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Abstract Preschool children with recurrent wheezing are a heterogeneous population with many underlying biological pathways that contribute to clinical presentations. Although the morbidity of recurrent wheezing in preschool children is significant, biological studies in this population remain quite limited. To address this gap, this study performed untargeted plasma metabolomic analyses in 68 preschool children with recurrent wheezing to identify metabolomic endotypes of wheezing. K-means cluster analysis was performed on metabolomic dataset including a total of 1382 named and unnamed metabolites. We identified three metabolomic clusters which differed in symptom severity, exacerbation occurrence, and variables associated with social disadvantage. Metabolites that distinguished the clusters included those involved in fatty acid metabolism, fatty acids (long chain monounsaturated fatty acids, long chain polyunsaturated fatty acids, and long chain saturated fatty acids), lysophospholipids, phosphatidylcholines, and phosphatidylethanolamines. Pathway analyses identified pathways of interest in each cluster, including steroid metabolism, histidine metabolism, sphingomyelins, and sphingosines, among others. This study highlights the biologic complexity of recurrent wheezing in preschool children and offers novel metabolites and pathways that may be amenable to future study and intervention.

IntroductionElasmobranchs, such as sharks and rays, are among the world’s most endangered vertebrates, with over 70% loss in abundance over the past 50 years due to human impacts. Zooarchaeological baselines of elasmobranch diversity, distribution, and exploitation hold great promise for contributing essential historical contexts in the assessment of contemporary patterns in their taxonomic diversity and vulnerability to human-caused extinction. Yet, the historical ecology of elasmobranchs receives relatively less archaeological attention compared to that of ray-finned fishes or marine mammals, largely due to issues of taxonomic resolution across zooarchaeological identifications.MethodsWe explore the use of Zooarchaeology by Mass Spectrometry (ZooMS) for species identification in this unstudied group, using an archaeological case study from the marine environments of the Florida Keys, a marine biodiversity hotspot that is home to an array of elasmobranch species and conservation efforts. By comparison with 39 modern reference species, we could distinguish 12 taxa within the zooarchaeological assemblage from the Clupper archaeological site (Upper Matecumbe Key) that included nine sharks, two rays and a sawfish.Results and discussionThe results indicate that, through additional complexity of the collagen peptide mass fingerprint, obtained due to the presence of the cartilaginous type II collagen, ZooMS collagen peptide mass fingerprinting provides exceptionally high taxonomic resolution in this group, yielding species-level identifications in all cases where sufficient reference material was used. This case study also highlights the added value of ZooMS for taxa that are more difficult to distinguish in zooarchaeological analyses, such as vertebrae of the Atlantic sharpnose shark (Rhizoprionodon terraenovae) and the hammerhead sharks (Sphyrna spp.) in the Florida Keys. Therefore, the application of collagen peptide mass fingerprinting to elasmobranchs offers great potential to improve our understanding of their archaeological past and historical ecology.

