C/EBPß deletion in macrophages impairs mammary gland alveolar budding during the estrous cycle.

Macrophages have important roles in mammary gland development and tissue homeostasis, but the specific mechanisms that regulate macrophage function need further elucidation. We have identified C/EBPß as an important transcription factor expressed by multiple macrophage populations in the normal mammary gland. Mammary glands from mice with C/EBPß-deficient macrophages (Cebpb ΔM) show a significant decrease in alveolar budding during the diestrus stage of the reproductive cycle, whereas branching morphogenesis remains unchanged. Defects in alveolar budding were found to be the result of both systemic hormones and local macrophage-directed signals. RNA sequencing shows significant changes in PR-responsive genes and alterations in the Wnt landscape of mammary epithelial cells of Cebpb ΔM mice, which regulate stem cell expansion during diestrus. Cebpb ΔM macrophages demonstrate a shift from a pro-inflammatory to a tissue-reparative phenotype, and exhibit increased phagocytic capacity as compared to WT. Finally, Cebpb ΔM macrophages down-regulate Notch2 and Notch3, which normally promote stem cell expansion during alveolar budding. These results suggest that C/EBPß is an important macrophage factor that facilitates macrophage-epithelial crosstalk during a key stage of mammary gland tissue homeostasis.

Fertility in the Digital Age: A Survey-Based Evaluation of Fertility App Users' Quality of Life.

This study sought to characterize fertility app use among women seen for infertility care and to investigate the association between fertility app use and quality of life. This survey-based study was conducted at an academic infertility clinic. Surveys were administered to patients who presented for a new infertility visit. One survey collected information regarding app use and the second survey was FertiQoL, an internationally validated instrument measuring quality of life in those with infertility. Descriptive statistics were used to characterize the patient population regarding app use and FertiQoL scores. Comparisons between those who did and didn't use an app were evaluated using t-tests and Cochran Armitage test for trend. 149 surveys were collected. Most (75.5%) participants reported using a fertility app. Most participants (85.1%) used a free app and nearly all (97.2%) found their app helpful. There was a significant difference (p = 0.0034) in satisfaction with one's quality of life between app users and non-app users with app users demonstrating higher satisfaction. There were no significant differences between app users and non-app users with their overall FertiQoL scores however there was a statistically significant difference (p = 0.031) in Relational sub-scores with app users displaying higher scores. While overall quality of life, measured by standardized measures, did not differ, self-perceived satisfaction with quality of life improved with more satisfaction reported in those using an app. This self-perceived satisfaction and increased quality of life surrounding relationships carries important implications, especially when one may face the stress of infertility and its treatment.

A scoping review of incidence and assessment tools for post-intensive care syndrome following cardiac surgery.

BACKGROUND: Post-intensive care syndrome is a new or worsening persistent deterioration in cognitive, mental, and/or physical health following a prolonged admission to an intensive care unit. Post-intensive care syndrome remains underexplored following cardiac surgery, with a lack of understanding of the incidence and tools used to measure the symptoms. A scoping review was conducted to determine the incidence and to identify the tools commonly used to measure symptoms of post-intensive care syndrome following cardiac surgery. METHODS: The electronic databases Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Scopus, and CINAHL (EBSCOhost) and Google Scholar were searched with keywords and controlled vocabulary to describe both cardiac surgery and post-intensive care syndrome (cardiac surgical procedures, heart surgery, and post-intensive care symptoms) and symptoms (delirium, depression, mobility and quality of life). Included were articles written in English and published after 2005 that described cognitive, mental, and physical symptoms of post-intensive care syndrome following cardiac surgery. 3,131 articles were found, with 565 duplicates, leaving 2,566 articles to be screened. Of these, seven unique studies were included. RESULTS: Five studies explored cognitive health, three mental health, one cognitive and mental health, and none physical health. No identified studies reported the overall incidence of post-intensive care syndrome following cardiac surgery. The incidence of cognitive health issues ranged from 21% to 38%, and mental health issues ranged from 16% to 99%. In total, 17 different tools were identified - 14 for cognitive health and three for mental health. No identified studies used the same tools to measure symptoms. No single tool was found to measure all three domains. CONCLUSION: This scoping review identified a literature gap specific to the incidence and inconsistency of assessment tools for post-intensive care syndrome in cardiac surgery patients. CLINICAL IMPLICATIONS: This work impacts clinical practice for the bedside nurse by raising awareness of an emerging health issue.

