were a feasible approach for providing data on selected self-care activities and lifestyle risk factors for HF and offer the potential to be a valuable tool for improving our understanding of self-care.

Current research suggests that faculty development should address a cross-section of personal and professional needs of the faculty, as well as support the institution's mission. Using evidence to support faculty development can foster reflective practitioners and close the gap between teaching and research by creating "sustainable collaboration practices" between faculty and administration.

Previous randomized controlled trials (RCTs) comparing intermittent feeding versus continuous feeding used different methods, employed shorter fasting intervals, ignored patients' posture in bed during feeds, and showed mixed results. Prolonged fasting intervals are hypothesized to have several benefits. Additionally, there is evidence for more efficient gastric emptying in the right lateral position. In this multicenter RCT, we aimed to compare the effects of three-times-a-day gastric feeding while in the right lateral tilt position (intermittent postural feeding) versus standard continuous gastric feeding (standard feeding) on gastrointestinal intolerance and mortality among mechanically ventilated patients in ICU. Adult ICU patients with gastric feeding tube in-situ and requiring invasive mechanical ventilation were randomized to either intermittent postural feeding group or to the standard feeding group. The feeding formula, target daily feed volume and posture turns were determined as per standard practice for all patients. Primary outcome was an incidence rate per 100 patient-days of gastrointestinal intolerance, a composite outcome of vomiting, diarrhea or constipation. Secondary outcomes were all-cause hospital mortality, gastrointestinal intolerance-free days, ventilator-free days, episodes of vomiting or diarrhea per patient, and mean diet volume ratio (diet received/diet prescribed). At five multidisciplinary ICUs, 120 mechanically ventilated, adult ICU patients (median age 65 years, 60% males) were randomly allocated to intermittent postural feeding (n = 61) and standard feeding (n = 59). The primary outcome did not differ between intermittent feeding arm versus standard arm (8.5, 95% confidence interval (CI): 5.9–11.8, versus 6.2, 95% CI: 4.1–9.1 per 100 patient-days; p = 0.23). Gastrointestinal intolerance-free days until day 14 were similar (6 [2–8] versus 5 [2–10]; p = 0.68) in both groups. Number of episodes per patient of vomiting, diarrhea, or constipation also did not differ in between groups. All-cause hospital mortality between intermittent feeding arm versus standard arm was 20% versus 31% (p = 0.17). There were no significant between-group differences in any of the other secondary outcomes. Intermittent gastric feeds delivered three-times-a-day while in the right lateral tilt position among mechanically ventilated patients was as well tolerated as the continuous enteral feeding. A definitive RCT to assess other clinically important outcomes is justified. ACTRN12616000212459 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365526&isReview=true. [ABSTRACT FROM AUTHOR]

Understanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly understood. We tested the hypothesis that cell surface carbohydrates contribute to NSPC membrane capacitance and fate. We found NSPCs differing in fate potential express distinct patterns of glycosylation enzymes. Screening several glycosylation pathways revealed that the one forming highly branched N-glycans differs between neurogenic and astrogenic populations of cells in vitro and in vivo. Enhancing highly branched N-glycans on NSPCs significantly increases membrane capacitance and leads to the generation of more astrocytes at the expense of neurons with no effect on cell size, viability, or proliferation. These data identify the N-glycan branching pathway as a significant regulator of membrane capacitance and fate choice in the neural lineage.

BackgroundThe management of heart failure is complex. Innovative solutions are required to support health care providers and people with heart failure with decision-making and self-care behaviors. In recent years, more sophisticated technologies have enabled new health care models, such as smart health ecosystems. Smart health ecosystems use data collection, intelligent data processing, and communication to support the diagnosis, management, and primary and secondary prevention of chronic conditions. Currently, there is little information on the characteristics of smart health ecosystems for people with heart failure. ObjectiveWe aimed to identify and describe the characteristics of smart health ecosystems that support heart failure self-care. MethodsWe conducted a scoping review using the Joanna Briggs Institute methodology. The MEDLINE, Embase, CINAHL, PsycINFO, IEEE Xplore, and ACM Digital Library databases were searched from January 2008 to September 2021. The search strategy focused on identifying articles describing smart health ecosystems that support heart failure self-care. A total of 2 reviewers screened the articles and extracted relevant data from the included full texts. ResultsAfter removing duplicates, 1543 articles were screened, and 34 articles representing 13 interventions were included in this review. To support self-care, the interventions used sensors and questionnaires to collect data and used tailoring methods to provide personalized support. The interventions used a total of 34 behavior change techniques, which were facilitated by a combination of 8 features for people with heart failure: automated feedback, monitoring (integrated and manual input), presentation of data, education, reminders, communication with a health care provider, and psychological support. Furthermore, features to support health care providers included data presentation, alarms, alerts, communication tools, remote care plan modification, and health record integration. ConclusionsThis scoping review identified that there are few reports of smart health ecosystems that support heart failure self-care, and those that have been reported do not provide comprehensive support across all domains of self-care. This review describes the technical and behavioral components of the identified interventions, providing information that can be used as a starting point for designing and testing future smart health ecosystems.

Cells constantly encounter mechanical stimuli in their environment, such as dynamic forces and mechanical features of the extracellular matrix. These mechanical cues are transduced into biochemical signals, and integrated with genetic and chemical signals to modulate diverse physiological processes. Cells also actively generate forces to internally transport cargo, to explore the physical properties of their environment and to spatially position themselves and other cells during development. Mechanical forces are therefore central to development, homeostasis, and repair. Several molecular and biophysical strategies are utilized by cells for detecting and generating mechanical forces. Here we discuss an important class of molecules involved in sensing and transducing mechanical forces - mechanically-activated ion channels. We focus primarily on the Piezo1 ion channel, and examine its relationship with the cellular cytoskeleton.