Background Older people living in care homes are at high risk of poor health outcomes and mortality if they contract coronavirus disease 2019. Protective measures include social distancing and isolation, although implementation is challenging. Objectives To explore the real-life experiences of social distancing and isolation in care homes for older people, and to develop a toolkit of guidance and resources. Design A mixed-methods, phased design. Setting Six care homes in England caring for older adults. Participants Care home staff (n = 31), residents (n = 17), family members (n = 17), senior health and care leaders (n = 13). Methods A rapid review to assess the social distancing and isolation measures used by care homes to control the transmission of coronavirus disease 2019 and other infectious diseases (phase 1), in-depth case studies of six care homes, involving remote individual interviews with staff, residents and families, collection of policies, protocols and routinely collected care home data, remote focus groups with senior health and care leaders (phase 2) and stakeholder workshops to co-design the toolkit (phase 3). Interview and focus group data and care home documents were analysed using thematic analysis and care home data using descriptive statistics. Results The rapid review of 103 records demonstrated limited empirical evidence and the limited nature of policy documentation around social distancing and isolation measures in care homes. The case studies found that social distancing and isolation measures presented moral dilemmas for staff and often were difficult, and sometimes impossible to implement. Social distancing and isolation measures made care homes feel like an institution and denied residents, staff and families of physical touch and other forms of non-verbal communication. This was particularly important for residents with cognitive impairment. Care homes developed new visiting modalities to work around social distancing measures. Residents and families valued the work of care homes to keep residents safe and support remote communication. Social distancing, isolation and related restrictions negatively impacted on residents’ physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government was described as chaotic, and trauma was inflicted on care home staff, residents, families and friends. These multiple data sources have informed the co-design of a toolkit to care for residents, families, friends and care home staff. Limitations The review included papers published in English language only. The six care homes had a Care Quality Commission rating of either ‘good’ or ‘outstanding’. There was a lack of ethnic diversity in resident and family participants. Conclusions Care homes implemented innovative approaches to social distancing and isolation with varying degrees of success. A legacy of learning can help rebuild trust at multiple levels and address trauma-informed care for residents, families, friends and staff. Future work can include evaluation of the toolkit, research to develop a trauma-informed approach to caring for the care home sector and co-designing and evaluating an intervention to enable residents with different needs to transition to living well in a care home. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information. Plain language summary Older people living in care homes are at risk of poor health and death if they get coronavirus disease 2019 (COVID-19). To protect older people from COVID-19, care homes use different measures, including social distancing and isolation. These measures can be challenging. Our research aimed to explore the challenges and solutions to using social distancing and isolation in care homes. We reviewed existing evidence to examine how care homes have used social distancing and isolation measures to control the spread of COVID-19 and other contagious diseases. We investigated how social distancing and isolation measures have been used in six care homes in England. We spoke with residents, families and staff. We collected care home documents and other data. We held group discussions with senior health and care leaders. The review showed limited research and the limited nature of policy documentation on social distancing and isolation measures. Interviews revealed that social distancing and isolation measures were difficult, and sometimes impossible, for staff to implement. These measures made care homes feel less homely and inhibited touch, for example hugs. Residents and families valued the work of care homes to keep residents safe and the use of technology for keeping connected. Social distancing, isolation and related restrictions negatively affected residents’ physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government to the care home sector was described as chaotic and trauma was inflicted on care home staff, residents, families and friends. These findings have been used to design guidance to help care homes implement social distancing and isolation measures both now and for any future outbreaks. Scientific summary Background Older people living in care homes (CHs) (i.e. homes that provide residential and/or nursing care) often have complex health and care needs and are at high risk of poor health outcomes and mortality, especially if they contract coronavirus disease 2019 (COVID-19). To protect older people from COVID-19, CHs use interventions such as social distancing and isolation, but these measures have been reported as challenging. Research is needed to explore and understand the challenges experienced by CHs endeavouring to implement these interventions while mitigating any negative consequences. Objectives The overall aim of the study was to explore and understand the real-life experiences of social distancing and isolation measures for older people living in CHs in England from the perspective of multiple stakeholders, and to develop a toolkit of evidence-informed guidance and resources for CHs now and for future outbreaks. The study objectives were as follows: (1) to investigate the mechanisms and measures used by CHs currently and previously to socially distance and isolate older people to prevent and control the spread of COVID-19 and other infectious and contagious diseases (2) to examine the experiences of residents and families/friends of social distancing and isolation measures during the COVID-19 pandemic, including how these measures impacted upon their well-being and how they adapted to change (3) to explore how registered nurses and care staff adapted to and managed the delivery of personal, social and psychological care for residents with different needs while maintaining social distancing and isolation measures (4) to identify how CH managers, owners and external stakeholders developed, managed and adapted policies, procedures and protocols to implement social distancing and isolation measures including workforce organisation, training and support, use of communal spaces, visiting, and working with external health and social care professionals (5) to use the findings to develop a toolkit of evidence-informed guidance and resources, including a mosaic film, detailing which interventions and strategies for social distancing and isolation work well and which do not work in specific situations and contexts to support decision-making about health and care delivery in CHs and to facilitate resilience-building for future planning. Methods A mixed-methods, phased design was undertaken to identify the challenges, consequences and solutions to implementing social distancing and isolation measures in CHs for older adults to prevent and control the spread of COVID-19. The study was conducted in three phases: (1) a rapid evidence review of measures used to prevent or control the transmission of COVID-19 and other infectious diseases in CHs for older people, following the guidance for conducting rapid reviews1 (2) in-depth case studies of six purposively sampled CHs in England involving individual interviews with care staff, managers, residents and family/friends, the collection of social distancing and isolation policies/protocols and routinely collected CH data, and focus groups with purposively sampled CH owners and external stakeholders. Reporting guidance for qualitative research was used2 (3) development of a toolkit of evidence-informed guidance and resources, and a mosaic film for CHs. The findings from earlier phases were used in two co-design workshops with external stakeholders to develop the toolkit. Findings from the 103 papers included in the rapid review were synthesised using tables and a narrative summary organised around the review questions. Interview audio-recordings were transcribed verbatim and data analysed using thematic analysis. Descriptive summary statistics described the quantitative data collected. For the CH documents, information was collated around the key themes of social distancing, isolation, cohorting, zoning and other restrictions. Concurrent data collection and analysis informed decision-making about the need for further data and from which source. Patient and public involvement (PPI) was an integral part of this study, informing its design, method, analysis and dissemination. PPI group members also participated in online workshops to contribute to the co-design of the toolkit. Results The rapid review highlighted the following: There is a lack of empirical evidence around how measures to prevent or control COVID-19 and other infectious diseases are implemented in CHs. Most papers were grey literature or policy documents, which were mainly descriptive, or opinion based. Furthermore, these interventions were generally mentioned as part of a wider discussion of COVID-19 strategies and were not the primary focus of the papers. Key interventions for preventing and controlling the transmission of COVID-19 and other infectious diseases in CHs for older people include social distancing; isolation of residents and staff; restrictions for residents, family members and staff; zoning and cohorting; and surveillance. Evaluative research on the use of these interventions in CHs is needed urgently. The six case study sites were geographically spread and all had a Care Quality Commission rating of good (n = 4) or outstanding (n = 2). All were part of organisations (ranging in size from 7 to 114 CHs per organisation, and between 767 and 5875 beds per organisation). Four of the CHs were part of privately run organisations, and two were part of voluntary/not-for-profit organisations. One CH had a ‘dual’ registration, three had a ‘nursing’ registration and two were registered as ‘without nursing’. Most provided some specialist care such as for dementia, learning disabilities, physical and mental health problems. The number of beds offered ranged between 37 and 73. One CH comprised a household of 12 residents within a village complex. Care homes varied on the number of positive COVID-19 cases, for example one reported only one case between March 2020 and February 2021, while another reported 27 cases within the month November 2020 alone – this home had opened a specially allocated ‘COVID-ward’. In one CH no residents had died within 28 days of a positive COVID-19 test, while 10 residents had died from another home. Policies and protocols about social distancing and isolation measures were collected from each CH and compared. Key findings were as follows: There was significant variation between CHs in the content, length and level of detail presented in policy and guidance documents. Capturing the frequent updates in guidance was challenging with documents sometimes being repetitive and unclear. Many documents had further, embedded documents or links to government guidance that provided a great deal of information, which might be unrealistic for CH staff to read. Shorter documents were less comprehensive and may not provide the necessary detail to guide CH staff. None of the documents included guidance on staff training and development. Research at the case study sites included individual interviews with 31 CH staff. Key findings were as follows: The impact that the COVID-19 pandemic had upon CH staff must not be underestimated. Staff reported trauma and emotional distress. For many staff, the difficulties experienced during the pandemic were compounded by the government’s response to CHs. Some staff felt they had been abandoned by the government, while others criticised the ‘blanket approach’ to government guidance and the rapidly changing rules for CHs. Care home managers valued the support of their senior leadership to help them interpret and implement government guidance. Staff talked of the difficulties of ‘policing’ social distancing measures while simultaneously trying to maintain a sense of ‘normality’ for their residents. Although staff and residents were supposed to maintain a social distance from each other, this was often impossible to uphold when providing personal care. Care homes were perceived as a resident’s home rather than an institution, which made some staff question whether social distancing was appropriate. Many staff felt that social distancing measures denied residents (and themselves) of the important need for touch, as hugs were felt to have a vital role in CH life. Understanding fully the impact on residents living with dementia was recognised as a challenge and not always possible to achieve. The design and layout of CHs meant that there was not always the physical space for social distancing to be implemented. Staff felt that new admissions to CHs had the most difficult experience with isolation regulations. For some managers, isolation measures went against the ethos of the CH environment and ruined the family feel of the CH. The requirement for residents to isolate when returning from hospital could lead to a reluctance in residents to attend hospital appointments and a disinclination of staff to refer residents for hospital care. Several different resident restrictions were implemented in CHs, but restrictions around residents leaving the home, changes to food preparation/delivery and visitor restrictions were perceived to have the greatest negative impact. On occasions, staff became a target of anger and frustration from residents and their families, who could not comprehend that they were being prevented from seeing each other. Good support from CH management was considered by staff to make the process of implementing these measures easier. Individual interviews were conducted with 17 residents and 17 family members. Key findings were as follows: The experiences of residents and families were varied, and their impact was influenced by the existing pattern of relationships residents and families maintained within and beyond the CH. Residents and families valued the work of the CHs in keeping residents safe. They accepted the need for restrictions. Residents and families appreciated the support they received in communicating with one another virtually and the importance of this communication for residents’ health and well-being. Measures relating to isolation were particularly difficult for residents, particularly for those unable to communicate with the outside world through technology. Measures to make isolation less difficult for residents included ensuring that they were entertained purposefully with regular socially distanced visits from staff and various resources to occupy their time. Creative approaches to activities for residents not isolating were also evidenced, for example indoor gardening, yoga and quizzes. Social distancing made aspects of CH life and social visiting difficult and sometimes unsatisfactory; residents and families missed physical touch and other non-verbal forms of communication. This was particularly important for residents with cognitive impairment. Residents and families were involved with staff in complex judgements of risk, choice and control, which were complicated by two factors. First, families (and some residents) were aware that those in CHs were in the twilight of their lives and that time was ebbing away. Second, many families and residents were also learning how to manage their relationships in the new living context of a CH. Two focus groups were conducted with a purposive sample of 13 external senior health and care leaders. Key findings were as follows: Isolation of the sector: the sector felt cut off from the National Health Service (NHS) and pre-pandemic sources of service and support. Government guidance for CHs and communication processes: ‘chaos’ described the approach to cascading information to CHs, especially in the first wave of the pandemic. Visiting: regulations evolved throughout the different waves of the pandemic and led to variations in interpreting and implementing visiting guidance. Trauma: as the pandemic wore on and the different waves and variants emerged, there was a need to take account of the broader health and well-being of residents, families, visitors and the workforce. Trauma impacted at several different levels – for staff, residents and family members. Implications for practice and policy For practice Implications of the study findings for practice are captured in our toolkit for supporting CHs with social distancing and isolation measures. These are framed around six areas: caring for residents when they are social distancing; caring for residents when they are isolating; supporting residents, families and friends to communicate when visiting is not permitted; supporting visits from families and friends when visiting is allowed but with restrictions; caring for care staff; and caring for managers. For policy The study findings can inform discussions involving CH providers, managers and external stakeholders to enhance understanding of social distancing and isolation measures for residents – consequences, challenges, solutions and learning. Our findings also have implications about how guidelines are developed and disseminated. They reinforce the need for CHs and social care to be considered as an integral part of integrated care systems, to ensure that actions taken during national emergencies fully account for the impact on all parts of health and social care. Our findings can inform discussions about developing digital technologies to help residents with different needs stay connected with families and friends, and for CHs to communicate effectively with residents’ families and friends. Our findings can contribute to the content of the digital hub for the social care workforce. Recommendations for further research This study has identified that research is needed in several areas including the following: Evaluations of the toolkit. Evaluation of social distancing and isolation measures used in CHs to prepare for future pandemics. Research to develop and evaluate remote social interaction for residents living with dementia and their families. Research to understand what a trauma-informed approach looks like for the CH sector – to care for residents, families, friends and staff in CHs caring for older people. Research to co-design and evaluate an intervention to enable residents with different needs to transition to living well in a CH. The study of an intervention that cares for families and friends. Conclusions The CH sector was ill-prepared and under-resourced for the COVID-19 pandemic. During the pandemic and for any further surges, it is paramount that CH services are safe, effective, caring, responsive to individual needs and well-led. The loss of older people living in CHs due to COVID-19 has been substantial; it is essential to learn from this devastation, to understand the consequences, challenges, solutions and to evaluate these solutions. Evidence to support learning and recovery of the CH sector from the pandemic and to inform policy-making is paramount. Care homes need evidence-informed guidance that sets out what and how social distancing and isolation measures should be operationalised, while meeting residents’ individual needs. Our toolkit is designed to capture such innovative approaches. Our study makes an important contribution to this learning and recovery, as one of the first to study the challenges and solutions to implementing social distancing and isolation measures for older people living in CHs in England. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information.