Why behaviour matters: Studying inter-brain coordination during child-caregiver interaction.

Modern technology allows for simultaneous neuroimaging from interacting caregiver-child dyads. Whereas most analyses that examine the coordination between brain regions within an individual brain do so by measuring changes relative to observed events, studies that examine coordination between two interacting brains generally do this by measuring average intra-brain coordination across entire blocks or experimental conditions. In other words, they do not examine changes in inter-brain coordination relative to individual behavioural events. Here, we discuss the limitations of this approach. First, we present data suggesting that fine-grained temporal interdependencies in behaviour can leave residual artifact in neuroimaging data. We show how artifact can manifest as both power and (through that) phase synchrony effects in EEG and affect wavelet transform coherence in fNIRS analyses. Second, we discuss different possible mechanistic explanations of how inter-brain coordination is established and maintained. We argue that non-event-locked approaches struggle to differentiate between them. Instead, we contend that approaches which examine how interpersonal dynamics change around behavioural events have better potential for addressing possible artifactual confounds and for teasing apart the overlapping mechanisms that drive changes in inter-brain coordination.

Connectome-driven neural inventory of a complete visual system.

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the fly's visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the ~53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

A strengths-based qualitative exploration of critical care nurses' reasons for remaining in critical care.

AIMS: Globally, the nursing shortage is a growing concern. Much of the research on retention of nurses focuses on the experience of those who left positions. In this study, we set out to listen to critical care nurses (CCRNs) who have chosen to remain in their positions to understand the factors retaining them in critical care. DESIGN: This interpretive descriptive study was guided by the following research question: 'what factors influence CCRN's decision to continue to work in critical care?' METHODS: Digitally recorded interviews and a focus group were conducted between July 2022 and January 2023 using a semi-structured, strengths-based interview guide with CCRNs from three critical care units at a tertiary hospital in a city in a central Canadian province. Transcribed interviews were analysed using open, axial and selective coding and constant comparative analysis. RESULTS: Twenty-two CCRNs participated in interviews and three in a focus group. The theme of Respect, demonstrated through the interconnected concepts of Working to Full Scope, Team, Rotations and Compensation was identified. Working to Full Scope was described as providing nursing care aligned with how each nurse envisions what nursing is. Being part of a Team led by strong nurse leaders that provides opportunities and supports the sharing of their perspectives was also found. Respect was also found to be demonstrated through Rotations that recognize that work is one part of these nurses' lives. Compensation that reflects the increased education, knowledge and skills required in critical care was the final concept of Respect. CONCLUSION: Organizations should focus their efforts across the identified concepts to demonstrate Respect for CCRNs and retain them. IMPLICATIONS FOR PRACTICE: The findings of this study provide ways to support the retention of CCRNs. IMPACT: This research will have an impact on nursing leaders by providing tangible ways to retain CCRNs. REPORTING METHOD: Reporting of this work was guided by the Standards for Reporting Qualitative Research. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Annual Research Review: 'There, the dance is - at the still point of the turning world' - dynamic systems perspectives on coregulation and dysregulation during early development.