OBJECTIVES:. Monocytes are plastic cells that assume different polarization states that can either promote inflammation or tissue repair and inflammation resolution. Polarized monocytes are partially defined by their transcriptional profiles that are influenced by environmental stimuli. The airway monocyte response in pediatric acute respiratory distress syndrome (PARDS) is undefined. To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor monocytes exposed to the airway fluid of intubated children with and at-risk for PARDS. To determine differences in gene expression at two time points using the donor monocyte assay exposed to airway fluid from intubated children with PARDS obtained 48–96 hours following initial tracheal aspirate sampling. DESIGN:. In vitro pilot study carried out using airway fluid supernatant. SETTING:. Academic 40-bed PICU. PARTICIPANTS:. Fifty-seven children: 44 children with PARDS and 13 children at-risk for PARDS. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We performed bulk RNA sequencing using a transcriptomic reporter assay of monocytes exposed to airway fluid from intubated children to discover gene networks differentiating PARDS from at-risk for PARDS and those differentiating mild/moderate from severe PARDS. We also report differences in gene expression in children with PARDS 48–96 hours following initial tracheal aspirate sampling. We found that interleukin (IL)-10, IL-4, and IL-13, cytokine/chemokine signaling, and the senescence-associated secretory phenotype are upregulated in monocytes exposed to airway fluid from intubated children with PARDS compared with those at-risk for PARDS. Signaling by NOTCH, histone deacetylation/acetylation, DNA methylation, chromatin modifications (B-WICH complex), and RNA polymerase I transcription and its associated regulatory apparatus were upregulated in children with PARDS 48–96 hours following initial tracheal aspirate sampling. CONCLUSIONS:. We identified gene networks important to the PARDS airway immune response using bulk RNA sequencing from a monocyte reporter assay that exposed monocytes to airway fluid from intubated children with and at-risk for PARDS. Mechanistic investigations are needed to validate our findings.

Introduction: The diversity of information on social media provides a ubiquitous possibility for social comparison. Online social comparisons have both detrimental and beneficial effects; besides lowering one’s self-esteem, heightening loneliness and addiction, they also bring together people with similar interests which may offer a form of social support. Aims: This study examines a path model for understanding the link between social comparison and social media addiction while examining online social support, loneliness, and self-esteem. Methods: Hungarian university students (N = 201, 70.6% women, aged between 18 and 30 years, SD = 2.77) completed an online survey in the spring of 2022. Results: The final path model suggests that social comparison can directly contribute to social media addiction. This link was mediated by loneliness and self-esteem, resulting in a path with different outcomes: a) social comparison may strengthen loneliness (β = .22, p < .001) which can lead to lower self-esteem (β = .60, p < .001), and b) social comparison may have a negative effect on self-esteem (β = -.22, p < .001) which can reduce social media addiction (β = -.26, p < .001). In addition, social comparison may help obtain online social support (β = .15, p < .050) which can reduce loneliness (β = -.41, p < .001) but increase the likelihood of addiction (β = .26, p < .001). Conclusions: These findings draw attention to the double-edged sword of social comparison and online social support: we need to learn to consciously manage online social comparison tendencies.

Abstract Background There is a growing interest in employing community wellness worker models in Indigenous populations to address inequities in healthcare access and outcomes, concerns about shortage in health and mental health human resources, and escalating burden of chronic and complex diseases driving significant increase in health services demand and costs. A thorough review of Indigenous community wellness worker models has yet to be conducted. This rapid review sought to outline the characteristics of a community wellness worker model in Indigenous contexts across the globe, detailing factors shaping implementation challenges and success. Methods A rapid review of the international peer-reviewed and grey literature of OVID Medline, Global Index Medicus, Google, and Google Scholar was conducted from January to June 2022 for Indigenous community wellness/mental health worker models and comparative models. Articles were screened and assessed for eligibility. From eligible articles, data pertaining to study design and sample; description of the program, service, or intervention; model development and implementation; terminology used to describe workers; training features; job roles; funding considerations; facilitators and barriers to success; key findings; outcomes measured; and models or frameworks utilized were extracted. Data were synthesized by descriptive and pattern coding. Results Twenty academic and eight grey literature articles were examined. Our findings resulted in four overarching and interconnected themes: (1) worker roles and responsibilities; (2) worker training, education, and experience; (3) decolonized approaches; and (4) structural supports. Conclusion Community wellness worker models present a promising means to begin to address the disproportionately elevated demand for mental wellness support in Indigenous communities worldwide. This model of care acts as a critical link between Indigenous communities and mainstream health and social service providers and workers fulfill distinctive roles in delivering heightened mental wellness supports to community members by leveraging strong ties to community and knowledge of Indigenous culture. They employ innovative structural solutions to bolster their efficacy and cultivate positive outcomes for service delivery and mental wellness. Barriers to the success of community wellness worker models endure, including power imbalances, lack of role clarity, lack of recognition, mental wellness needs of workers and Indigenous communities, and more.