During development we transition from coregulation (where regulatory processes are shared between child and caregiver) to self-regulation. Most early coregulatory interactions aim to manage fluctuations in the infant's arousal and alertness; but over time, coregulatory processes become progressively elaborated to encompass other functions such as sociocommunicative development, attention and executive control. The fundamental aim of coregulation is to help maintain an optimal 'critical state' between hypo- and hyperactivity. Here, we present a dynamic framework for understanding child-caregiver coregulatory interactions in the context of psychopathology. Early coregulatory processes involve both passive entrainment, through which a child's state entrains to the caregiver's, and active contingent responsiveness, through which the caregiver changes their behaviour in response to behaviours from the child. Similar principles, of interactive but asymmetric contingency, drive joint attention and the maintenance of epistemic states as well as arousal/alertness, emotion regulation and sociocommunicative development. We describe three ways in which active child-caregiver regulation can develop atypically, in conditions such as Autism, ADHD, anxiety and depression. The most well-known of these is insufficient contingent responsiveness, leading to reduced synchrony, which has been shown across a range of modalities in different disorders, and which is the target of most current interventions. We also present evidence that excessive contingent responsiveness and excessive synchrony can develop in some circumstances. And we show that positive feedback interactions can develop, which are contingent but mutually amplificatory child-caregiver interactions that drive the child further from their critical state. We discuss implications of these findings for future intervention research, and directions for future work.

Diffuse bilateral 18F-Fluoroestradiol pulmonary uptake in patients with metastatic estrogen receptor positive breast cancer: A case report.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer in women and hormonal therapy is an established treatment for estrogen receptor (ER) positive breast cancers. 18F-Fluoroestradiol (FES) is an emerging radiotracer used to determine hormone status in patients with ER positive breast cancer as FES specifically binds to the alpha subtype of estrogen receptors. As with all radiotracers, FES demonstrates background uptake within various tissues and organs besides the targeted breast cancer and metastatic disease. To date, FES has mostly been shown to demonstrate uptake within the lungs from metastatic disease or in a more focal region after radiation therapy. CASE AND OUTCOMES: We present two patients with stage IV ER positive breast cancer who underwent FES positron emission tomography and computed tomography (PET/CT) scans to evaluate for metastatic disease; both of which demonstrated diffuse bilateral mild-moderate pulmonary uptake. The first patient had a severe lung injury which was improving but still present at the time of her FES PET/CT. The second patient had a remote history of prior right breast radiation therapy for a prior breast cancer as well as emphysema and mild interstitial disease. DISCUSSION: To date, FES uptake within the lungs has been shown to be secondary to fibrotic changes secondary to prior radiation therapy and the uptake is localized to a focal region within the lung corresponding to the localized region around the tumor needing radiation therapy. We present two FES PET/CT scans that demonstrate diffuse bilateral mild-moderate uptake. We believe the first patient's bilateral FES uptake was secondary to inflammatory changes from her acute lung injury. Our second patient has a remote history of right breast radiation therapy that would not account for her diffuse lung uptake but does have emphysema and mild interstitial disease which can account for the FES uptake seen in her FES PET/CT. CONCLUSION: 18F-Fluoroestradiol is an emerging radiotracer that binds to estrogen receptors and is being used to determine hormone receptor status in women with ER positive breast cancers, which is the most commonly diagnosed cancer in women. Therefore, it's important to understand where it might demonstrate uptake and why. We highlighted two unique cases of mild-moderate pulmonary uptake of FES to provide further information about FES. Overall, we conclude that diffuse bilateral mild-moderate FES uptake within the lungs is likely secondary to inflammation, interstitial disease, or a combination thereof.

Proactive or reactive? Neural oscillatory insight into the leader-follower dynamics of early infant-caregiver interaction.

We know that infants' ability to coordinate attention with others toward the end of the first year is fundamental to language acquisition and social cognition. Yet, we understand little about the neural and cognitive mechanisms driving infant attention in shared interaction: do infants play a proactive role in creating episodes of joint attention? Recording electroencephalography (EEG) from 12-mo-old infants while they engaged in table-top play with their caregiver, we examined the communicative behaviors and neural activity preceding and following infant- vs. adult-led joint attention. Infant-led episodes of joint attention appeared largely reactive: they were not associated with increased theta power, a neural marker of endogenously driven attention, and infants did not increase their ostensive signals before the initiation. Infants were, however, sensitive to whether their initiations were responded to. When caregivers joined their attentional focus, infants showed increased alpha suppression, a pattern of neural activity associated with predictive processing. Our results suggest that at 10 to 12 mo, infants are not routinely proactive in creating joint attention episodes yet. They do, however, anticipate behavioral contingency, a potentially foundational mechanism for the emergence of intentional communication.