Abstract Asthma exacerbations are a leading cause of pediatric hospitalizations despite multiple efforts to educate patients and families on disease course and medication management. Asthma education in the pediatric emergency department (ED) is challenging, and although the use of written action plans has been associated with reduction in hospitalizations and ED visits, written tools may not be useful for individuals with low health literacy. Moreover, asthmatic children should participate in their asthma education. In this prospective randomized study of 53 families presenting to a pediatric ED with a child experiencing an asthma exacerbation, education on asthma was presented via an interactive mobile-based video-game versus a standard-of-care asthma education video (SAV). Median age was 10 years; 64% were males. Many patients had moderate-to-severe asthma, with 57% experiencing ≥ 2 asthma-related ED visits in the last year, 58% requiring hospitalization and 32% reporting a critical care admission. In this cohort, the mobile-based video-game was found to be a feasible, acceptable educational tool; 86% of parents and 96% of children liked the game, while 96% of parents and 76% of children preferred playing the game over watching a SAV. Despite a history of persistent asthma, only 34% of children used an inhaled corticosteroid while 70% required rescue inhaler use in the prior week. Basic asthma knowledge was sub-optimal with only 60% of parents and 43% of children correctly recognizing symptoms that should prompt immediate medical care. This reflects a major gap in asthma knowledge that coexists with parental misconceptions regarding optimal asthma management.

Background: The innate mechanisms associated with viral exacerbations in preschool children with recurrent wheezing are not understood. Objective: We sought to assess differential gene expression in blood neutrophils from preschool children with recurrent wheezing, stratified by aeroallergen sensitization, at baseline and after exposure to polyinosinic:polycytidylic acid (poly(I:C)) and also to examine whether poly(I:C)-stimulated blood neutrophils influenced airway epithelial gene expression. Methods: Blood neutrophils were purified and cultured overnight with poly(I:C) and underwent next-generation sequencing with Reactome pathway analysis. Primary human small airway epithelial cells were treated with poly(I:C)-treated neutrophil culture supernatants and were analyzed for type 1 interferon gene expression with a targeted array. Symptoms and exacerbations were assessed in participants over 12 months. Results: A total of 436 genes were differently expressed in neutrophils from children with versus without aeroallergen sensitization at baseline, with significant downregulation of type 1 interferons. These type 1 interferons were significantly upregulated in sensitized children after poly(I:C) stimulation. Confirmatory experiments demonstrated similar upregulation of type 1 interferons in IL-4–treated neutrophils stimulated with poly(I:C). Poly(I:C)-treated neutrophil supernatants from children with aeroallergen sensitization also induced a type 1 interferon response in epithelial cells. Children with aeroallergen sensitization also had higher symptom scores during exacerbations, and these symptom differences persisted for 3 days after prednisolone treatment. Conclusions: Type 1 interferon responses are dysregulated in preschool children with aeroallergen sensitization, which is in turn associated with exacerbation severity. Given the importance of type 1 interferon signaling in viral resolution, additional studies of neutrophil type 1 interferon responses are needed in this population.

Objective There is a lack of longitudinal population-based research comparing women’s experiences of intimate partner violence (IPV) prior to and during the COVID-19 pandemic. Using data from the Mothers’ and Young People’s Study, the prevalence of physical and emotional IPV in the first year of the pandemic is compared with earlier waves of data.Design A prospective pregnancy cohort of first-time mothers in Melbourne, Australia was followed up over the first decade of motherhood, with a quick response study conducted during the COVID-19 pandemic. 422 women completed the primary exposure measure (IPV; Composite Abuse Scale) in the 1st, 4th and 10th year postpartum and the additional pandemic survey (June 2020–April 2021).Outcome measures Depressive symptoms; anxiety symptoms; IPV disclosure to a doctor, friends or family, or someone else.Results Maternal report of emotional IPV alone was higher during the pandemic (14.4%, 95% CI 11.4% to 18.2%) than in the 10th (9.5%, 95% CI 7.0% to 12.7%), 4th (9.2%, 95% CI 6.8% to 12.4%) and 1st year after the birth of their first child (5.9%, 95% CI 4.0% to 8.6%). Conversely, physical IPV was lowest during the pandemic (3.1%, 95% CI 1.8% to 5.0%). Of women experiencing IPV during the pandemic: 29.7% were reporting IPV for the first time, 52.7% reported concurrent depressive symptoms and just 6.8% had told their doctor.Conclusions Findings suggest that the spike in IPV-related crime statistics following the onset of the pandemic (typically incidents of physical violence) is the tip of the iceberg for women’s IPV experiences. There is a need to increase the capacity of health practitioners to recognise emotional as well as physical IPV, and IPV ought to be considered where women present with mental health problems.

Apalutamide is a novel nonsteroidal androgen receptor inhibitor that has been shown to improve outcomes for patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer when combined with androgen deprivation therapy. Apalutamide-induced skin rash occurred commonly in clinical trials, with 23.8–27.1% of patients experiencing a rash of any grade, and 5.2–6.3% experiencing a rash of grade three or higher. There were no cases of severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) reported in clinical trials; however, there are rare cases reported in the literature with the majority occurring in Asian patients. An 83-year-old Caucasian male was commenced on apalutamide, combined with degarelix, for the management of metastatic castration-sensitive prostate cancer. During week five of apalutamide treatment, the patient developed a widespread erythematous maculopapular rash. On presentation, the rash affected 80% of his body surface area (BSA) and a diagnosis of a severe cutaneous drug eruption was made. He was commenced on methylprednisolone (MP) therapy. Despite 5 days of MP, the rash continued to deteriorate involving 95% of his BSA. Nikolsky’s sign was positive. A diagnosis of overlap SJS/TEN was made, supported by skin biopsy. His SCORTEN score was three. He was then commenced on intravenous immunoglobulin and transferred to the intensive care unit. Over the coming days, the rash began to stabilise, and his steroid dose was weaned. He was discharged from hospital 38 days after rash onset. We report the first suggested case of apalutamide-induced SJS/TEN in a Caucasian patient. We discuss other cases of apalutamide-induced SCARs reported in the literature. Risk factors seem to include low body weight and Japanese race, as well as short time to onset of rash.

Abstract Background Medical students are at high risk for sleep disturbance. One possible cause of their sleeping problem is impulsivity. We aim to investigate the possible mediators between medical students’ impulsivity and sleep outcomes. Thus, we developed and investigated a model where the predictors were attentional, non-planning, and motor impulsivity subtraits. In the final model, subjective cognitive capacity decrease was the outcome variable. In light of previous findings, academic procrastination, smartphone addiction, and bedtime procrastination were considered important mediators as well as two variables of poor sleep, sleeping insufficiency, and daytime fatigue. Methods Medical students (N = 211; ageM = 22.15 years; ageSD = 3.47 years; 71.6% women) were recruited to complete an online survey comprised of demographics (age, gender), self-administered scales (Abbreviated Impulsiveness Scale, Bedtime Procrastination Scale, Abbreviated Impulsiveness Scale, Academic Procrastination Scale-Short Form) and questions on tiredness, daily fatigue and subjective cognitive capacity decrease. Correlation and path analyses were implemented to examine hypothesized relationships between the variables. Results Both attentional impulsivity (β = 0.33, p

BackgroundDuring the COVID-19 pandemic, care homes for older adults in England implemented isolation, social distancing and other restriction measures to help protect residents from contracting the virus. Little was known about the physical and psychological impacts that these measures would have upon residents and their relatives.AimTo explore the experiences of residents and their relatives of living restricted lives during the pandemic.MethodsThis qualitative study was conducted as part of a 12-month, mixed-methods, phased design. From six purposively sampled care homes in England, 17 purposively sampled residents (all older adults) and 17 purposively sampled relatives participated in an individual, on-line interview, where they discussed their experiences of the restrictive measures implemented within their care home. Interviews were audio- and video-recorded with participants' permission and analysed using an inductive orientation to thematic analysis, with coding and theme development driven by the data content.ResultsParticipants' experiences of care home restrictions varied; their impact was influenced by the existing pattern of relationships that residents and their relatives maintained within and beyond the care home. It was further influenced by the fact that many residents and relatives were still learning how to manage their relationships in the new context of living in a care home. Social distancing measures made care homes feel less homely and denied residents, staff and relatives physical touch and other forms of non-verbal communication. Many residents expressed a broad sense of gratitude that was associated with safety and well-being beyond the pandemic. As older adults, they put the pandemic, and its associated restrictions, within the larger context of their lives.ConclusionsLearning from the COVID-19 pandemic is paramount for governments, societies, policy makers, care home providers, care homes and their staff, residents and their families and friends, and researchers. Our study makes an important contribution as one of the first to study the impact of implementing isolation, social distancing and other restrictive measures for care home residents and their relatives in England.

Abstract Background Virtual care has become an increasingly useful tool for the virtual delivery of care across the globe. With the unexpected emergence of COVID-19 and ongoing public health restrictions, it has become evident that the delivery of high-quality telemedicine is critical to ensuring the health and wellbeing of Indigenous peoples, especially those living in rural and remote communities. Methods We conducted a rapid evidence review from August to December 2021 to understand how high quality Indigenous primary healthcare is defined in virtual modalities. After completing data extraction and quality appraisal, a total of 20 articles were selected for inclusion. The following question was used to guide the rapid review: How is high quality Indigenous primary healthcare defined in virtual modalities? Results We discuss key limitations to the delivery of virtual care, including the increasing cost of technology, lack of accessibility, challenges with digital literacy, and language barriers. This review further yielded four main themes that highlight Indigenous virtual primary healthcare quality: (1) limitations and barriers of virtual primary healthcare, (2) Indigenous-centred virtual primary healthcare, (3) virtual Indigenous relationality, (4) collaborative approaches to ensuring holistic virtual care. Discussion: For virtual care to be Indigenous-centred, Indigenous leadership and users need to be partners in the development, implementation and evaluation of the intervention, service or program. In terms of virtual models of care, time must be allocated to educate Indigenous partners on digital literacy, virtual care infrastructure, benefits and limitations. Relationality and culture must be prioritized as well as digital health equity. Conclusion These findings highlight important considerations for strengthening virtual primary healthcare approaches to meet the needs of Indigenous peoples worldwide.

Abstract Introduction During the pandemic many Canadian hospitals made significant changes to their ‘open family presence’ and ‘visitor policies’ to reduce the spread of COVID-19 by instituting restrictive or ‘zero visiting’ policies in healthcare facilities. These policies have the potential to create great hardship, anxiety and stress for patients, families, caregivers and frontline healthcare providers (HCPs); along with concerns about the quality and safety of patient care. The presence of family members and other caregivers as essential partners in care is an explicit expression of the philosophy of patient- and family-centred care (PFCC) in action. The purpose of this study is to increase our understanding of how changes to family presence and visiting policies and practices during the COVID-19 pandemic have impacted patients, family caregivers and frontline healthcare providers (HCPs) in acute care hospitals. Methods A total of 38 in-depth semi-structured interviews were conducted with patients, family caregivers and HCPs in Canadian provinces who had experience with visiting policies in acute care settings during the pandemic. COVID patients, and the caregivers of COVID patients, were excluded from this study. A maximum variation sampling strategy was used to guide the selection and recruitment of patients, family caregivers and HCPs, based on our interest in gaining a diversity of perspectives and experiences. Results Many patients, family caregivers, and HCPs view family caregiver presence as integral to PFCC, describing the essential roles played by family caregivers prior to the pandemic. There were commonalities across all three groups with respect to their perspectives on the impacts of restrictive visiting policies on patients, family caregivers and HCPs. They fell into four broad integrated categories: (1) emotional and mental health; (2) communication and advocacy; (3) safety and quality of care; and (4) PFCC, trust in the healthcare system, and future decisions regarding accessing needed healthcare. Recommendations for pandemic visiting policies were also identified. Conclusions The findings from this study highlighted several impacts of restrictive family caregiver presence or visiting policies implemented during COVID-19 on patients, family caregivers and HCPs in acute healthcare settings across Canada. Participants emphasized that there is no “one-size-fits-all” caregiver presence policy that will address all patient needs. To be consistent with the practice of PFCC, patients and family caregivers are welcomed as part of the healthcare team in ways that work for them, demonstrating that flexibility in family presence and visiting policies is essential.

Abstract Biofluorescence occurs when a living organism absorbs high energy light and reemits it at longer wavelengths. Many species within clades of vertebrates are known to fluoresce including mammals, reptiles, birds, and fish. Most, if not all, amphibians exhibit biofluorescence when exposed to either blue (440–460 nm) or ultra-violet (360–380 nm) wavelengths of light. Salamanders (Lissamphibia: Caudata) appear to consistently fluoresce in green wavelengths (520–560 nm) when excited by blue light. Biofluorescence is theorized to have many ecological functions including mate signaling, camouflage, and mimicry. Despite the discovery of their biofluorescence, its role in salamander ecology and behavior remains unresolved. In this study we present the first case of biofluorescent sexual dimorphism within Amphibia and the first documentation of the biofluorescent pattern of a salamander within the Plethodon jordani species complex. This sexually dimorphic trait was discovered in the southern Appalachian endemic species, Southern Gray-Cheeked Salamander (Plethodon metcalfi, Brimley in Proc Biol Soc Wash 25:135–140, 1912), and may extend into other species within the Plethodon jordani and Plethodon glutinosus species complexes. We propose that this sexually dimorphic trait could be related to fluorescence of ventral modified granular glands used in plethodontid chemosensory communication.

Abstract Children with life-threatening asthma exacerbations who are admitted to a pediatric intensive care unit (PICU) are a heterogeneous group with poorly studied inflammatory features. We hypothesized that distinct clusters of children with asthma in a PICU would be identified based on differences in plasma cytokine levels and that these clusters would have differing underlying inflammation and asthma outcomes within 1 year. Plasma cytokines and differential gene expression were measured in neutrophils isolated from children admitted to a PICU for asthma. Participants were clustered by differential plasma cytokine abundance. Gene expression differences were compared by cluster and pathway over-representation analysis was performed. We identified two clusters in 69 children with no clinical differences. Cluster 1 (n = 41) had higher cytokines compared to Cluster 2 (n = 28). Cluster 2 had a hazard ratio of 2.71 (95% CI 1.11–6.64) compared to Cluster 1 for time to subsequent exacerbation. Gene expression pathways that differed by cluster included interleukin-10 signaling; nucleotide-binding domain, leucine rich repeat containing receptor (NLR signaling); and toll-like receptor (TLR) signaling. These observations suggest that a subset of children may have a unique pattern of inflammation during PICU hospitalization that might require alternative treatment approaches.

Abstract Purpose Breast cancer is one of the most prevalent malignant diseases in women. The development of dose dense chemotherapy regimens has improved clinical outcomes but has been associated with increased hematological toxicity. Currently there is a paucity of data on the use of lipegfilgrastim in dose dense AC treatment in early breast cancer. The purpose of this study was to assess the use of lipegfilgrastim in the treatment of early breast cancer and to examine the incidence of treatment-related neutropenia during the dose dense AC phase and subsequent paclitaxel treatment. Methods This was a single arm, non-interventional, prospective study. The primary endpoint was to determine the rate of neutropenia defined as ANC of 38 °C and ANC

Abstract The host immune response to a viral immune stimulus has not been examined in children during a life-threatening asthma attack. We determined whether we could identify clusters of children with critical asthma by functional immunophenotyping using an intracellular viral analog stimulus. We performed a single-center, prospective, observational cohort study of 43 children ages 6–17 years admitted to a pediatric intensive care unit for an asthma attack between July 2019 to February 2021. Neutrophils were isolated from children, stimulated overnight with LyoVec poly(I:C), and mRNA was analyzed using a targeted Nanostring immunology array. Network analysis of the differentially expressed transcripts for the paired LyoVec poly(I:C) samples was performed. We identified two clusters by functional immunophenotyping that differed by the Asthma Control Test score. Cluster 1 (n = 23) had a higher proportion of children with uncontrolled asthma in the four weeks prior to PICU admission compared with cluster 2 (n = 20). Pathways up-regulated in cluster 1 versus cluster 2 included chemokine receptor/chemokines, interleukin-10 (IL-10), IL-4, and IL-13 signaling. Larger validation studies and clinical phenotyping of children with critical asthma are needed to determine the predictive utility of these clusters in a larger clinical setting.