Barriers and Facilitators to Hepatitis C Virus (HCV) Treatment for Aboriginal and Torres Strait Islander Peoples in Rural South Australia: A Service Providers' Perspective.

This study explored the barriers and facilitators to hepatitis C virus (HCV) treatment for Aboriginal and Torres Strait Islander peoples in rural South Australia as viewed from a healthcare provider perspective in the era of direct acting antivirals (DAAs). Phase 1 was a qualitative systematic review examining the barriers and enablers to diagnosis and treatment amongst Indigenous peoples living with HCV worldwide. Phase 2 was a qualitative descriptive study with healthcare workers from six de-identified rural and regional Aboriginal Community-Controlled Health Services in South Australia. The results from both methods were integrated at the analysis phase to understand how HCV treatment could be improved for rural Aboriginal and Torres Strait Islander peoples. Five main themes emerged: the importance of HCV education, recognizing competing social and cultural demands, the impact of holistic care delivery and client experience, the effect of internal barriers, and overlapping stigma, discrimination, and shame determine how Indigenous peoples navigate the healthcare system and their decision to engage in HCV care. Continued efforts to facilitate the uptake of DAA medications by Aboriginal and Torres Strait peoples in rural areas should utilize a multifaceted approach incorporating education to community and cultural awareness to reduce stigma and discrimination.

Parental Scaffolding during Book-Sharing Predicts Child General Intelligence.

While much variance in general intelligence or g is genetic, a substantial environmental component suggests a possible role for parent-child interaction. In particular, previous evidence suggests the importance of parental scaffolding, or provision of cognitive structure to shape child behaviour. A role for scaffolding is consistent with the proposal that, in adult cognition, a critical aspect of g is decomposition of complex problems into a structure of simpler parts. Building on previous work, we recruited 162 parents attending Children's Centres with a child aged 2-4 years, and examined parental scaffolding during a book-sharing activity. Scaffolding was measured as the first principal component of a variety of parental behaviours, including sensitivity, focusing attention, extending comprehension, and promoting child participation. Child g was measured as the first principal component of a broad cognitive battery, including language, attention, working memory, and executive function. Importantly, we assessed contributions of the parent's own intelligence, education, and family income. Though these variables were all associated with both child g and parental scaffolding, scaffolding remained predictive of child g even once the influence of these variables was removed. In contrast to the correlation with cognitive proficiency, scaffolding did not predict child pro-social behaviour. We suggest that parental scaffolding supports the child's development of a broad skill of attentional structuring, promoting the across-the-board cognitive proficiency that is reflected in g.

Emerging functions of C/EBPß in breast cancer.

Breast tumorigenesis relies on complex interactions between tumor cells and their surrounding microenvironment, orchestrated by tightly regulated transcriptional networks. C/EBPß is a key transcription factor that regulates the proliferation and differentiation of multiple cell types and modulates a variety of biological processes such as tissue homeostasis and the immune response. In addition, C/EBPß has well-established roles in mammary gland development, is overexpressed in breast cancer, and has tumor-promoting functions. In this review, we discuss context-specific roles of C/EBPß during breast tumorigenesis, isoform-specific gene regulation, and regulation of the tumor immune response. We present challenges in C/EBPß biology and discuss the importance of C/EBPß isoform-specific gene regulation in devising new therapeutic strategies.

Vocal communication is tied to interpersonal arousal coupling in caregiver-infant dyads.

It has been argued that a necessary condition for the emergence of speech in humans is the ability to vocalise irrespective of underlying affective states, but when and how this happens during development remains unclear. To examine this, we used wearable microphones and autonomic sensors to collect multimodal naturalistic datasets from 12-month-olds and their caregivers. We observed that, across the day, clusters of vocalisations occur during elevated infant and caregiver arousal. This relationship is stronger in infants than caregivers: caregivers vocalisations show greater decoupling with their own states of arousal, and their vocal production is more influenced by the infant's arousal than their own. Different types of vocalisation elicit different patterns of change across the dyad. Cries occur following reduced infant arousal stability and lead to increased child-caregiver arousal coupling, and decreased infant arousal. Speech-like vocalisations also occur at elevated arousal, but lead to longer-lasting increases in arousal, and elicit more parental verbal responses. Our results suggest that: 12-month-old infants' vocalisations are strongly contingent on their arousal state (for both cries and speech-like vocalisations), whereas adults' vocalisations are more flexibly tied to their own arousal; that cries and speech-like vocalisations alter the intra-dyadic dynamics of arousal in different ways, which may be an important factor driving speech development; and that this selection mechanism which drives vocal development is anchored in our stress physiology.

DOT1L inhibitors block abnormal self-renewal induced by cohesin loss.

Acute myeloid leukemia (AML) is a high-risk malignancy characterized by a diverse spectrum of somatic genetic alterations. The mechanisms by which these mutations contribute to leukemia development and how this informs the use of targeted therapies is critical to improving outcomes for patients. Importantly, how to target loss-of-function mutations has been a critical challenge in precision medicine. Heterozygous inactivating mutations in cohesin complex genes contribute to AML in adults by increasing the self-renewal capacity of hematopoietic stem and progenitor cells (HSPCs) by altering PRC2 targeting to induce HOXA9 expression, a key self-renewal transcription factor. Here we sought to delineate the epigenetic mechanism underpinning the enhanced self-renewal conferred by cohesin-haploinsufficiency. First, given the substantial difference in the mutational spectrum between pediatric and adult AML patients, we first sought to identify if HOXA9 was also elevated in children. Next, using primary HSPCs as a model we demonstrate that abnormal self-renewal due to cohesin loss is blocked by DOT1L inhibition. In cohesin-depleted cells, DOT1L inhibition is associated with H3K79me2 depletion and a concomitant increase in H3K27me3. Importantly, we find that there are cohesin-dependent gene expression changes that promote a leukemic profile, including HoxA overexpression, that are preferentially reversed by DOT1L inhibition. Our data further characterize how cohesin mutations contribute to AML development, identifying DOT1L as a potential therapeutic target for adult and pediatric AML patients harboring cohesin mutations.

A decentralised point-of-care testing model to address inequities in the COVID-19 response.

The COVID-19 pandemic is growing rapidly, with over 37 million cases and more than 1 million deaths reported by mid-October, 2020, with true numbers likely to be much higher in the many countries with low testing rates. Many communities are highly vulnerable to the devastating effects of COVID-19 because of overcrowding in domestic settings, high burden of comorbidities, and scarce access to health care. Access to testing is crucial to globally recommended control strategies, but many communities do not have adequate access to timely laboratory services. Geographic dispersion of small populations across islands and other rural and remote settings presents a key barrier to testing access. In this Personal View, we describe a model for the implementation of decentralised COVID-19 point-of-care testing in remote locations by use of the GeneXpert platform, which has been successfully scaled up in remote Aboriginal and Torres Strait Islander communities across Australia. Implementation of the decentralised point-of-care testing model should be considered for communities in need, especially those that are undertested and socially vulnerable. The decentralised testing model should be part of the core global response towards suppressing COVID-19.

E-Cigarette or Vaping Product Use-Associated Lung Injury: A Severe Case That Responded to Corticosteroid Treatment.

Vaping is associated with an increased risk of lung injury; however, each case of vaping-associated lung injury leads to varying degrees of lung injury, and the response to therapy can be heterogeneous. Corticosteroid use has been suggested as a treatment for lung injuries associated with vaping. We report a case of e-cigarette or vaping product use-associated lung injury (EVALI) that resulted in acute hypoxic respiratory failure. A 20-year-old woman presented with complaints of sore throat, dry cough, shortness of breath, and pleuritic chest pain. The patient admitted to vaping regularly for the past three years. The patient was found to be severely hypoxemic with respiratory distress and was intubated shortly after her arrival at the emergency department. She was treated with a short course of corticosteroids with tapering of the dose based on her response with significant improvement, and she was extubated on the seventh day of her admission. EVALI is a syndrome associated with severe lung injury that results in acute respiratory failure that is clinically indistinguishable from acute respiratory distress syndrome, and it is largely a diagnosis of exclusion. The use of systemic corticosteroids in treating these patients should be considered after excluding an infectious etiology.