Abstract Conservation practitioners often rely on captive breeding programs to supplement wild populations at risk of extinction. While supplementation has been successful for some taxa, the success of using hatchery fish to supplement wild populations is severely impacted by predation. Elevated predation on hatchery fish may arise because hatchery environments often differ from wild environments and constrain the ability of hatchery fish to be adapted to the environments in which they are released. We assessed the effects of abiotic enrichment on the expression of behavioral and morphological phenotypes across three populations of a species of conservation concern, the Arkansas darter (Etheostoma cragini). We also used a factorial approach to assess whether abiotic enrichment and predator training increases survival during encounters with a novel predator. We found that abiotic enrichment affected ecomorphological attributes associated with fins; generally, measures of the caudal and pectoral fin decreased in the treatment group compared to the control treatment. Behaviorally, darters reared with abiotic enrichment increased feeding and decreased movement compared to the control group. Importantly, we found that in combination with predator training, abiotic enrichment increased the probability of surviving first encounters with a predator. We therefore recommend conservation practitioners incorporate abiotic enrichment and predator training in hatchery programs. Captive breeding programs are used to supplement wild populations at risk of extinction, but hatchery‐reared fish often do not survive after release. Using the threatened Arkansas darter, we show that abiotic enrichment and predator training of hatchery populations impact behavior and morphology and increase the probability of surviving first encounters with a non‐native predator.

It is now possible for real-life activities, unfolding over their natural range of temporal and spatial scales, to become the primary targets of cognitive studies. Movement toward this type of research will require an integrated methodological approach currently uncommon in the field. When executed hand in hand with thorough and ecologically valid empirical description, properly developed laboratory tasks can serve as model systems to capture the essentials of a targeted real-life activity. When integrated together, data from these two kinds of studies can facilitate causal analysis and modeling of the mental and neural processes that govern that activity, enabling a fuller account than either method can provide on its own. The resulting account, situated in the activity’s natural environmental, social, and motivational context, can then enable effective and efficient development of interventions to support and improve the activity as it actually unfolds in real time. We believe that such an integrated multi-level research program should be common rather than rare and is necessary to achieve scientifically and societally important goals. The time is right to finally abandon the boundaries that separate the laboratory from the outside world.

Background: Asthma exacerbations are highly prevalent in children, but only a few studies have examined the biologic mechanisms underlying exacerbations in this population. Objective: High-resolution metabolomics analyses were performed to understand the differences in metabolites in children with exacerbating asthma who were hospitalized in a pediatric intensive care unit for status asthmaticus. We hypothesized that compared with a similar population of stable outpatients with asthma, children with exacerbating asthma would have differing metabolite abundance patterns with distinct clustering profiles. Methods: A total of 98 children aged 6 through 17 years with exacerbating asthma (n = 69) and stable asthma (n = 29) underwent clinical characterization procedures and submitted plasma samples for metabolomic analyses. High-confidence metabolites were retained and utilized for pathway enrichment analyses to identify the most relevant metabolic pathways that discriminated between groups. Results: In all, 118 and 131 high-confidence metabolites were identified in positive and negative ionization mode, respectively. A total of 103 unique metabolites differed significantly between children with exacerbating asthma and children with stable asthma. In all, 8 significantly enriched pathways that were largely associated with alterations in arginine, phenylalanine, and glycine metabolism were identified. However, other metabolites and pathways of interest were also identified. Conclusion: Metabolomic analyses identified multiple perturbed metabolites and pathways that discriminated children with exacerbating asthma who were hospitalized for status asthmaticus. These results highlight the complex biology of inflammation in children with exacerbating asthma and argue for additional studies of the metabolic determinants of asthma exacerbations in children because many of the identified metabolites of interest may be amenable to targeted interventions.

IMPORTANCE:. CD4+ T cells contribute to lung inflammation in acute respiratory distress syndrome. The CD4+ T-cell response in pediatric acute respiratory distress syndrome (PARDS) is unknown. OBJECTIVES:. To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor CD4+ T cells exposed to the airway fluid of intubated children with mild versus severe PARDS. DESIGN:. In vitro pilot study. SETTING:. Laboratory-based study using human airway fluid samples admitted to a 36-bed university-affiliated pediatric intensive care unit. PATIENTS/SUBJECTS:. Seven children with severe PARDS, nine children with mild PARDS, and four intubated children without lung injury as controls. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We performed bulk RNA sequencing using a transcriptomic reporter assay of CD4+ T cells exposed to airway fluid from intubated children to discover gene networks differentiating severe from mild PARDS. We found that innate immunity pathways, type I (α and β), and type II (γ) interferon response and cytokine/chemokine signaling are downregulated in CD4+ T cells exposed to airway fluid from intubated children with severe PARDS compared with those with mild PARDS. CONCLUSIONS:. We identified gene networks important to the PARDS airway immune response using bulk RNA sequencing from a novel CD4+ T-cell reporter assay that exposed CD4+ T cells to airway fluid from intubated children with severe and mild PARDS. These pathways will help drive mechanistic investigations into PARDS. Validation of our findings using this transcriptomic reporter assay strategy is needed.

Social differences are evident in both developed and developing countries. During adolescence, there are limited differences in morbidity and mortality, but differences do appear in terms of health behaviours. This study aims to examine the relationship(s) between social differences and students’ health behaviours. A cross-sectional study was conducted in 2020 with a sample of high school students (N = 2741, aged 13–18 years) in Jordan. Besides descriptive statistics, bivariate logistic regression analysis was used to detect the odds risk for each social difference indicator. Females were engaged in more healthy dietary and hygienic behaviours and less engaged in smoking. Males were more physically active. Adolescents with a higher parental education level were more engaged in healthy behaviours; however, they drank carbonated soft drinks and ate fast food more often. Higher SES (socioeconomic status) self-evaluation was positively associated with eating breakfast and fruit and vegetables, being physically active, drinking carbonated soft drinks, eating fast food, and smoking. Our findings suggest that socioeconomic differences are important to understanding Jordanian adolescents’ health behaviours. While females tend to engage in more healthy behaviours, the role of parental education and perceived family affluence is not always beneficial in terms of adolescents’ dietary habits, hygienic behaviour, or smoking.