Epidemiology of the First Wave of COVID-19 ICU Admissions in South Wales-The Interplay Between Ethnicity and Deprivation.

On the 9th March 2020, the first patient with COVID-19 was admitted to ICU in the Royal Gwent Hospital (RGH), Newport, Wales. We prospectively recorded the rate of ICU admissions of 52 patients with COVID-19 over 60 days, focusing on the epidemiology of ethnicity and deprivation because these factors have emerged as significant risk factors. Patients were 65% (34 of 52) male and had a median (IQR) age of 55 (48-62) years. Prevalent comorbidities included obesity (52%); diabetes (33%), and asthma (23%). COVID-19 hospital and ICU inpatient numbers peaked on days 23 and 39, respectively-a lag of 16 days. The ICU mortality rate was 33% (17 of 52). People of black, Asian, and minority ethnic descent (BAME group) represented 35% of ICU COVID-19 admissions (18 of 52) and 35% of deaths (6 of 17). Amongst the BAME group, 72% (13 of 18) of patients were found to reside in geographical areas representing the 20% most deprived in Wales, vs. 27% of patients in the Caucasian group (9 of 33). Less than 5% of the population within the area covered by RGH are of BAME descent, yet this group had a disproportionately high ICU admission and mortality rate from COVID-19. The interplay between ethnicity and deprivation, which is complex, may be a factor in our findings. This in turn could be related to an increased prevalence of co-morbidities; higher community exposure; larger proportion of lower band key worker roles; or genetic polymorphisms.

Motivation Predicts Change in Nurses' Physical Activity Levels During a Web-Based Worksite Intervention: Results From a Randomized Trial.

BACKGROUND: Low physical activity levels can negatively affect the health of nurses. Given the low physical activity levels reported by nurses, there is a clear need for brief and economical interventions designed to increase physical activity levels in this population. We developed a web-based intervention that used motivational strategies to increase nurses' physical activity levels. The intervention provided the nurses with feedback from an activity monitor coupled with a web-based individual, friend, or team physical activity challenge. OBJECTIVE: In this parallel-group randomized trial, we examine whether nurses' motivation at baseline predicted changes in objectively measured physical activity levels during the 6-week intervention. METHODS: The participants were 76 nurses (n=74, 97% female; mean age 46, SD 11 years) randomly assigned to 1 of 3 physical activity challenge conditions: (1) individual, (2) friend, or (3) team. The nurses completed a web-based questionnaire designed to assess motivational regulations for physical activity levels before the intervention and wore a Tractivity activity monitor before and during the 6-week intervention. We analyzed data using multilevel modeling for repeated measures. RESULTS: The nurses' physical activity levels increased (linear estimate=10.30, SE 3.15; P=.001), but the rate of change decreased over time (quadratic estimate=-2.06, SE 0.52; P<.001). External and identified regulations (ß=-2.08 to 11.55; P=.02 to .04), but not intrinsic and introjected regulations (ß=-.91 to 6.29; P=.06 to .36), predicted changes in the nurses' physical activity levels. CONCLUSIONS: Our findings provide evidence that an intervention that incorporates self-monitoring and physical activity challenges can be generally effective in increasing nurses' physical activity levels in the short term. They also suggest that drawing solely on organismic integration theory to predict changes in physical activity levels among the nurses participating in web-based worksite interventions may have been insufficient. Future research should examine additional personal (eg, self-efficacy) and occupational factors (eg, shift length and shift type) that influence physical activity levels to identify potential targets for intervention among nurses. TRIAL REGISTRATION: ClinicalTrials.gov NCT04524572; https://clinicaltrials.gov/ct2/show/NCT04524572.