IntroductionThe aim of this study was to quantify the amount of deterioration in hearing and to document the trajectory of hearing loss in early identified children with unilateral hearing loss (UHL). We also examined whether clinical characteristics were associated with the likelihood of having progressive hearing loss.MethodsAs part of the Mild and Unilateral Hearing Loss Study, we followed a population-based cohort of 177 children diagnosed with UHL from 2003 to 2018. We applied linear mixed models to examine hearing trends over time including the average amount of change in hearing. Logistic regression models were used to examine the relationship between age and severity at diagnosis, etiology, and the likelihood of progressive loss and amount of deterioration in hearing.ResultsThe median age of the children at diagnosis was 4.1 months (IQR 2.1, 53.9) and follow-up time was 58.9 months (35.6, 92.0). Average hearing loss in the impaired ear was 58.8 dB HL (SD 28.5). Over the 16-year period, 47.5% (84/177) of children showed deterioration in hearing in one or both ears from their initial diagnostic assessment to most recent assessment including 21 (11.9%) who developed bilateral hearing loss. Average deterioration in the impaired ear ranged from 27 to 31 dB with little variation across frequencies. Deterioration resulted in a change in category of severity for 67.5% (52/77) of the children. Analysis for children who were followed for at least 8 years showed that most lost a significant amount of hearing rapidly in the first 4 years, with the decrease stabilizing and showing a plateau in the last 4 years. Age and severity at diagnosis were not significantly associated with progressive/stable loss after adjusting for time since diagnosis. Etiologic factors (ENT external/middle ear anomalies, inner ear anomalies, syndromic hearing loss, hereditary/genetic) were found to be positively associated with stable hearing loss.ConclusionAlmost half of children with UHL are at risk for deterioration in hearing in one or both ears. Most deterioration occurs within the first 4 years following diagnosis. Most children did not experience sudden “large” drops in hearing but more gradual decrease over time. These results suggest that careful monitoring of UHL especially in the early years is important to ensure optimal benefit from early hearing loss detection.

Wastewater treatment plant effluent can increase stream water temperature from near freezing to 5°C–12°C in winter months. Recent research in the South Platte River Basin in Colorado showed that this warming alters the reproductive timing of some fishes. However, the spatial extent and magnitude of this warming are unknown. Thus, we created winter water temperature models both upstream and downstream of effluent inputs for two urban tributaries of the South Platte River, the Big Thompson River, and St. Vrain Creek. We examined the influence of air temperature, discharge, effluent temperature, and distance downstream on water temperature over the winter period (December–February). The models were also used to predict water temperature in the absence of effluent and based on air temperature predictions in 2052 and 2082. Effluent temperature was the largest driver of water temperature downstream of the effluent, while the impact of air temperature was comparatively small. Streams cooled after an initially sharp temperature increase, though were still predicted to be ∼2°C greater than they would be in the absence of effluent at ∼0.5 km. Predicted air temperatures in 2052 and 2082 had a negligible effect on water temperature, suggesting that mitigating effluent temperature is key to protecting the winter thermal regimes of effluent-impacted rivers. Our models can be used to gain insight into the magnitude and downstream extent of the impact of effluent temperature on small urban streams in winter and provide a baseline for models in other watersheds and at larger scales.

The novel coronavirus (Covid-19) pandemic has had a significant impact on the mental health of the general U.S. population. Extant literature has increasingly linked social vulnerabilities, risky behavior, and limited social and psychological resources to the growing mental health crisis during the virus's spread. The purpose of this study was to examine the impact of pertinent social vulnerabilities and subjective risk factors for both men and women on mental health (i.e., depression, anxiety, isolation) with a closer examination of the influence of pregnancy during the pandemic on mental health. The sample included 740,640 respondents participating in the U.S. Covid-19 Trends and Impact Survey that was deployed between February and March 2021. Descriptive statistics and ordinary least squares regression models are presented with a focus on the factors that shape negative mental health outcomes, particularly on the disparities between pregnant and non-pregnant women relative to men, but also subjective/perception factors (e.g., fear/worry) and social vulnerabilities. Results show that pregnant women were at significantly greater risk of negative mental health outcomes at this stage of the pandemic than either men or non-pregnant women. Overall, respondents who were younger, without children in the household, unemployed, worried generally about infection or their finances, or had ever tested positive for Covid were also more likely to report feelings of anxiety, isolation, and depression than their counterparts. Pregnant women may be especially vulnerable to depression, anxiety, and isolation during the pandemic and our findings suggest the importance of developing targeted mental health support for this sub-population.

Prehistoric colonization of East Polynesia represents the last and most extensive of human migrations into regions previously uninhabited. Although much of East Polynesia is tropical, the southern third, dominated by New Zealand-by far the largest Polynesian landmass-ranges from a warm- to cool-temperate climate with some islands extending into the Subantarctic. The substantial latitudinal variation implies questions about biocultural adaptations of tropical people to conditions in which most of their familiar resources were absent and their agriculture marginal. Perhaps the most basic question, but one which has never been explored, is the extent to which sailing out of the tropics on long-distance colonizing voyages imposed physiological stress on canoe crews and passengers. In this paper we use trajectories of simulated voyages from Tahiti to New Zealand and Tahiti to Hawaii to obtain along-trip environmental parameters which are then used to model the energy expenditure of these long overseas journeys. Results show that travelers to New Zealand are exposed to much harsher environmental conditions, leading to significantly greater in-trip thermoregulatory demands. For both destinations, travelers with larger body sizes exhibit lower modeled heat loss and hence obtain an energetic advantage, with greater gains for females. Such physiological features, notably of Samoans who probably formed the founding population in East Polynesia, may help explain successful voyaging to temperate latitudes.

IntroductionFemale cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health needs of emerging adult female survivors of childhood cancer and to identify decisional and contextual factors that influence pursuit of FSA using an explanatory sequential quantitative to qualitative mixed methods design.Methods and analysisThis study will enroll 325 female survivors (aged 18 to 29 years and >1-year post treatment; diagnosed with cancer < age 21 years) from four cancer centers in the United States. Sociodemographic and developmental factors, reproductive knowledge and values, decisional needs, and receipt of an FSA will be assessed through a web-based survey. Informed by survey findings, a subset of participants will be recruited for qualitative interviews to explore decisional factors associated with uptake of an FSA. Clinical data will be abstracted from the medical records. Multivariable logistic regression models will be developed to identify factors associated with FSA and qualitative descriptive analysis will be used to develop themes from the interviews. Quantitative and qualitative findings will be merged using a joint display to develop integrated study conclusions and direct future interventional research.

The application of induced pluripotent stem cells (iPSCs) in advanced therapies is increasing at pace, but concerns remain over their clinical safety profile. We report the first-ever application of doggybone DNA (dbDNA) vectors to generate human iPSCs. dbDNA vectors are closed-capped linear double-stranded DNA gene expression cassettes that contain no bacterial DNA and are amplified by a chemically defined, current good manufacturing practice (cGMP)-compliant methodology. We achieved comparable iPSC reprogramming efficiencies using transiently expressing dbDNA vectors with the same iPSC reprogramming coding sequences as the state-of-the-art OriP/EBNA1 episomal vectors but, crucially, in the absence of p53 shRNA repression. Moreover, persistent expression of EBNA1 from bacterially derived episomes resulted in stimulation of the interferon response, elevated DNA damage, and increased spontaneous differentiation. These cellular activities were diminished or absent in dbDNA-iPSCs, resulting in lines with a greater stability and safety potential for cell therapy.

Abstract Hierarchal clustering of amino acid metabolites may identify a metabolic signature in children with pediatric acute hypoxemic respiratory failure. Seventy-four immunocompetent children, 41 (55.4%) with pediatric acute respiratory distress syndrome (PARDS), who were between 2 days to 18 years of age and within 72 h of intubation for acute hypoxemic respiratory failure, were enrolled. We used hierarchal clustering and partial least squares-discriminant analysis to profile the tracheal aspirate airway fluid using quantitative LC–MS/MS to explore clusters of metabolites that correlated with acute hypoxemia severity and ventilator-free days. Three clusters of children that differed by severity of hypoxemia and ventilator-free days were identified. Quantitative pathway enrichment analysis showed that cysteine and methionine metabolism, selenocompound metabolism, glycine, serine and threonine metabolism, arginine biosynthesis, and valine, leucine, and isoleucine biosynthesis were the top five enriched, impactful pathways. We identified three clusters of amino acid metabolites found in the airway fluid of intubated children important to acute hypoxemia severity that correlated with ventilator-free days

OBJECTIVES:. Pediatric acute respiratory distress syndrome (PARDS) is a heterogeneous illness affecting 6% of mechanically ventilated children and with an overall mortality of 17%. Studies in PARDS have mainly focused on plasma biomarkers which may not reflect airway biomarkers. We lack adequate understanding of the inflammatory mediators and underlying immune responses in the airways of PARDS patients. Our objective was to compare the levels of cytokines in the airway fluid of intubated children with severe versus nonsevere acute respiratory distress syndrome. DESIGN:. Prospective observational cohort study. SETTING:. Single 36-bed quaternary care academic safety-net hospital PICU. PATIENTS:. Children intubated for acute respiratory failure between January 2018 and November 2021 stratified by Pediatric Acute Lung Injury Consensus Conference-1 criteria for PARDS. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We measured levels of 23 cytokines, chemokines, and protein biomarkers in the tracheal aspirate from 82 intubated children, between 14 days and 17 years old, at risk for or with PARDS. Levels of interleukin-4, -5, -7, -8, -12(p-70), -17a, -21, and fractalkine were higher in patients with severe versus nonsevere PARDS. There were no associations between airway and plasma cytokines. CONCLUSIONS:. Proinflammatory cytokines are elevated in the airway fluid from intubated children with severe PARDS and reflect diverse patterns of airway inflammation.

Connectivity is critical for stream fish persistence, and fish passage structures are a useful conservation tool to reconnect fragmented systems. The design of fish passage structures is a tradeoff between the area available for construction, slope, and costs associated with the structure. The Longrie–Fecteau fish passage structure was designed to be modular, adjustable to barrier-specific needs, and to have a low slope (2%) to pass small-bodied fishes. We evaluated fish passage through this structure in Fountain Creek, Colorado, USA, via a PIT tag mark–recapture study. We documented four native Great Plains fish species successfully ascending the passage structure, with most passage occurring at night. We estimated a 3% probability of a released fish entering the structure, then 89% and 99% passage to the midpoint and exit of the 123 m structure, respectively. Low entrance efficiency was due to low recapture probability of small-bodied study organisms in a relatively large system, and the low percentage of space of the entryway on this barrier (

Adverse childhood experiences (ACEs) are linked to adverse health outcomes for adults and children in the United States. The prevalence of critically ill children who are exposed to ACEs is not known. Our objective was to compare the frequency of ACEs of critically ill children with that of the general pediatric population of Georgia and the United States using publicly available National Survey of Children’s Health (NSCH) data. The impact of ACEs on patient-reported outcome measures of emotional, social, and physical health in critically ill children is not known. We sought to determine whether a higher total number of ACEs was associated with poorer patient-reported measures of emotional, social, and physical health. We conducted a prospective cross-sectional study of children < 18 years of age who were admitted to a 36-bed free-standing, quaternary academic pediatric intensive care unit in Atlanta, Georgia from June 2020—December 2021. Parents of patients who were admitted to the pediatric intensive care unit completed a survey regarding their child’s ACEs, health care use patterns, and patient-reported outcome measures (PROMIS) of emotional, social, and physical health. Prevalence estimates of ACEs were compared with national and state data from the NSCH using Rao-Scott Chi-square tests. PROMIS measures reported within the PICU cohort were compared with population normed T-scores. The association of cumulative ACEs within the PICU cohort with patient-reported outcomes of emotional, social, and physical health were evaluated with a t-test. Among the 84 participants, 54% had ≥ 1 ACE, 29% had ≥ 2 ACEs, and 10% had ≥ 3 ACEs. Children with ≥ 2 ACEs had poorer anxiety and family relationship T-scores compared to those with ≤ 1 ACE. Given the high burden of ACEs in critically ill children, screening for ACEs may identify vulnerable children that would benefit from interventions and support to mitigate the negative effects of ACEs and toxic stress on emotional, social, and physical health.

Abstract Background Worse health outcomes are consistently reported for First Nations people in Canada. Social, political and economic inequities as well as inequities in health care are major contributing factors to these health disparities. Emergency care is an important health services resource for First Nations people. First Nations partners, academic researchers, and health authority staff are collaborating to examine emergency care visit characteristics for First Nations and non-First Nations people in the province of Alberta. Methods We conducted a population-based retrospective cohort study examining all Alberta emergency care visits from April 1, 2012 to March 31, 2017 by linking administrative data. Patient demographics and emergency care visit characteristics for status First Nations persons in Alberta, and non-First Nations persons, are reported. Frequencies and percentages (%) describe patients and visits by categorical variables (e.g., Canadian Triage and Acuity Scale). Means, medians, standard deviations and interquartile ranges describe continuous variables (e.g., age). Results The dataset contains 11,686,288 emergency care visits by 3,024,491 unique persons. First Nations people make up 4% of the provincial population and 9.4% of provincial emergency visits. The population rate of emergency visits is nearly 3 times higher for First Nations persons than non-First Nations persons. First Nations women utilize emergency care more than non-First Nations women (54.2% of First Nations visits are by women compared to 50.9% of non-First Nations visits). More First Nations visits end in leaving without completing treatment (6.7% v. 3.6%). Conclusions Further research is needed on the impact of First Nations identity on emergency care drivers and outcomes, and on emergency care for First Nations women.

Social support from family, friends, and others enhances the quality of life and acts as an important protective mechanism against mental health problems. The purpose of this study is to investigate how social support is related to mental health outcomes among Jordanian adolescents. Data were collected in 2020 from public and private schools in Irbid governorate, Jordan. Multistage cluster sampling was used to recruit students from 8th – 12th grades (N = 2741; ages 13–18 years). The study finds social support is related to higher levels of life satisfaction and self-esteem. The negative association between social support and depressive symptoms is also significant. Our findings underscore the importance of the role of social support, especially support from family. This support is important to adolescents’ mental health and underscores the importance of policymakers giving greater attention to the family dynamic and its impact on student well-being.

Sex bias in autoimmune disease (AID) prevalence is known, but the role of estrogen in disease progression is more complex. Estrogen can even be protective in some AIDs; but in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc), estrogen, its metabolites, and its receptors have been demonstrated to play critical, localized inflammatory roles. Estrogen is instrumental to the fibrosis seen in RA, SLE, SSc and other disease states, including breast cancer and uterine leiomyomas. Fibrotic diseases tend to share a common pattern in which lymphocyte–monocyte interactions generate cytokines which stimulate the deposition of fibrogenic connective tissue. RA, SLE, SSc and thyroid eye disease (TED) have very similar inflammatory and fibrotic patterns—from pathways to tissue type. The thorough investigations that demonstrated estrogen’s role in the pathology of RA, SLE, and SSc could, and possibly should, be carried out in TED. One might even expect to find an even greater role for estrogen, and sex steroid homeostasis in TED, given that TED is typically sequalae to Graves’ disease (GD), or Hashimoto’s disease (HD), and these are endocrine disorders that can create considerable sex steroid hormone dysregulation. This paper highlights the pathophysiology similarities in 4 AIDs, examines the evidence of sex steroid mediated pathology across 3 AIDs and offers a case study and speculation on how this may be germane to TED.